Dublecortin-like domain 2; Members in doublecortin (DCX) gene family are microtubule-associated proteins (MAPs). Microtubules are key components of cytoskeleton that are involved in cell movement, shape determination, division and transport. The DCX gene family consists of eleven paralogs in human and mouse, and its protein domains can occur in double tandem or as a single repeat. The first repeat of DCX domain has a stable ubiquitin-like tertiary fold. Proteins with DCX double tandem domains in general have roles in microtubule (MT) regulation and signal transduction such as X-linked doublecortin (DCX), retinitis pigmentosa-1 (RP1) and doublecortin-like kinase (DCLK).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 193 FIKPKLVTVIRSGVKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGVVKRLCTLDGKQVTCLQDFFGDDDVFIACGPE 272
Cdd:cd17069     1 FIKPKLVTVIRNGTKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGAVRKLFTLDGRQVTCLQDFFGDDDVFIAYGPE 80

                  ....
gi 1370486355 273 KFRY 276
Cdd:cd17069    81 KFSH 84

Dublecortin-like domain 2; Members in doublecortin (DCX) gene family are microtubule-associated proteins (MAPs). Microtubules are key components of cytoskeleton that are involved in cell movement, shape determination, division and transport. The DCX gene family consists of eleven paralogs in human and mouse, and its protein domains can occur in double tandem or as a single repeat. The first repeat of DCX domain has a stable ubiquitin-like tertiary fold. Proteins with DCX double tandem domains in general have roles in microtubule (MT) regulation and signal transduction such as X-linked doublecortin (DCX), retinitis pigmentosa-1 (RP1) and doublecortin-like kinase (DCLK).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 193 FIKPKLVTVIRSGVKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGVVKRLCTLDGKQVTCLQDFFGDDDVFIACGPE 272
Cdd:cd17069     1 FIKPKLVTVIRNGTKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGAVRKLFTLDGRQVTCLQDFFGDDDVFIAYGPE 80

                  ....
gi 1370486355 273 KFRY 276
Cdd:cd17069    81 KFSH 84

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355  394 YKIGKVIGDGNFAVVKECIDRSTGKEFALKIIDKAKCCGK----------------------------------VCEYPD 439
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKDrerilreikilkklkhpnivrlydvfededklylVMEYCE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355  440 G---------------------------------------------------TKSLKLGDFGLATVVEGP--LYTVCGTP 466
Cdd:smart00220  81 GgdlfdllkkrgrlsedearfylrqilsaleylhskgivhrdlkpenilldeDGHVKLADFGLARQLDPGekLTTFVGTP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355  467 TYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNLQEdLFDQILAGKLEFPAPYWdNITDSAKELISQMLQVN 546
Cdd:smart00220 161 EYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLE-LFKKIGKPKPPFPPPEW-DISPEAKDLIRKLLVKD 238

                          250
                   ....*....|....*.
gi 1370486355  547 VEARCTAGQILSHPWV 562
Cdd:smart00220 239 PEKRLTAEEALQHPFF 254

Domain in the Doublecortin (DCX) gene product; Tandemly-repeated domain in doublin, the Doublecortin gene product. Proposed to bind tubulin. Doublecortin (DCX) is mutated in human X-linked neuronal migration defects.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355   67 SEKKAKKARFYRNGDRYFKGLVFAISSDRFRSFDALLIELTRslSDNVNLPQGVRTIYTIDGsRKVTSLDELLEGESYVC 146
Cdd:smart00537   1 SLVKPKRIRFYRNGDRFFKGVRLVVNRKRFKSFEALLQDLTE--VVKLDLPHGVRKLYTLDG-KKVTSLDELEDGGSYVA 77

                           90
                   ....*....|.
gi 1370486355  147 ASNEPFRKVDY 157
Cdd:smart00537  78 SGTEAFKKVDY 88

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 439 DGTKSLKLGDFGLATVVEGPLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNLQedLFDQILA 518
Cdd:PTZ00263  152 DNKGHVKVTDFGFAKKVPDRTFTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFR--IYEKILA 229

