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 1370510825 105 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ 184
Cdd:cd14217     1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 185 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 264
Cdd:cd14217    81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                         170       180
                  ....*....|....*....|....*....
gi 1370510825 265 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 293
Cdd:cd14217   161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

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

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 1370510825  378 DNGEAEDQEEKEDAEKENIEKDEDDVDQELANIDPTWIESPKT 420
Cdd:TIGR00927  859 DGGDSEEEEEEEEEEEEEEEEEEEEEEEEEENEEPLSLEWPET 901

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 1370510825 105 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ 184
Cdd:cd14217     1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 185 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 264
Cdd:cd14217    81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                         170       180
                  ....*....|....*....|....*....
gi 1370510825 265 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 293
Cdd:cd14217   161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825  118 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVK--SAQHYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFKisgmN 195
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKLKH-----PN---IVRLYDVFE----D 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370510825  196 GIHVCMVFEVLGHHLLKWIIKSNyQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 262
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSK-GIVHRDLKPENILLDED 133

protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 112 DLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ--LIDDf 189
Cdd:PTZ00284  125 DVSTQRFKILSLLGEGTFGKVVEAWDRKRKEYCAVKIVRNVPKYTRDAKIEIQFMEKVRQADPADRFPLMKIQryFQNE- 203

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 190 kiSGmngiHVCMVFEVLGHHLLKWIIKsnYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVRRM 269
Cdd:PTZ00284  204 --TG----HMCIVMPKYGPCLLDWIMK--HGPFSHRHLAQIIFQTGVALDYFHTELHLMHTDLKPENILMETSDTVVDPV 275

                  ....*
gi 1370510825 270 AAEAT 274
Cdd:PTZ00284  276 TNRAL 280

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 110 IGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKsaqhyTETALDEIKLLKCVRE----SDPSDPNkdmVVQL 185
Cdd:NF033483    1 IGKLLGGRYEIGERIGRGGMAEVYLAKDTRLDRDVAVKVLR-----PDLARDPEFVARFRREaqsaASLSHPN---IVSV 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370510825 186 IDdfkiSGMNGIHVCMVFE-VLGhHLLKWIIKSNYQgLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILM 259
Cdd:NF033483   73 YD----VGEDGGIPYIVMEyVDG-RTLKDYIREHGP-LSPEEAVEIMIQILSALEHAH-RNGIVHRDIKPQNILI 140

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 118 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQ---HYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFkisgM 194
Cdd:pfam00069   1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKikkKKDKNILREIKILKKLNH-----PN---IVRLYDAF----E 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1370510825 195 NGIHVCMVFE-VLGHHLLKWIikSNYQGLPVRCVKSIIRQVLQGLD 239
Cdd:pfam00069  69 DKDNLYLVLEyVEGGSLFDLL--SEKGAFSEREAKFIMKQILEGLE 112

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370510825 562 RVKIADLGNACWVHK-HFTED---IQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSGED 628
Cdd:COG0515   145 RVKLIDFGIARALGGaTLTQTgtvVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAE 215

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 1370510825 105 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQ 184
Cdd:cd14217     1 YHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLRCVRESDPEDPNKDMVVQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 185 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 264
Cdd:cd14217    81 LIDDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPIRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDA 160

                         170       180
                  ....*....|....*....|....*....
gi 1370510825 265 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 293
Cdd:cd14217   161 YVRRMAAEATEWQKAGAPPPSGSAVSTAP 189

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 1370510825 541 AKTRAADLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYL 620
Cdd:cd14217   184 AVSTAPDLLVNPLDPRNADKIRVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYL 263

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 621 FEPHSGEDYSRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRRdhialiiellgkvprkyamlgkyskefftrkGELRH 700
Cdd:cd14217   264 FEPHSGEDYSRDEDHIAHIIELLGCIPRHFALSGKYSREFFNRR-------------------------------GELRH 312

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370510825 701 ITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 754
Cdd:cd14217   313 ITKLKPWSLFDVLVEKYGWPHEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 366

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 1370510825 108 VKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLID 187
Cdd:cd14216     2 VKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKRFVAMKVVKSAEHYTETALDEIKLLKSVRNSDPNDPNREMVVQLLD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 188 DFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYVR 267
Cdd:cd14216    82 DFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIRQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYIR 161

