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 38201644   6 QIRYISQTQGLPAEYLLSAGTKTTRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 85
Cdd:cd14228 227 QIRYISQTQGLPAEYLLSAGTKTSRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 306

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 38201644  86 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQFVTMTHLLDFPH 134
Cdd:cd14228 307 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHPFVTMTHLLDFPH 355

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 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 38201644   6 QIRYISQTQGLPAEYLLSAGTKTTRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 85
Cdd:cd14228 227 QIRYISQTQGLPAEYLLSAGTKTSRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 306

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 38201644  86 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQFVTMTHLLDFPH 134
Cdd:cd14228 307 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHPFVTMTHLLDFPH 355

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 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 38201644   6 QIRYISQTQGLPAEYLLSAGTKTTRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 85
Cdd:cd14228 227 QIRYISQTQGLPAEYLLSAGTKTSRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 306

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 38201644  86 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQFVTMTHLLDFPH 134
Cdd:cd14228 307 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHPFVTMTHLLDFPH 355

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK 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 38201644   6 QIRYISQTQGLPAEYLLSAGTKTTRFFNRDPNLGYPLWRLKTPEEHELETGIKSKEARKYIFNCLDDMAQVNMSTDLEGT 85
Cdd:cd14211 211 QIRYISQTQGLPAEHLLNAATKTSRFFNRDPDSPYPLWRLKTPEEHEAETGIKSKEARKYIFNCLDDMAQVNGPSDLEGS 290

                        90       100       110
                ....*....|....*....|....*....|....*....
gi 38201644  86 DMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQFV 124
Cdd:cd14211 291 ELLAEKADRREFIDLLKRMLTIDQERRITPGEALNHPFV 329

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 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 38201644   6 QIRYISQTQGLPAEYLLSAGTKTTRFFNR-DPNLGYPLWRLKTPEEHELETGIKSKEARKYI-FNCLDDMAQ-----VNM 78
Cdd:cd14212 210 QLSRIIEMLGMPPDWMLEKGKNTNKFFKKvAKSGGRSTYRLKTPEEFEAENNCKLEPGKRYFkYKTLEDIIMnypmkKSK 289

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 38201644  79 STDLEgtdmlAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQFV 124
Cdd:cd14212 290 KEQID-----KEMETRLAFIDFLKGLLEYDPKKRWTPDQALNHPFI 330

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha 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 38201644  44 RLKTPEEHELETGIKSKEARKYIfNCLDDMAQVNMSTDLEGTDMLAekadrreyIDLLKKMLTIDADKRITPLKTLNHQF 123
Cdd:cd07877 232 RLVGTPGAELLKKISSESARNYI-QSLTQMPKMNFANVFIGANPLA--------VDLLEKMLVLDSDKRITAAQALAHAY 302

                ....*
gi 38201644 124 VTMTH 128
Cdd:cd07877 303 FAQYH 307

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta 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 38201644  47 TPEEhELETGIKSKEARKYIfNCLDDMAQVNMSTDLEGTDMLAekadrreyIDLLKKMLTIDADKRITPLKTLNHQFVTM 126
Cdd:cd07878 234 TPSP-EVLKKISSEHARKYI-QSLPHMPQQDLKKIFRGANPLA--------IDLLEKMLVLDSDKRISASEALAHPYFSQ 303

                ..
gi 38201644 127 TH 128
Cdd:cd07878 304 YH 305

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 38201644  45 LKTPEEHELEtGIKSKEARKYIFNcLDDMAQVNMSTDLEGTDMLAekadrreyIDLLKKMLTIDADKRITPLKTLNHQF 123
Cdd:cd07834 222 LGTPSEEDLK-FISSEKARNYLKS-LPKKPKKPLSEVFPGASPEA--------IDLLEKMLVFNPKKRITADEALAHPY 290

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
                ....*....|....*....|....*....|....*....|....*....|...
gi 38201644  71 DDMAQVNMSTDLEGTDMLaekadrreyIDLLKKMLTIDADKRITPLKTLNHQF 123
Cdd:cd05118 205 SEVDQLAKIVRLLGTPEA---------LDLLSKMLKYDPAKRITASQALAHPY 248

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 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 38201644  45 LKTPEEHELETgIKSKEARKYIFNcLDDMAQVNMSTDLEGTDMLAekadrreyIDLLKKMLTIDADKRITPLKTLNHQFV 124
Cdd:cd07857 226 LGTPDEETLSR-IGSPKAQNYIRS-LPNIPKKPFESIFPNANPLA--------LDLLEKLLAFDPTKRISVEEALEHPYL 295

                ....
gi 38201644 125 TMTH 128
Cdd:cd07857 296 AIWH 299

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 38201644  43 WRLKTPEeheletGIKSKEARKYIFNCLDdmaqvnmstdlegTDMLAEKADRREYIDLLKKMLTIDADKRITPLKTLNHQ 122
Cdd:cd14134 270 GRLDWPE------GSSSGRSIKRVCKPLK-------------RLMLLVDPEHRLLFDLIRKMLEYDPSKRITAKEALKHP 330

                .
gi 38201644 123 F 123
Cdd:cd14134 331 F 331

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30
                ....*....|....*....|....*....|
gi 38201644  95 REYIDLLKKMLTIDADKRITPLKTLNHQFV 124
Cdd:cd07864 273 TPALDLLDHMLTLDPSKRCTAEQALNSPWL 302

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

                           10        20        30
                   ....*....|....*....|....*....|
gi 38201644     95 REYIDLLKKMLTIDADKRITPLKTLNHQFV 124
Cdd:smart00220 225 PEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254