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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 499 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 578
Cdd:cd14217 186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 579 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 658
Cdd:cd14217 266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 345

                       170       180
                ....*....|....*....|.
gi 68566064 659 MLEMVPEKRASAGECLRHPWL 679
Cdd:cd14217 346 MLEMVPEKRASAGECLRHPWL 366

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK2 mediates neuronal cell cycle and cell death through regulation of nuclear cyclin D1. It has also been found to promote leukemia cell proliferation by regulating cyclin A1. SRPK2 also plays a role in regulating pre-mRNA splicing and is required for spliceosomal B complex formation. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 499 TRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 578
Cdd:cd14217 186 STAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFE 265

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 579 PHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 658
Cdd:cd14217 266 PHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIP 345

                       170       180
                ....*....|....*....|.
gi 68566064 659 MLEMVPEKRASAGECLRHPWL 679
Cdd:cd14217 346 MLEMVPEKRASAGECLRHPWL 366

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  73 DLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALD----EIKLLKCVResdpsDPNkdmVVQLID 148
Cdd:COG0515   3 ALLLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARErfrrEARALARLN-----HPN---IVRVYD 74

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 68566064 149 DFKISGmngiHVCMVFE-VLGHHLLKWIikSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 223
Cdd:COG0515  75 VGEEDG----RPYLVMEyVEGESLADLL--RRRGPLPPAEALRILAQLAEALAAAHAA-GIVHRDIKPANILLTPD 143

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064    518 RVKIADLGNACWVH--KHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEphsgedysrDEDHIAHI 595
Cdd:smart00220 135 HVKLADFGLARQLDpgEKLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFP---------GDDQLLEL 205

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064    596 IELLGSIPRHFAL-SGKYSREFFNrrgelrhitklkpwslfdvLVEKygwphedaaqftdflipMLEMVPEKRASAGECL 674
Cdd:smart00220 206 FKKIGKPKPPFPPpEWDISPEAKD-------------------LIRK-----------------LLVKDPEKRLTAEEAL 249

                   ....*
gi 68566064    675 RHPWL 679
Cdd:smart00220 250 QHPFF 254

protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  502 ADLLVNPLDPRN--ADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEP 579
Cdd:PTZ00284 268 SDTVVDPVTNRAlpPDPCRVRICDLGGCCDERHSRTAIVSTRHYRSPEVVLGLGWMYSTDMWSMGCIIYELYTGKLLYDT 347

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  580 HSgedysrDEDHIaHIIE-LLGSIPRHFAL--SGKYSREFFNRRGELR------HITKL-KPWSLFDVLVEKYgwpheda 649
Cdd:PTZ00284 348 HD------NLEHL-HLMEkTLGRLPSEWAGrcGTEEARLLYNSAGQLRpctdpkHLARIaRARPVREVIRDDL------- 413

                        170       180       190
                 ....*....|....*....|....*....|
gi 68566064  650 aqFTDFLIPMLEMVPEKRASAGECLRHPWL 679
Cdd:PTZ00284 414 --LCDLIYGLLHYDRQKRLNARQMTTHPYV 441

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064    79 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQ---HYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFkisgM 155
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKikkKKDKNILREIKILKKLNH-----PN---IVRLYDAF----E 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 68566064   156 NGIHVCMVFE-VLGHHLLKWIikSNYQGLPVRCVKSIIRQVLQGLD 200
Cdd:pfam00069  69 DKDNLYLVLEyVEGGSLFDLL--SEKGAFSEREAKFIMKQILEGLE 112

K+-dependent Na+/Ca+ exchanger; [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 68566064    306 SAEASGEQDGEyqpevtlkAADLEDTTEEETAKDNGEVEDQEEKEDAEKENAEKDEDDVEQELANLDPTWVESPK 380
Cdd:TIGR00927  834 EQELNAENQGE--------AKQDEKGVDGGGGSDGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEPLSLEWPE 900

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  68 PVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLI 147
Cdd:cd14218   1 PVKIGDLFNGRYHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLKCVRDSDPSDPKRETIVQLI 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 148 DDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYV 227
Cdd:cd14218  81 DDFKISGVNGVHVCMVLEVLGHQLLKWIIKSNYQGLPLPCVKSILRQVLQGLDYLHTKCKIIHTDIKPENILMCVDEGYV 160