                         170
                  ....*....|.
gi 1370510825 268 RMAAEATEWQK 278
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 1370510825 107 PVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKDMVVQLI 186
Cdd:cd14136     1 PVKIGEVYNGRYHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLKCVREADPKDPGREHVVQLL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 187 DDFKISGMNGIHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKCKIIHTDIKPENILMCVDDAYV 266
Cdd:cd14136    81 DDFKHTGPNGTHVCMVFEVLGPNLLKLIKRYNYRGIPLPLVKKIARQVLQGLDYLHTKCGIIHTDIKPENVLLCISKIEV 160

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 1370510825 108 VKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLID 187
Cdd:cd14134     4 YKPGDLLTNRYKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKDPN--GKSHCVQLRD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 188 DFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHsKCKIIHTDIKPENILMcVDDAYVR 267
Cdd:cd14134    82 WFDYRG----HMCIVFELLGPSLYDFLKKNNYGPFPLEHVQHIAKQLLEAVAFLH-DLKLTHTDLKPENILL-VDSDYVK 155

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. 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. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). 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. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B 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. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 104 GYHPVKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDpnKDMVV 183
Cdd:cd14210     1 GDYKVVLGDHIAYRYEVLSVLGKGSFGQVVKCLDHKTGQLVAIKIIRNKKRFHQQALVEVKILKHLNDNDPDD--KHNIV 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370510825 184 QLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMC 260
Cdd:cd14210    79 RYKDSFIFRG----HLCIVFELLSINLYELLKSNNFQGLSLSLIRKFAKQILQALQFLHKL-NIIHCDLKPENILLK 150

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825  118 YHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVK--SAQHYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFKisgmN 195
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKkkKIKKDRERILREIKILKKLKH-----PN---IVRLYDVFE----D 68

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370510825  196 GIHVCMVFEVLGHHLLKWIIKSNyQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVD 262
Cdd:smart00220  69 EDKLYLVMEYCEGGDLFDLLKKR-GRLSEDEARFYLRQILSALEYLHSK-GIVHRDLKPENILLDED 133

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 1370510825 108 VKIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSDPNKdmVVQLID 187
Cdd:cd14226     5 VKNGEKWMDRYEIDSLIGKGSFGQVVKAYDHVEQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHDTENKYY--IVRLKR 82

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370510825 188 DFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYL-HSKCKIIHTDIKPENILMC 260
Cdd:cd14226    83 HFMFRN----HLCLVFELLSYNLYDLLRNTNFRGVSLNLTRKFAQQLCTALLFLsTPELSIIHCDLKPENILLC 152

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 1370510825 562 RVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFEPHSgedysrDEDHIAHIIE 641
Cdd:cd14134   172 DIKLIDFGSATFDDEYHSSIVSTRHYRAPEVILGLGWSYPCDVWSIGCILVELYTGELLFQTHD------NLEHLAMMER 245

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 642 LLGSIPRHFALSGKYSREFFNRRDhialiiellGKVPR-KYAMLGKYSKefftrkgelRHITKLKPWSLFDvlvekygwp 720
Cdd:cd14134   246 ILGPLPKRMIRRAKKGAKYFYFYH---------GRLDWpEGSSSGRSIK---------RVCKPLKRLMLLV--------- 298

                         170       180       190
                  ....*....|....*....|....*....|....
gi 1370510825 721 HEDAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 754
Cdd:cd14134   299 DPEHRLLFDLIRKMLEYDPSKRITAKEALKHPFF 332

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 1370510825 548 LLVNPldPRNAdkirVKIADLGNACWVHKHFTEDIQTRQYRSIEVLIGAGYSTPADIWSTACMAFELATGDYLFephSGe 627
Cdd:cd14226   150 LLCNP--KRSA----IKIIDFGSSCQLGQRIYQYIQSRFYRSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLF---SG- 219

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 628 dySRDEDHIAHIIELLGSIPRHFALSGKYSREFFNRrdhialiIELLGKVPRKYAMLGKYsKEFFTRKgelrhitklkpw 707
Cdd:cd14226   220 --ANEVDQMNKIVEVLGMPPVHMLDQAPKARKFFEK-------LPDGTYYLKKTKDGKKY-KPPGSRK------------ 277

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 708 sLFDVLVEKYGWP---------H--EDAAQFTDFLIPMLEMVPEKRASAGECLRHPWLNS 756
Cdd:cd14226   278 -LHEILGVETGGPggrragepgHtvEDYLKFKDLILRMLDYDPKTRITPAEALQHSFFKR 336

