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Database: UniProt
Entry: M3K12_RAT
LinkDB: M3K12_RAT
Original site: M3K12_RAT 
ID   M3K12_RAT               Reviewed;         888 AA.
AC   Q63796;
DT   26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 142.
DE   RecName: Full=Mitogen-activated protein kinase kinase kinase 12;
DE            EC=2.7.11.25 {ECO:0000250|UniProtKB:Q60700};
DE   AltName: Full=Dual leucine zipper bearing kinase;
DE            Short=DLK;
DE   AltName: Full=Leucine-zipper protein kinase;
DE            Short=ZPK;
DE   AltName: Full=MAPK-upstream kinase;
DE            Short=MUK;
DE   AltName: Full=Mixed lineage kinase;
GN   Name=Map3k12; Synonyms=Muk;
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 [MRNA].
RX   PubMed=8637721;
RA   Hirai S., Izawa M., Osada S., Spyrou G., Ohno S.;
RT   "Activation of the JNK pathway by distantly related protein kinases, MEKK
RT   and MUK.";
RL   Oncogene 12:641-650(1996).
RN   [2]
RP   PROTEIN SEQUENCE OF 440-448, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RA   Lubec G., Kang S.U.;
RL   Submitted (JUL-2007) to UniProtKB.
CC   -!- FUNCTION: Part of a non-canonical MAPK signaling pathway. Activated by
CC       APOE, enhances the AP-1-mediated transcription of APP, via a MAP kinase
CC       signal transduction pathway composed of MAP2K7 and MAPK1/ERK2 and
CC       MAPK3/ERK1. May be an activator of the JNK/SAPK pathway.
CC       {ECO:0000250|UniProtKB:Q12852}.
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         Evidence={ECO:0000250|UniProtKB:Q60700};
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; Evidence={ECO:0000250|UniProtKB:Q60700};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC   -!- SUBUNIT: Homodimer (By similarity). Interacts with MBIP (By
CC       similarity). {ECO:0000250|UniProtKB:Q12852,
CC       ECO:0000250|UniProtKB:Q60700}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q60700}. Cell
CC       membrane {ECO:0000250|UniProtKB:Q60700}. Note=Behaves essentially as an
CC       integral membrane protein. {ECO:0000250|UniProtKB:Q60700}.
CC   -!- DOMAIN: Interacts with MBIP through the leucine-zipper motif.
CC       {ECO:0000250|UniProtKB:Q12852}.
CC   -!- PTM: Autophosphorylated on Ser/Thr. Phosphorylated in cytosol under
CC       basal conditions and dephosphorylated when membrane-associated (By
CC       similarity). {ECO:0000250|UniProtKB:Q60700}.
CC   -!- PTM: The activity of MAP3K12 can be regulated through its proteasomal
CC       degradation. APOE, through a receptor-mediated mechanism, activates
CC       MAP3K12 by preventing its proteasomal degradation.
CC       {ECO:0000250|UniProtKB:Q12852}.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC       protein kinase family. MAP kinase kinase kinase subfamily.
CC       {ECO:0000305}.
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DR   EMBL; D49785; BAA08621.1; -; mRNA.
DR   PIR; JC5399; JC5399.
DR   RefSeq; NP_037187.1; NM_013055.1.
DR   AlphaFoldDB; Q63796; -.
DR   SMR; Q63796; -.
DR   STRING; 10116.ENSRNOP00000020437; -.
DR   PhosphoSitePlus; Q63796; -.
DR   SwissPalm; Q63796; -.
DR   PaxDb; 10116-ENSRNOP00000020437; -.
DR   ABCD; Q63796; 2 sequenced antibodies.
DR   GeneID; 25579; -.
DR   KEGG; rno:25579; -.
DR   UCSC; RGD:3988; rat.
DR   AGR; RGD:3988; -.
DR   CTD; 7786; -.
DR   RGD; 3988; Map3k12.
DR   eggNOG; KOG4721; Eukaryota.
