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 71981195 310 QLISKGRFGKVFKAQYTpdsgeKRLVAVKKLNEFQKASFLAEKRIFDELNEypkWYKSIVEFVCAEKIG----DEYWIVT 385
Cdd:cd14053   1 EIKARGRFGAVWKAQYL-----NRLVAVKIFPLQEKQSWLTEREIYSLPGM---KHENILQFIGAEKHGesleAEYWLIT 72

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 386 EFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRPYFFGHPKKPIIHRLVENEN 445
Cdd:cd14053  73 EFHERGSLCDYLKGNVISWNELCKIAESMARGLAYLHEDIPATNGGHKPSIAHRDFKSKN 132

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 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 71981195 310 QLISKGRFGKVFKAQYTpdsgeKRLVAVKKLNEFQKASFLAEKRIFDELNEypkWYKSIVEFVCAEKIG----DEYWIVT 385
Cdd:cd14053   1 EIKARGRFGAVWKAQYL-----NRLVAVKIFPLQEKQSWLTEREIYSLPGM---KHENILQFIGAEKHGesleAEYWLIT 72

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 386 EFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRPYFFGHPKKPIIHRLVENEN 445
Cdd:cd14053  73 EFHERGSLCDYLKGNVISWNELCKIAESMARGLAYLHEDIPATNGGHKPSIAHRDFKSKN 132

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195    310 QLISKGRFGKVFKAQYTPDsgeKRLVAVKKLN----EFQKASFLAEKRIFDELNEypkwyKSIVEFVCAEKIGDEYWIVT 385
Cdd:smart00220   5 EKLGEGSFGKVYLARDKKT---GKLVAIKVIKkkkiKKDRERILREIKILKKLKH-----PNIVRLYDVFEDEDKLYLVM 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 71981195    386 EFHERLSLYELLKNNV-ISITSANRIIMSMIDGLQFLHddrpyffghpKKPIIHR 439
Cdd:smart00220  77 EYCEGGDLFDLLKKRGrLSEDEARFYLRQILSALEYLH----------SKGIVHR 121

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 310 QLISKGRFGKVFKAQytpDSGEKRLVAVKKL------NEFQKASFLAEKRIFDELNeYPkwykSIVEFVCAEKIGDEYWI 383
Cdd:COG0515  13 RLLGRGGMGVVYLAR---DLRLGRPVALKVLrpelaaDPEARERFRREARALARLN-HP----NIVRVYDVGEEDGRPYL 84

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71981195 384 VTEFHERLSLYELLK-NNVISITSANRIIMSMIDGLQFLHDdrpyffghpkKPIIHR 439
Cdd:COG0515  85 VMEYVEGESLADLLRrRGPLPPAEALRILAQLAEALAAAHA----------AGIVHR 131

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 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 71981195 310 QLISKGRFGKVFKAQYTpdsgeKRLVAVKKLNEFQKASFLAEKRIFDELNEypkWYKSIVEFVCAEKIG----DEYWIVT 385
Cdd:cd14053   1 EIKARGRFGAVWKAQYL-----NRLVAVKIFPLQEKQSWLTEREIYSLPGM---KHENILQFIGAEKHGesleAEYWLIT 72

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 386 EFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRPYFFGHPKKPIIHRLVENEN 445
Cdd:cd14053  73 EFHERGSLCDYLKGNVISWNELCKIAESMARGLAYLHEDIPATNGGHKPSIAHRDFKSKN 132

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 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 71981195 310 QLISKGRFGKVFKAQYTPDSGEK-RLVAVKKLNEFQKASFLAEKRIFDELNEYpkwYKSIVEFVCAEK----IGDEYWIV 384
Cdd:cd14055   1 KLVGKGRFAEVWKAKLKQNASGQyETVAVKIFPYEEYASWKNEKDIFTDASLK---HENILQFLTAEErgvgLDRQYWLI 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71981195 385 TEFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRpYFFGHPKKPIIHRLVENEN 445
Cdd:cd14055  78 TAYHENGSLQDYLTRHILSWEDLCKMAGSLARGLAHLHSDR-TPCGRPKIPIAHRDLKSSN 137

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2b 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 71981195 310 QLISKGRFGKVFKAQYTPDsgekrLVAVKKLNEFQKASFLAEKRIFdelNEYPKWYKSIVEFVCAEKIGD----EYWIVT 385
Cdd:cd14140   1 EIKARGRFGCVWKAQLMNE-----YVAVKIFPIQDKQSWQSEREIF---STPGMKHENLLQFIAAEKRGSnlemELWLIT 72

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71981195 386 EFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRPYFFGHPKKP-IIHRLVENEN 445
Cdd:cd14140  73 AFHDKGSLTDYLKGNIVSWNELCHIAETMARGLSYLHEDVPRCKGEGHKPaIAHRDFKSKN 133