                       170       180
                ....*....|....*....|....
gi 68566064 228 RRMAAEATEWQKAGAPPPSGSAVS 251
Cdd:cd14218 161 RRLAAEATIWQQAGAPPPSGSSVS 184

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 501 AADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPH 580
Cdd:cd14218 187 ASDFLVNPLEPQNADKIRVKIADLGNACWVHKHFTEDIQTRQYRALEVLIGAEYGTPADIWSTACMAFELATGDYLFEPH 266

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 581 SGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGELRHITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPML 660
Cdd:cd14218 267 SGEDYTRDEDHIAHIVELLGDIPPHFALSGRYSREYFNRRGELRHIKNLKHWGLYEVLVEKYEWPLEQAAQFTDFLLPMM 346

                       170
                ....*....|....*....
gi 68566064 661 EMVPEKRASAGECLRHPWL 679
Cdd:cd14218 347 EFLPEKRATAAQCLQHPWL 365

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  69 VKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLID 148
Cdd:cd14216   2 VKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKRFVAMKVVKSAEHYTETALDEIKLLKSVRNSDPNDPNREMVVQLLD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 149 DFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVR 228
Cdd:cd14216  82 DFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYIR 161

                       170
                ....*....|.
gi 68566064 229 RMAAEATEWQK 239
Cdd:cd14216 162 RLAAEATEWQR 172

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  68 PVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLI 147
Cdd:cd14136   1 PVKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGREHVVQLL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 148 DDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYV 227
Cdd:cd14136  81 DDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCISKIEV 160

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  79 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVREsdpsDPNKDMVVQLIDDFKISGMNgi 158
Cdd:cd05118   1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLND----VEGHPNIVKLLDVFEHRGGN-- 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 68566064 159 HVCMVFEVLGHHLLKwIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSkCKIIHTDIKPENILMC 221
Cdd:cd05118  75 HLCLVFELMGMNLYE-LIKDYPRGLPLDLIKSYLYQLLQALDFLHS-NGIIHRDLKPENILIN 135

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  79 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDpnKDMVVQLIDDFkisgMNGI 158
Cdd:cd14133   1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLNKKDKAD--KYHIVRLKDVF----YFKN 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 68566064 159 HVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSkCKIIHTDIKPENILMCVDDAY 226
Cdd:cd14133  75 HLCIVFELLSQNLYEFLKQNKFQYLSLPRIRKIAQQILEALVFLHS-LGLIHCDLKPENILLASYSRC 141

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064     79 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVK--SAQHYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFKisgmN 156
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKLKH-----PN---IVRLYDVFE----D 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 68566064    157 GIHVCMVFEVLGHHLLKWIIKSNyQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 223
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSK-GIVHRDLKPENILLDED 133

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 518 RVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIAHIIE 597
Cdd:cd14134 172 DIKLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHD------NLEHLAMMER 245

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 598 LLGSIPRHFA-LSGKYSREFFNRRGEL---------RHITKL-KPWSLFDVLVekygwpHEDAAQFTDFLIPMLEMVPEK 666
Cdd:cd14134 246 ILGPLPKRMIrRAKKGAKYFYFYHGRLdwpegsssgRSIKRVcKPLKRLMLLV------DPEHRLLFDLIRKMLEYDPSK 319

                       170
                ....*....|...
gi 68566064 667 RASAGECLRHPWL 679
Cdd:cd14134 320 RITAKEALKHPFF 332

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 513 NADKIRVKIADLGNACWVHKHF-TEDIQTRQYRSIEVLIGA-GYSTPADIWSTACMAFELATGDYLFEPHSgedysrDED 590
Cdd:cd05118 135 NLELGQLKLADFGLARSFTSPPyTPYVATRWYRAPEVLLGAkPYGSSIDIWSLGCILAELLTGRPLFPGDS------EVD 208

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 591 HIAHIIELLGsiprhfalsgkysreffnrrgelrhitklkpwslfdvlvekygwphedAAQFTDFLIPMLEMVPEKRASA 670
Cdd:cd05118 209 QLAKIVRLLG------------------------------------------------TPEALDLLSKMLKYDPAKRITA 240

