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 158121075   2 LASRQSFWAELNVARLSHNNVVRVIAASACspTNEDSLGTIIMEYVGNSSLHHVIYGtgsmikrkdsfvcGHEPLSVRQT 81
Cdd:cd13979   41 RASRQSFWAELNAARLRHENIVRVLAAETG--TDFASLGLIIMEYCGNGTLQQLIYE-------------GSEPLPLAHR 105

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 158121075  82 LSYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:cd13979  106 ILISLDIARALRFCHSHGIVHLDVKPANILISEQGVC 142

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 158121075   2 LASRQSFWAELNVARLSHNNVVRVIAASACspTNEDSLGTIIMEYVGNSSLHHVIYGtgsmikrkdsfvcGHEPLSVRQT 81
Cdd:cd13979   41 RASRQSFWAELNAARLRHENIVRVLAAETG--TDFASLGLIIMEYCGNGTLQQLIYE-------------GSEPLPLAHR 105

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 158121075  82 LSYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:cd13979  106 ILISLDIARALRFCHSHGIVHLDVKPANILISEQGVC 142

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075   5 RQSFWAELNV-ARLSHNNVVRVIAASAcsptnEDSLGTIIMEYVGNSSLHHVIYGTGsmikrkdsfvcghePLSVRQTLS 83
Cdd:COG0515   51 RERFRREARAlARLNHPNIVRVYDVGE-----EDGRPYLVMEYVEGESLADLLRRRG--------------PLPPAEALR 111

                         90       100       110
                 ....*....|....*....|....*....|.
gi 158121075  84 YSCDIVAGLVFLHSQFIVHLDLKPANIFITE 114
Cdd:COG0515  112 ILAQLAEALAAAHAAGIVHRDIKPANILLTP 142

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 158121075    4 SRQSFWAELNV-ARLSHNNVVRVIAAsaCspTNEDSLgTIIMEYVGNSSLHHViygtgsMIKRKdsfvcghEPLSVRQTL 82
Cdd:pfam07714  44 EREDFLEEASImKKLDHPNIVKLLGV--C--TQGEPL-YIVTEYMPGGDLLDF------LRKHK-------RKLTLKDLL 105

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 158121075   83 SYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:pfam07714 106 SMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVV 141

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos 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 158121075   2 LASRQSFWAELNVARLSHNNVVRVIAASACspTNEDSLGTIIMEYVGNSSLHHVIYGtgsmikrkdsfvcGHEPLSVRQT 81
Cdd:cd13979   41 RASRQSFWAELNAARLRHENIVRVLAAETG--TDFASLGLIIMEYCGNGTLQQLIYE-------------GSEPLPLAHR 105

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 158121075  82 LSYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:cd13979  106 ILISLDIARALRFCHSHGIVHLDVKPANILISEQGVC 142

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075     5 RQSFWAELNV-ARLSHNNVVRVIaasaCSPTNEDSLgTIIMEYVGNSSLHhviygtgSMIKRKDSFvcgheplSVRQTLS 83
Cdd:smart00220  41 RERILREIKIlKKLKHPNIVRLY----DVFEDEDKL-YLVMEYCEGGDLF-------DLLKKRGRL-------SEDEARF 101

                           90       100       110
                   ....*....|....*....|....*....|....
gi 158121075    84 YSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNV 117
Cdd:smart00220 102 YLRQILSALEYLHSKGIVHRDLKPENILLDEDGH 135

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 158121075   5 RQSFWAELNV-ARLSHNNVVRVIAASacspTNEDSLgTIIMEYVGNSSLHHVIygtgsmikRKDSFvcghePLSVRQTLS 83
Cdd:cd13999   34 LKEFRREVSIlSKLRHPNIVQFIGAC----LSPPPL-CIVTEYMPGGSLYDLL--------HKKKI-----PLSWSLRLK 95

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 158121075  84 YSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:cd13999   96 IALDIARGMNYLHSPPIIHRDLKSLNILLDENFTV 130

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They 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. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 158121075  16 RLSHNNVVRVIAASacspTNEDSLgTIIMEYVGNSSLhhviygtGSMIKRKDSFvcgHEPLsVRqtlSYSCDIVAGLVFL 95
Cdd:cd06606   55 SLKHPNIVRYLGTE----RTENTL-NIFLEYVPGGSL-------ASLLKKFGKL---PEPV-VR---KYTRQILEGLEYL 115