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 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 71981195 310 QLISKGRFGKVFKAQYTpdsgeKRLVAVKKLNEFQKASFLAEKRIFD-ELNEYPkwykSIVEFVCA-EKIG----DEYWI 383
Cdd:cd14054   1 QLIGQGRYGTVWKGSLD-----ERPVAVKVFPARHRQNFQNEKDIYElPLMEHS----NILRFIGAdERPTadgrMEYLL 71

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 71981195 384 VTEFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRPYFFGHpkKP-IIHR 439
Cdd:cd14054  72 VLEYAPKGSLCSYLRENTLDWMSSCRMALSLTRGLAYLHTDLRRGDQY--KPaIAHR 126

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase 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 mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 312 ISKGRFGKVFKAQYtpdsgEKRLVAVKKL-----NEFQKASFLAEKRIFDELNeypkwYKSIVEFVCAEKIGDEYWIVTE 386
Cdd:cd13999   1 IGSGSFGEVYKGKW-----RGTDVAIKKLkveddNDELLKEFRREVSILSKLR-----HPNIVQFIGACLSPPPLCIVTE 70

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 71981195 387 FHERLSLYELLKNNVISITSANRIIMsMID---GLQFLHDdrpyffghpkKPIIHR 439
Cdd:cd13999  71 YMPGGSLYDLLHKKKIPLSWSLRLKI-ALDiarGMNYLHS----------PPIIHR 115

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195    310 QLISKGRFGKVFKAQYTPDsgeKRLVAVKKLN----EFQKASFLAEKRIFDELNEypkwyKSIVEFVCAEKIGDEYWIVT 385
Cdd:smart00220   5 EKLGEGSFGKVYLARDKKT---GKLVAIKVIKkkkiKKDRERILREIKILKKLKH-----PNIVRLYDVFEDEDKLYLVM 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 71981195    386 EFHERLSLYELLKNNV-ISITSANRIIMSMIDGLQFLHddrpyffghpKKPIIHR 439
Cdd:smart00220  77 EYCEGGDLFDLLKKRGrLSEDEARFYLRQILSALEYLH----------SKGIVHR 121

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195   310 QLISKGRFGKVFKAQYTPDSGEKRL-VAVKKLNEF----QKASFLAEKRIFDELNeypkwYKSIVEF--VCAEkiGDEYW 382
Cdd:pfam07714   5 EKLGEGAFGEVYKGTLKGEGENTKIkVAVKTLKEGadeeEREDFLEEASIMKKLD-----HPNIVKLlgVCTQ--GEPLY 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 71981195   383 IVTEFHERLSLYELLKNNVISITSANRIIMSM-I-DGLQFLHDdrpyffghpkKPIIHR 439
Cdd:pfam07714  78 IVTEYMPGGDLLDFLRKHKRKLTLKDLLSMALqIaKGMEYLES----------KNFVHR 126

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195    310 QLISKGRFGKVFKAQYTPDSGEKRL-VAVKKL----NEFQKASFLAEKRIFDELNeypkwYKSIVEF--VCAEkiGDEYW 382
Cdd:smart00221   5 KKLGEGAFGEVYKGTLKGKGDGKEVeVAVKTLkedaSEQQIEEFLREARIMRKLD-----HPNIVKLlgVCTE--EEPLM 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195    383 IVTEFHERLSLYELLKNN-VISITSANRIIMSM-I-DGLQFLHDdrpyffghpkKPIIHR 439
Cdd:smart00221  78 IVMEYMPGGDLLDYLRKNrPKELSLSDLLSFALqIaRGMEYLES----------KNFIHR 127

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 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 71981195 306 ITDFQLISKGRFGKVFKAQYTPDSgekrlVAVKKLNEFQKASFLAEKRIFdelNEYPKWYKSIVEFVCAEKIG----DEY 381
Cdd:cd14142   7 ITLVECIGKGRYGEVWRGQWQGES-----VAVKIFSSRDEKSWFRETEIY---NTVLLRHENILGFIASDMTSrnscTQL 78

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 71981195 382 WIVTEFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDrpyFFGHPKKP-IIHRLVENEN 445
Cdd:cd14142  79 WLITHYHENGSLYDYLQRTTLDHQEMLRLALSAASGLVHLHTE---IFGTQGKPaIAHRDLKSKN 140

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK 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 71981195 308 DFQLISKGRFGKVFKAQytpDSGEKRLVAVKKLNEFQKasflAEKRIFDE---LNEYPkwYKSIVEFVCAEKIGDEYWIV 384
Cdd:cd06614   4 NLEKIGEGASGEVYKAT---DRATGKEVAIKKMRLRKQ----NKELIINEiliMKECK--HPNIVDYYDSYLVGDELWVV 74