                ....*....
gi 68566064 671 GECLRHPWL 679
Cdd:cd05118 241 SQALAHPYF 249

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 504 LLVNPldPRNAdkirVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGe 583
Cdd:cd14226 150 LLCNP--KRSA----IKIIDFGSSCQLGQRIYQYIQSRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLF---SG- 219

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 584 dySRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRGE-----LRHITKLKPW-----SLFDVLVEKYGWP-------- 645
Cdd:cd14226 220 --ANEVDQMNKIVEVLGMPPVHMLDQAPKARKFFEKLPDgtyylKKTKDGKKYKppgsrKLHEILGVETGGPggrragep 297

                       170       180       190
                ....*....|....*....|....*....|....*....
gi 68566064 646 -H--EDAAQFTDFLIPMLEMVPEKRASAGECLRHPWLNS 681
Cdd:cd14226 298 gHtvEDYLKFKDLILRMLDYDPKTRITPAEALQHSFFKR 336

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  65 GYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDM-QGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMV 143
Cdd:cd14214   1 GHLVCRIGDWLQERYEIVGDLGEGTFGKVVECLDHaRGKSQVALKIIRNVGKYREAARLEINVLKKIKEKDKE--NKFLC 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 68566064 144 VQLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENIL 219
Cdd:cd14214  79 VLMSDWFNFHG----HMCIAFELLGKNTFEFLKENNFQPYPLPHIRHMAYQLCHALKFLHEN-QLTHTDLKPENIL 149

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  70 KIGDLFNGRYHVIRKLGWGHFSTVWLCWD-MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLID 148
Cdd:cd14215   5 RSGDWLQERYEIVSTLGEGTFGRVVQCIDhRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPE--NKNLCVQMFD 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 149 DFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVDDAYVR 228
Cdd:cd14215  83 WFDYHG----HMCISFELLGLSTFDFLKENNYLPYPIHQVRHMAFQVCQAVKFLHDN-KLTHTDLKPENILFVNSDYELT 157

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  85 LGWGHFSTVWLCWDMQGKRFVAMKVVK--SAQHYTETALDEIKLLKCVResdpsDPNkdmVVQLIDDFKisgmNGIHVCM 162
Cdd:cd00180   1 LGKGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLN-----HPN---IVKLYDVFE----TENFLYL 68

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 68566064 163 VFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILM 220
Cdd:cd00180  69 VMEYCEGGSLKDLLKENKGPLSEEEALSILRQLLSALEYLHSN-GIIHRDLKPENILL 125

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  49 GSDDEEqedpadyckGGYHPVkIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLK 128
Cdd:cd14225  25 GYDDEN---------GSYLKV-LHDHIAYRYEILEVIGKGSFGQVVKALDHKTNEHVAIKIIRNKKRFHHQALVEVKILD 94

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064 129 CVRESDPSdpNKDMVVQLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHsKCKI 208
Cdd:cd14225  95 ALRRKDRD--NSHNVIHMKEYFYFRN----HLCITFELLGMNLYELIKKNNFQGFSLSLIRRFAISLLQCLRLLY-RERI 167

                       170
                ....*....|..
gi 68566064 209 IHTDIKPENILM 220
Cdd:cd14225 168 IHCDLKPENILL 179

The catalytic domain of CAMK family Serine/Threonine Kinases; 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. 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. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 68566064  78 RYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVV---KSAQHYTETALDEIKLLKCVresdpSDPNkdmVVQLIDDFKisg 154
Cdd:cd05117   1 KYELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkkKLKSEDEEMLRREIEILKRL-----DHPN---IVKLYEVFE--- 69

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 68566064 155 mNGIHVCMVFEVL-GHHLLKWIIKSNYqgLPVRCVKSIIRQVLQGLDYLHSKCkIIHTDIKPENILMCVDDAY 226
Cdd:cd05117  70 -DDKNLYLVMELCtGGELFDRIVKKGS--FSEREAAKIMKQILSAVAYLHSQG-IVHRDLKPENILLASKDPD 138