                         90
                 ....*....|....*....
gi 158121075  96 HSQFIVHLDLKPANIFITE 114
Cdd:cd06606  116 HSNGIVHRDIKGANILVDS 134

Stk1 family PASTA domain-containing Ser/Thr kinase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075  13 NVARLSHNNVVRVIAASAcsptnEDSLGTIIMEYVGNSSLHHVIygtgsmikrKDsfvcgHEPLSVRQTLSYSCDIVAGL 92
Cdd:NF033483  60 SAASLSHPNIVSVYDVGE-----DGGIPYIVMEYVDGRTLKDYI---------RE-----HGPLSPEEAVEIMIQILSAL 120

                         90       100
                 ....*....|....*....|..
gi 158121075  93 VFLHSQFIVHLDLKPANIFITE 114
Cdd:NF033483 121 EHAHRNGIVHRDIKPQNILITK 142

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK 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 158121075  16 RLSHNNVVR---VIAasacSPtNEDSLgTIIMEYVGNSSLHHVIYGTGSmikrkdsfvcghEPLSVRQTLSYSCDIVAGL 92
Cdd:cd14008   60 KLDHPNIVRlyeVID----DP-ESDKL-YLVLEYCEGGPVMELDSGDRV------------PPLPEETARKYFRDLVLGL 121

                         90       100
                 ....*....|....*....|....*.
gi 158121075  93 VFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:cd14008  122 EYLHENGIVHRDIKPENLLLTADGTV 147

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075     5 RQSFWAELNV-ARLSHNNVVRVIAAsaCspTNEDSLgTIIMEYVGNSSLHHVIygtgsmikrKDSfvcgHEPLSVRQTLS 83
Cdd:smart00219  45 IEEFLREARImRKLDHPNVVKLLGV--C--TEEEPL-YIVMEYMEGGDLLSYL---------RKN----RPKLSLSDLLS 106

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 158121075    84 YSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:smart00219 107 FALQIARGMEYLESKNFIHRDLAARNCLVGENLVV 141

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075  15 ARLSHNNVVRVIAasacSPTNEDSLgTIIMEYVGNSSLHHviygtgsMIKRKDSfvcGHEPLSVRQTLSYSCDIVAGLVF 94
Cdd:cd08215   54 SKLKHPNIVKYYE----SFEENGKL-CIVMEYADGGDLAQ-------KIKKQKK---KGQPFPEEQILDWFVQICLALKY 118

                         90       100
                 ....*....|....*....|...
gi 158121075  95 LHSQFIVHLDLKPANIFITEHNV 117
Cdd:cd08215  119 LHSRKILHRDLKTQNIFLTKDGV 141

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 158121075    4 SRQSFWAELNV-ARLSHNNVVRVIAAsaCspTNEDSLgTIIMEYVGNSSLHHViygtgsMIKRKdsfvcghEPLSVRQTL 82
Cdd:pfam07714  44 EREDFLEEASImKKLDHPNIVKLLGV--C--TQGEPL-YIVTEYMPGGDLLDF------LRKHK-------RKLTLKDLL 105

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 158121075   83 SYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNVC 118
Cdd:pfam07714 106 SMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVV 141

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075   4 SRQSFWAELNV-ARLSHNNVVRVIAASacsptnEDSLGT-IIMEYVGNSSLHHviygtgsMIKRKDSFvcgHEPlSVRQt 81
Cdd:cd14099   44 QREKLKSEIKIhRSLKHPNIVKFHDCF------EDEENVyILLELCSNGSLME-------LLKRRKAL---TEP-EVRY- 105

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 158121075  82 lsYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHN 116
Cdd:cd14099  106 --FMRQILSGVKYLHSNRIIHRDLKLGNLFLDENM 138

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 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 158121075  13 NVARLSHNNVVRVIAASAcsptnEDSLGTIIMEYVGNSSLHHVIygTGSMIKRKDsfvcgheplsvrQTLSYSCDIVAGL 92
Cdd:cd14046   57 LLSRLNHQHVVRYYQAWI-----ERANLYIQMEYCEKSTLRDLI--DSGLFQDTD------------RLWRLFRQILEGL 117

