Concanavalin A-like lectin protein kinase family protein [Arabidopsis thaliana]
Protein Classification
L-type lectin domain-containing receptor kinase( domain architecture ID 10160928)
L-type lectin domain-containing receptor kinase (LecRK) plays crucial roles during development and in the adaptive response to various stimuli
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| lectin_legume_LecRK_Arcelin_ConA | cd06899 | legume lectins, lectin-like receptor kinases, arcelin, concanavalinA, and alpha-amylase ... |
27-265 | 5.58e-99 | |||||
legume lectins, lectin-like receptor kinases, arcelin, concanavalinA, and alpha-amylase inhibitor; This alignment model includes the legume lectins (also known as agglutinins), the arcelin (also known as phytohemagglutinin-L) family of lectin-like defense proteins, the LecRK family of lectin-like receptor kinases, concanavalinA (ConA), and an alpha-amylase inhibitor. Arcelin is a major seed glycoprotein discovered in kidney beans (Phaseolus vulgaris) that has insecticidal properties and protects the seeds from predation by larvae of various bruchids. Arcelin is devoid of monosaccharide binding properties and lacks a key metal-binding loop that is present in other members of this family. Phytohaemagglutinin (PHA) is a lectin found in plants, especially beans, that affects cell metabolism by inducing mitosis and by altering the permeability of the cell membrane to various proteins. PHA agglutinates most mammalian red blood cell types by binding glycans on the cell surface. Medically, PHA is used as a mitogen to trigger cell division in T-lymphocytes and to activate latent HIV-1 from human peripheral lymphocytes. Plant L-type lectins are primarily found in the seeds of leguminous plants where they constitute about 10% of the total soluble protein of the seed extracts. They are synthesized during seed development several weeks after flowering and transported to the vacuole where they become condensed into specialized vesicles called protein bodies. L-type lectins have a dome-shaped beta-barrel carbohydrate recognition domain with a curved seven-stranded beta-sheet referred to as the "front face" and a flat six-stranded beta-sheet referred to as the "back face". This domain homodimerizes so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely. : Pssm-ID: 173887 Cd Length: 236 Bit Score: 301.84 E-value: 5.58e-99
|
|||||||||
| PKc_like super family | cl21453 | Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ... |
358-612 | 9.41e-70 | |||||
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins. The actual alignment was detected with superfamily member cd14066: Pssm-ID: 473864 [Multi-domain] Cd Length: 272 Bit Score: 227.16 E-value: 9.41e-70
|
|||||||||
| Name | Accession | Description | Interval | E-value | ||||||
| lectin_legume_LecRK_Arcelin_ConA | cd06899 | legume lectins, lectin-like receptor kinases, arcelin, concanavalinA, and alpha-amylase ... |
27-265 | 5.58e-99 | ||||||
legume lectins, lectin-like receptor kinases, arcelin, concanavalinA, and alpha-amylase inhibitor; This alignment model includes the legume lectins (also known as agglutinins), the arcelin (also known as phytohemagglutinin-L) family of lectin-like defense proteins, the LecRK family of lectin-like receptor kinases, concanavalinA (ConA), and an alpha-amylase inhibitor. Arcelin is a major seed glycoprotein discovered in kidney beans (Phaseolus vulgaris) that has insecticidal properties and protects the seeds from predation by larvae of various bruchids. Arcelin is devoid of monosaccharide binding properties and lacks a key metal-binding loop that is present in other members of this family. Phytohaemagglutinin (PHA) is a lectin found in plants, especially beans, that affects cell metabolism by inducing mitosis and by altering the permeability of the cell membrane to various proteins. PHA agglutinates most mammalian red blood cell types by binding glycans on the cell surface. Medically, PHA is used as a mitogen to trigger cell division in T-lymphocytes and to activate latent HIV-1 from human peripheral lymphocytes. Plant L-type lectins are primarily found in the seeds of leguminous plants where they constitute about 10% of the total soluble protein of the seed extracts. They are synthesized during seed development several weeks after flowering and transported to the vacuole where they become condensed into specialized vesicles called protein bodies. L-type lectins have a dome-shaped beta-barrel carbohydrate recognition domain with a curved seven-stranded beta-sheet referred to as the "front face" and a flat six-stranded beta-sheet referred to as the "back face". This domain homodimerizes so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely. Pssm-ID: 173887 Cd Length: 236 Bit Score: 301.84 E-value: 5.58e-99
|
||||||||||
| Lectin_legB | pfam00139 | Legume lectin domain; |
27-274 | 6.35e-92 | ||||||
Legume lectin domain; Pssm-ID: 459688 Cd Length: 245 Bit Score: 283.76 E-value: 6.35e-92
|
||||||||||
| STKc_IRAK | cd14066 | Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ... |
358-612 | 9.41e-70 | ||||||
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 227.16 E-value: 9.41e-70
|
||||||||||
| PK_Tyr_Ser-Thr | pfam07714 | Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ... |
356-610 | 7.94e-33 | ||||||
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases. Pssm-ID: 462242 [Multi-domain] Cd Length: 258 Bit Score: 126.84 E-value: 7.94e-33
|
||||||||||
| TyrKc | smart00219 | Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily. |
355-610 | 5.59e-32 | ||||||
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily. Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 124.57 E-value: 5.59e-32
|
||||||||||
| SPS1 | COG0515 | Serine/threonine protein kinase [Signal transduction mechanisms]; |
356-601 | 1.52e-23 | ||||||
Serine/threonine protein kinase [Signal transduction mechanisms]; Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 104.32 E-value: 1.52e-23
|
||||||||||
| PLN00113 | PLN00113 | leucine-rich repeat receptor-like protein kinase; Provisional |
314-613 | 4.50e-17 | ||||||
leucine-rich repeat receptor-like protein kinase; Provisional Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 85.28 E-value: 4.50e-17
|
||||||||||
| PknB_PASTA_kin | NF033483 | Stk1 family PASTA domain-containing Ser/Thr kinase; |
422-537 | 1.58e-03 | ||||||
Stk1 family PASTA domain-containing Ser/Thr kinase; Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 41.32 E-value: 1.58e-03
|
||||||||||
| Name | Accession | Description | Interval | E-value | ||||||
| lectin_legume_LecRK_Arcelin_ConA | cd06899 | legume lectins, lectin-like receptor kinases, arcelin, concanavalinA, and alpha-amylase ... |
27-265 | 5.58e-99 | ||||||
legume lectins, lectin-like receptor kinases, arcelin, concanavalinA, and alpha-amylase inhibitor; This alignment model includes the legume lectins (also known as agglutinins), the arcelin (also known as phytohemagglutinin-L) family of lectin-like defense proteins, the LecRK family of lectin-like receptor kinases, concanavalinA (ConA), and an alpha-amylase inhibitor. Arcelin is a major seed glycoprotein discovered in kidney beans (Phaseolus vulgaris) that has insecticidal properties and protects the seeds from predation by larvae of various bruchids. Arcelin is devoid of monosaccharide binding properties and lacks a key metal-binding loop that is present in other members of this family. Phytohaemagglutinin (PHA) is a lectin found in plants, especially beans, that affects cell metabolism by inducing mitosis and by altering the permeability of the cell membrane to various proteins. PHA agglutinates most mammalian red blood cell types by binding glycans on the cell surface. Medically, PHA is used as a mitogen to trigger cell division in T-lymphocytes and to activate latent HIV-1 from human peripheral lymphocytes. Plant L-type lectins are primarily found in the seeds of leguminous plants where they constitute about 10% of the total soluble protein of the seed extracts. They are synthesized during seed development several weeks after flowering and transported to the vacuole where they become condensed into specialized vesicles called protein bodies. L-type lectins have a dome-shaped beta-barrel carbohydrate recognition domain with a curved seven-stranded beta-sheet referred to as the "front face" and a flat six-stranded beta-sheet referred to as the "back face". This domain homodimerizes so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely. Pssm-ID: 173887 Cd Length: 236 Bit Score: 301.84 E-value: 5.58e-99
|
||||||||||
| Lectin_legB | pfam00139 | Legume lectin domain; |
27-274 | 6.35e-92 | ||||||
Legume lectin domain; Pssm-ID: 459688 Cd Length: 245 Bit Score: 283.76 E-value: 6.35e-92
|
||||||||||
| STKc_IRAK | cd14066 | Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ... |
358-612 | 9.41e-70 | ||||||
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 227.16 E-value: 9.41e-70
|
||||||||||
| STK_BAK1_like | cd14664 | Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ... |
358-612 | 4.16e-53 | ||||||
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271134 [Multi-domain] Cd Length: 270 Bit Score: 183.08 E-value: 4.16e-53
|
||||||||||
| STKc_IRAK1 | cd14159 | Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ... |
358-541 | 5.65e-38 | ||||||
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271061 [Multi-domain] Cd Length: 296 Bit Score: 142.66 E-value: 5.65e-38
|
||||||||||
| PK_Tyr_Ser-Thr | pfam07714 | Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ... |
356-610 | 7.94e-33 | ||||||
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases. Pssm-ID: 462242 [Multi-domain] Cd Length: 258 Bit Score: 126.84 E-value: 7.94e-33
|
||||||||||
| STKc_MAP3K-like | cd13999 | Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ... |
358-610 | 2.02e-32 | ||||||
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway. Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 125.34 E-value: 2.02e-32
|
||||||||||
| TyrKc | smart00219 | Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily. |
355-610 | 5.59e-32 | ||||||
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily. Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 124.57 E-value: 5.59e-32
|
||||||||||
| STYKc | smart00221 | Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ... |
356-610 | 8.21e-32 | ||||||
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase. Pssm-ID: 214568 [Multi-domain] Cd Length: 258 Bit Score: 123.81 E-value: 8.21e-32
|
||||||||||
| PTKc | cd00192 | Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ... |
356-610 | 1.33e-31 | ||||||
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270623 [Multi-domain] Cd Length: 262 Bit Score: 123.42 E-value: 1.33e-31
|
||||||||||
| PKc | cd00180 | Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ... |
358-533 | 5.69e-31 | ||||||
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase. Pssm-ID: 270622 [Multi-domain] Cd Length: 215 Bit Score: 120.45 E-value: 5.69e-31
|
||||||||||
| STKc_IRAK4 | cd14158 | Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ... |
353-546 | 4.12e-29 | ||||||
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271060 [Multi-domain] Cd Length: 288 Bit Score: 117.21 E-value: 4.12e-29
|
||||||||||
| S_TKc | smart00220 | Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ... |
352-608 | 4.87e-26 | ||||||
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily. Pssm-ID: 214567 [Multi-domain] Cd Length: 254 Bit Score: 107.23 E-value: 4.87e-26