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1370486355 519 GKLEFPApyWdnITDSAKELISQMLQVNVEAR 550
Cdd:PTZ00263  230 GRLKFPN--W--FDGRARDLVKGLLQTDHTKR 257

Doublecortin;

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370486355 215 LLNKKTAHSFEQVLTDITEAI-KLDSGVVKRLCTLDGKQVTCLqDFFGDDDVFIACGPEKF 274
Cdd:pfam03607   1 VVNKRRFRSFDALLDELTEKVvKLPFGAVRKLYTLDGKRVTSL-DELEDGGVYVAAGREKF 60

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 393 KYKIGKVIGDGNFAVVKECIDRSTGKEFALKIIDKAKCCGK--------------------------------------- 433
Cdd:cd14095     1 KYDIGRVIGDGNFAVVKECRDKATDKEYALKIIDKAKCKGKehmienevailrrvkhpnivqlieeydtdtelylvmelv 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 434 --------------------------------------------------VCEYPDGTKSLKLGDFGLATVVEGPLYTVC 463
Cdd:cd14095    81 kggdlfdaitsstkfterdasrmvtdlaqalkylhslsivhrdikpenllVVEHEDGSKSLKLADFGLATEVKEPLFTVC 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 464 GTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNLQEDLFDQILAGKLEFPAPYWDNITDSAKELISQML 543
Cdd:cd14095   161 GTPTYVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDRDQEELFDLILAGEFEFLSPYWDNISDSAKDLISRML 240

                         250
                  ....*....|....*...
gi 1370486355 544 QVNVEARCTAGQILSHPW 561
Cdd:cd14095   241 VVDPEKRYSAGQVLDHPW 258

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 1370486355 393 KYKIGKVIGDGNFAVVKECIDRSTGKEFALKIIDKAKCCGK-----------------------------------VCEY 437
Cdd:cd05117     1 KYELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIDKKKLKSEdeemlrreieilkrldhpnivklyevfeddknlylVMEL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 438 ------------------------------------------------------PDGTKSLKLGDFGLATVVEG--PLYT 461
Cdd:cd05117    81 ctggelfdrivkkgsfsereaakimkqilsavaylhsqgivhrdlkpenillasKDPDSPIKIIDFGLAKIFEEgeKLKT 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 462 VCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENnlQEDLFDQILAGKLEFPAPYWDNITDSAKELISQ 541
Cdd:cd05117   161 VCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGET--EQELFEKILKGKYSFDSPEWKNVSEEAKDLIKR 238

                         250       260
                  ....*....|....*....|
gi 1370486355 542 MLQVNVEARCTAGQILSHPW 561
Cdd:cd05117   239 LLVVDPKKRLTAAEALNHPW 258

Dublecortin-like domain 2; Members in doublecortin (DCX) gene family are microtubule-associated proteins (MAPs). Microtubules are key components of cytoskeleton that are involved in cell movement, shape determination, division and transport. The DCX gene family consists of eleven paralogs in human and mouse, and its protein domains can occur in double tandem or as a single repeat. The first repeat of DCX domain has a stable ubiquitin-like tertiary fold. Proteins with DCX double tandem domains in general have roles in microtubule (MT) regulation and signal transduction such as X-linked doublecortin (DCX), retinitis pigmentosa-1 (RP1) and doublecortin-like kinase (DCLK).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 193 FIKPKLVTVIRSGVKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGVVKRLCTLDGKQVTCLQDFFGDDDVFIACGPE 272
Cdd:cd17069     1 FIKPKLVTVIRNGTKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGAVRKLFTLDGRQVTCLQDFFGDDDVFIAYGPE 80

