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Protein

Dual specificity mitogen-activated protein kinase kinase 3

Gene

MAP2K3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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: GO_Central
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: GO_Central
  • protein tyrosine kinase activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000034152.18
HGNCiHGNC:6843 MAP2K3
MIMi602315 gene
neXtProtiNX_P46734

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi55750
55751 [P46734-2]
55752 [P46734-3]

PTM databases

iPTMnetiP46734
PhosphoSitePlusiP46734

Miscellaneous databases

PMAP-CutDBiP46734

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000034152 Expressed in 241 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_MAP2K3
ExpressionAtlasiP46734 baseline and differential
GenevisibleiP46734 HS

Organism-specific databases

HPAiCAB018548

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111592, 38 interactors
DIPiDIP-34242N
IntActiP46734, 21 interactors
MINTiP46734
STRINGi9606.ENSP00000345083

Chemistry databases

BindingDBiP46734

Structurei

3D structure databases

ProteinModelPortaliP46734
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PRZ0E9PRZ0_HUMAN
Dual-specificity mitogen-activated ...
MAP2K3
160Annotation score:
J3QR49J3QR49_HUMAN
Dual-specificity mitogen-activated ...
MAP2K3
173Annotation score:
J3KRV4J3KRV4_HUMAN
Dual-specificity mitogen-activated ...
MAP2K3
136Annotation score:
E9PMA8E9PMA8_HUMAN
Dual-specificity mitogen-activated ...
MAP2K3
101Annotation score:
J3QL77J3QL77_HUMAN
Dual-specificity mitogen-activated ...
MAP2K3
46Annotation score:
X6RB39X6RB39_HUMAN
Dual-specificity mitogen-activated ...
MAP2K3
46Annotation score:

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 → T1 Publication1
Natural variantiVAR_04606240P → T. Corresponds to variant dbSNP:rs33911218Ensembl.1
Natural variantiVAR_06174255R → T. Corresponds to variant dbSNP:rs36047035Ensembl.1
Natural variantiVAR_04606368S → P1 PublicationCorresponds to variant dbSNP:rs34105301Ensembl.1
Natural variantiVAR_04606484A → T1 PublicationCorresponds to variant dbSNP:rs2305873Ensembl.1
Natural variantiVAR_04606590M → I1 PublicationCorresponds to variant dbSNP:rs36076766Ensembl.1
Natural variantiVAR_04606694R → L1 PublicationCorresponds to variant dbSNP:rs56067280Ensembl.1
Natural variantiVAR_04606796R → W1 PublicationCorresponds to variant dbSNP:rs56216806Ensembl.1
Natural variantiVAR_014208175R → W in colon cancer. 1 Publication1
Natural variantiVAR_014209215L → V in colon cancer. 1 Publication1
Natural variantiVAR_046068293R → H1 PublicationCorresponds to variant dbSNP:rs35206134Ensembl.1
Natural variantiVAR_046069339V → M1 PublicationCorresponds to variant dbSNP:rs2363198Ensembl.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

Similar proteinsi

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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111592, 38 interactors
DIPiDIP-34242N
IntActiP46734, 21 interactors
MINTiP46734
STRINGi9606.ENSP00000345083

Chemistry databases

BindingDBiP46734
ChEMBLiCHEMBL2109
GuidetoPHARMACOLOGYi2064

PTM databases

iPTMnetiP46734
PhosphoSitePlusiP46734

Polymorphism and mutation databases

BioMutaiMAP2K3
DMDMi24638466

Proteomic databases

EPDiP46734
PaxDbiP46734
PeptideAtlasiP46734
PRIDEiP46734
ProteomicsDBi55750
55751 [P46734-2]
55752 [P46734-3]

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
EuPathDBiHostDB:ENSG00000034152.18
GeneCardsiMAP2K3
HGNCiHGNC:6843 MAP2K3
HPAiCAB018548
MIMi602315 gene
neXtProtiNX_P46734
OpenTargetsiENSG00000034152
PharmGKBiPA30588
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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-CutDBiP46734
PROiPR:P46734
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000034152 Expressed in 241 organ(s), highest expression level in buccal mucosa cell
CleanExiHS_MAP2K3
ExpressionAtlasiP46734 baseline and differential
GenevisibleiP46734 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMP2K3_HUMAN
AccessioniPrimary (citable) accession number: P46734
Secondary accession number(s): B3KSK7
, Q99441, Q9UE71, Q9UE72
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 2002
Last modified: November 7, 2018
This is version 195 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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 chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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