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Protein

Dual specificity mitogen-activated protein kinase kinase 3

Gene

MAP2K3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Enzyme regulationi

Activated by dual phosphorylation on Ser-218 and Thr-222.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei93ATPPROSITE-ProRule annotation1
Active sitei190Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi70 – 78ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase kinase activity Source: ProtInc
  • protein kinase binding Source: UniProtKB
  • protein tyrosine kinase activity Source: UniProtKB-KW
  • receptor signaling protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  • activation of MAPK activity Source: Reactome
  • positive regulation of protein kinase activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • proteolysis in other organism Source: Reactome
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS00498-MONOMER.
BRENDAi2.7.12.2. 2681.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-5210891. Uptake and function of anthrax toxins.
SignaLinkiP46734.
SIGNORiP46734.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 3 (EC:2.7.12.21 Publication)
Short name:
MAP kinase kinase 3
Short name:
MAPKK 3
Alternative name(s):
MAPK/ERK kinase 3
Short name:
MEK 3
Stress-activated protein kinase kinase 2
Short name:
SAPK kinase 2
Short name:
SAPKK-2
Short name:
SAPKK2
Gene namesi
Name:MAP2K3
Synonyms:MEK3, MKK3, PRKMK3, SKK2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:6843. MAP2K3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: GO_Central
  • cytosol Source: Reactome
  • membrane Source: UniProtKB
  • nucleoplasm Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Involvement in diseasei

Defects in MAP2K3 may be involved in colon cancer.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi218S → A: Inactivation. 1 Publication1
Mutagenesisi218S → E: Constitutive activation. 1 Publication1
Mutagenesisi222T → A: Inactivation. 1 Publication1
Mutagenesisi222T → E: Constitutive activation. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5606.
OpenTargetsiENSG00000034152.
PharmGKBiPA30588.

Chemistry databases

ChEMBLiCHEMBL2109.
GuidetoPHARMACOLOGYi2064.

Polymorphism and mutation databases

BioMutaiMAP2K3.
DMDMi24638466.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863781 – 347Dual specificity mitogen-activated protein kinase kinase 3Add BLAST347

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei3PhosphoserineCombined sources1
Modified residuei15PhosphoserineCombined sources1
Modified residuei218Phosphoserine1 Publication1
Modified residuei222Phosphothreonine1 Publication1

Post-translational modificationi

Autophosphorylated. Phosphorylation on Ser-218 and Thr-222 by MAP kinase kinase kinases regulates positively the kinase activity (PubMed:8622669). Phosphorylated by TAOK2 (PubMed:11279118).2 Publications
Yersinia yopJ may acetylate Ser/Thr residues, preventing phosphorylation and activation, thus blocking the MAPK signaling pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP46734.
PaxDbiP46734.
PeptideAtlasiP46734.
PRIDEiP46734.

PTM databases

iPTMnetiP46734.
PhosphoSitePlusiP46734.

Miscellaneous databases

PMAP-CutDBP46734.

Expressioni

Tissue specificityi

Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.

Gene expression databases

BgeeiENSG00000034152.
CleanExiHS_MAP2K3.
ExpressionAtlasiP46734. baseline and differential.
GenevisibleiP46734. HS.

Organism-specific databases

HPAiCAB018548.
HPA044497.

Interactioni

Subunit structurei

Component of a signaling complex containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK (PubMed:21224381). Binds to DYRK1B/MIRK and increases its kinase activity (PubMed:11980910). Part of a complex with MAP3K3, RAC1 and CCM2 (By similarity). Interacts with ARRB1 (PubMed:16709866). Interacts with Yersinia yopJ (PubMed:16728640).By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DYRK1BQ9Y4632EBI-602462,EBI-634187
LRRK2Q5S0075EBI-602462,EBI-5323863
MAP3K5Q996832EBI-602462,EBI-476263
MAPK14Q165392EBI-602462,EBI-73946
TINF2Q9BSI42EBI-602462,EBI-717399

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111592. 33 interactors.
DIPiDIP-34242N.
IntActiP46734. 18 interactors.
MINTiMINT-4300215.
STRINGi9606.ENSP00000345083.

Chemistry databases

BindingDBiP46734.