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 71981195 385 TEFHERLSLYELLKNNVISITSAN--RIIMSMIDGLQFLHddrpyffghpKKPIIHRLVENEN 445
Cdd:cd06614  75 MEYMDGGSLTDIITQNPVRMNESQiaYVCREVLQGLEYLH----------SQNVIHRDIKSDN 127

extracellular domain (ECD) found in the bone morphogenetic protein receptor type-2 (BMPR2)-like family; The BMPR2-like family includes BMPR2, activin receptor type-2A (ACTR-IIA), activin receptor type-2B (ACTR-IIB), and anti-Muellerian hormone type-2 receptor (AMHR2). On ligand binding, they form a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. BMPR2 binds to BMP7, BMP2, and less efficiently, BMP4. ACTR-IIA is the receptor for activin A, activin B, and inhibin A. It also interacts with type I receptor ACVR1 and bone morphogenetic protein 7 (BMP7). ACTR-IIB interacts with vacuolar protein sorting 39 (Vps39), dynein light chain Tctex-type 1 (DYNLT1), bone morphogenetic protein 2 (BMP2), and bone morphogenetic protein 3 (BMP3). AMHR2 is the receptor for anti-Muellerian hormone. Members in this family contain an extracellular domain (ECD), which belongs to Ly-6 antigen/uPA receptor-like (LU) superfamily and exhibits a snake toxin-like fold (also known as three-finger toxin/3FTx fold or three-fingered protein/TFP domain fold).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195  88 IECVYYDEMECEKSGD-----CEITKKTCYSEAHlkavGCLAVFGlptqeinstepYLKVDKPQYKSLGCMPyqHADSMN 162
Cdd:cd23533   1 IKCAYYKSSVSLSSTDesditSCNTTETCKSGSS----YCFALWR-----------EDSNGNIEILLQGCWD--SSGPNE 63

                        90       100       110
                ....*....|....*....|....*....|.
gi 71981195 163 CEnESSCR-QGRSFRGGIGMCCCSTNNCNMP 192
Cdd:cd23533  64 CD-SSECIaSKSPSLNNTKFCCCSGDLCNAN 93

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a 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 71981195 310 QLISKGRFGKVFKAQYtpdSGEKrlVAVKKLNEFQKASFLAEKRIFDELneyPKWYKSIVEFVCAEKIGDEYW----IVT 385
Cdd:cd14220   1 RQIGKGRYGEVWMGKW---RGEK--VAVKVFFTTEEASWFRETEIYQTV---LMRHENILGFIAADIKGTGSWtqlyLIT 72

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 71981195 386 EFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDrpyFFGHPKKP-IIHRLVENEN 445
Cdd:cd14220  73 DYHENGSLYDFLKCTTLDTRALLKLAYSAACGLCHLHTE---IYGTQGKPaIAHRDLKSKN 130

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK 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 71981195 315 GRFGKVFKAQYTPDSGEkrlVAVKKLNEFQKasflaEKRIFDELNeypkwYKSIVEFVCAEKIGDEYWIVTEFHERLSLY 394
Cdd:cd14060   4 GSFGSVYRAIWVSQDKE---VAVKKLLKIEK-----EAEILSVLS-----HRNIIQFYGAILEAPNYGIVTEYASYGSLF 70

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 71981195 395 ELLKNNVISITSANRII---MSMIDGLQFLHDDRPYffghpkkPIIHRLVENEN 445
Cdd:cd14060  71 DYLNSNESEEMDMDQIMtwaTDIAKGMHYLHMEAPV-------KVIHRDLKSRN 117

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK 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 71981195 312 ISKGRFGKVFKAQYtpDSGekRLVAVKKLNEFQKAS----FLAEKRIFDELNeypkwYKSIVEFV--CAEkiGDEYWIVT 385
Cdd:cd14066   1 IGSGGFGTVYKGVL--ENG--TVVAVKRLNEMNCAAskkeFLTELEMLGRLR-----HPNLVRLLgyCLE--SDEKLLVY 69

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 71981195 386 EFHERLSLYELLKNN----VISITSANRIIMSMIDGLQFLHDDRPyffghpkKPIIHR 439
Cdd:cd14066  70 EYMPNGSLEDRLHCHkgspPLPWPQRLKIAKGIARGLEYLHEECP-------PPIIHG 120

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin 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 71981195 312 ISKGRFGKVFKAQYTPDSGekrLVAVKKLNEFQKA--SFLAEKRIFDELNEYPKWYKSIVEFVCAEK-IGDEYWIVTEFH 388
Cdd:cd06639  30 IGKGTYGKVYKVTNKKDGS---LAAVKILDPISDVdeEIEAEYNILRSLPNHPNVVKFYGMFYKADQyVGGQLWLVLELC 106