DR   InParanoid; Q63796; -.
DR   OrthoDB; 876955at2759; -.
DR   PhylomeDB; Q63796; -.
DR   PRO; PR:Q63796; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0030424; C:axon; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0030426; C:growth cone; ISO:RGD.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004706; F:JUN kinase kinase kinase activity; IBA:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR   GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR   GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; ISO:RGD.
DR   GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB.
DR   GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR   CDD; cd14059; STKc_MAP3K12_13; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR017419; MAP3K12_MAP3K13.
DR   InterPro; IPR027257; MAPKKK12.
DR   InterPro; IPR000719; Prot_kinase_dom.
DR   InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR23257:SF707; MITOGEN-ACTIVATED PROTEIN KINASE KINASE KINASE 12; 1.
DR   PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1.
DR   Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR   PIRSF; PIRSF500741; MAPKKK12; 1.
DR   PIRSF; PIRSF038165; MAPKKK12_MAPKKK13; 1.
DR   PRINTS; PR00109; TYRKINASE.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR   PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Cytoplasm; Direct protein sequencing; Kinase;
KW   Magnesium; Membrane; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..888
FT                   /note="Mitogen-activated protein kinase kinase kinase 12"
FT                   /id="PRO_0000086263"
FT   DOMAIN          158..399
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          26..104
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          423..444
FT                   /note="Leucine-zipper 1"
FT   REGION          476..497
FT                   /note="Leucine-zipper 2"
FT   REGION          557..620
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          654..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          743..888
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        772..811
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        841..857
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        269
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         164..172
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         185
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         37
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q60700"
FT   MOD_RES         43
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q60700"
FT   MOD_RES         640
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q60700"
SQ   SEQUENCE   888 AA;  96308 MW;  52AD964006BAE149 CRC64;
     MACLHETRTP SPSFGGFVST LSEASMRKLD PDTSDCTPEK DLTPTQCVLR DVVPLGGQGG
     GGPSPSPGGE PPPEPFANSV LQLHEQDTGG PGGATGSPES RASRVRADEV RLQCQSGSGF
     LEGLFGCLRP VWTMIGKAYS TEHKQQQEDL WEVPFEEILD LQWVGSGAQG AVFLGRFHGE
     EVAVKKVRDL KETDIKHLRK LKHPNIITFK GVCTQAPCYC ILMEFCAQGQ LYEVLRAGRP
     VTPSLLVDWS MGIAGGMNYL HLHKIIHRDL KSPNMLITYD DVVKISDFGT SKELSDKSTK
     MSFAGTVAWM APEVIRNEPV SEKVDIWSFG VVLWELLTGE IPYKDVDSSA IIWGVGSNSL
     HLPVPSSCPD GFKILLRQCW NRKPRNRPSF RQILLHLDIA SADVLSTPQE TYFKSQAEWR
     EEVKLHFEKI KSEGTCLHRL EEELVMRRRE ELRHALDIRE HYERKLERAN NLYMELNALM
     LQLELKEREL LRREQALERR CPGLLKSHTS RSLLHGNTME KLIKKRNVPQ KLSPHSKRPD
     ILKTESLLPK LDAALSGVGL PGCPKAPPSP GRSRRGKTRH RKASAKGSCG DLPGLRAALP
     PHEPGGLGSP GGLGVGPTAW DASPPALRGL HHDLLLRKMS SSSPDLLSAA LGARGRGATG
     GARDPGSPPP PQGDTPPSEG SAPGSTSPDS PGGAKGEPPP PVGPGEGVGL LGTGREGTTG
     RGGSRAGYQH LTPAALLYRA AVTRSQKRGI SSEEEEGEVD SEVELPPSQR WPQGPNMRQS
     LSTFSSENPS DVEEGTASEP SPSGTPEVGS TNTDERPDER SDDMCSQGSE IPLDLPTSEV
     VPERETSSLP MQHQDDQGPN PEDSDCDSTE LDNSNSIDAL PPPASLPP
//
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