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 2462596744 186 TFRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIKKR 265
Cdd:cd05631     1 TFRHYRVLGKGGFGE---------------------------------------VCACQVRATGKMYACKKLEKKRIKKR 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 266 KGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQRE 345
Cdd:cd05631    42 KGEAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFDEQRAIFYAAELCCGLEDLQRE 121

                         170
                  ....*....|....*...
gi 2462596744 346 RIVYRDLKPENILLDDRG 363
Cdd:cd05631   122 RIVYRDLKPENILLDDRG 139

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 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 2462596744 186 TFRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIKKR 265
Cdd:cd05631     1 TFRHYRVLGKGGFGE---------------------------------------VCACQVRATGKMYACKKLEKKRIKKR 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 266 KGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQRE 345
Cdd:cd05631    42 KGEAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFDEQRAIFYAAELCCGLEDLQRE 121

                         170
                  ....*....|....*...
gi 2462596744 346 RIVYRDLKPENILLDDRG 363
Cdd:cd05631   122 RIVYRDLKPENILLDDRG 139

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  187 FRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIKKRk 266
Cdd:smart00220   1 YEILEKLGEGSFGK---------------------------------------VYLARDKKTGKLVAIKVIKKKKIKKD- 40

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  267 gEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNlgNPGFDEQRAVFYAAELCCGLEDLQRER 346
Cdd:smart00220  41 -RERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLKK--RGRLSEDEARFYLRQILSALEYLHSKG 117

                          170
                   ....*....|....*..
gi 2462596744  347 IVYRDLKPENILLDDRG 363
Cdd:smart00220 118 IVHRDLKPENILLDEDG 134

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  52 DYSSLCDKQPiGRRLFRQFCDTKpTLKRHIEFLDAVAEYEVAD-DEDRSDCGLSILDRFFNDKLAAPLpEIPPDVVTECR 130
Cdd:pfam00615   1 SFDSLLEDQP-GRRLFRQFLESE-FSEENLEFWLACEEFKKADpDEERLKKAKEIYNEFLAPGSPKEI-NLDSDLREEIR 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2462596744 131 LGLKEEnPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQF 171
Cdd:pfam00615  78 ENLEKE-PTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 269 AMALNEKRILEKVQSRFVVSLaYAY-ETKDALCLVLTIMNGGDLKFHIYNLGnpGFDEQRAVFYAAELCCGLEDLQRERI 347
Cdd:COG0515    52 ERFRREARALARLNHPNIVRV-YDVgEEDGRPYLVMEYVEGESLADLLRRRG--PLPPAEALRILAQLAEALAAAHAAGI 128

                          90
                  ....*....|....*...
gi 2462596744 348 VYRDLKPENILLDDRGLP 365
Cdd:COG0515   129 VHRDIKPANILLTPDGRV 146

Stk1 family PASTA domain-containing Ser/Thr kinase;

                          10        20        30
                  ....*....|....*....|....*....|....*...
gi 2462596744 326 QRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRG 363
Cdd:NF033483  107 EEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDG 144

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 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 2462596744 186 TFRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIKKR 265
Cdd:cd05631     1 TFRHYRVLGKGGFGE---------------------------------------VCACQVRATGKMYACKKLEKKRIKKR 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 266 KGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQRE 345
Cdd:cd05631    42 KGEAMALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFDEQRAIFYAAELCCGLEDLQRE 121

                         170
                  ....*....|....*...
gi 2462596744 346 RIVYRDLKPENILLDDRG 363
Cdd:cd05631   122 RIVYRDLKPENILLDDRG 139

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 4 (GRK4); The RGS domain is an essential part of the GRK4 (G protein-coupled receptor kinase4) proteins, which are membrane-associated serine/threonine protein kinases that phosphorylate G protein-coupled receptors (GPCRs) upon agonist stimulation. This phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events. GRK4 is a member of the GRK kinase family which includes three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. GRK4 plays a key role in regulating dopaminergic-mediated natriuresis and is associated with essential hypertension and/or salt-sensitive hypertension. GRK4 exists in four splice variants involved in hyperphosphorylation, desensitization, and internalization of two dopamine receptors (D1R and D3R). GRK4 also increases the expression of a key receptor of the renin-angiotensin system, the AT1R (angiotensin type 1 receptor). RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  52 DYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEYEVADDEDRSDCGLSILDRFFNDKLAAPLPEIPPDVVTECRL 131
Cdd:cd08750     1 DYSSLCDKQPIGRLLFRQFCDTRPTLKRCIEFLDAVAEYEVAPDEKRSDCGLSILDTYFNNGSAAHLPEIPQDVVTECRL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462596744 132 GLkEENPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKWLERQPVTK 184
Cdd:cd08750    81 KL-EENPSKELFEECTRVVHEYLSGEPFEAYQESMYFSRFLQWKWLERQPVTK 132