|
||||||||||
| lectin_L-type | cd01951 | legume lectins; The L-type (legume-type) lectins are a highly diverse family of carbohydrate ... |
50-262 | 1.24e-25 | ||||||
legume lectins; The L-type (legume-type) lectins are a highly diverse family of carbohydrate binding proteins that generally display no enzymatic activity toward the sugars they bind. This family includes arcelin, concanavalinA, the lectin-like receptor kinases, the ERGIC-53/VIP36/EMP46 type1 transmembrane proteins, and an alpha-amylase inhibitor. L-type lectins have a dome-shaped beta-barrel carbohydrate recognition domain with a curved seven-stranded beta-sheet referred to as the "front face" and a flat six-stranded beta-sheet referred to as the "back face". This domain homodimerizes so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely. Pssm-ID: 173886 [Multi-domain] Cd Length: 223 Bit Score: 105.20 E-value: 1.24e-25
|
||||||||||
| SPS1 | COG0515 | Serine/threonine protein kinase [Signal transduction mechanisms]; |
356-601 | 1.52e-23 | ||||||
Serine/threonine protein kinase [Signal transduction mechanisms]; Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 104.32 E-value: 1.52e-23
|
||||||||||
| STKc_TAK1 | cd14058 | Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ... |
358-611 | 1.15e-22 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270960 [Multi-domain] Cd Length: 253 Bit Score: 97.51 E-value: 1.15e-22
|
||||||||||
| PK_IRAK3 | cd14160 | Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ... |
358-613 | 3.82e-22 | ||||||
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271062 [Multi-domain] Cd Length: 276 Bit Score: 96.88 E-value: 3.82e-22
|
||||||||||
| PKc_STE | cd05122 | Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ... |
352-544 | 1.22e-21 | ||||||
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 94.58 E-value: 1.22e-21
|
||||||||||
| PK_GC | cd13992 | Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ... |
361-606 | 1.97e-20 | ||||||
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270894 [Multi-domain] Cd Length: 268 Bit Score: 91.30 E-value: 1.97e-20
|
||||||||||
| STKc_PknB_like | cd14014 | Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ... |
356-538 | 2.61e-20 | ||||||
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270916 [Multi-domain] Cd Length: 260 Bit Score: 90.72 E-value: 2.61e-20
|
||||||||||
| STKc_RIP | cd13978 | Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ... |
358-607 | 7.44e-20 | ||||||
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270880 [Multi-domain] Cd Length: 263 Bit Score: 89.82 E-value: 7.44e-20
|
||||||||||
| PKc_MAPKK_plant_like | cd06623 | Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ... |
352-608 | 9.98e-20 | ||||||
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132954 [Multi-domain] Cd Length: 264 Bit Score: 89.19 E-value: 9.98e-20
|
||||||||||
| PTKc_Csk_like | cd05039 | Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ... |
357-612 | 7.66e-18 | ||||||
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270635 [Multi-domain] Cd Length: 256 Bit Score: 83.55 E-value: 7.66e-18
|
||||||||||
| PTKc_Src_like | cd05034 | Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ... |
356-612 | 1.02e-17 | ||||||
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270630 [Multi-domain] Cd Length: 248 Bit Score: 83.10 E-value: 1.02e-17
|
||||||||||
| PLN00113 | PLN00113 | leucine-rich repeat receptor-like protein kinase; Provisional |
314-613 | 4.50e-17 | ||||||
leucine-rich repeat receptor-like protein kinase; Provisional Pssm-ID: 215061 [Multi-domain] Cd Length: 968 Bit Score: 85.28 E-value: 4.50e-17
|
||||||||||
| STKc_IRAK2 | cd14157 | Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ... |
360-608 | 7.42e-17 | ||||||
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271059 [Multi-domain] Cd Length: 289 Bit Score: 81.42 E-value: 7.42e-17
|
||||||||||
| PKc_MAPKK | cd06605 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ... |
350-542 | 1.02e-16 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270782 [Multi-domain] Cd Length: 265 Bit Score: 80.47 E-value: 1.02e-16
|
||||||||||
| PKc_Pek1_like | cd06621 | Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ... |
358-609 | 1.27e-16 | ||||||
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270793 [Multi-domain] Cd Length: 287 Bit Score: 80.54 E-value: 1.27e-16
|
||||||||||
| Pkinase | pfam00069 | Protein kinase domain; |
352-609 | 2.45e-16 | ||||||
Protein kinase domain; Pssm-ID: 459660 [Multi-domain] Cd Length: 217 Bit Score: 78.44 E-value: 2.45e-16
|
||||||||||
| STKc_RIP2 | cd14026 | Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ... |
356-549 | 4.34e-16 | ||||||
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270928 [Multi-domain] Cd Length: 284 Bit Score: 79.19 E-value: 4.34e-16
|
||||||||||
| PTKc_Tyk2_rpt2 | cd05080 | Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ... |
356-615 | 9.23e-16 | ||||||
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270664 [Multi-domain] Cd Length: 283 Bit Score: 78.02 E-value: 9.23e-16
|
||||||||||
| STKc_Cdc7_like | cd06627 | Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ... |
356-536 | 1.32e-15 | ||||||
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270797 [Multi-domain] Cd Length: 254 Bit Score: 76.88 E-value: 1.32e-15
|
||||||||||
| PTKc_Srm_Brk | cd05148 | Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ... |
358-611 | 1.46e-15 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133248 [Multi-domain] Cd Length: 261 Bit Score: 77.09 E-value: 1.46e-15
|
||||||||||
| STKc_Aurora | cd14007 | Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ... |
352-609 | 3.16e-15 | ||||||
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 75.97 E-value: 3.16e-15
|
||||||||||
| STKc_PAK | cd06614 | Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ... |
352-601 | 3.52e-15 | ||||||
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 75.71 E-value: 3.52e-15
|
||||||||||
| PTKc_Lck_Blk | cd05067 | Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ... |
356-608 | 4.16e-15 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270652 [Multi-domain] Cd Length: 264 Bit Score: 75.69 E-value: 4.16e-15
|
||||||||||
| PKc_Wee1_like | cd13997 | Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ... |
352-536 | 5.63e-15 | ||||||
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270899 [Multi-domain] Cd Length: 252 Bit Score: 75.11 E-value: 5.63e-15
|
||||||||||
| PTKc_EphR | cd05033 | Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ... |
356-533 | 3.01e-14 | ||||||
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270629 [Multi-domain] Cd Length: 266 Bit Score: 73.18 E-value: 3.01e-14
|
||||||||||
| PTKc_EphR_A2 | cd05063 | Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ... |
356-534 | 4.72e-14 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 133194 [Multi-domain] Cd Length: 268 Bit Score: 72.70 E-value: 4.72e-14
|
||||||||||
| STKc_Mos | cd13979 | Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ... |
353-601 | 4.87e-14 | ||||||
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270881 [Multi-domain] Cd Length: 265 Bit Score: 72.42 E-value: 4.87e-14
|
||||||||||
| PTKc_Lyn | cd05072 | Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ... |
356-601 | 6.06e-14 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270657 [Multi-domain] Cd Length: 272 Bit Score: 72.38 E-value: 6.06e-14
|
||||||||||
| PTKc_Hck | cd05073 | Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ... |
356-608 | 1.14e-13 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270658 [Multi-domain] Cd Length: 265 Bit Score: 71.60 E-value: 1.14e-13
|
||||||||||
| PTKc_Fer | cd05085 | Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ... |
356-532 | 1.24e-13 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells. Pssm-ID: 270668 [Multi-domain] Cd Length: 251 Bit Score: 71.19 E-value: 1.24e-13
|
||||||||||
| PK_GC_unk | cd14045 | Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ... |
367-533 | 1.37e-13 | ||||||
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270947 [Multi-domain] Cd Length: 269 Bit Score: 71.43 E-value: 1.37e-13
|
||||||||||
| PTKc_Chk | cd05083 | Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ... |
356-610 | 1.84e-13 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270666 [Multi-domain] Cd Length: 254 Bit Score: 70.67 E-value: 1.84e-13
|
||||||||||
| STKc_MLTK | cd14060 | Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ... |
359-534 | 2.25e-13 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270962 [Multi-domain] Cd Length: 242 Bit Score: 70.37 E-value: 2.25e-13
|
||||||||||
| STKc_MST1_2 | cd06612 | Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ... |
352-537 | 3.73e-13 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132943 [Multi-domain] Cd Length: 256 Bit Score: 69.60 E-value: 3.73e-13
|
||||||||||
| STKc_C-Raf | cd14149 | Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ... |
355-617 | 3.89e-13 | ||||||
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271051 [Multi-domain] Cd Length: 283 Bit Score: 70.06 E-value: 3.89e-13
|
||||||||||
| PKc_LIMK_like | cd14065 | Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ... |
358-546 | 4.76e-13 | ||||||
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270967 [Multi-domain] Cd Length: 252 Bit Score: 69.44 E-value: 4.76e-13
|
||||||||||
| STKc_AMPK-like | cd14003 | Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ... |
356-537 | 5.71e-13 | ||||||
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 69.08 E-value: 5.71e-13
|
||||||||||
| STKc_MAP3K12_13 | cd14059 | Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ... |
358-611 | 6.33e-13 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270961 [Multi-domain] Cd Length: 237 Bit Score: 68.68 E-value: 6.33e-13
|
||||||||||
| STKc_RIP4_like | cd14025 | Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ... |
356-538 | 7.46e-13 | ||||||
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270927 [Multi-domain] Cd Length: 267 Bit Score: 69.06 E-value: 7.46e-13
|
||||||||||
| PTKc_Tec_like | cd05059 | Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ... |
356-610 | 8.28e-13 | ||||||
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173637 [Multi-domain] Cd Length: 256 Bit Score: 68.63 E-value: 8.28e-13
|
||||||||||
| STKc_PLK | cd14099 | Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ... |
356-609 | 8.66e-13 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest. Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 68.73 E-value: 8.66e-13
|
||||||||||
| PTKc_Fes_like | cd05041 | Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ... |
358-533 | 9.41e-13 | ||||||
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions. Pssm-ID: 270637 [Multi-domain] Cd Length: 251 Bit Score: 68.62 E-value: 9.41e-13
|
||||||||||
| PKc_Byr1_like | cd06620 | Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ... |
358-537 | 9.54e-13 | ||||||
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270792 [Multi-domain] Cd Length: 286 Bit Score: 69.01 E-value: 9.54e-13
|
||||||||||
| PTKc_Jak_rpt2 | cd05038 | Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ... |
354-601 | 9.98e-13 | ||||||
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270634 [Multi-domain] Cd Length: 284 Bit Score: 68.95 E-value: 9.98e-13
|
||||||||||
| STKc_16 | cd13986 | Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ... |
356-610 | 1.46e-12 | ||||||
