M3K10_XENLA
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 03-AUG-2022, entry version 113.
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 CTD; 398612; -.
DR Xenbase; XB-GENE-920952; map3k10.L.
DR OrthoDB; 115270at2759; -.
DR Proteomes; UP000186698; Chromosome 8L.
DR Bgee; 398612; Expressed in zone of skin and 19 other 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:0046330; P:positive regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0048793; P:pronephros development; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR44329:SF39; PTHR44329:SF39; 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; 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; 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