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 1370510825 109 KIGDLFNGRYHVIRKLGWGHFSTVWLCWD-MQGKRFVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLID 187
Cdd:cd14215     5 RSGDWLQERYEIVSTLGEGTFGRVVQCIDhRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDPE--NKNLCVQMFD 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 188 DFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMCVDDAYVR 267
Cdd:cd14215    83 WFDYHG----HMCISFELLGLSTFDFLKENNYLPYPIHQVRHMAFQVCQAVKFLHDN-KLTHTDLKPENILFVNSDYELT 157

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 116 GRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVK---SAQHYTETALDEIKLLKCVREsdpsdPNkdmVVQLIDDFKIS 192
Cdd:cd07833     1 NKYEVLGVVGEGAYGVVLKCRNKATGEIVAIKKFKeseDDEDVKKTALREVKVLRQLRH-----EN---IVNLKEAFRRK 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370510825 193 GmngiHVCMVFEVLGHHLLKWIIKSNYqGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENIL 258
Cdd:cd07833    73 G----RLYLVFEYVERTLLELLEASPG-GLPPDAVRSYIWQLLQAIAYCHSH-NIIHRDIKPENIL 132

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 1370510825 124 LGWGHFSTVWLCWDMQGKRFVAMKVVK--SAQHYTETALDEIKLLKCVResdpsDPNkdmVVQLIDDFKisgmNGIHVCM 201
Cdd:cd00180     1 LGKGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLN-----HPN---IVKLYDVFE----TENFLYL 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370510825 202 VFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILM 259
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 1370510825  88 GSDDEEqedpadyckGGYHPVkIGDLFNGRYHVIRKLGWGHFSTVWLCWDMQGKRFVAMKVVKSAQHYTETALDEIKLLK 167
Cdd:cd14225    25 GYDDEN---------GSYLKV-LHDHIAYRYEILEVIGKGSFGQVVKALDHKTNEHVAIKIIRNKKRFHHQALVEVKILD 94

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 168 CVRESDPSdpNKDMVVQLIDDFKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHsKCKI 247
Cdd:cd14225    95 ALRRKDRD--NSHNVIHMKEYFYFRN----HLCITFELLGMNLYELIKKNNFQGFSLSLIRRFAISLLQCLRLLY-RERI 167

                         170
                  ....*....|..
gi 1370510825 248 IHTDIKPENILM 259
Cdd:cd14225   168 IHCDLKPENILL 179

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 1370510825 557 NADKIRVKIADLGNACWVHKHF-TEDIQTRQYRSIEVLIGA-GYSTPADIWSTACMAFELATGDYLFEPHSgedysrDED 634
Cdd:cd05118   135 NLELGQLKLADFGLARSFTSPPyTPYVATRWYRAPEVLLGAkPYGSSIDIWSLGCILAELLTGRPLFPGDS------EVD 208

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370510825 635 HIAHIIELLGsiprhfalsgkysreffnrrdhialiiellgkvprkyamlgkyskefftrkgelrhitklkpwslfdvlv 714
Cdd:cd05118   209 QLAKIVRLLG---------------------------------------------------------------------- 218

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1370510825 715 ekygwphedAAQFTDFLIPMLEMVPEKRASAGECLRHPWL 754
Cdd:cd05118   219 ---------TPEALDLLSKMLKYDPAKRITASQALAHPYF 249

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. 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 CLK1/4 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 1370510825 111 GDLFNGRYHVIRKLGWGHFSTVWLCWD--MQGKRfVAMKVVKSAQHYTETALDEIKLLKCVRESDPSdpNKDMVVQLIDD 188
Cdd:cd14213     7 GDVLRARYEIVDTLGEGAFGKVVECIDhkMGGMH-VAVKIVKNVDRYREAARSEIQVLEHLNTTDPN--STFRCVQMLEW 83

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370510825 189 FKISGmngiHVCMVFEVLGHHLLKWIIKSNYQGLPVRCVKSIIRQVLQGLDYLHSKcKIIHTDIKPENILMcVDDAYV 266
Cdd:cd14213    84 FDHHG----HVCIVFELLGLSTYDFIKENSFLPFPIDHIRNMAYQICKSVNFLHHN-KLTHTDLKPENILF-VQSDYV 155