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270888 [Multi-domain] Cd Length: 282 Bit Score: 68.48 E-value: 1.46e-12
|
||||||||||
| STKc_OSR1_SPAK | cd06610 | Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ... |
358-537 | 1.63e-12 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 68.15 E-value: 1.63e-12
|
||||||||||
| STKc_B-Raf | cd14151 | Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ... |
358-607 | 3.48e-12 | ||||||
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271053 [Multi-domain] Cd Length: 274 Bit Score: 67.39 E-value: 3.48e-12
|
||||||||||
| PTK_Jak_rpt1 | cd05037 | Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ... |
401-536 | 3.55e-12 | ||||||
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270633 [Multi-domain] Cd Length: 259 Bit Score: 67.12 E-value: 3.55e-12
|
||||||||||
| STKc_MLK4 | cd14146 | Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ... |
357-536 | 6.59e-12 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271048 [Multi-domain] Cd Length: 268 Bit Score: 66.21 E-value: 6.59e-12
|
||||||||||
| PTKc_FGFR | cd05053 | Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ... |
356-611 | 6.93e-12 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase . Pssm-ID: 270646 [Multi-domain] Cd Length: 294 Bit Score: 66.67 E-value: 6.93e-12
|
||||||||||
| PTKc_EphR_A | cd05066 | Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ... |
356-534 | 7.40e-12 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270651 [Multi-domain] Cd Length: 267 Bit Score: 66.04 E-value: 7.40e-12
|
||||||||||
| PTKc_EphR_B | cd05065 | Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ... |
356-534 | 9.19e-12 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173638 [Multi-domain] Cd Length: 269 Bit Score: 66.05 E-value: 9.19e-12
|
||||||||||
| PTKc_Wee1_fungi | cd14052 | Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ... |
352-533 | 9.28e-12 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270954 [Multi-domain] Cd Length: 278 Bit Score: 65.91 E-value: 9.28e-12
|
||||||||||
| STKc_PAK2 | cd06655 | Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ... |
358-536 | 9.57e-12 | ||||||
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132986 [Multi-domain] Cd Length: 296 Bit Score: 66.29 E-value: 9.57e-12
|
||||||||||
| PK_eIF2AK_GCN2_rpt1 | cd14012 | Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ... |
396-550 | 1.09e-11 | ||||||
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270914 [Multi-domain] Cd Length: 254 Bit Score: 65.46 E-value: 1.09e-11
|
||||||||||
| STKc_CMGC | cd05118 | Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ... |
352-548 | 1.28e-11 | ||||||
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270688 [Multi-domain] Cd Length: 249 Bit Score: 64.95 E-value: 1.28e-11
|
||||||||||
| PTKc_Itk | cd05112 | Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ... |
358-610 | 1.48e-11 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133243 [Multi-domain] Cd Length: 256 Bit Score: 64.97 E-value: 1.48e-11
|
||||||||||
| STKc_MLK1 | cd14145 | Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ... |
356-536 | 1.51e-11 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271047 [Multi-domain] Cd Length: 270 Bit Score: 65.45 E-value: 1.51e-11
|
||||||||||
| PTKc_Fes | cd05084 | Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ... |
358-532 | 2.03e-11 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270667 [Multi-domain] Cd Length: 252 Bit Score: 64.57 E-value: 2.03e-11
|
||||||||||
| PTKc_Frk_like | cd05068 | Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ... |
356-534 | 2.06e-11 | ||||||
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270653 [Multi-domain] Cd Length: 267 Bit Score: 64.74 E-value: 2.06e-11
|
||||||||||
| PTKc_Btk_Bmx | cd05113 | Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ... |
356-607 | 2.21e-11 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173657 [Multi-domain] Cd Length: 256 Bit Score: 64.52 E-value: 2.21e-11
|
||||||||||
| STKc_MLK2 | cd14148 | Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ... |
357-536 | 3.52e-11 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 271050 [Multi-domain] Cd Length: 258 Bit Score: 63.85 E-value: 3.52e-11
|
||||||||||
| PKc_MKK3_6 | cd06617 | Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ... |
358-548 | 3.59e-11 | ||||||
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173729 [Multi-domain] Cd Length: 283 Bit Score: 64.37 E-value: 3.59e-11
|
||||||||||
| PTKc_Syk_like | cd05060 | Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ... |
358-601 | 5.50e-11 | ||||||
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270650 [Multi-domain] Cd Length: 257 Bit Score: 63.52 E-value: 5.50e-11
|
||||||||||
| STKc_TAO3 | cd06633 | Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ... |
358-533 | 6.36e-11 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270803 [Multi-domain] Cd Length: 313 Bit Score: 63.90 E-value: 6.36e-11
|
||||||||||
| STKc_PLK2 | cd14188 | Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ... |
356-609 | 6.61e-11 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271090 [Multi-domain] Cd Length: 255 Bit Score: 63.11 E-value: 6.61e-11
|
||||||||||
| STKc_LRRK2 | cd14068 | Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ... |
357-611 | 6.76e-11 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270970 [Multi-domain] Cd Length: 252 Bit Score: 63.05 E-value: 6.76e-11
|
||||||||||
| STKc_MLK | cd14061 | Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ... |
357-536 | 7.98e-11 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270963 [Multi-domain] Cd Length: 258 Bit Score: 62.80 E-value: 7.98e-11
|
||||||||||
| STKc_SLK_like | cd06611 | Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ... |
358-537 | 1.09e-10 | ||||||
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132942 [Multi-domain] Cd Length: 280 Bit Score: 62.84 E-value: 1.09e-10
|
||||||||||
| STKc_Byr2_like | cd06628 | Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ... |
357-537 | 1.41e-10 | ||||||
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270798 [Multi-domain] Cd Length: 267 Bit Score: 62.17 E-value: 1.41e-10
|
||||||||||
| PTKc_Trk | cd05049 | Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ... |
358-611 | 1.61e-10 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270643 [Multi-domain] Cd Length: 280 Bit Score: 62.10 E-value: 1.61e-10
|
||||||||||
| PTKc_Jak2_rpt2 | cd14205 | Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ... |
356-606 | 1.64e-10 | ||||||
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271107 [Multi-domain] Cd Length: 284 Bit Score: 62.34 E-value: 1.64e-10
|
||||||||||
| PTKc_Jak1_rpt2 | cd05079 | Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ... |
358-578 | 1.81e-10 | ||||||
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173644 [Multi-domain] Cd Length: 284 Bit Score: 62.25 E-value: 1.81e-10
|
||||||||||
| STKc_GAK_like | cd13985 | Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ... |
356-615 | 1.85e-10 | ||||||
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270887 [Multi-domain] Cd Length: 272 Bit Score: 61.97 E-value: 1.85e-10
|
||||||||||
| PTKc_Tie | cd05047 | Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ... |
357-611 | 2.64e-10 | ||||||
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270641 [Multi-domain] Cd Length: 270 Bit Score: 61.60 E-value: 2.64e-10
|
||||||||||
| PTKc_Src | cd05071 | Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ... |
358-612 | 3.04e-10 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270656 [Multi-domain] Cd Length: 277 Bit Score: 61.63 E-value: 3.04e-10
|
||||||||||
| PTKc_EphR_A10 | cd05064 | Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ... |
356-534 | 3.81e-10 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133195 [Multi-domain] Cd Length: 266 Bit Score: 61.09 E-value: 3.81e-10
|
||||||||||
| PTKc_Yes | cd05069 | Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ... |
358-610 | 3.87e-10 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 270654 [Multi-domain] Cd Length: 279 Bit Score: 61.24 E-value: 3.87e-10
|
||||||||||
| STKc_Nek | cd08215 | Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ... |
356-609 | 3.87e-10 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270855 [Multi-domain] Cd Length: 258 Bit Score: 60.94 E-value: 3.87e-10
|
||||||||||
| STKc_STK10 | cd06644 | Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ... |
358-609 | 3.95e-10 | ||||||
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132975 [Multi-domain] Cd Length: 292 Bit Score: 61.20 E-value: 3.95e-10
|
||||||||||
| STKc_SLK | cd06643 | Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ... |
358-542 | 3.96e-10 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270811 [Multi-domain] Cd Length: 283 Bit Score: 61.20 E-value: 3.96e-10
|
||||||||||
| PTKc_Src_Fyn_like | cd14203 | Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ... |
356-610 | 4.72e-10 | ||||||
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271105 [Multi-domain] Cd Length: 248 Bit Score: 60.32 E-value: 4.72e-10
|
||||||||||
| STKc_CDKL | cd07833 | Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ... |
357-607 | 5.19e-10 | ||||||
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 60.79 E-value: 5.19e-10
|
||||||||||
| PTK_Tyk2_rpt1 | cd05076 | Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ... |
400-533 | 5.32e-10 | ||||||
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270661 [Multi-domain] Cd Length: 273 Bit Score: 60.69 E-value: 5.32e-10
|
||||||||||
| STKc_MLK3 | cd14147 | Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ... |
356-536 | 6.70e-10 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271049 [Multi-domain] Cd Length: 267 Bit Score: 60.43 E-value: 6.70e-10
|
||||||||||
| STKc_A-Raf | cd14150 | Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ... |
356-607 | 7.19e-10 | ||||||
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271052 [Multi-domain] Cd Length: 265 Bit Score: 60.03 E-value: 7.19e-10
|
||||||||||
| STKc_Aurora-A | cd14116 | Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ... |
352-541 | 7.47e-10 | ||||||
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271018 [Multi-domain] Cd Length: 258 Bit Score: 59.97 E-value: 7.47e-10
|
||||||||||
| PTKc_PDGFR | cd05055 | Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ... |
377-533 | 7.64e-10 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase . Pssm-ID: 133186 [Multi-domain] Cd Length: 302 Bit Score: 60.58 E-value: 7.64e-10
|
||||||||||
| PTKc_Fyn | cd05070 | Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ... |
356-612 | 8.50e-10 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase. Pssm-ID: 270655 [Multi-domain] Cd Length: 274 Bit Score: 60.08 E-value: 8.50e-10
|
||||||||||
| PTKc_DDR_like | cd05097 | Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ... |
376-610 | 8.50e-10 | ||||||
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133228 [Multi-domain] Cd Length: 295 Bit Score: 60.37 E-value: 8.50e-10
|
||||||||||
| STKc_NAK1_like | cd06917 | Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ... |
352-536 | 1.05e-09 | ||||||
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270822 [Multi-domain] Cd Length: 277 Bit Score: 59.80 E-value: 1.05e-09
|
||||||||||
| STKc_PAK3 | cd06656 | Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ... |
358-536 | 1.09e-09 | ||||||
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation. Pssm-ID: 132987 [Multi-domain] Cd Length: 297 Bit Score: 60.12 E-value: 1.09e-09