                  ....
gi 1370486355 273 KFRY 276
Cdd:cd17069    81 KFSH 84

Dublecortin-like domain 1 found in doublecortin-like kinase 1 (DCLK1); DCLK1 is a member of doublecortin (DCX) protein superfamily that functions as a microtubule-associated protein (MAP), and contains two conserved tubulin binding domains. The DCX domain has a stable ubiquitin-like tertiary fold. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes, including transcriptional regulation, cell cycle control, and DNA repair. In addition to microtubule-binding domains, DCLK encodes a serine/threonine kinase domain that is similar to Ca/calmodulin-dependent (Cam) protein kinases. DCLK1 appears to regulate cyclic AMP signaling and is involved in neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. Unlike DCX, this DCLK has varying levels of expression throughout embryonic and adult life.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355  70 KAKKARFYRNGDRYFKGLVFAISSDRFRSFDALLIELTRSLSDNVNLPQGVRTIYTIDGSRKVTSLDELLEGESYVCASN 149
Cdd:cd17140     1 KAKKVRFYRNGDRYFKGIVYAISPDRFRSFEALLADLTRTLSDNVNLPQGVRTIYTIDGLKKISSLDQLVEGESYVCGSI 80

                  ....*....
gi 1370486355 150 EPFRKVDYT 158
Cdd:cd17140    81 EPFKKLEYT 89

Dublecortin-like domain 1; Members of the doublecortin (DCX) gene family are microtubule-associated proteins (MAPs). Microtubules are key components of cytoskeleton that are involved in cell movement, shape determination, division and transport. The DCX gene family consists of eleven paralogs in human and mouse, and its protein domains can occur in double tandem or single repeats. The family represents the first repeat of the DCX domain which has a stable ubiquitin-like tertiary fold. Proteins with DCX double tandem domains in general have roles in microtubule (MT) regulation and signal transduction such as X-linked doublecortin (DCX), retinitis pigmentosa-1 (RP1) and doublecortin-like kinase (DCLK).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355  70 KAKKARFYRNGDRYFKGLVFAISSDRFRSFDALLIELTRSLSDNVNLPQGVRTIYTIDGSRKVTSLDELLEGESYVCASN 149
Cdd:cd16109     1 KAKKVRFYRNGDRFFKGIVYAVSSERFRSFEALLADLTRSLSDNVNLPQGVRTIFTIDGSRKITSLDELEDGESYVCAST 80

                  ....*
gi 1370486355 150 EPFRK 154
Cdd:cd16109    81 DAFKK 85

Dublecortin-like domain 1 found in neuronal migration protein doublecortin (DCX); DCX, also termed doublin or lissencephalin-X (Lis-XDCX), is a microtubule-associated protein (MAP). It belongs to the doublecortin (DCX) family, has double tandem DCX repeats, and is expressed in migrating neurons. Structure studies show that the N-terminal DCX domain has a stable ubiquitin-like fold. DCX is not only a unique MAP in terms of structure, it also interacts with multiple additional proteins. Mutations in the human DCX genes are associated with abnormal neuronal migration, epilepsy, and mental retardation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355  70 KAKKARFYRNGDRYFKGLVFAISSDRFRSFDALLIELTRSLSDNVNLPQGVRTIYTIDGSRKVTSLDELLEGESYVCASN 149
Cdd:cd16112     1 KAKKVRFYRNGDRYFKGIVYAVSSDRFRSFDALLADLTRSLSDNINLPQGVRYIYTIDGSRKIGSMDELEEGESYVCSSD 80

                  ....*....
gi 1370486355 150 EPFRKVDYT 158
Cdd:cd16112    81 NFFKKVEYT 89

Dublecortin-like domain 2 found in doublecortin-like kinase 1 (DCLK1); DCLK1 is a member of doublecortin (DCX) protein family that functions as a microtubule-associated protein (MAP), and contains two conserved tubulin binding domains. The DCX domain has a stable ubiquitin-like tertiary fold. Ubiquitin (Ub) is a protein modifier in eukaryotes that is involved in various cellular processes including transcriptional regulation, cell cycle control, and DNA repair. In addition to microtubule binding domains, DCLK encodes a serine/threonine kinase-domain that is similar to Ca/calmodulin-dependent (Cam) protein kinases. DCLK1 appears to regulate cyclic AMP signaling and is involved in neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. Unlike DCX, the DCLK has varying levels of expression throughout embryonic and adult life.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 193 FIKPKLVTVIRSGVKPRKAVRILLNKKTAHSFEQVLTDITEAIKLDSGVVKRLCTLDGKQVTCLQDFFGDDDVFIACGPE 272
Cdd:cd17143     1 FIRPKLVTIIRSGVKPRKAVRILLNKKTAHSFEQVLTDITDAIKLDSGVVKRLYTLDGKQVMCLQDFFGDDDIFIACGPE 80

