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 03-MAY-2023, entry version 94. 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; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC 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., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., 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., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., 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., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT 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., Gire S., RA Maes M.E., Xu Z., Greene L.A.; RT "Sh3rf2/POSHER protein promotes cell survival by RING-mediated proteasomal RT degradation of the c-Jun N-terminal kinase scaffold POSH (Plenty of SH3s) RT 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., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT 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, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; 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 domains is CC required for autophosphorylation and subsequent activation. CC {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 the CC activation loop plays a role in enzyme activation. {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 AlphaFoldDB; D3ZG83; -. DR SMR; D3ZG83; -. DR STRING; 10116.ENSRNOP00000031328; -. DR iPTMnet; D3ZG83; -. DR PhosphoSitePlus; D3ZG83; -. DR PaxDb; D3ZG83; -. DR Ensembl; ENSRNOT00000034609.7; ENSRNOP00000031328.6; ENSRNOG00000023521.7. DR GeneID; 308463; -. DR AGR; RGD:1308381; -. DR CTD; 4294; -. DR RGD; 1308381; Map3k10. DR eggNOG; KOG0192; Eukaryota. DR GeneTree; ENSGT00940000160518; -. DR HOGENOM; CLU_000288_7_14_1; -. DR InParanoid; D3ZG83; -. DR OMA; THVTAAC; -. DR OrthoDB; 876955at2759; -. DR PRO; PR:D3ZG83; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000023521; Expressed in frontal cortex and 18 other tissues. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD. DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central. DR GO; GO:0004672; F:protein kinase activity; ISO:RGD. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0003714; F:transcription corepressor activity; ISO:RGD. DR GO; GO:0008219; P:cell death; IMP:RGD. DR GO; GO:0006351; P:DNA-templated transcription; ISO:RGD. DR GO; GO:0006354; P:DNA-templated transcription elongation; ISO:RGD. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:RGD. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:RGD. DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD. DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD. DR GO; GO:0007224; P:smoothened signaling pathway; ISO:RGD. DR CDD; cd12059; SH3_MLK1-3; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. 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; PTHR44329:SF39; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 10; 1. DR PANTHER; PTHR44329; SERINE/THREONINE-PROTEIN KINASE TNNI3K-RELATED; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 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; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF50044; SH3-domain; 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; Kinase; Methylation; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; Serine/threonine-protein kinase; SH3 domain; KW Transferase. FT CHAIN 1..940 FT /note="Mitogen-activated protein kinase kinase kinase 10" FT /id="PRO_0000444892" FT DOMAIN 16..81 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 98..360 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 384..405 FT /note="Leucine-zipper 1" FT REGION 419..440 FT /note="Leucine-zipper 2" FT REGION 490..599 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 639..658 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 687..733 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 748..916 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 763..777 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 222 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 104..112 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 125 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 258 FT /note="Phosphothreonine; by autocatalysis" FT /evidence="ECO:0000250" FT MOD_RES 262 FT /note="Phosphoserine; by autocatalysis and MAP4K1" FT /evidence="ECO:0000250" FT MOD_RES 498 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q66L42" FT MOD_RES 502 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q66L42" FT MOD_RES 506 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q66L42" FT MOD_RES 552 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q66L42" FT MOD_RES 843 FT /note="Omega-N-methylarginine" FT /evidence="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 //