|
||||||||||
| PTK_Jak2_rpt1 | cd05078 | Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ... |
358-536 | 1.28e-09 | ||||||
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270663 [Multi-domain] Cd Length: 262 Bit Score: 59.19 E-value: 1.28e-09
|
||||||||||
| STKc_PAK_I | cd06647 | Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ... |
358-536 | 1.40e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270814 [Multi-domain] Cd Length: 261 Bit Score: 59.17 E-value: 1.40e-09
|
||||||||||
| PTKc_Ror | cd05048 | Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ... |
358-533 | 1.73e-09 | ||||||
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270642 [Multi-domain] Cd Length: 283 Bit Score: 59.31 E-value: 1.73e-09
|
||||||||||
| STKc_PAK1 | cd06654 | Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ... |
358-536 | 2.05e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270820 [Multi-domain] Cd Length: 296 Bit Score: 58.97 E-value: 2.05e-09
|
||||||||||
| STKc_TAO1 | cd06635 | Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ... |
352-533 | 2.56e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270805 [Multi-domain] Cd Length: 317 Bit Score: 58.91 E-value: 2.56e-09
|
||||||||||
| STKc_TNIK | cd06637 | Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ... |
350-536 | 2.65e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270807 [Multi-domain] Cd Length: 296 Bit Score: 58.96 E-value: 2.65e-09
|
||||||||||
| STKc_CDK_like | cd07829 | Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ... |
358-511 | 2.68e-09 | ||||||
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 58.65 E-value: 2.68e-09
|
||||||||||
| STKc_WNK | cd13983 | Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ... |
386-608 | 3.79e-09 | ||||||
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270885 [Multi-domain] Cd Length: 258 Bit Score: 58.01 E-value: 3.79e-09
|
||||||||||
| STKc_Bck1_like | cd06629 | Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ... |
356-538 | 3.87e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270799 [Multi-domain] Cd Length: 270 Bit Score: 58.16 E-value: 3.87e-09
|
||||||||||
| PK_KSR | cd14063 | Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ... |
355-617 | 4.07e-09 | ||||||
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270965 [Multi-domain] Cd Length: 271 Bit Score: 57.74 E-value: 4.07e-09
|
||||||||||
| STKc_TAO2 | cd06634 | Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ... |
352-533 | 4.17e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270804 [Multi-domain] Cd Length: 308 Bit Score: 58.50 E-value: 4.17e-09
|
||||||||||
| PLN00009 | PLN00009 | cyclin-dependent kinase A; Provisional |
358-496 | 4.37e-09 | ||||||
cyclin-dependent kinase A; Provisional Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 58.29 E-value: 4.37e-09
|
||||||||||
| STKc_AGC | cd05123 | Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ... |
358-537 | 4.41e-09 | ||||||
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase. Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 57.53 E-value: 4.41e-09
|
||||||||||
| PKc_PBS2_like | cd06622 | Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ... |
358-542 | 4.64e-09 | ||||||
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132953 [Multi-domain] Cd Length: 286 Bit Score: 57.94 E-value: 4.64e-09
|
||||||||||
| PTKc_c-ros | cd05044 | Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ... |
356-611 | 5.30e-09 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270640 [Multi-domain] Cd Length: 268 Bit Score: 57.43 E-value: 5.30e-09
|
||||||||||
| STKc_myosinIII_N_like | cd06608 | N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ... |
349-512 | 5.70e-09 | ||||||
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270785 [Multi-domain] Cd Length: 275 Bit Score: 57.70 E-value: 5.70e-09
|
||||||||||
| STKc_LRRK | cd14000 | Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ... |
357-611 | 6.99e-09 | ||||||
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270902 [Multi-domain] Cd Length: 275 Bit Score: 57.24 E-value: 6.99e-09
|
||||||||||
| STKc_PLK3 | cd14189 | Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ... |
356-609 | 8.05e-09 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 56.86 E-value: 8.05e-09
|
||||||||||
| PTKc_Csk | cd05082 | Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ... |
358-533 | 8.75e-09 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133213 [Multi-domain] Cd Length: 256 Bit Score: 56.91 E-value: 8.75e-09
|
||||||||||
| PKc_TNNI3K | cd14064 | Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ... |
358-536 | 9.05e-09 | ||||||
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270966 [Multi-domain] Cd Length: 254 Bit Score: 56.77 E-value: 9.05e-09
|
||||||||||
| PTKc_FGFR3 | cd05100 | Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ... |
356-611 | 9.45e-09 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173652 [Multi-domain] Cd Length: 334 Bit Score: 57.34 E-value: 9.45e-09
|
||||||||||
| STKc_IKK | cd13989 | Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ... |
414-548 | 9.49e-09 | ||||||
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 270891 [Multi-domain] Cd Length: 289 Bit Score: 57.07 E-value: 9.49e-09
|
||||||||||
| PTKc_TrkA | cd05092 | Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ... |
358-533 | 9.56e-09 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270674 [Multi-domain] Cd Length: 280 Bit Score: 56.90 E-value: 9.56e-09
|
||||||||||
| STKc_CaMKI_gamma | cd14166 | Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ... |
349-558 | 1.02e-08 | ||||||
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 56.92 E-value: 1.02e-08
|
||||||||||
| PK_GC-C | cd14044 | Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ... |
396-606 | 1.09e-08 | ||||||
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270946 [Multi-domain] Cd Length: 271 Bit Score: 56.82 E-value: 1.09e-08
|
||||||||||
| PTKc_InsR_like | cd05032 | Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ... |
358-610 | 1.44e-08 | ||||||
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173625 [Multi-domain] Cd Length: 277 Bit Score: 56.20 E-value: 1.44e-08
|
||||||||||
| PKc_Dusty | cd13975 | Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ... |
404-613 | 1.51e-08 | ||||||
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270877 [Multi-domain] Cd Length: 262 Bit Score: 55.96 E-value: 1.51e-08
|
||||||||||
| PTKc_RET | cd05045 | Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ... |
356-606 | 1.65e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173631 [Multi-domain] Cd Length: 290 Bit Score: 56.12 E-value: 1.65e-08
|
||||||||||
| PTKc_Tec_Rlk | cd05114 | Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ... |
356-610 | 1.67e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270685 [Multi-domain] Cd Length: 260 Bit Score: 56.02 E-value: 1.67e-08
|
||||||||||
| STKc_BMPR2_AMHR2 | cd14054 | Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ... |
357-496 | 1.71e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270956 [Multi-domain] Cd Length: 300 Bit Score: 56.22 E-value: 1.71e-08
|
||||||||||
| STKc_CDK1_CdkB_like | cd07835 | Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ... |
358-496 | 1.76e-08 | ||||||
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 56.14 E-value: 1.76e-08
|
||||||||||
| STKc_DCKL | cd14095 | Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ... |
352-536 | 1.77e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 55.79 E-value: 1.77e-08
|
||||||||||
| STKc_Nek5 | cd08225 | Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ... |
352-533 | 1.96e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173765 [Multi-domain] Cd Length: 257 Bit Score: 55.73 E-value: 1.96e-08
|
||||||||||
| PTKc_ALK_LTK | cd05036 | Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ... |
353-611 | 2.02e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270632 [Multi-domain] Cd Length: 277 Bit Score: 55.86 E-value: 2.02e-08
|
||||||||||
| PTKc_FAK | cd05056 | Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ... |
355-533 | 2.14e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133187 [Multi-domain] Cd Length: 270 Bit Score: 55.89 E-value: 2.14e-08
|
||||||||||
| STKc_Kin1_2 | cd14077 | Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ... |
372-537 | 2.15e-08 | ||||||
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270979 [Multi-domain] Cd Length: 267 Bit Score: 55.53 E-value: 2.15e-08
|
||||||||||
| STKc_MLCK2 | cd14190 | Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ... |
347-536 | 2.15e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271092 [Multi-domain] Cd Length: 261 Bit Score: 55.70 E-value: 2.15e-08
|
||||||||||
| STKc_MEKK1_plant | cd06632 | Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ... |
356-609 | 2.19e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270802 [Multi-domain] Cd Length: 259 Bit Score: 55.49 E-value: 2.19e-08
|
||||||||||
| PTKc_EGFR_like | cd05057 | Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ... |
356-545 | 2.24e-08 | ||||||
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270648 [Multi-domain] Cd Length: 279 Bit Score: 55.88 E-value: 2.24e-08
|
||||||||||
| PTKc_FGFR1 | cd05098 | Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ... |
356-611 | 2.37e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270678 [Multi-domain] Cd Length: 302 Bit Score: 55.79 E-value: 2.37e-08
|
||||||||||
| PTKc_TrkC | cd05094 | Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ... |
358-610 | 2.50e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270676 [Multi-domain] Cd Length: 287 Bit Score: 55.79 E-value: 2.50e-08
|
||||||||||
| STKc_ACVR2 | cd14053 | Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ... |
361-534 | 2.53e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270955 [Multi-domain] Cd Length: 290 Bit Score: 55.80 E-value: 2.53e-08
|
||||||||||
| STKc_MARK | cd14072 | Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ... |
356-536 | 2.60e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270974 [Multi-domain] Cd Length: 253 Bit Score: 55.22 E-value: 2.60e-08
|
||||||||||
| STKc_EIF2AK | cd13996 | Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ... |
352-537 | 2.73e-08 | ||||||
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270898 [Multi-domain] Cd Length: 273 Bit Score: 55.38 E-value: 2.73e-08
|
||||||||||
| STKc_MAP4K4_6_N | cd06636 | N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ... |
350-536 | 3.08e-08 | ||||||
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270806 [Multi-domain] Cd Length: 282 Bit Score: 55.40 E-value: 3.08e-08
|
||||||||||
| STKc_TGFbR2_like | cd14055 | Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ... |
356-496 | 3.45e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270957 [Multi-domain] Cd Length: 295 Bit Score: 55.46 E-value: 3.45e-08
|
||||||||||
| STKc_PAK_II | cd06648 | Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ... |
352-584 | 3.53e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270815 [Multi-domain] Cd Length: 261 Bit Score: 55.14 E-value: 3.53e-08
|
||||||||||
| PKc_Myt1 | cd14050 | Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ... |
352-535 | 3.87e-08 | ||||||
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270952 [Multi-domain] Cd Length: 249 Bit Score: 54.62 E-value: 3.87e-08
|
||||||||||
| STKc_TGFbR-like | cd13998 | Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ... |
357-534 | 3.90e-08 | ||||||