                  ....
gi 1370486355 273 KFRY 276
Cdd:cd17143    81 KFRY 84

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 393 KYKIGKVIGDGNFAVVKECIDRSTGKEFALKIIDKAKCCGKVCEY-------------P--------------------- 438
Cdd:cd14003     1 NYELGKTLGEGSFGKVKLARHKLTGEKVAIKIIDKSKLKEEIEEKikreieimkllnhPniiklyevietenkiylvmey 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 439 ----------------------------------------------------DGTKSLKLGDFGLATVVEG--PLYTVCG 464
Cdd:cd14003    81 asggelfdyivnngrlsedearrffqqlisavdychsngivhrdlklenillDKNGNLKIIDFGLSNEFRGgsLLKTFCG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 465 TPTYVAPEIIAETGY-GLKVDIWAAGVITYILLCGFPPFRSENnlQEDLFDQILAGKLEFPapywDNITDSAKELISQML 543
Cdd:cd14003   161 TPAYAAPEVLLGRKYdGPKADVWSLGVILYAMLTGYLPFDDDN--DSKLFRKILKGKYPIP----SHLSPDARDLIRRML 234

                         250
                  ....*....|....*...
gi 1370486355 544 QVNVEARCTAGQILSHPW 561
Cdd:cd14003   235 VVDPSKRITIEEILNHPW 252

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 446 LGDFGLATVVE-GPLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNLQedLFDQILAGKLEFP 524
Cdd:cd14169   145 ISDFGLSKIEAqGMLSTACGTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSE--LFNQILKAEYEFD 222

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370486355 525 APYWDNITDSAKELISQMLQVNVEARCTAGQILSHPWVSDDASQENNMQAEVT 577
Cdd:cd14169   223 SPYWDDISESAKDFIRHLLERDPEKRFTCEQALQHPWISGDTALDRDIHGSVS 275

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; 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. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. 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. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 392 EKYKIGKVIGDGNFAVVKECIDRSTGKEFALKIID--------------KAKCC-------------------------- 431
Cdd:cd14086     1 DEYDLKEELGKGAFSVVRRCVQKSTGQEFAAKIINtkklsardhqklerEARICrllkhpnivrlhdsiseegfhylvfd 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 432 ----GKVCE-------YPDGTKS--------------------------------------LKLGDFGLATVVEGPL--- 459
Cdd:cd14086    81 lvtgGELFEdivarefYSEADAShciqqilesvnhchqngivhrdlkpenlllaskskgaaVKLADFGLAIEVQGDQqaw 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 460 YTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENnlQEDLFDQILAGKLEFPAPYWDNITDSAKELI 539
Cdd:cd14086   161 FGFAGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDED--QHRLYAQIKAGAYDYPSPEWDTVTPEAKDLI 238

                         250       260
                  ....*....|....*....|....
gi 1370486355 540 SQMLQVNVEARCTAGQILSHPWVS 563
Cdd:cd14086   239 NQMLTVNPAKRITAAEALKHPWIC 262

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 439 DGTKSLKLGDFGLATVV-EGP-LYTVCGTPTYVAPEIIAET------GYGLKVDIWAAGVITYILLCGFPPFRSENNLQe 510
Cdd:cd14093   143 DDNLNVKISDFGFATRLdEGEkLRELCGTPGYLAPEVLKCSmydnapGYGKEVDMWACGVIMYTLLAGCPPFWHRKQMV- 221

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370486355 511 dLFDQILAGKLEFPAPYWDNITDSAKELISQMLQVNVEARCTAGQILSHPW 561
Cdd:cd14093   222 -MLRNIMEGKYEFGSPEWDDISDTAKDLISKLLVVDPKKRLTAEEALEHPF 271