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71981195 389 ERLSLYELLKNNVISITSANRIIMSMI-----DGLQFLHDDRpyffghpkkpIIHRLVENEN 445
Cdd:cd06639 107 NGGSVTELVKGLLKCGQRLDEAMISYIlygalLGLQHLHNNR----------IIHRDVKGNN 158

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 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 71981195 310 QLISKGRFGKVFKAQytpDSGEKRLVAVKKLNEFQKASFLA-EKRIFDELNEYP-----KWYKsivefvcaeKIGDEYWI 383
Cdd:cd14016   6 KKIGSGSFGEVYLGI---DLKTGEEVAIKIEKKDSKHPQLEyEAKVYKLLQGGPgiprlYWFG---------QEGDYNVM 73

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 71981195 384 VTEFHERlSLYELLK--NNVISITSANRIIMSMIDGLQFLHddrpyffghpKKPIIHR 439
Cdd:cd14016  74 VMDLLGP-SLEDLFNkcGRKFSLKTVLMLADQMISRLEYLH----------SKGYIHR 120

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 71981195 309 FQLIS---KGRFGKVFKAQytpDSGEKRLVAVKKLN---EFQKASfLAEKRIFDELNEYPKWYKS-IV---------EFV 372
Cdd:cd14210  15 YEVLSvlgKGSFGQVVKCL---DHKTGQLVAIKIIRnkkRFHQQA-LVEVKILKHLNDNDPDDKHnIVrykdsfifrGHL 90

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 71981195 373 CaekigdeywIVTEFHErLSLYELLKNNV---ISITSANRIIMSMIDGLQFLHddrpyffghpKKPIIH 438
Cdd:cd14210  91 C---------IVFELLS-INLYELLKSNNfqgLSLSLIRKFAKQILQALQFLH----------KLNIIH 139

Catalytic domain of Mammalian Ste20-like protein kinase 3-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 MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-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 71981195 307 TDFQLISKGRFGKVFKAQytpDSGEKRLVAVKKLN---------EFQKA-SFLAEKRIfdelnEY-PKWYKSIVEfvcae 375
Cdd:cd06609   4 TLLERIGKGSFGEVYKGI---DKRTNQVVAIKVIDleeaedeieDIQQEiQFLSQCDS-----PYiTKYYGSFLK----- 70

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 71981195 376 kiGDEYWIVTEFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRPyffghpkkpiIHR 439
Cdd:cd06609  71 --GSKLWIIMEYCGGGSVLDLLKPGPLDETYIAFILREVLLGLEYLHSEGK----------IHR 122

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 311 LISKGRFGKVFKAQytpDSGEKRLVAVKKLNEfQKASF---LAEKRIFDELNEY-PKWYKSIVE----FVCAEKIgdeyW 382
Cdd:cd14133   6 VLGKGTFGQVVKCY---DLLTGEEVALKIIKN-NKDYLdqsLDEIRLLELLNKKdKADKYHIVRlkdvFYFKNHL----C 77

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 71981195 383 IVTEFHERlSLYELLKNNVISITSANR---IIMSMIDGLQFLHD 423
Cdd:cd14133  78 IVFELLSQ-NLYEFLKQNKFQYLSLPRirkIAQQILEALVFLHS 120

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP 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 71981195 312 ISKGRFGKVFKAQYTPDSGEkrlVAVKKLNEFQKASFLAEkrifDELNEYPKWYKSIVEFV------CAEKIgdEYWIVT 385
Cdd:cd13978   1 LGSGGFGTVSKARHVSWFGM---VAIKCLHSSPNCIEERK----ALLKEAEKMERARHSYVlpllgvCVERR--SLGLVM 71

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 71981195 386 EFHERLSLYELLKNNVISITSA--NRIIMSMIDGLQFLHDDRPyffghpkkPIIHRLVENEN 445
Cdd:cd13978  72 EYMENGSLKSLLEREIQDVPWSlrFRIIHEIALGMNFLHNMDP--------PLLHHDLKPEN 125

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK 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 71981195 291 EEEMIEMVET------PKElPITDFQLISKGRFGKVFKAQytpDSGEKRLVAVKKLNEFQ--KASFLAEKRIFDELNEYP 362
Cdd:cd06654   2 DEEILEKLRSivsvgdPKK-KYTRFEKIGQGASGTVYTAM---DVATGQEVAIRQMNLQQqpKKELIINEILVMRENKNP 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71981195 363 kwykSIVEFVCAEKIGDEYWIVTEFHERLSLYELLKNNVISITSANRIIMSMIDGLQFLHDDRpyffghpkkpIIHRLVE 442
Cdd:cd06654  78 ----NIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQ----------VIHRDIK 143

                ...
gi 71981195 443 NEN 445
Cdd:cd06654 144 SDN 146