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270900 [Multi-domain] Cd Length: 289 Bit Score: 55.14 E-value: 3.90e-08
|
||||||||||
| STKc_TAO | cd06607 | Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ... |
358-533 | 4.92e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270784 [Multi-domain] Cd Length: 258 Bit Score: 54.38 E-value: 4.92e-08
|
||||||||||
| PKc_MKK4 | cd06616 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ... |
357-537 | 5.08e-08 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270790 [Multi-domain] Cd Length: 291 Bit Score: 54.68 E-value: 5.08e-08
|
||||||||||
| STKc_STK25 | cd06642 | Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ... |
352-536 | 5.56e-08 | ||||||
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270810 [Multi-domain] Cd Length: 277 Bit Score: 54.68 E-value: 5.56e-08
|
||||||||||
| PTK_Jak1_rpt1 | cd05077 | Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ... |
358-533 | 5.82e-08 | ||||||
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270662 [Multi-domain] Cd Length: 266 Bit Score: 54.56 E-value: 5.82e-08
|
||||||||||
| STKc_CDKL2_3 | cd07846 | Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ... |
352-536 | 5.95e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270836 [Multi-domain] Cd Length: 286 Bit Score: 54.74 E-value: 5.95e-08
|
||||||||||
| STKc_CDK1_euk | cd07861 | Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ... |
358-537 | 6.31e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270845 [Multi-domain] Cd Length: 285 Bit Score: 54.35 E-value: 6.31e-08
|
||||||||||
| STKc_CDK7 | cd07841 | Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ... |
356-532 | 6.60e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 54.50 E-value: 6.60e-08
|
||||||||||
| STKc_PDK1 | cd05581 | Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ... |
356-537 | 8.19e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270733 [Multi-domain] Cd Length: 278 Bit Score: 54.14 E-value: 8.19e-08
|
||||||||||
| PKc_TESK | cd14155 | Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ... |
393-534 | 8.84e-08 | ||||||
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271057 [Multi-domain] Cd Length: 253 Bit Score: 53.63 E-value: 8.84e-08
|
||||||||||
| PTKc_Abl | cd05052 | Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ... |
358-533 | 8.85e-08 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270645 [Multi-domain] Cd Length: 263 Bit Score: 53.96 E-value: 8.85e-08
|
||||||||||
| STKc_CaMKI_alpha | cd14167 | Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ... |
352-536 | 8.88e-08 | ||||||
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 53.88 E-value: 8.88e-08
|
||||||||||
| STKc_PAK4 | cd06657 | Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ... |
352-536 | 9.47e-08 | ||||||
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132988 [Multi-domain] Cd Length: 292 Bit Score: 53.87 E-value: 9.47e-08
|
||||||||||
| PKc_LIMK_like_unk | cd14156 | Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ... |
393-546 | 9.67e-08 | ||||||
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271058 [Multi-domain] Cd Length: 256 Bit Score: 53.68 E-value: 9.67e-08
|
||||||||||
| STKc_EIF2AK2_PKR | cd14047 | Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ... |
352-610 | 1.21e-07 | ||||||
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270949 [Multi-domain] Cd Length: 267 Bit Score: 53.26 E-value: 1.21e-07
|
||||||||||
| STKc_PLK1 | cd14187 | Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ... |
350-541 | 1.23e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 53.40 E-value: 1.23e-07
|
||||||||||
| STKc_MST3_like | cd06609 | Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ... |
352-496 | 1.37e-07 | ||||||
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270786 [Multi-domain] Cd Length: 274 Bit Score: 53.40 E-value: 1.37e-07
|
||||||||||
| STKc_IKK_beta | cd14038 | Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ... |
437-548 | 1.42e-07 | ||||||
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270940 [Multi-domain] Cd Length: 290 Bit Score: 53.43 E-value: 1.42e-07
|
||||||||||
| PTKc_FGFR2 | cd05101 | Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ... |
356-611 | 1.47e-07 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270679 [Multi-domain] Cd Length: 313 Bit Score: 53.48 E-value: 1.47e-07
|
||||||||||
| STKc_MLCK4 | cd14193 | Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ... |
353-536 | 1.48e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 52.99 E-value: 1.48e-07
|
||||||||||
| STKc_CDK10 | cd07845 | Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ... |
352-537 | 1.71e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 53.52 E-value: 1.71e-07
|
||||||||||
| STKc_MST4 | cd06640 | Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ... |
352-536 | 1.80e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132971 [Multi-domain] Cd Length: 277 Bit Score: 53.13 E-value: 1.80e-07
|
||||||||||
| STKc_GRK4_like | cd05605 | Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ... |
457-547 | 2.28e-07 | ||||||
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270756 [Multi-domain] Cd Length: 285 Bit Score: 52.74 E-value: 2.28e-07
|
||||||||||
| STKc_Chk1 | cd14069 | Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ... |
351-551 | 2.39e-07 | ||||||
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 52.33 E-value: 2.39e-07
|
||||||||||
| STKc_cGK | cd05572 | Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ... |
358-600 | 2.46e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 52.23 E-value: 2.46e-07
|
||||||||||
| STKc_STK36 | cd14002 | Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ... |
357-537 | 2.73e-07 | ||||||
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 52.25 E-value: 2.73e-07
|
||||||||||
| STKc_SnRK3 | cd14663 | Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ... |
356-536 | 2.94e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271133 [Multi-domain] Cd Length: 256 Bit Score: 52.02 E-value: 2.94e-07
|
||||||||||
| STKc_YSK4 | cd06631 | Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ... |
357-537 | 2.97e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270801 [Multi-domain] Cd Length: 266 Bit Score: 52.05 E-value: 2.97e-07
|
||||||||||
| STKc_Raf | cd14062 | Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ... |
358-610 | 3.02e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270964 [Multi-domain] Cd Length: 253 Bit Score: 52.01 E-value: 3.02e-07
|
||||||||||
| STKc_LKB1_CaMKK | cd14008 | Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ... |
363-573 | 3.14e-07 | ||||||
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 52.17 E-value: 3.14e-07
|
||||||||||
| PTKc_Axl | cd05075 | Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ... |
356-549 | 3.17e-07 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270660 [Multi-domain] Cd Length: 277 Bit Score: 52.32 E-value: 3.17e-07
|
||||||||||
| STKc_LIMK2 | cd14222 | Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ... |
358-534 | 3.46e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271124 [Multi-domain] Cd Length: 272 Bit Score: 52.25 E-value: 3.46e-07
|
||||||||||
| STKc_SBK1 | cd13987 | Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ... |
453-536 | 3.66e-07 | ||||||
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 51.94 E-value: 3.66e-07
|
||||||||||
| PTKc_Tie2 | cd05088 | Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ... |
357-611 | 3.70e-07 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133219 [Multi-domain] Cd Length: 303 Bit Score: 52.31 E-value: 3.70e-07
|
||||||||||
| STKc_PAK5 | cd06658 | Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ... |
351-583 | 4.00e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132989 [Multi-domain] Cd Length: 292 Bit Score: 51.96 E-value: 4.00e-07
|
||||||||||
| PTKc_InsR | cd05061 | Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ... |
358-615 | 4.36e-07 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133192 [Multi-domain] Cd Length: 288 Bit Score: 51.89 E-value: 4.36e-07
|
||||||||||
| STKc_CDC2L1 | cd07843 | Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ... |
360-547 | 4.48e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 51.84 E-value: 4.48e-07
|
||||||||||
| STKc_CNK2-like | cd08530 | Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ... |
351-537 | 4.48e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 51.62 E-value: 4.48e-07
|
||||||||||
| STKc_Pho85 | cd07836 | Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ... |
358-537 | 5.12e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 51.71 E-value: 5.12e-07
|
||||||||||
| STKc_PKC | cd05570 | Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ... |
457-537 | 5.19e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270722 [Multi-domain] Cd Length: 318 Bit Score: 51.83 E-value: 5.19e-07
|
||||||||||
| PTK_CCK4 | cd05046 | Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ... |
356-533 | 5.28e-07 | ||||||
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133178 [Multi-domain] Cd Length: 275 Bit Score: 51.70 E-value: 5.28e-07
|
||||||||||
| STKc_MAK_like | cd07830 | Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ... |
356-537 | 5.64e-07 | ||||||
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 51.38 E-value: 5.64e-07
|
||||||||||
| STKc_ACVR2b | cd14140 | Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ... |
361-545 | 6.15e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271042 [Multi-domain] Cd Length: 291 Bit Score: 51.57 E-value: 6.15e-07
|
||||||||||
| PTKc_DDR1 | cd05096 | Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ... |
376-534 | 6.60e-07 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133227 [Multi-domain] Cd Length: 304 Bit Score: 51.47 E-value: 6.60e-07
|
||||||||||
| PTKc_TrkB | cd05093 | Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ... |
358-567 | 6.74e-07 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270675 [Multi-domain] Cd Length: 288 Bit Score: 51.19 E-value: 6.74e-07
|
||||||||||
| STKc_NUAK2 | cd14161 | Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ... |
358-556 | 7.87e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271063 [Multi-domain] Cd Length: 255 Bit Score: 50.72 E-value: 7.87e-07
|
||||||||||
| PKc_MEK1 | cd06650 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ... |
352-542 | 8.64e-07 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270816 [Multi-domain] Cd Length: 319 Bit Score: 51.21 E-value: 8.64e-07
|
||||||||||
| STKc_ASK | cd06624 | Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ... |
352-537 | 8.82e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270794 [Multi-domain] Cd Length: 268 Bit Score: 50.87 E-value: 8.82e-07
|
||||||||||
| PKc_MEK | cd06615 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ... |
358-542 | 8.88e-07 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132946 [Multi-domain] Cd Length: 308 Bit Score: 51.28 E-value: 8.88e-07
|
||||||||||
| STKc_ACVR2a | cd14141 | Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ... |
361-533 | 9.27e-07 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271043 [Multi-domain] Cd Length: 290 Bit Score: 50.81 E-value: 9.27e-07
|
||||||||||
| STKc_EIF2AK4_GCN2_rpt2 | cd14046 | Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ... |
352-513 | 9.30e-07 | ||||||
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270948 [Multi-domain] Cd Length: 278 Bit Score: 50.83 E-value: 9.30e-07