                         90       100
                 ....*....|....*....|....
gi 158121075  93 VFLHSQFIVHLDLKPANIFITEHN 116
Cdd:cd14046  118 AYIHSQGIIHRDLKPVNIFLDSNG 141

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK 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 158121075  19 HNNVVRVIAASacsptNEDSLGTIIMEYVGnSSLHHVIygtgsmikrKDSfvcgHEPLSVRQTLSYSCDIVAGLVFLHSQ 98
Cdd:cd07832   59 HPYVVKLRDVF-----PHGTGFVLVFEYML-SSLSEVL---------RDE----ERPLTEAQVKRYMRMLLKGVAYMHAN 119

                         90
                 ....*....|....*....
gi 158121075  99 FIVHLDLKPANIFITEHNV 117
Cdd:cd07832  120 RIMHRDLKPANLLISSTGV 138

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 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 includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-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 158121075  19 HNNVVRVIAasacSPTNEDSLgTIIMEYVGNSSLHHVIYGTGSMIKRKDSFVCgheplsvRQTLSyscdivaGLVFLHSQ 98
Cdd:cd06613   56 HPNIVAYFG----SYLRRDKL-WIVMEYCGGGSLQDIYQVTGPLSELQIAYVC-------RETLK-------GLAYLHST 116

                         90
                 ....*....|....*..
gi 158121075  99 FIVHLDLKPANIFITEH 115
Cdd:cd06613  117 GKIHRDIKGANILLTED 133

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 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 158121075   2 LASRQSFWAEL-NVARLSHNNVVRVIAAsaCSPTNEDSLgtiIMEYVGNSSLHHVIYGTGSmikrkdsfvcghEPL-SVR 79
Cdd:cd14058   27 ESEKKAFEVEVrQLSRVDHPNIIKLYGA--CSNQKPVCL---VMEYAEGGSLYNVLHGKEP------------KPIyTAA 89

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 158121075  80 QTLSYSCDIVAGLVFLHS---QFIVHLDLKPANIFITE 114
Cdd:cd14058   90 HAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLTN 127

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like 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 158121075  19 HNNVVRVIAASACSPTNEdSLGTIIMEYVGNSsLHHVIYGTGSmikrkdsfvcghEPLSVRQTLSYSCDIVAGLVFLHSQ 98
Cdd:cd13985   57 HPNIVQYYDSAILSSEGR-KEVLLLMEYCPGS-LVDILEKSPP------------SPLSEEEVLRIFYQICQAVGHLHSQ 122

                         90       100
                 ....*....|....*....|..
gi 158121075  99 F--IVHLDLKPANIFITEHNVC 118
Cdd:cd13985  123 SppIIHRDIKIENILFSNTGRF 144

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075  11 ELNVAR-LSHNNVVRVIAASacspTNEDSLgTIIMEYVGNSsLHHVIygtgsmikrkDSFVCGHEPLSVRqtlSYSCDIV 89
Cdd:cd07833   50 EVKVLRqLRHENIVNLKEAF----RRKGRL-YLVFEYVERT-LLELL----------EASPGGLPPDAVR---SYIWQLL 110

                         90       100
                 ....*....|....*....|....*...
gi 158121075  90 AGLVFLHSQFIVHLDLKPANIFITEHNV 117
Cdd:cd07833  111 QAIAYCHSHNIIHRDIKPENILVSESGV 138

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075   9 WAELNV-ARLSHNNVVRViaasACSPTNEDSLGtIIMEYVGNSSLHHVIYGTGSmikrkdsfvcghepLSVRQTLSYSCD 87
Cdd:cd05123   41 LNERNIlERVNHPFIVKL----HYAFQTEEKLY-LVLDYVPGGELFSHLSKEGR--------------FPEERARFYAAE 101

                         90       100
                 ....*....|....*....|....*...
gi 158121075  88 IVAGLVFLHSQFIVHLDLKPANIFITEH 115
Cdd:cd05123  102 IVLALEYLHSLGIIYRDLKPENILLDSD 129

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075   3 ASRQSFWAELNVAR-LSHNNVVRVIAAsaCSPTNEDSLGtIIMEYVGNSSLhhviygtgsmikrkDSFVCGHEP-LSVRQ 80
Cdd:cd05038   48 QHMSDFKREIEILRtLDHEYIVKYKGV--CESPGRRSLR-LIMEYLPSGSL--------------RDYLQRHRDqIDLKR 110

