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 03-AUG-2022, entry version 136.
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 SwissPalm; Q63796; -.
DR PaxDb; Q63796; -.
DR PRIDE; Q63796; -.
DR ABCD; Q63796; 2 sequenced antibodies.
DR GeneID; 25579; -.
DR KEGG; rno:25579; -.
DR UCSC; RGD:3988; rat.
DR CTD; 7786; -.
DR RGD; 3988; Map3k12.
DR eggNOG; KOG4721; Eukaryota.
DR InParanoid; Q63796; -.
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:0016572; P:histone phosphorylation; ISO:RGD.
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:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
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 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; SSF56112; 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
