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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06612 155 KRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKPPPTLSDPEKWSPEFNDFVK 234

                        90       100
                ....*....|....*....|..
gi 12833249  81 KCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06612 235 KCLVKDPEERPSAIQLLQHPFI 256

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06612 155 KRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKPPPTLSDPEKWSPEFNDFVK 234

                        90       100
                ....*....|....*....|..
gi 12833249  81 KCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06612 235 KCLVKDPEERPSAIQLLQHPFI 256

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12833249     1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:pfam00069 116 SLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLK 195

                          90       100
                  ....*....|....*....|..
gi 12833249    81 KCLVKSPEQRATATQLLQHPFI 102
Cdd:pfam00069 196 KLLKKDPSKRLTATQALQHPWF 217

C-terminal SARAH domain found in the mammalian STE20-like protein kinase (MST) subfamily; The MST subfamily includes MST1 and MST2, as well as Drosophila melanogaster homolog protein, Hippo (Hpo). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 and MST2 are STE20 family stress-activated, pro-apoptotic serine/threonine-protein kinases which, following caspase-cleavage, enter the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. They are key components of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Hpo, also called STE20-like kinase MST (dMST), is the Drosophila homolog of STE20-like protein kinases, MST1 and MST2. It is a STE20 family serine/threonine-protein kinase that functions as a tumor suppressor by restricting cell proliferation, and promotes apoptosis in conjunction with salvador and warts. Hpo plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. This model corresponds to the C-terminal SARAH (Salvador-RassF-Hippo) domain of mammalian STE20-like protein kinases and the Drosophila melanogaster homolog Hippo.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*...
gi 12833249 267 FDFLKNLSLEELQMRLKALDPMMEREIEELHQRYSAKRQPILDAMDAK 314
Cdd:cd21884   1 FEFLKSLSYEELQERLALLDPEMEREIEELRKRYQAKRQPILDAIEAK 48

mitogen-activated protein kinase kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12833249    3 NTVIGTPFWMTPEVIQ----EIGYN-CVADIWSLGITSIEMAEGKPPYA-----DIHP-MRAIFMI-PTNPPPTFrkpel 70
Cdd:PLN00034 226 NSSVGTIAYMSPERINtdlnHGAYDgYAGDIWSLGVSILEFYLGRFPFGvgrqgDWASlMCAICMSqPPEAPATA----- 300

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 12833249   71 wSDDFTDFVKKCLVKSPEQRATATQLLQHPFIKNAKP 107
Cdd:PLN00034 301 -SREFRHFISCCLQREPAKRWSAMQLLQHPFILRAQP 336

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06612 155 KRNTVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKPPPTLSDPEKWSPEFNDFVK 234

                        90       100
                ....*....|....*....|..
gi 12833249  81 KCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06612 235 KCLVKDPEERPSAIQLLQHPFI 256

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12833249   2 RNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKK 81
Cdd:cd05122 154 RNTFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIATNGPPGLRNPKKWSKEFKDFLKK 233

                        90       100
                ....*....|....*....|.
gi 12833249  82 CLVKSPEQRATATQLLQHPFI 102
Cdd:cd05122 234 CLQKDPEKRPTAEQLLKHPFI 254

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 12833249   1 KRNTVIGTPFWMTPEVIQE---IGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIP--TNPPPTFRKPELWSDDF 75
Cdd:cd06613 153 KRKSFIGTPYWMAPEVAAVerkGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLIPksNFDPPKLKDKEKWSPDF 232

                        90       100
                ....*....|....*....|....*..
gi 12833249  76 TDFVKKCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06613 233 HDFIKKCLTKNPKKRPTATKLLQHPFV 259

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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06614 153 KRNSVVGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPLRALFLITTKGIPPLKNPEKWSPEFKDFLN 232

                        90       100
                ....*....|....*....|...
gi 12833249  81 KCLVKSPEQRATATQLLQHPFIK 103
Cdd:cd06614 233 KCLVKDPEKRPSAEELLQHPFLK 255

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 12833249   1 KRNTVIGTPFWMTPEVIQ-----EIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDF 75
Cdd:cd06639 184 RRNTSVGTPFWMAPEVIAceqqyDYSYDARCDVWSLGITAIELADGDPPLFDMHPVKALFKIPRNPPPTLLNPEKWCRGF 263

                        90       100
                ....*....|....*....|....*...
gi 12833249  76 TDFVKKCLVKSPEQRATATQLLQHPFIK 103
Cdd:cd06639 264 SHFISQCLIKDFEKRPSVTHLLEHPFIK 291