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 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 2462596744 184 KNTFRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIK 263
Cdd:cd05632     1 KNTFRQYRVLGKGGFGE---------------------------------------VCACQVRATGKMYACKRLEKKRIK 41

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 264 KRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQ 343
Cdd:cd05632    42 KRKGESMALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDLKFHIYNMGNPGFEEERALFYAAEILCGLEDLH 121

                         170       180
                  ....*....|....*....|
gi 2462596744 344 RERIVYRDLKPENILLDDRG 363
Cdd:cd05632   122 RENTVYRDLKPENILLDDYG 141

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 6 (GRK6); The RGS domain is an essential part of the GRK6 (G protein-coupled receptor kinase 6) protein which plays an important role in the regulating of dopamine, opioids, M3 muscarinic, and chemokine receptor signaling. GRK6 is a member of the GRK kinase family which includes three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. The RH domain of GRK6 does not have structural determinants that are required for binding G-alpha subunit, in contrast to GRK2 and many other RGS proteins. GRK6 is an important target for treatment of addiction and Parkinson disease. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  36 LPPVSQCSELRHSIEKDYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEYEVADDEDRSDCGLSILDRFFNDKLA 115
Cdd:cd08751     2 FPHISLCEELRQSLERDYHSLCERQPIGRLLFRQFCATRPELSRCVAFLDAVAEYEVTPDEKRKECGQNLTQKYLSHKSE 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2462596744 116 APLPEIPPDVVTECRLGLKEEnPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKWLERQ 180
Cdd:cd08751    82 DYIPEVPRQLVTNCTQRLEQE-PCKELFQELTKLIHDYLSVAPFADYLDSIYFNRFLQWKWLERQ 145

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 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 2462596744 187 FRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIKKRK 266
Cdd:cd05607     4 FYEFRVLGKGGFGE---------------------------------------VCAVQVKNTGQMYACKKLDKKRLKKKS 44

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 267 GEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNPGFDEQRAVFYAAELCCGLEDLQRER 346
Cdd:cd05607    45 GEKMALLEKEILEKVNSPFIVSLAYAFETKTHLCLVMSLMNGGDLKYHIYNVGERGIEMERVIFYSAQITCGILHLHSLK 124

                         170
                  ....*....|....*..
gi 2462596744 347 IVYRDLKPENILLDDRG 363
Cdd:cd05607   125 IVYRDMKPENVLLDDNG 141

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 5 (GRK5); The RGS domain is an essential part of the GRK5 (G protein-coupled receptor kinase 5) protein, a membrane-associated serine/threonine protein kinases which phosphorylates G protein-coupled receptors (GPCRs) upon agonist stimulation. This phosphorylation initiates beta-arrestin-mediated receptor desensitization, internalization, and signaling events. GRK5 is a member of the GRK kinase family which include three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  53 YSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEYEVADDEDRSDCGLSILDRFFNDKLAAPLPEIPPDVVTECRLG 132
Cdd:cd08752     1 YCSLCDKQPIGRLLFRQFCETRPGLECYIQFLDSVAEYEVTPDEKLGEKGKEIMTKYLTPKSPVFIPQVGQDLVSQTEEK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2462596744 133 LkEENPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWKW 176
Cdd:cd08752    81 L-LQKPCKELFSACTQSVHDYLRGEPFHEYLDSMYFDRFLQWKW 123