|
||||||||||
| STKc_DCKL2 | cd14184 | Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ... |
356-536 | 1.21e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271086 [Multi-domain] Cd Length: 259 Bit Score: 50.42 E-value: 1.21e-06
|
||||||||||
| PK_NRBP1_like | cd13984 | Pseudokinase domain of Nuclear Receptor Binding Protein 1 and similar proteins; The ... |
398-607 | 1.24e-06 | ||||||
Pseudokinase domain of Nuclear Receptor Binding Protein 1 and similar proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. This subfamily is composed of NRBP1, also called MLF1-adaptor molecule (MADM), and MADML. NRBP1 was originally named based on the presence of nuclear binding and localization motifs prior to functional analyses. It is expressed ubiquitously and is found to localize in the cytoplasm, not the nucleus. NRBP1 is an adaptor protein that interacts with myeloid leukemia factor 1 (MLF1), an oncogene that enhances myeloid development of hematopoietic cells. It also interacts with the small GTPase Rac3. NRBP1 may also be involved in Golgi to ER trafficking. MADML (for MADM-Like) has been shown to be expressed throughout development in Xenopus laevis with highest expression found in the developing lens and retina. The NRBP1-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270886 [Multi-domain] Cd Length: 256 Bit Score: 50.23 E-value: 1.24e-06
|
||||||||||
| PKc_MKK5 | cd06619 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ... |
358-537 | 1.24e-06 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132950 [Multi-domain] Cd Length: 279 Bit Score: 50.26 E-value: 1.24e-06
|
||||||||||
| STKc_NUAK | cd14073 | Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ... |
352-557 | 1.26e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270975 [Multi-domain] Cd Length: 254 Bit Score: 50.08 E-value: 1.26e-06
|
||||||||||
| PTKc_FGFR4 | cd05099 | Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ... |
356-611 | 1.29e-06 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133230 [Multi-domain] Cd Length: 314 Bit Score: 50.73 E-value: 1.29e-06
|
||||||||||
| STKc_nPKC_theta_like | cd05592 | Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ... |
457-537 | 1.32e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270744 [Multi-domain] Cd Length: 320 Bit Score: 50.85 E-value: 1.32e-06
|
||||||||||
| STKc_MELK | cd14078 | Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ... |
342-536 | 1.33e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270980 [Multi-domain] Cd Length: 257 Bit Score: 50.07 E-value: 1.33e-06
|
||||||||||
| STKc_SIK | cd14071 | Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ... |
352-536 | 1.40e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270973 [Multi-domain] Cd Length: 253 Bit Score: 50.08 E-value: 1.40e-06
|
||||||||||
| PTKc_DDR2 | cd05095 | Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ... |
376-606 | 1.49e-06 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 270677 [Multi-domain] Cd Length: 297 Bit Score: 50.38 E-value: 1.49e-06
|
||||||||||
| STKc_MLCK | cd14103 | Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ... |
358-528 | 1.58e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 49.92 E-value: 1.58e-06
|
||||||||||
| STKc_STK33 | cd14097 | Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ... |
358-536 | 1.80e-06 | ||||||
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270999 [Multi-domain] Cd Length: 266 Bit Score: 49.85 E-value: 1.80e-06
|
||||||||||
| STKc_MST3 | cd06641 | Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ... |
352-536 | 1.97e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270809 [Multi-domain] Cd Length: 277 Bit Score: 49.69 E-value: 1.97e-06
|
||||||||||
| STKc_TSSK4-like | cd14162 | Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ... |
351-537 | 2.09e-06 | ||||||
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 49.60 E-value: 2.09e-06
|
||||||||||
| STKc_PAK6 | cd06659 | Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ... |
377-536 | 2.19e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270821 [Multi-domain] Cd Length: 297 Bit Score: 49.98 E-value: 2.19e-06
|
||||||||||
| PTKc_Ror2 | cd05091 | Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ... |
358-533 | 2.46e-06 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270673 [Multi-domain] Cd Length: 284 Bit Score: 49.63 E-value: 2.46e-06
|
||||||||||
| STKc_NAK_like | cd14037 | Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ... |
356-529 | 2.53e-06 | ||||||
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270939 [Multi-domain] Cd Length: 277 Bit Score: 49.59 E-value: 2.53e-06
|
||||||||||
| PTKc_Ack_like | cd05040 | Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ... |
356-610 | 2.59e-06 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270636 [Multi-domain] Cd Length: 258 Bit Score: 49.26 E-value: 2.59e-06
|
||||||||||
| STKc_CDK12 | cd07864 | Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ... |
352-496 | 3.42e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270847 [Multi-domain] Cd Length: 302 Bit Score: 49.42 E-value: 3.42e-06
|
||||||||||
| STKc_DCKL1 | cd14183 | Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ... |
346-536 | 3.71e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 48.84 E-value: 3.71e-06
|
||||||||||
| PKc_MEK2 | cd06649 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ... |
358-542 | 4.31e-06 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 132980 [Multi-domain] Cd Length: 331 Bit Score: 49.28 E-value: 4.31e-06
|
||||||||||
| PTZ00263 | PTZ00263 | protein kinase A catalytic subunit; Provisional |
349-536 | 4.52e-06 | ||||||
protein kinase A catalytic subunit; Provisional Pssm-ID: 140289 [Multi-domain] Cd Length: 329 Bit Score: 49.05 E-value: 4.52e-06
|
||||||||||
| STKc_Yank1 | cd05578 | Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ... |
457-538 | 4.62e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 48.41 E-value: 4.62e-06
|
||||||||||
| PTKc_Tie1 | cd05089 | Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ... |
357-534 | 4.76e-06 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development. Pssm-ID: 270671 [Multi-domain] Cd Length: 297 Bit Score: 48.84 E-value: 4.76e-06
|
||||||||||
| STKc_Nek7 | cd08229 | Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ... |
352-601 | 5.19e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270866 [Multi-domain] Cd Length: 292 Bit Score: 48.49 E-value: 5.19e-06
|
||||||||||
| PTKc_Jak3_rpt2 | cd05081 | Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ... |
357-604 | 5.24e-06 | ||||||
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270665 [Multi-domain] Cd Length: 283 Bit Score: 48.74 E-value: 5.24e-06
|
||||||||||
| STKc_Rad53_Cds1 | cd14098 | Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ... |
352-512 | 5.62e-06 | ||||||
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 48.24 E-value: 5.62e-06
|
||||||||||
| STKc_RSK_N | cd05582 | N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ... |
356-536 | 5.90e-06 | ||||||
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270734 [Multi-domain] Cd Length: 317 Bit Score: 48.55 E-value: 5.90e-06
|
||||||||||
| STKc_DCKL3 | cd14185 | Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ... |
384-536 | 6.10e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 48.02 E-value: 6.10e-06
|
||||||||||
| STKc_CDKL5 | cd07848 | Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ... |
352-537 | 6.77e-06 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270838 [Multi-domain] Cd Length: 287 Bit Score: 48.07 E-value: 6.77e-06
|
||||||||||
| PTKc_Syk | cd05116 | Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ... |
358-601 | 6.99e-06 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133247 [Multi-domain] Cd Length: 257 Bit Score: 48.04 E-value: 6.99e-06
|
||||||||||
| PHA03210 | PHA03210 | serine/threonine kinase US3; Provisional |
380-534 | 7.56e-06 | ||||||
serine/threonine kinase US3; Provisional Pssm-ID: 165476 [Multi-domain] Cd Length: 501 Bit Score: 48.92 E-value: 7.56e-06
|
||||||||||
| STKc_MAP4K3_like | cd06613 | Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ... |
358-496 | 8.87e-06 | ||||||
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270788 [Multi-domain] Cd Length: 259 Bit Score: 47.69 E-value: 8.87e-06
|
||||||||||
| STKc_PASK | cd14004 | Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ... |
453-608 | 1.13e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270906 [Multi-domain] Cd Length: 256 Bit Score: 47.38 E-value: 1.13e-05
|
||||||||||
| PTKc_Ror1 | cd05090 | Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ... |
358-533 | 1.19e-05 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270672 [Multi-domain] Cd Length: 283 Bit Score: 47.31 E-value: 1.19e-05
|
||||||||||
| STKc_CDK9 | cd07865 | Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ... |
358-511 | 1.29e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 47.36 E-value: 1.29e-05
|
||||||||||
| STKc_LIMK1 | cd14221 | Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ... |
358-546 | 1.29e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271123 [Multi-domain] Cd Length: 267 Bit Score: 47.26 E-value: 1.29e-05
|
||||||||||
| STKc_PCTAIRE1 | cd07873 | Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ... |
358-537 | 1.33e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 47.30 E-value: 1.33e-05
|
||||||||||
| STKc_aPKC_iota | cd05618 | Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ... |
352-537 | 1.48e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270769 [Multi-domain] Cd Length: 364 Bit Score: 47.72 E-value: 1.48e-05
|
||||||||||
| STKc_NIM1 | cd14075 | Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ... |
356-511 | 1.52e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270977 [Multi-domain] Cd Length: 255 Bit Score: 46.95 E-value: 1.52e-05
|
||||||||||
| STKc_nPKC_delta | cd05620 | Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ... |
457-537 | 1.53e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173710 [Multi-domain] Cd Length: 316 Bit Score: 47.25 E-value: 1.53e-05
|
||||||||||
| PTK_Jak3_rpt1 | cd14208 | Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ... |
358-496 | 1.58e-05 | ||||||
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271110 [Multi-domain] Cd Length: 260 Bit Score: 46.82 E-value: 1.58e-05
|
||||||||||
| STKc_Aurora-B_like | cd14117 | Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ... |
352-536 | 1.77e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271019 [Multi-domain] Cd Length: 270 Bit Score: 46.78 E-value: 1.77e-05
|
||||||||||
| PTKc_Musk | cd05050 | Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ... |
358-601 | 1.85e-05 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133181 [Multi-domain] Cd Length: 288 Bit Score: 46.75 E-value: 1.85e-05
|
||||||||||
| PTKc_TAM | cd05035 | Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ... |
356-610 | 2.16e-05 | ||||||
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270631 [Multi-domain] Cd Length: 273 Bit Score: 46.76 E-value: 2.16e-05
|
||||||||||
| STKc_nPKC_eta | cd05590 | Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ... |
457-545 | 2.17e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270742 [Multi-domain] Cd Length: 323 Bit Score: 46.82 E-value: 2.17e-05
|
||||||||||
| PK_GC-2D | cd14043 | Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ... |
423-535 | 2.47e-05 | ||||||
