ID M3K10_RAT Reviewed; 940 AA. AC D3ZG83; DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2015, sequence version 3. DT 18-SEP-2019, entry version 78. DE RecName: Full=Mitogen-activated protein kinase kinase kinase 10; DE EC=2.7.11.25; GN Name=Map3k10; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., RA Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., RA Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., RA Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., RA Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., RA Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., RA Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., RA Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., RA Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., RA D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., RA Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., RA Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., RA Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., RA Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., RA Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., RA Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., RA Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., RA Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., RA Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., RA Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., RA Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., RA Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., RA Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., RA Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., RA Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., RA Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., RA Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., RA Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., RA Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., RA Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., RA Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., RA Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., RA Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., RA Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., RA Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into RT mammalian evolution."; RL Nature 428:493-521(2004). RN [2] RP INTERACTION WITH SH3RF2. RX PubMed=22128169; DOI=10.1074/jbc.m111.269431; RA Wilhelm M., Kukekov N.V., Schmit T.L., Biagas K.V., Sproul A.A., RA Gire S., Maes M.E., Xu Z., Greene L.A.; RT "Sh3rf2/POSHER protein promotes cell survival by RING-mediated RT proteasomal degradation of the c-Jun N-terminal kinase scaffold POSH RT (Plenty of SH3s) protein."; RL J. Biol. Chem. 287:2247-2256(2012). RN [3] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., RA Lundby C., Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 RT different rat organs and tissues."; RL Nat. Commun. 3:876-876(2012). CC -!- FUNCTION: Activates the JUN N-terminal pathway. {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; CC EC=2.7.11.25; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.25; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Homodimerization via the leucine zipper CC domains is required for autophosphorylation and subsequent CC activation. {ECO:0000250}. CC -!- SUBUNIT: Homodimer (By similarity). Interacts with SH3RF2 CC (PubMed:22128169). {ECO:0000250, ECO:0000269|PubMed:22128169}. CC -!- PTM: Autophosphorylation on serine and threonine residues within CC the activation loop plays a role in enzyme activation. CC {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr CC protein kinase family. MAP kinase kinase kinase subfamily. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC120811; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR RefSeq; XP_006228638.1; XM_006228576.3. DR SMR; D3ZG83; -. DR STRING; 10116.ENSRNOP00000031328; -. DR iPTMnet; D3ZG83; -. DR PhosphoSitePlus; D3ZG83; -. DR PaxDb; D3ZG83; -. DR PRIDE; D3ZG83; -. DR Ensembl; ENSRNOT00000034609; ENSRNOP00000031328; ENSRNOG00000023521. DR GeneID; 308463; -. DR CTD; 4294; -. DR RGD; 1308381; Map3k10. DR eggNOG; KOG0192; Eukaryota. DR eggNOG; COG0515; LUCA. DR GeneTree; ENSGT00940000160518; -. DR InParanoid; D3ZG83; -. DR OMA; ARAPWEP; -. DR OrthoDB; 115270at2759; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000023521; Expressed in 9 organ(s), highest expression level in brain. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0043425; F:bHLH transcription factor binding; IEA:Ensembl. DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl. DR GO; GO:0007257; P:activation of JUN kinase activity; IBA:GO_Central. DR GO; GO:0008219; P:cell death; IMP:RGD. DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IEA:Ensembl. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl. DR CDD; cd12059; SH3_MLK1-3; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR015785; MAP3K10. DR InterPro; IPR035779; MLK1-3_SH3. DR InterPro; IPR016231; MLK1-4. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR23257:SF755; PTHR23257:SF755; 1. DR Pfam; PF07714; Pkinase_Tyr; 1. DR Pfam; PF14604; SH3_9; 1. DR PIRSF; PIRSF000556; MAPKKK9_11; 1. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00220; S_TKc; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SSF50044; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50002; SH3; 1. PE 1: Evidence at protein level; KW ATP-binding; Complete proteome; Kinase; Methylation; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; SH3 domain; Transferase. FT CHAIN 1 940 Mitogen-activated protein kinase kinase FT kinase 10. FT /FTId=PRO_0000444892. FT DOMAIN 16 81 SH3. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 98 360 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 104 112 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 384 405 Leucine-zipper 1. FT REGION 419 440 Leucine-zipper 2. FT ACT_SITE 222 222 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT BINDING 125 125 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 258 258 Phosphothreonine; by autocatalysis. FT {ECO:0000250}. FT MOD_RES 262 262 Phosphoserine; by autocatalysis and FT MAP4K1. {ECO:0000250}. FT MOD_RES 498 498 Phosphoserine. FT {ECO:0000250|UniProtKB:Q66L42}. FT MOD_RES 502 502 Phosphoserine. FT {ECO:0000250|UniProtKB:Q66L42}. FT MOD_RES 506 506 Phosphoserine. FT {ECO:0000250|UniProtKB:Q66L42}. FT MOD_RES 552 552 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q66L42}. FT MOD_RES 843 843 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:Q66L42}. SQ SEQUENCE 940 AA; 103060 MW; B39EDB486730A42D CRC64; MEEEEGAAAR EWGATPAGPV WTAVFDYEAV GDEELTLRRG DRVQVLSQDC AVSGDEGWWT GQLPSGRVGV FPSNYVAPAA PAAPTDLQLP QEIPFHELQL EEIIGVGGFG KVYRALWRGE EVAVKAARLD PERDPAVTAE QVRQEARLFG ALQHPNIIAL RGACLSPPNL CLVMEYARGG ALSRVLAGRR VPPHVLVNWA VQVARGMNYL HNDAPVPIIH RDLKSINILI LEAIENHNLA DTVLKITDFG LAREWHKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFARLLEECW DPDPHGRPDF GSILKQLEVI EQSALFQMPL ESFHSLQEDW KLEIQHMFDD LRTKEKELRS REEELLRAAQ EQRFQEEQLR RREQELAERE MDIVERELHL LMSQLSQEKP RVRKRKGNFK RSRLLKLREG SSHISLPSGF EHKITVQASP TLDKRKGSDG ASPPASPSII PRLRAIRLTP VDCGSSGGSG TWSRSGPPKK EELVGGKKKG RTWGPSSTLQ KERAGGEERL KALGEGSKQW SSSAPNLGKS PKHTPMAPGF ASLNEMEEFA EADEGNNVPP SPYSTPSYLK VPLPAEASPC AQPPWEPPAA TPSRPGHGAR RRCDLALLGC ATLLSAVGLG ADVAEARAGD GEEQRGWLDG LFFPRPGRFP RGLSPTGRPG GRREETAPGF GLAPSATLVS LSSVSDCNST RSLLRSDSDE AAPTAPSPPP SLLPPSPSTN PLVDVELESF KKDPRQSLTP THVTAAHAVS RGHRRTPSDG ALRQREPPEL TNHGPRDPLD FPRLPDPQAL FPTRRRPLEF PGRPTTLTFA PRPRPAASRP RLDPWKLVSF GRTLSISPPS RPDTPESPGP LSVQPTLLDM DMEGQSQDNT VPLCGAYGSH //