ID M3K10_XENLA Reviewed; 1005 AA. AC Q7T2V3; DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 27-MAR-2024, entry version 118. DE RecName: Full=Mitogen-activated protein kinase kinase kinase 10; DE EC=2.7.11.25; DE AltName: Full=Mixed lineage kinase 2; DE Short=xMLK2; GN Name=map3k10; Synonyms=mlk2; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH RAC1, TISSUE RP SPECIFICITY, AND DEVELOPMENTAL STAGE. RC TISSUE=Tail bud; RX PubMed=12591241; DOI=10.1016/s0012-1606(02)00040-4; RA Poitras L., Bisson N., Islam N., Moss T.; RT "A tissue restricted role for the Xenopus Jun N-terminal kinase kinase RT kinase MLK2 in cement gland and pronephric tubule differentiation."; RL Dev. Biol. 254:200-214(2003). RN [2] RP FUNCTION, AND INTERACTION WITH PAK1. RX PubMed=12753919; DOI=10.1016/s0014-5793(03)00424-1; RA Poitras L., Jean S., Islam N., Moss T.; RT "PAK interacts with NCK and MLK2 to regulate the activation of jun N- RT terminal kinase."; RL FEBS Lett. 543:129-135(2003). RN [3] RP INTERACTION WITH UBE2D4, HOMODIMERIZATION, AND UBIQUITINATION. RX PubMed=18021256; DOI=10.1111/j.1432-0436.2007.00239.x; RA Jean S., Moss T.; RT "A ubiquitin-conjugating enzyme, ube2d3.2, regulates xMLK2 and pronephros RT formation in Xenopus."; RL Differentiation 76:431-441(2008). CC -!- FUNCTION: Activates the JUN N-terminal pathway. Essential for CC pronephros and cement gland development. {ECO:0000269|PubMed:12591241, CC ECO:0000269|PubMed:12753919}. 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. Binds to the GTPase rac1 but not cdc42 or rhoA. CC Interacts (via kinase domain) with pak1 (via kinase domain). Interacts CC with the ubiquitin-conjugating enzyme ube2d4. CC {ECO:0000269|PubMed:12591241, ECO:0000269|PubMed:12753919, CC ECO:0000269|PubMed:18021256}. CC -!- TISSUE SPECIFICITY: In adults, strongly expressed in the brain and CC spleen with lower levels in pancreas, heart, muscle and kidney (at CC protein level). In the developing embryo, expressed at stage 22 in the CC cement gland. Weakly expressed in the pronephros from stage 24 or 25, CC with expression increasing in strength by stage 30 and continuing at CC least until stage 37. Expression in the developing pronephros CC correlates with epithelialization of the proximal pronephric tubules. CC {ECO:0000269|PubMed:12591241}. CC -!- DEVELOPMENTAL STAGE: Expressed zygotically from stages 12 to 14 (late CC gastrula to early neurula), increasing in concentration up to stages 40 CC to 45 (late tadpole). Expression continues through to adults. CC {ECO:0000269|PubMed:12591241}. CC -!- PTM: Autophosphorylation on serine and threonine residues within the CC activation loop plays a role in enzyme activation. {ECO:0000250}. CC -!- PTM: Mono- and poly-ubiquitinated. {ECO:0000269|PubMed:18021256}. 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; AF510499; AAP46399.1; -; mRNA. DR RefSeq; NP_001082629.1; NM_001089160.1. DR AlphaFoldDB; Q7T2V3; -. DR SMR; Q7T2V3; -. DR BioGRID; 99942; 2. DR GeneID; 398612; -. DR KEGG; xla:398612; -. DR AGR; Xenbase:XB-GENE-920952; -. DR CTD; 398612; -. DR Xenbase; XB-GENE-920952; map3k10.L. DR OrthoDB; 876955at2759; -. DR Proteomes; UP000186698; Chromosome 8L. DR Bgee; 398612; Expressed in zone of skin and 19 other cell types or tissues. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004706; F:JUN kinase kinase kinase activity; IDA:UniProtKB. DR GO; GO:0019900; F:kinase binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB. DR GO; GO:0031624; F:ubiquitin conjugating enzyme binding; IPI:UniProtKB. DR GO; GO:0071570; P:cement gland development; IMP:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB. DR GO; GO:0048793; P:pronephros development; IMP:UniProtKB. DR CDD; cd12059; SH3_MLK1-3; 1. DR CDD; cd14148; STKc_MLK2; 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; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR23257:SF755; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE; 1. DR PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00018; SH3_1; 1. DR PIRSF; PIRSF000556; MAPKKK9_11; 1. DR PRINTS; PR00452; SH3DOMAIN. DR PRINTS; PR00109; TYRKINASE. 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; PS50002; SH3; 1. PE 1: Evidence at protein level; KW ATP-binding; Kinase; Nucleotide-binding; Reference proteome; Repeat; KW Serine/threonine-protein kinase; SH3 domain; Transferase; Ubl conjugation. FT CHAIN 1..1005 FT /note="Mitogen-activated protein kinase kinase kinase 10" FT /id="PRO_0000277827" FT DOMAIN 32..96 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 118..380 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 404..425 FT /note="Leucine-zipper 1" FT REGION 439..460 FT /note="Leucine-zipper 2" FT REGION 551..611 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 647..676 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 712..736 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 758..940 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 591..606 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 764..780 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 810..824 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 837..858 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 860..876 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 914..932 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 242 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 124..132 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 145 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" SQ SEQUENCE 1005 AA; 111875 MW; B406102A77244309 CRC64; MDGLPKDEAF LWQSSKDNKE NGVWSDVQSY GVSNPLWMAV FDYEPTAEEE LTLRRGDLVE ILSKDSTVSG DEGWWTGKIK DKVGIFPSNY VVSDDKYTTL TGAPKQCPLP LEIEFDELNL DEIIGVGGFG KVYKGLWRDE EVAVKAVRHD PDEDINVTAE NVRQEAKIFC MLCHPNIIAL TGVCLKPPHL CLVMEYARGG PLHRALAGKK VPAHVLVNWA VQIAKGMTYL HNEAIVPIIH RDLGSSNILI LEKAENDDLF NKTLNITDFG LAREWQKTTK MSAAGTYAWM APEVIRLSLF SKSSDVWSFG VLLWELLTGE VPYREIDALA VAYGVAMNKL TLPIPSTCPE PFVRILEACW DPDPHSRPTF SCILEQLTTI EQSAMFQMPL ESFHSLQEDW RLEIQQMFDE LRTKEKELRS REEELVRAAE EQRILEDLLK RREQELAERE IDIVERELNI IMYQMYQEKP KVKKRKGNFK KSRLKLKDGN RISLPSGFEH KITVQASPML DKCKGQGTSS YSPPGSPLII PRLRAIRLTP VDGSKTWGRS SVLKKEEVTT SNKKKGRTWG PSSTQQKERV GGEERLKTLG EGNKQWSSSA PNLGKSPKHT PISVGFASLT EMEEYADSDG SVPQSPYSQS YLTLPVQSDH RSHPEDTAHA GAPSSDSPKR GSQSRRKSEL VLLGCASLLA AVALGSDLSE LVPQEEKRKG IFQWAGRGPR RRASSPSRSM SYGEDSVIPS SSVTLISLSS ISDCNSTRSL IRSDSDDIGL DHDNVSSGRG VKEDRGQQPN VGSNPLVDYK VESFKRDPKQ SLTPTHVTVG RNNTTETRGH RRTPSDGAIR QVTQGHKRSP SDGSTPYQCE PEPSPFPRLP DPHFVFPPPV RRKDTGVERP TSLEFAPRPR PSSNRPRMDP WKFVSLSQTH SSSPSSGGGD ACSSGSAEGA QVADVEETLL DMEVEGQRLD STVPLCGLGL RPTTDPFFKY GNRRVLMKEL SISLLQYKVE SGVLL //