Regulator of G protein signaling domain (RGS) found in G protein-coupled receptor kinase 7 (GRK7); The RGS domain is an essential part of the GRK7 (G protein-coupled receptor kinases 7) proteins which together with GRK1 (Rhodopsin kinase) have been implicated in the shutoff of the photoresponse and adaptation to changing light conditions via rod and cone opsin phosphorylation. GRK7 is a member of the GRK kinase family which includes three major subfamilies: the GRK4 subfamily (GRK4, GRK5 and GRK6), the rhodopsin kinase or visual GRK subfamily (GRK1 and GRK7), and the beta-adrenergic receptor kinases subfamily (GRK2/GRK3). The RGS domain of the GRKs has very little sequence similarity with the canonical RGS domain of the RGS proteins and therefore is often refered to as the RH (RGS Homology) domain. GRK7 is expressed in all vertebrate cones except that of mice and rats, which do not have the gene for GRK7. Lack of either GRK7 or both GRK1 and GRK7 in human leads to a vision defect called Enhanced S Cone syndrome. RGS proteins regulate many aspects of embryonic development such as glial differentiation, embryonic axis formation, skeletal and muscle development, cell migration during early embryogenesis, as well as apoptosis, cell proliferation, and modulation of cardiac development.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  37 PPVSQCSELRHSIEKDYSSLCDKQPIGRRLFRQFCDTKPTLKRHIEFLDAVAEYEVADDEDRSDCGLSILDRFFNDKLAA 116
Cdd:cd08749     1 PKPEQCAELRQSLSKDFESLCEQQPIGKRLFRDFLATVPEYTVAADFLDDVQNWELAEEAAKDKARQNIIANFCKAGSKN 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462596744 117 PLPEIPPDVVTECRLGLKEEnpSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQFLQWK 175
Cdd:cd08749    81 PLSFLSGDVATKCKAATEKD--FEEVVGQAKDETKEFLQGKPFTDFQTSPFYDKFLQWK 137

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  187 FRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKRIKKRk 266
Cdd:smart00220   1 YEILEKLGEGSFGK---------------------------------------VYLARDKKTGKLVAIKVIKKKKIKKD- 40

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  267 gEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNlgNPGFDEQRAVFYAAELCCGLEDLQRER 346
Cdd:smart00220  41 -RERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLKK--RGRLSEDEARFYLRQILSALEYLHSKG 117

                          170
                   ....*....|....*..
gi 2462596744  347 IVYRDLKPENILLDDRG 363
Cdd:smart00220 118 IVHRDLKPENILLDEDG 134

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 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 2462596744 182 VTKNTFRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQKKR 261
Cdd:cd05633     2 LTMNDFSVHRIIGRGGFGE---------------------------------------VYGCRKADTGKMYAMKCLDKKR 42

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 262 IKKRKGEAMALNEKRILEKVQS---RFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNpgFDEQRAVFYAAELCCG 338
Cdd:cd05633    43 IKMKQGETLALNERIMLSLVSTgdcPFIVCMTYAFHTPDKLCFILDLMNGGDLHYHLSQHGV--FSEKEMRFYATEIILG 120

                         170       180
                  ....*....|....*....|....*
gi 2462596744 339 LEDLQRERIVYRDLKPENILLDDRG 363
Cdd:cd05633   121 LEHMHNRFVVYRDLKPANILLDEHG 145

Regulator of G protein signaling domain; RGS family members are GTPase-activating proteins for heterotrimeric G-protein alpha-subunits.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744  52 DYSSLCDKQPiGRRLFRQFCDTKpTLKRHIEFLDAVAEYEVAD-DEDRSDCGLSILDRFFNDKLAAPLpEIPPDVVTECR 130
Cdd:pfam00615   1 SFDSLLEDQP-GRRLFRQFLESE-FSEENLEFWLACEEFKKADpDEERLKKAKEIYNEFLAPGSPKEI-NLDSDLREEIR 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 2462596744 131 LGLKEEnPSKKAFEECTRVAHNYLRGEPFEEYQESSYFSQF 171
Cdd:pfam00615  78 ENLEKE-PTRDLFDEAQAEVYELMEKDSYPRFLKSPLYLRL 117

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 271 ALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNpgFDEQRAVFYAAELCCGLEDLQRERIVYR 350
Cdd:cd05579    40 VLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDLYSLLENVGA--LDEDVARIYIAEIVLALEYLHSHGIIHR 117

                          90       100
                  ....*....|....*....|.
gi 2462596744 351 DLKPENILLDDRG---LPDHG 368
Cdd:cd05579   118 DLKPDNILIDANGhlkLTDFG 138

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 271 ALNEKRILEKVQSR-FVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNpgFDEQRAVFYAAELCCGLEDLQRERIVY 349
Cdd:cd05570    42 TMTEKRVLALANRHpFLTGLHACFQTEDRLYFVMEYVNGGDLMFHIQRARR--FTEERARFYAAEICLALQFLHERGIIY 119