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 158121075  81 TLSYSCDIVAGLVFLHSQFIVHLDLKPANIFI-TEHNV 117
Cdd:cd05038  111 LLLFASQICKGMEYLGSQRYIHRDLAARNILVeSEDLV 148

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 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 158121075  16 RLSHNNVVRVIAASacspTNEDSLGT-IIMEYVGNsslhhviyGTGSMIKRkdsfvCGHEPLSVRQTLSYSCDIVAGLVF 94
Cdd:cd14119   50 RLNHRNVIKLVDVL----YNEEKQKLyMVMEYCVG--------GLQEMLDS-----APDKRLPIWQAHGYFVQLIDGLEY 112

                         90
                 ....*....|....*....
gi 158121075  95 LHSQFIVHLDLKPANIFIT 113
Cdd:cd14119  113 LHSQGIIHKDIKPGNLLLT 131

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 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 158121075  42 IIMEYVGNSSLHHVI-YGTG---SMIKRkdsfvcgheplsvrqtlsYSCDIVAGLVFLHSQFIVHLDLKPANIFITEHNV 117
Cdd:cd06626   76 IFMEYCQEGTLEELLrHGRIldeAVIRV------------------YTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGL 137

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK 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 158121075  17 LSHNNVVRVIAASACSptNEdslGTIIMEYVGNSSL-HHVIygtgsmikrKDSFVcghepLSVRQTLSYSCDIVAGLVFL 95
Cdd:cd14103   47 LRHPRLLQLYDAFETP--RE---MVLVMEYVAGGELfERVV---------DDDFE-----LTERDCILFMRQICEGVQYM 107

                         90
                 ....*....|....*
gi 158121075  96 HSQFIVHLDLKPANI 110
Cdd:cd14103  108 HKQGILHLDLKPENI 122

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 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 158121075  16 RLSHNNVVRV--IAASACSPTNED-----SLGT--IIMEYVgNSSLHHVIygtgsmikrkdsfvcGHEPLSVRQTLSYSC 86
Cdd:cd07854   58 RLDHDNIVKVyeVLGPSGSDLTEDvgsltELNSvyIVQEYM-ETDLANVL---------------EQGPLSEEHARLFMY 121

                         90       100
                 ....*....|....*....|....*.
gi 158121075  87 DIVAGLVFLHSQFIVHLDLKPANIFI 112
Cdd:cd07854  122 QLLRGLKYIHSANVLHRDLKPANVFI 147

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 158121075  42 IIMEYVGNSSLHHVIYGTGSMIKRKD-SFVCgheplsvRQTLSyscdivaGLVFLHSQFIVHLDLKPANIFITEH 115
Cdd:cd05122   74 IVMEFCSGGSLKDLLKNTNKTLTEQQiAYVC-------KEVLK-------GLEYLHSHGIIHRDIKAANILLTSD 134

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075  16 RLSHNNVVRVIAasacSPTNEDSLgTIIMEYVGNSSLhhviygtGSMIKRkdsFVCGHEPLSVRQTLSYSCDIVAGLVFL 95
Cdd:cd08224   56 QLNHPNIIKYLA----SFIENNEL-NIVLELADAGDL-------SRLIKH---FKKQKRLIPERTIWKYFVQLCSALEHM 120

                         90       100
                 ....*....|....*....|..
gi 158121075  96 HSQFIVHLDLKPANIFITEHNV 117
Cdd:cd08224  121 HSKRIMHRDIKPANVFITANGV 142

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK 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. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 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 158121075  42 IIMEYVGNSSLHHVIYGTGSMIKRKDSFVCgheplsvRQTLSyscdivaGLVFLHSQFIVHLDLKPANIFITEH 115
Cdd:cd06646   83 ICMEYCGGGSLQDIYHVTGPLSELQIAYVC-------RETLQ-------GLAYLHSKGKMHRDIKGANILLTDN 142

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 158121075   5 RQSFWAELNV-ARLSHNNVVRVIAASacspTNEDSLgTIIMEYVGNSSLH-----HVIYGTGSMIkrkdsfvCGHEPLSv 78
Cdd:cd05051   63 REDFLKEVKImSQLKDPNIVRLLGVC----TRDEPL-CMIVEYMENGDLNqflqkHEAETQGASA-------TNSKTLS- 129