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270945 [Multi-domain] Cd Length: 267 Bit Score: 46.25 E-value: 2.47e-05
|
||||||||||
| STKc_MEKK3_like_u1 | cd06653 | Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ... |
356-534 | 2.63e-05 | ||||||
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270819 [Multi-domain] Cd Length: 264 Bit Score: 46.17 E-value: 2.63e-05
|
||||||||||
| STKc_ULK4 | cd14010 | Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ... |
358-537 | 2.65e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 46.13 E-value: 2.65e-05
|
||||||||||
| STKc_nPKC_theta | cd05619 | Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ... |
356-537 | 2.66e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270770 [Multi-domain] Cd Length: 331 Bit Score: 46.84 E-value: 2.66e-05
|
||||||||||
| STKc_DRAK | cd14106 | Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ... |
407-529 | 2.95e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 46.19 E-value: 2.95e-05
|
||||||||||
| STKc_IKK_alpha | cd14039 | Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ... |
358-547 | 3.08e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270941 [Multi-domain] Cd Length: 289 Bit Score: 46.06 E-value: 3.08e-05
|
||||||||||
| STKc_MEKK2 | cd06652 | Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ... |
356-537 | 3.72e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270818 [Multi-domain] Cd Length: 264 Bit Score: 45.81 E-value: 3.72e-05
|
||||||||||
| STKc_MLCK-like | cd14006 | Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ... |
386-529 | 3.94e-05 | ||||||
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 45.72 E-value: 3.94e-05
|
||||||||||
| STKc_DRAK2 | cd14198 | The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ... |
354-536 | 4.54e-05 | ||||||
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271100 [Multi-domain] Cd Length: 270 Bit Score: 45.68 E-value: 4.54e-05
|
||||||||||
| STKc_CaMKI_delta | cd14168 | Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ... |
348-536 | 4.59e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 45.81 E-value: 4.59e-05
|
||||||||||
| STKc_ACVR1_ALK1 | cd14142 | Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ... |
420-540 | 5.02e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271044 [Multi-domain] Cd Length: 298 Bit Score: 45.51 E-value: 5.02e-05
|
||||||||||
| PKc_like | cd13968 | Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ... |
358-496 | 5.46e-05 | ||||||
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine. Pssm-ID: 270870 [Multi-domain] Cd Length: 136 Bit Score: 43.20 E-value: 5.46e-05
|
||||||||||
| STKc_IRE1 | cd13982 | Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ... |
355-536 | 5.83e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270884 [Multi-domain] Cd Length: 269 Bit Score: 45.34 E-value: 5.83e-05
|
||||||||||
| STKc_PKB_alpha | cd05594 | Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ... |
350-537 | 5.92e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270746 [Multi-domain] Cd Length: 356 Bit Score: 45.79 E-value: 5.92e-05
|
||||||||||
| PTKc_IGF-1R | cd05062 | Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ... |
355-607 | 6.48e-05 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133193 [Multi-domain] Cd Length: 277 Bit Score: 45.02 E-value: 6.48e-05
|
||||||||||
| STKc_Rim15_like | cd05611 | Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ... |
371-541 | 6.50e-05 | ||||||
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 45.16 E-value: 6.50e-05
|
||||||||||
| STKc_LRRK1 | cd14067 | Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ... |
457-612 | 7.14e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270969 [Multi-domain] Cd Length: 276 Bit Score: 44.96 E-value: 7.14e-05
|
||||||||||
| STKc_MLCK3 | cd14192 | Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ... |
356-536 | 7.87e-05 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271094 [Multi-domain] Cd Length: 261 Bit Score: 44.95 E-value: 7.87e-05
|
||||||||||
| STKc_PKA | cd14209 | Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ... |
349-537 | 8.33e-05 | ||||||
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271111 [Multi-domain] Cd Length: 290 Bit Score: 44.70 E-value: 8.33e-05
|
||||||||||
| STKc_EIF2AK3_PERK | cd14048 | Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ... |
352-534 | 9.07e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270950 [Multi-domain] Cd Length: 281 Bit Score: 44.86 E-value: 9.07e-05
|
||||||||||
| STKc_PRKX_like | cd05612 | Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ... |
349-536 | 9.14e-05 | ||||||
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270763 [Multi-domain] Cd Length: 292 Bit Score: 44.73 E-value: 9.14e-05
|
||||||||||
| STKc_PIM2 | cd14101 | Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ... |
357-551 | 9.18e-05 | ||||||
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271003 [Multi-domain] Cd Length: 257 Bit Score: 44.45 E-value: 9.18e-05
|
||||||||||
| lectin_leg-like | cd07308 | legume-like lectins: ERGIC-53, ERGL, VIP36, VIPL, EMP46, and EMP47; The legume-like (leg-like) ... |
50-254 | 9.52e-05 | ||||||
legume-like lectins: ERGIC-53, ERGL, VIP36, VIPL, EMP46, and EMP47; The legume-like (leg-like) lectins are eukaryotic intracellular sugar transport proteins with a carbohydrate recognition domain similar to that of the legume lectins. This domain binds high-mannose-type oligosaccharides for transport from the endoplasmic reticulum to the Golgi complex. These leg-like lectins include ERGIC-53, ERGL, VIP36, VIPL, EMP46, EMP47, and the UIP5 (ULP1-interacting protein 5) precursor protein. Leg-like lectins have different intracellular distributions and dynamics in the endoplasmic reticulum-Golgi system of the secretory pathway and interact with N-glycans of glycoproteins in a calcium-dependent manner, suggesting a role in glycoprotein sorting and trafficking. L-type lectins have a dome-shaped beta-barrel carbohydrate recognition domain with a curved seven-stranded beta-sheet referred to as the "front face" and a flat six-stranded beta-sheet referred to as the "back face". This domain homodimerizes so that adjacent back sheets form a contiguous 12-stranded sheet and homotetramers occur by a back-to-back association of these homodimers. Though L-type lectins exhibit both sequence and structural similarity to one another, their carbohydrate binding specificities differ widely. Pssm-ID: 173892 Cd Length: 218 Bit Score: 43.88 E-value: 9.52e-05
|
||||||||||
| STKc_MASTL | cd05610 | Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ... |
350-496 | 1.06e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270761 [Multi-domain] Cd Length: 349 Bit Score: 44.87 E-value: 1.06e-04
|
||||||||||
| PTZ00283 | PTZ00283 | serine/threonine protein kinase; Provisional |
460-538 | 1.22e-04 | ||||||
serine/threonine protein kinase; Provisional Pssm-ID: 240344 [Multi-domain] Cd Length: 496 Bit Score: 44.86 E-value: 1.22e-04
|
||||||||||
| PK_GC-A_B | cd14042 | Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ... |
366-601 | 1.22e-04 | ||||||
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270944 [Multi-domain] Cd Length: 279 Bit Score: 44.12 E-value: 1.22e-04
|
||||||||||
| PTK_HER3 | cd05111 | Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ... |
356-534 | 1.29e-04 | ||||||
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173656 [Multi-domain] Cd Length: 279 Bit Score: 44.18 E-value: 1.29e-04
|
||||||||||
| STKc_MAPK15-like | cd07852 | Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ... |
418-496 | 1.31e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 44.47 E-value: 1.31e-04
|
||||||||||
| STKc_PhKG2 | cd14181 | Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ... |
336-522 | 1.36e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 44.19 E-value: 1.36e-04
|
||||||||||
| STKc_aPKC_zeta | cd05617 | Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ... |
408-537 | 1.39e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270768 [Multi-domain] Cd Length: 357 Bit Score: 44.63 E-value: 1.39e-04
|
||||||||||
| STKc_BRSK1_2 | cd14081 | Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ... |
356-528 | 1.40e-04 | ||||||
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 43.78 E-value: 1.40e-04
|
||||||||||
| STKc_GAK | cd14036 | Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs ... |
348-499 | 1.50e-04 | ||||||
Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270938 [Multi-domain] Cd Length: 282 Bit Score: 44.04 E-value: 1.50e-04
|
||||||||||
| STKc_CDKL1_4 | cd07847 | Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ... |
358-536 | 1.52e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270837 [Multi-domain] Cd Length: 286 Bit Score: 43.90 E-value: 1.52e-04
|
||||||||||
| PTKc_DDR | cd05051 | Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ... |
377-611 | 1.55e-04 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270644 [Multi-domain] Cd Length: 297 Bit Score: 44.25 E-value: 1.55e-04
|
||||||||||
| STKc_MRCK_beta | cd05624 | Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control ... |
352-536 | 1.55e-04 | ||||||
Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain. Pssm-ID: 270774 [Multi-domain] Cd Length: 409 Bit Score: 44.61 E-value: 1.55e-04
|
||||||||||
| STKc_HUNK | cd14070 | Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ... |
356-536 | 1.56e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270972 [Multi-domain] Cd Length: 262 Bit Score: 44.04 E-value: 1.56e-04
|
||||||||||
| STKc_TSSK1_2-like | cd14165 | Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ... |
396-536 | 1.64e-04 | ||||||
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271067 [Multi-domain] Cd Length: 263 Bit Score: 43.62 E-value: 1.64e-04
|
||||||||||
| STKc_MSK_N | cd05583 | N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ... |
349-536 | 1.64e-04 | ||||||
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270735 [Multi-domain] Cd Length: 268 Bit Score: 43.92 E-value: 1.64e-04
|
||||||||||
| STKc_PKB_beta | cd05595 | Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ... |
350-537 | 1.66e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173686 [Multi-domain] Cd Length: 323 Bit Score: 44.23 E-value: 1.66e-04
|
||||||||||
| STKc_PKB_gamma | cd05593 | Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ... |
352-537 | 1.69e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270745 [Multi-domain] Cd Length: 348 Bit Score: 44.30 E-value: 1.69e-04
|
||||||||||
| PTKc_Aatyk | cd05042 | Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ... |
357-557 | 1.69e-04 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270638 [Multi-domain] Cd Length: 269 Bit Score: 43.73 E-value: 1.69e-04
|
||||||||||
| STKc_TSSK-like | cd14080 | Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ... |
356-536 | 2.06e-04 | ||||||
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270982 [Multi-domain] Cd Length: 262 Bit Score: 43.33 E-value: 2.06e-04
|
||||||||||
| STKc_cPKC_beta | cd05616 | Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ... |
352-545 | 2.08e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270767 [Multi-domain] Cd Length: 323 Bit Score: 43.83 E-value: 2.08e-04
|
||||||||||
| STKc_TGFbR1_ACVR1b_ACVR1c | cd14143 | Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ... |
357-538 | 2.32e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271045 [Multi-domain] Cd Length: 288 Bit Score: 43.58 E-value: 2.32e-04
|
||||||||||
| PTKc_Aatyk3 | cd14206 | Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ... |