                          90
                  ....*....|....
gi 2462596744 350 RDLKPENILLDDRG 363
Cdd:cd05570   120 RDLKLDNVLLDAEG 133

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 246 RATGKMYACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNlgNPGFDE 325
Cdd:cd05595    17 KATGRYYAMKILRKEVIIAKDEVAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGELFFHLSR--ERVFTE 94

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462596744 326 QRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRG 363
Cdd:cd05595    95 DRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDG 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 2462596744 236 FSTfVCACQVRATGKMYACKKLQKKRIKKRKGeaMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHI 315
Cdd:cd00180     6 FGK-VYKARDKETGKKVAVKVIPKEKLKKLLE--ELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLL 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2462596744 316 YNLGNPgFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRG 363
Cdd:cd00180    83 KENKGP-LSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDG 129

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 274 EKRILEKVQSR---FVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNlgnPGFDEQRAVFYAAELCCGLEDLQRERIVYR 350
Cdd:cd05589    49 EKRIFETVNSArhpFLVNLFACFQTPEHVCFVMEYAAGGDLMMHIHE---DVFSEPRAVFYAACVVLGLQFLHEHKIVYR 125

                          90
                  ....*....|...
gi 2462596744 351 DLKPENILLDDRG 363
Cdd:cd05589   126 DLKLDNLLLDTEG 138

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 2462596744 230 EAHDTIFS-TF--VCACQVRATGKMYACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIM 306
Cdd:cd05580     4 EFLKTLGTgSFgrVRLVKHKDSGKYYALKILKKAKIIKLKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEYV 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2462596744 307 NGGDLKFHIYNLGNpgFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRG 363
Cdd:cd05580    84 PGGELFSLLRRSGR--FPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDG 138

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K 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 2462596744 274 EKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNpgFDEQRAVFYAAELCCGLEDLQRERIVYRDLK 353
Cdd:cd05584    50 ERNILEAVKHPFIVDLHYAFQTGGKLYLILEYLSGGELFMHLEREGI--FMEDTACFYLAEITLALGHLHSLGIIYRDLK 127

                          90
                  ....*....|....*...
gi 2462596744 354 PENILLDDRG---LPDHG 368
Cdd:cd05584   128 PENILLDAQGhvkLTDFG 145

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 246 RATGKMYACKKLQKKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNlgNPGFDE 325
Cdd:cd05593    37 KASGKYYAMKILKKEVIIAKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGELFFHLSR--ERVFSE 114

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462596744 326 QRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRG 363
Cdd:cd05593   115 DRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDG 152

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 179 RQPVTKNTFRHYRVLGKGGFGEqspvgcavdgswkkqqpnvddteargpepeahdtifstfVCACQVRATGKMYACKKLQ 258
Cdd:cd05594    19 KHKVTMNDFEYLKLLGKGTFGK---------------------------------------VILVKEKATGRYYAMKILK 59

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 259 KKRIKKRKGEAMALNEKRILEKVQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNlgNPGFDEQRAVFYAAELCCG 338
Cdd:cd05594    60 KEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSR--ERVFSEDRARFYGAEIVSA 137

                         170       180
                  ....*....|....*....|....*.
gi 2462596744 339 LEDLQRER-IVYRDLKPENILLDDRG 363
Cdd:cd05594   138 LDYLHSEKnVVYRDLKLENLMLDKDG 163

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 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 2462596744 240 VCACQVRATGKMYACKKLQKKRIKKRKGEAMALNEKRILEK-VQSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNl 318
Cdd:cd05603    11 VLLAKRKCDGKFYAVKVLQKKTILKKKEQNHIMAERNVLLKnLKHPFLVGLHYSFQTSEKLYFVLDYVNGGELFFHLQR- 89

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 2462596744 319 gNPGFDEQRAVFYAAELCCGLEDLQRERIVYRDLKPENILLDDRG---LPDHG 368
Cdd:cd05603    90 -ERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGhvvLTDFG 141

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462596744 274 EKRILEKV-QSRFVVSLAYAYETKDALCLVLTIMNGGDLKFHIYNLGNpgFDEQRAVFYAAELCCGLEDLQRERIVYRDL 352
Cdd:cd05620    45 EKRVLALAwENPFLTHLYCTFQTKEHLFFVMEFLNGGDLMFHIQDKGR--FDLYRATFYAAEIVCGLQFLHSKGIIYRDL 122

                          90
                  ....*....|.
gi 2462596744 353 KPENILLDDRG 363
Cdd:cd05620   123 KLDNVMLDRDG 133