Structurei

3D structure databases

ProteinModelPortaliP46734.
SMRiP46734.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini64 – 325Protein kinasePROSITE-ProRule annotationAdd BLAST262

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0984. Eukaryota.
ENOG410XT3F. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiP46734.
KOiK04432.
OMAiPFFTSHK.
OrthoDBiEOG091G0A9H.
PhylomeDBiP46734.
TreeFamiTF350701.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 3 (identifier: P46734-1) [UniParc]FASTAAdd to basket
Also known as: 3b

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MESPASSQPA SMPQSKGKSK RKKDLRISCM SKPPAPNPTP PRNLDSRTFI
60 70 80 90 100
TIGDRNFEVE ADDLVTISEL GRGAYGVVEK VRHAQSGTIM AVKRIRATVN
110 120 130 140 150
SQEQKRLLMD LDINMRTVDC FYTVTFYGAL FREGDVWICM ELMDTSLDKF
160 170 180 190 200
YRKVLDKNMT IPEDILGEIA VSIVRALEHL HSKLSVIHRD VKPSNVLINK
210 220 230 240 250
EGHVKMCDFG ISGYLVDSVA KTMDAGCKPY MAPERINPEL NQKGYNVKSD
260 270 280 290 300
VWSLGITMIE MAILRFPYES WGTPFQQLKQ VVEEPSPQLP ADRFSPEFVD
310 320 330 340
FTAQCLRKNP AERMSYLELM EHPFFTLHKT KKTDIAAFVK EILGEDS
Length:347
Mass (Da):39,318
Last modified:November 1, 2002 - v2
Checksum:iA80BA4FDFF8F75A2
GO
Isoform 1 (identifier: P46734-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: Missing.

Show »
Length:318
Mass (Da):36,173
Checksum:i966821BE4B76E8FA
GO
Isoform 2 (identifier: P46734-3) [UniParc]FASTAAdd to basket
Also known as: 3c

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: MESPASSQPASMPQSK → MGVQGTLMSRDSQTPHLLSIL

Show »
Length:352
Mass (Da):39,940
Checksum:iF59612D9001EA9C5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti341E → K (PubMed:7839144).Curated1
Sequence conflicti341E → K (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04081726R → T.1 Publication1
Natural variantiVAR_04606240P → T.Corresponds to variant rs33911218dbSNPEnsembl.1
Natural variantiVAR_06174255R → T.Corresponds to variant rs36047035dbSNPEnsembl.1
Natural variantiVAR_04606368S → P.1 PublicationCorresponds to variant rs34105301dbSNPEnsembl.1
Natural variantiVAR_04606484A → T.1 PublicationCorresponds to variant rs2305873dbSNPEnsembl.1
Natural variantiVAR_04606590M → I.1 PublicationCorresponds to variant rs36076766dbSNPEnsembl.1
Natural variantiVAR_04606694R → L.1 PublicationCorresponds to variant rs56067280dbSNPEnsembl.1
Natural variantiVAR_04606796R → W.1 PublicationCorresponds to variant rs56216806dbSNPEnsembl.1
Natural variantiVAR_014208175R → W in colon cancer. 1 Publication1
Natural variantiVAR_014209215L → V in colon cancer. 1 Publication1
Natural variantiVAR_046068293R → H.1 PublicationCorresponds to variant rs35206134dbSNPEnsembl.1
Natural variantiVAR_046069339V → M.1 PublicationCorresponds to variant rs2363198dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0048781 – 29Missing in isoform 1. 2 PublicationsAdd BLAST29
Alternative sequenceiVSP_0048771 – 16MESPA…MPQSK → MGVQGTLMSRDSQTPHLLSI L in isoform 2. CuratedAdd BLAST16

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36719 mRNA. Translation: AAC41718.1.
D87116 mRNA. Translation: BAA13248.1.
U66839 mRNA. Translation: AAB40652.1.
U66840 Genomic DNA. Translation: AAB40653.1.
AK093838 mRNA. Translation: BAG52769.1.
BC032478 mRNA. Translation: AAH32478.1.
CCDSiCCDS11217.1. [P46734-1]
CCDS11218.1. [P46734-2]
RefSeqiNP_001303261.1. NM_001316332.1. [P46734-2]
NP_002747.2. NM_002756.4. [P46734-2]
NP_659731.1. NM_145109.2. [P46734-1]
XP_005256780.1. XM_005256723.2. [P46734-2]
XP_011522261.1. XM_011523959.1. [P46734-2]
XP_016880347.1. XM_017024858.1. [P46734-2]
XP_016880348.1. XM_017024859.1. [P46734-2]
UniGeneiHs.514012.