389-533 | 2.37e-04 | ||||||
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 271108 [Multi-domain] Cd Length: 276 Bit Score: 43.40 E-value: 2.37e-04
|
||||||||||
| STKc_MEKK1 | cd06630 | Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ... |
356-537 | 2.97e-04 | ||||||
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270800 [Multi-domain] Cd Length: 268 Bit Score: 43.19 E-value: 2.97e-04
|
||||||||||
| STKc_PKN | cd05589 | Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ... |
358-536 | 3.01e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270741 [Multi-domain] Cd Length: 326 Bit Score: 43.44 E-value: 3.01e-04
|
||||||||||
| STKc_SPEG_rpt2 | cd14111 | Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ... |
348-549 | 3.01e-04 | ||||||
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271013 [Multi-domain] Cd Length: 257 Bit Score: 42.89 E-value: 3.01e-04
|
||||||||||
| STKc_Chk2 | cd14084 | Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ... |
355-608 | 3.15e-04 | ||||||
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 43.15 E-value: 3.15e-04
|
||||||||||
| STKc_PhKG | cd14093 | Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ... |
453-512 | 3.39e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 42.73 E-value: 3.39e-04
|
||||||||||
| PHA03207 | PHA03207 | serine/threonine kinase US3; Provisional |
396-540 | 3.54e-04 | ||||||
serine/threonine kinase US3; Provisional Pssm-ID: 165473 [Multi-domain] Cd Length: 392 Bit Score: 43.29 E-value: 3.54e-04
|
||||||||||
| STKc_Twitchin_like | cd14114 | The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ... |
352-529 | 3.54e-04 | ||||||
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 42.57 E-value: 3.54e-04
|
||||||||||
| STKc_ULK1_2-like | cd14120 | Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ... |
358-537 | 4.01e-04 | ||||||
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 42.36 E-value: 4.01e-04
|
||||||||||
| PK_NRBP1 | cd14034 | Pseudokinase domain of Nuclear Receptor Binding Protein 1; The pseudokinase domain shows ... |
385-533 | 4.25e-04 | ||||||
Pseudokinase domain of Nuclear Receptor Binding Protein 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. NRBP1, also called MLF1-adaptor molecule (MADM), was originally named based on the presence of nuclear binding and localization motifs prior to functional analyses. It is expressed ubiquitously and is found to localize in the cytoplasm, not the nucleus. NRBP1 is an adaptor protein that interacts with myeloid leukemia factor 1 (MLF1), an oncogene that enhances myeloid development of hematopoietic cells. It also interacts with the small GTPase Rac3. NRBP1 may also be involved in Golgi to ER trafficking and actin dynamics. The NRBP1-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270936 [Multi-domain] Cd Length: 277 Bit Score: 42.81 E-value: 4.25e-04
|
||||||||||
| STKc_CaMKI | cd14083 | Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ... |
352-536 | 4.45e-04 | ||||||
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 42.36 E-value: 4.45e-04
|
||||||||||
| STKc_PFTAIRE2 | cd07870 | Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ... |
354-559 | 4.92e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 42.64 E-value: 4.92e-04
|
||||||||||
| STKc_PKA_like | cd05580 | Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ... |
342-536 | 5.36e-04 | ||||||
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270732 [Multi-domain] Cd Length: 290 Bit Score: 42.18 E-value: 5.36e-04
|
||||||||||
| STKc_MSK2_N | cd05614 | N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ... |
376-536 | 5.49e-04 | ||||||
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 42.60 E-value: 5.49e-04
|
||||||||||
| STKc_RIP1 | cd14027 | Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ... |
384-608 | 6.76e-04 | ||||||
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270929 [Multi-domain] Cd Length: 267 Bit Score: 42.10 E-value: 6.76e-04
|
||||||||||
| STKc_HAL4_like | cd13994 | Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ... |
378-537 | 7.12e-04 | ||||||
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 41.91 E-value: 7.12e-04
|
||||||||||
| STKc_NIK | cd13991 | Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ... |
358-512 | 7.30e-04 | ||||||
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270893 [Multi-domain] Cd Length: 268 Bit Score: 41.73 E-value: 7.30e-04
|
||||||||||
| STKc_MEKK3 | cd06651 | Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ... |
347-534 | 7.92e-04 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270817 [Multi-domain] Cd Length: 271 Bit Score: 41.61 E-value: 7.92e-04
|
||||||||||
| STKc_CaMKI_beta | cd14169 | Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ... |
361-536 | 8.57e-04 | ||||||
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 41.80 E-value: 8.57e-04
|
||||||||||
| PTKc_PDGFR_alpha | cd05105 | Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ... |
356-440 | 8.83e-04 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 173653 [Multi-domain] Cd Length: 400 Bit Score: 41.93 E-value: 8.83e-04
|
||||||||||
| PTZ00426 | PTZ00426 | cAMP-dependent protein kinase catalytic subunit; Provisional |
352-536 | 1.02e-03 | ||||||
cAMP-dependent protein kinase catalytic subunit; Provisional Pssm-ID: 173616 [Multi-domain] Cd Length: 340 Bit Score: 41.89 E-value: 1.02e-03
|
||||||||||
| PTKc_Zap-70 | cd05115 | Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ... |
358-552 | 1.09e-03 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270686 [Multi-domain] Cd Length: 269 Bit Score: 41.47 E-value: 1.09e-03
|
||||||||||
| STKc_aPKC | cd05588 | Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ... |
457-537 | 1.16e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270740 [Multi-domain] Cd Length: 328 Bit Score: 41.64 E-value: 1.16e-03
|
||||||||||
| PKc_TOPK | cd14001 | Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ... |
457-534 | 1.18e-03 | ||||||
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270903 [Multi-domain] Cd Length: 292 Bit Score: 41.23 E-value: 1.18e-03
|
||||||||||
| STKc_WNK4 | cd14033 | Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ... |
358-533 | 1.34e-03 | ||||||
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270935 [Multi-domain] Cd Length: 261 Bit Score: 41.14 E-value: 1.34e-03
|
||||||||||
| STKc_Kalirin_C | cd14115 | C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ... |
377-536 | 1.56e-03 | ||||||
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271017 [Multi-domain] Cd Length: 248 Bit Score: 40.71 E-value: 1.56e-03
|
||||||||||
| PknB_PASTA_kin | NF033483 | Stk1 family PASTA domain-containing Ser/Thr kinase; |
422-537 | 1.58e-03 | ||||||
Stk1 family PASTA domain-containing Ser/Thr kinase; Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 41.32 E-value: 1.58e-03
|
||||||||||
| PKc_MKK7 | cd06618 | Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ... |
352-537 | 1.74e-03 | ||||||
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270791 [Multi-domain] Cd Length: 295 Bit Score: 40.82 E-value: 1.74e-03
|
||||||||||
| STKc_Sck1_like | cd05586 | Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ... |
460-536 | 1.79e-03 | ||||||
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270738 [Multi-domain] Cd Length: 330 Bit Score: 41.02 E-value: 1.79e-03
|
||||||||||
| PTKc_PDGFR_beta | cd05107 | Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ... |
377-440 | 1.94e-03 | ||||||
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 133238 [Multi-domain] Cd Length: 401 Bit Score: 41.15 E-value: 1.94e-03
|
||||||||||
| PTK_Ryk | cd05043 | Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ... |
355-610 | 1.98e-03 | ||||||
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270639 [Multi-domain] Cd Length: 279 Bit Score: 40.51 E-value: 1.98e-03
|
||||||||||
| STKc_Nek6_7 | cd08224 | Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ... |
351-609 | 1.99e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270863 [Multi-domain] Cd Length: 262 Bit Score: 40.33 E-value: 1.99e-03
|
||||||||||
| PKc_Mps1 | cd14131 | Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ... |
356-496 | 2.01e-03 | ||||||
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271033 [Multi-domain] Cd Length: 271 Bit Score: 40.28 E-value: 2.01e-03
|
||||||||||
| STKc_TLK2 | cd14041 | Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ... |
357-584 | 2.01e-03 | ||||||
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). Pssm-ID: 270943 [Multi-domain] Cd Length: 309 Bit Score: 40.81 E-value: 2.01e-03
|
||||||||||
| STKc_Kin4 | cd14076 | Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ... |
358-536 | 2.29e-03 | ||||||
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270978 [Multi-domain] Cd Length: 270 Bit Score: 40.16 E-value: 2.29e-03
|
||||||||||
| STKc_PhKG1 | cd14182 | Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ... |
352-536 | 2.60e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 40.28 E-value: 2.60e-03
|
||||||||||
| STKc_SPEG_rpt1 | cd14108 | Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ... |
342-529 | 2.73e-03 | ||||||
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 39.89 E-value: 2.73e-03
|
||||||||||
| STKc_MAP4K5 | cd06646 | Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ... |
358-504 | 3.66e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270813 [Multi-domain] Cd Length: 268 Bit Score: 39.63 E-value: 3.66e-03
|
||||||||||
| STKc_cPKC_alpha | cd05615 | Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ... |
408-537 | 4.51e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270766 [Multi-domain] Cd Length: 341 Bit Score: 39.60 E-value: 4.51e-03
|
||||||||||
| PHA03209 | PHA03209 | serine/threonine kinase US3; Provisional |
436-534 | 4.56e-03 | ||||||
serine/threonine kinase US3; Provisional Pssm-ID: 177557 [Multi-domain] Cd Length: 357 Bit Score: 39.86 E-value: 4.56e-03
|
||||||||||
| STKc_nPKC_epsilon | cd05591 | Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze ... |
457-545 | 4.69e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270743 [Multi-domain] Cd Length: 321 Bit Score: 39.40 E-value: 4.69e-03
|
||||||||||
| STKc_Titin | cd14104 | Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ... |
352-536 | 4.69e-03 | ||||||
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 271006 [Multi-domain] Cd Length: 277 Bit Score: 39.46 E-value: 4.69e-03
|
||||||||||
| STKc_PIM | cd14005 | Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ... |
452-608 | 5.19e-03 | ||||||
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270907 [Multi-domain] Cd Length: 255 Bit Score: 39.14 E-value: 5.19e-03
|
||||||||||
| STKc_MRCK_alpha | cd05623 | Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 ... |
352-536 | 5.43e-03 | ||||||
Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain. Pssm-ID: 270773 [Multi-domain] Cd Length: 409 Bit Score: 39.61 E-value: 5.43e-03
|
||||||||||
| PK_STRAD | cd08216 | Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ... |
377-506 | 6.26e-03 | ||||||
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270856 [Multi-domain] Cd Length: 315 Bit Score: 39.20 E-value: 6.26e-03
|
||||||||||
| STKc_TLK | cd13990 | Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ... |
357-538 | 7.32e-03 | ||||||
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. Pssm-ID: 270892 [Multi-domain] Cd Length: 279 Bit Score: 38.84 E-value: 7.32e-03
|
||||||||||
| Blast search parameters | ||||
|