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK 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 12833249   1 KRNTVIGTPFWMTPEVI-----QEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDF 75
Cdd:cd06643 159 RRDSFIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGVTLIEMAQIEPPHHELNPMRVLLKIAKSEPPTLAQPSRWSPEF 238

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 12833249  76 TDFVKKCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLIAEA 118
Cdd:cd06643 239 KDFLRKCLEKNVDARWTTSQLLQHPFVSVLVSNKPLRELIAEA 281

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK 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 12833249   1 KRNTVIGTPFWMTPEVIQEI-GYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTF---RKPELWSDDFT 76
Cdd:cd06610 162 VRKTFVGTPCWMAPEVMEQVrGYDFKADIWSFGITAIELATGAAPYSKYPPMKVLMLTLQNDPPSLetgADYKKYSKSFR 241

                        90       100
                ....*....|....*....|....*.
gi 12833249  77 DFVKKCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06610 242 KMISLCLQKDPSKRPTAEELLKHKFF 267

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPelWSDDFTDFVK 80
Cdd:cd06640 157 KRNTFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLIPKNNPPTLVGD--FSKPFKEFID 234

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 12833249  81 KCLVKSPEQRATATQLLQHPFI-KNAKPVSILRDLI 115
Cdd:cd06640 235 ACLNKDPSFRPTAKELLKHKFIvKNAKKTSYLTELI 270

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06655 171 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSPIFRDFLN 250

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 12833249  81 KCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLIAEAME-IKAKR 125
Cdd:cd06655 251 RCLEMDVEKRGSAKELLQHPFLKLAKPLSSLTPLILAAKEaMKSNR 296

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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06654 172 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLN 251

                        90       100       110       120
                ....*....|....*....|....*....|....*....|
gi 12833249  81 KCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLIAEAME 120
Cdd:cd06654 252 RCLEMDVEKRGSAKELLQHQFLKIAKPLSSLTPLIAAAKE 291

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFrkPELWSDDFTDFVK 80
Cdd:cd06627 155 DENSVVGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQPMAALFRIVQDDHPPL--PENISPELRDFLL 232

                        90       100
                ....*....|....*....|..
gi 12833249  81 KCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06627 233 QCFQKDPTLRPSAKELLKHPWL 254

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. 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). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, 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. 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. 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06647 159 KRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIATNGTPELQNPEKLSAIFRDFLN 238

                        90       100
                ....*....|....*....|...
gi 12833249  81 KCLVKSPEQRATATQLLQHPFIK 103
Cdd:cd06647 239 RCLEMDVEKRGSAKELLQHPFLK 261

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK 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 12833249   1 KRNTVIGTPFWMTPEVIQ-----EIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFrKPELWSDDF 75
Cdd:cd06637 167 RRNTFIGTPYWMAPEVIAcdenpDATYDFKSDLWSLGITAIEMAEGAPPLCDMHPMRALFLIPRNPAPRL-KSKKWSKKF 245

                        90       100
                ....*....|....*....|....*....
gi 12833249  76 TDFVKKCLVKSPEQRATATQLLQHPFIKN 104
Cdd:cd06637 246 QSFIESCLVKNHSQRPSTEQLMKHPFIRD 274

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPelWSDDFTDFVK 80
Cdd:cd06641 157 KRN*FVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLIPKNNPPTLEGN--YSKPLKEFVE 234

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 12833249  81 KCLVKSPEQRATATQLLQHPFI-KNAKPVSILRDLI 115
Cdd:cd06641 235 ACLNKEPSFRPTAKELLKHKFIlRNAKKTSYLTELI 270

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 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 12833249   3 NTVIGTPFWMTPEVI---QEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPElWSDDFTDFV 79
Cdd:cd06633 175 NSFVGTPYWMAPEVIlamDEGQYDGKVDIWSLGITCIELAERKPPLFNMNAMSALYHIAQNDSPTLQSNE-WTDSFRGFV 253

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 12833249  80 KKCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLI 115
Cdd:cd06633 254 DYCLQKIPQERPSSAELLRHDFVRRERPPRVLIDLI 289

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 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 12833249   7 GTPFWMTPEVI--QEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNP--PPTfrkPELWSDDFTDFVKKC 82
Cdd:cd06632 163 GSPYWMAPEVImqKNSGYGLAVDIWSLGCTVLEMATGKPPWSQYEGVAAIFKIGNSGelPPI---PDHLSPDAKDFIRLC 239