Genome annotation databases

EnsembliENST00000316920; ENSP00000319139; ENSG00000034152. [P46734-2]
ENST00000342679; ENSP00000345083; ENSG00000034152. [P46734-1]
ENST00000361818; ENSP00000355081; ENSG00000034152. [P46734-2]
ENST00000613338; ENSP00000478619; ENSG00000034152. [P46734-2]
GeneIDi5606.
KEGGihsa:5606.
UCSCiuc021tsq.2. human. [P46734-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L36719 mRNA. Translation: AAC41718.1.
D87116 mRNA. Translation: BAA13248.1.
U66839 mRNA. Translation: AAB40652.1.
U66840 Genomic DNA. Translation: AAB40653.1.
AK093838 mRNA. Translation: BAG52769.1.
BC032478 mRNA. Translation: AAH32478.1.
CCDSiCCDS11217.1. [P46734-1]
CCDS11218.1. [P46734-2]
RefSeqiNP_001303261.1. NM_001316332.1. [P46734-2]
NP_002747.2. NM_002756.4. [P46734-2]
NP_659731.1. NM_145109.2. [P46734-1]
XP_005256780.1. XM_005256723.2. [P46734-2]
XP_011522261.1. XM_011523959.1. [P46734-2]
XP_016880347.1. XM_017024858.1. [P46734-2]
XP_016880348.1. XM_017024859.1. [P46734-2]
UniGeneiHs.514012.

3D structure databases

ProteinModelPortaliP46734.
SMRiP46734.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111592. 33 interactors.
DIPiDIP-34242N.
IntActiP46734. 18 interactors.
MINTiMINT-4300215.
STRINGi9606.ENSP00000345083.

Chemistry databases

BindingDBiP46734.
ChEMBLiCHEMBL2109.
GuidetoPHARMACOLOGYi2064.

PTM databases

iPTMnetiP46734.
PhosphoSitePlusiP46734.

Polymorphism and mutation databases

BioMutaiMAP2K3.
DMDMi24638466.

Proteomic databases

EPDiP46734.
PaxDbiP46734.
PeptideAtlasiP46734.
PRIDEiP46734.

Protocols and materials databases

DNASUi5606.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000316920; ENSP00000319139; ENSG00000034152. [P46734-2]
ENST00000342679; ENSP00000345083; ENSG00000034152. [P46734-1]
ENST00000361818; ENSP00000355081; ENSG00000034152. [P46734-2]
ENST00000613338; ENSP00000478619; ENSG00000034152. [P46734-2]
GeneIDi5606.
KEGGihsa:5606.
UCSCiuc021tsq.2. human. [P46734-1]

Organism-specific databases

CTDi5606.
DisGeNETi5606.
GeneCardsiMAP2K3.
HGNCiHGNC:6843. MAP2K3.
HPAiCAB018548.
HPA044497.
MIMi602315. gene.
neXtProtiNX_P46734.
OpenTargetsiENSG00000034152.
PharmGKBiPA30588.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0984. Eukaryota.
ENOG410XT3F. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiP46734.
KOiK04432.
OMAiPFFTSHK.
OrthoDBiEOG091G0A9H.
PhylomeDBiP46734.
TreeFamiTF350701.

Enzyme and pathway databases

BioCyciZFISH:HS00498-MONOMER.
BRENDAi2.7.12.2. 2681.
ReactomeiR-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-450302. activated TAK1 mediates p38 MAPK activation.
R-HSA-5210891. Uptake and function of anthrax toxins.
SignaLinkiP46734.
SIGNORiP46734.

Miscellaneous databases

ChiTaRSiMAP2K3. human.
GeneWikiiMAP2K3.
GenomeRNAii5606.
PMAP-CutDBP46734.
PROiP46734.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000034152.
CleanExiHS_MAP2K3.
ExpressionAtlasiP46734. baseline and differential.
GenevisibleiP46734. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMP2K3_HUMAN
AccessioniPrimary (citable) accession number: P46734
Secondary accession number(s): B3KSK7
, Q99441, Q9UE71, Q9UE72
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 2002
Last modified: November 2, 2016
This is version 178 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.