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 438 PDGTKSLKLGDFGLATVvEGP---LYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNlqEDLFD 514
Cdd:cd14168   144 QDEESKIMISDFGLSKM-EGKgdvMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDEND--SKLFE 220

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370486355 515 QILAGKLEFPAPYWDNITDSAKELISQMLQVNVEARCTAGQILSHPWVSDDASQENNMQAEVTGKLKQHFNNALPKQ 591
Cdd:cd14168   221 QILKADYEFDSPYWDDISDSAKDFIRNLMEKDPNKRYTCEQALRHPWIAGDTALCKNIHESVSAQIRKNFAKSKWRQ 297

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 444 LKLGDFGLATVVE--GPLYTVCGTPTYVAPEIIA---ETGYGLKVDIWAAGVITYILLCGFPPFrSENNLQEDLFDQILA 518
Cdd:cd14084   153 IKITDFGLSKILGetSLMKTLCGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPF-SEEYTQMSLKEQILS 231

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1370486355 519 GKLEFPAPYWDNITDSAKELISQMLQVNVEARCTAGQILSHPWV 562
Cdd:cd14084   232 GKYTFIPKAWKNVSEEAKDLVKKMLVVDPSRRPSIEEALEHPWL 275

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 393 KYKIGKVIGDGNFAVVKECIDRSTGKEFALKIIDKAK--------------CCGKVCEYPD--------GTKS------- 443
Cdd:cd14663     1 RYELGRTLGEGTFAKVKFARNTKTGESVAIKIIDKEQvaregmveqikreiAIMKLLRHPNivelhevmATKTkiffvme 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 444 ----------------------------------------------------------LKLGDFGLATVVE-----GPLY 460
Cdd:cd14663    81 lvtggelfskiakngrlkedkarkyfqqlidavdychsrgvfhrdlkpenllldedgnLKISDFGLSALSEqfrqdGLLH 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 461 TVCGTPTYVAPEIIAETGY-GLKVDIWAAGVITYILLCGFPPFRSEnNLQEdLFDQIlaGKLEFPAPYWdnITDSAKELI 539
Cdd:cd14663   161 TTCGTPNYVAPEVLARRGYdGAKADIWSCGVILFVLLAGYLPFDDE-NLMA-LYRKI--MKGEFEYPRW--FSPGAKSLI 234

                         250       260
                  ....*....|....*....|..
gi 1370486355 540 SQMLQVNVEARCTAGQILSHPW 561
Cdd:cd14663   235 KRILDPNPSTRITVEQIMASPW 256

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-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 uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 446 LGDFGLATVVEGPLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSE------NNLQEDLFDQILAG 519
Cdd:cd14088   143 ISDFHLAKLENGLIKEPCGTPEYLAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEaeeddyENHDKNLFRKILAG 222

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1370486355 520 KLEFPAPYWDNITDSAKELISQMLQVNVEARCTAGQILSHPWV 562
Cdd:cd14088   223 DYEFDSPYWDDISQAAKDLVTRLMEVEQDQRITAEEAISHEWI 265

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 444 LKLGDFGLATVV-EGPLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENnlQEDLFDQILAGKLE 522
Cdd:cd14007   139 LKLADFGWSVHApSNRRKTFCGTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKS--HQETYKRIQNVDIK 216

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1370486355 523 FPapywDNITDSAKELISQMLQVNVEARCTAGQILSHPWV 562
Cdd:cd14007   217 FP----SSVSPEAKDLISKLLQKDPSKRLSLEQVLNHPWI 252

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370486355 439 DGTKSLKLGDFGLATVVEGPLYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENnlQEDLFDQILA 518
Cdd:cd05580   135 DSDGHIKITDFGFAKRVKDRTYTLCGTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDEN--PMKIYEKILE 212

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370486355 519 GKLEFPAPYwdniTDSAKELISQMLQVNVEARC-----TAGQILSHPWVSD 564
Cdd:cd05580   213 GKIRFPSFF----DPDAKDLIKRLLVVDLTKRLgnlknGVEDIKNHPWFAG 259

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 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.