                        90       100
                ....*....|....*....|
gi 12833249  83 LVKSPEQRATATQLLQHPFI 102
Cdd:cd06632 240 LQRDPEDRPTASQLLEHPFV 259

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 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. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in 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 MAP4K3 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 12833249   1 KRNTVIGTPFWMTPEVI---QEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTN--PPPTFRKPELWSDDF 75
Cdd:cd06645 164 KRKSFIGTPYWMAPEVAaveRKGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMTKSnfQPPKLKDKMKWSNSF 243

                        90       100
                ....*....|....*....|....*..
gi 12833249  76 TDFVKKCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06645 244 HHFVKMALTKNPKKRPTAEKLLQHPFV 270

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 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 12833249   3 NTVIGTPFWMTPEVI---QEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPElWSDDFTDFV 79
Cdd:cd06635 179 NSFVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIAQNESPTLQSNE-WSDYFRNFV 257

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 12833249  80 KKCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLI 115
Cdd:cd06635 258 DSCLQKIPQDRPTSEELLKHMFVLRERPETVLIDLI 293

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK 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 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYAD------IHPMRAIFMIPTNPPPtfrkPELWSDD 74
Cdd:cd06623 156 QCNTFVGTVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLPpgqpsfFELMQAICDGPPPSLP----AEEFSPE 231

                        90       100       110
                ....*....|....*....|....*....|.
gi 12833249  75 FTDFVKKCLVKSPEQRATATQLLQHPFIKNA 105
Cdd:cd06623 232 FRDFISACLQKDPKKRPSAAELLQHPFIKKA 262

C terminal SARAH domain of Mst1; This family of proteins represents the C terminal SARAH domain of Mst1. SARAH controls apoptosis and cell cycle arrest via the Ras, RASSF, MST pathway. The Mst1 SARAH domain interacts with Rassf1 and Rassf5 by forming a heterodimer which mediates the apoptosis process.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 12833249   267 FDFLKNLSLEELQMRLKALDPMMEREIEELHQRYSAKRQPILDAMDAK 314
Cdd:pfam11629   1 FEFLKFLSVDELQQRLANLDPEMEREIEELRKRYQAKRQPILDAIDAK 48

C-terminal SARAH domain of mammalian STE20-like protein kinase 2 (MST2); MST2, also called serine/threonine-protein kinase 3, MST-2, STE20-like kinase MST2, or serine/threonine-protein kinase (STK) Krs-1, is a STE20 family stress-activated, pro-apoptotic STK which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. It is a key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. This model corresponds to the C-terminal SARAH (Salvador-RassF-Hippo) domain, which mediates homodimerization of MST2. Similar to MST1, MST2 may also form heterodimers with other SARAH domain-containing proteins.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*....
gi 12833249 266 DFDFLKNLSLEELQMRLKALDPMMEREIEELHQRYSAKRQPILDAMDAK 314
Cdd:cd21888   1 DFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAK 49

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. 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 STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 12833249   1 KRNTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVK 80
Cdd:cd06658 174 KRKSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDNLPPRVKDSHKVSSVLRGFLD 253

                        90       100       110
                ....*....|....*....|....*....|....*
gi 12833249  81 KCLVKSPEQRATATQLLQHPFIKNAKPVSILRDLI 115
Cdd:cd06658 254 LMLVREPSQRATAQELLQHPFLKLAGPPSCIVPLM 288

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK 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 12833249   3 NTVIGTPFWMTPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYA--DIHPMRAIF----MIPTNPPPtfRKP-ELWSDDF 75
Cdd:cd06605 156 KTFVGTRSYMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPppNAKPSMMIFellsYIVDEPPP--LLPsGKFSPDF 233

                        90       100
                ....*....|....*....|....*...
gi 12833249  76 TDFVKKCLVKSPEQRATATQLLQHPFIK 103
Cdd:cd06605 234 QDFVSQCLQKDPTERPSYKELMEHPFIK 261

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 12833249   3 NTVIGTPFWMTPEVI---QEIGYNCVADIWSLGITSIEMAEGKPPYADI-HPMRAIFMIPTNPPPTFRKPELWSDDFTDF 78
Cdd:cd06626 162 NSLVGTPAYMAPEVItgnKGEGHGRAADIWSLGCVVLEMATGKRPWSELdNEWAIMYHVGMGHKPPIPDSLQLSPEGKDF 241

                        90       100
                ....*....|....*....|....
gi 12833249  79 VKKCLVKSPEQRATATQLLQHPFI 102
Cdd:cd06626 242 LSRCLESDPKKRPTASELLDHPFI 265