UniProtKB - P46734 (MP2K3_HUMAN)
Dual specificity mitogen-activated protein kinase kinase 3
MAP2K3
Functioni
Catalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 93 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 190 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 70 – 78 | ATPPROSITE-ProRule annotation | 9 |
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
- activation of MAPK activity Source: GO_Central
- activation of protein kinase activity Source: GO_Central
- cardiac muscle contraction Source: Ensembl
- cellular response to vascular endothelial growth factor stimulus Source: BHF-UCL
- inflammatory response Source: Ensembl
- p38MAPK cascade Source: BHF-UCL
- positive regulation of blood vessel endothelial cell migration Source: BHF-UCL
- positive regulation of protein kinase activity Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- regulation of cytokine biosynthetic process Source: Ensembl
- signal transduction Source: ProtInc
- signal transduction by protein phosphorylation Source: GO_Central
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.12.2 2681 |
Reactomei | R-HSA-2559580 Oxidative Stress Induced Senescence R-HSA-450302 activated TAK1 mediates p38 MAPK activation R-HSA-5210891 Uptake and function of anthrax toxins [P46734-3] |
SignaLinki | P46734 |
SIGNORi | P46734 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6843 MAP2K3 |
MIMi | 602315 gene |
neXtProti | NX_P46734 |
Subcellular locationi
Cytosol
- cytosol Source: Reactome
Nucleus
- nucleoplasm Source: Reactome
Other locations
Pathology & Biotechi
Involvement in diseasei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 218 | S → A: Inactivation. 1 Publication | 1 | |
Mutagenesisi | 218 | S → E: Constitutive activation. 1 Publication | 1 | |
Mutagenesisi | 222 | T → A: Inactivation. 1 Publication | 1 | |
Mutagenesisi | 222 | T → E: Constitutive activation. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 5606 |
OpenTargetsi | ENSG00000034152 |
PharmGKBi | PA30588 |
Miscellaneous databases
Pharosi | P46734 |
Chemistry databases
ChEMBLi | CHEMBL2109 |
DrugBanki | DB12010 Fostamatinib |
DrugCentrali | P46734 |
GuidetoPHARMACOLOGYi | 2064 |
Polymorphism and mutation databases
BioMutai | MAP2K3 |
DMDMi | 24638466 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086378 | 1 – 347 | Dual specificity mitogen-activated protein kinase kinase 3Add BLAST | 347 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 1 | N-acetylmethionineCombined sources | 1 | |
Modified residuei | 3 | PhosphoserineCombined sources | 1 | |
Modified residuei | 15 | PhosphoserineCombined sources | 1 | |
Modified residuei | 218 | Phosphoserine1 Publication | 1 | |
Modified residuei | 222 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-814 CPTAC-815 |
EPDi | P46734 |
jPOSTi | P46734 |
MassIVEi | P46734 |
PaxDbi | P46734 |
PeptideAtlasi | P46734 |
PRIDEi | P46734 |
ProteomicsDBi | 55750 [P46734-1] 55751 [P46734-2] 55752 [P46734-3] |
PTM databases
iPTMneti | P46734 |
PhosphoSitePlusi | P46734 |
Miscellaneous databases
PMAP-CutDBi | P46734 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000034152 Expressed in 241 organ(s), highest expression level in buccal mucosa cell |
ExpressionAtlasi | P46734 baseline and differential |
Genevisiblei | P46734 HS |
Organism-specific databases
HPAi | CAB018548 |
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 PublicationsBinary interactionsi
GO - Molecular functioni
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 111592, 122 interactors |
CORUMi | P46734 |
DIPi | DIP-34242N |
IntActi | P46734, 22 interactors |
MINTi | P46734 |
STRINGi | 9606.ENSP00000345083 |
Chemistry databases
BindingDBi | P46734 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 64 – 325 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 262 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0984 Eukaryota ENOG410XT3F LUCA |
GeneTreei | ENSGT00940000160875 |
HOGENOMi | HOG000234206 |
InParanoidi | P46734 |
KOi | K04432 |
OMAi | ETDMASF |
OrthoDBi | 81952at2759 |
PhylomeDBi | P46734 |
TreeFami | TF350701 |
Family and domain databases
InterProi | View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069 Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketJ3QR49 | J3QR49_HUMAN | Dual-specificity mitogen-activated ... | MAP2K3 | 173 | Annotation score: | ||
E9PMA8 | E9PMA8_HUMAN | Dual-specificity mitogen-activated ... | MAP2K3 | 101 | Annotation score: | ||
E9PRZ0 | E9PRZ0_HUMAN | Dual-specificity mitogen-activated ... | MAP2K3 | 160 | Annotation score: | ||
J3QL77 | J3QL77_HUMAN | Dual-specificity mitogen-activated ... | MAP2K3 | 46 | Annotation score: | ||
J3KRV4 | J3KRV4_HUMAN | Dual-specificity mitogen-activated ... | MAP2K3 | 136 | Annotation score: | ||
X6RB39 | X6RB39_HUMAN | Dual-specificity mitogen-activated ... | MAP2K3 | 46 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 341 | E → K (PubMed:7839144).Curated | 1 | |
Sequence conflicti | 341 | E → K (Ref. 3) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040817 | 26 | R → T1 Publication | 1 | |
Natural variantiVAR_046062 | 40 | P → T. Corresponds to variant dbSNP:rs33911218Ensembl. | 1 | |
Natural variantiVAR_061742 | 55 | R → T. Corresponds to variant dbSNP:rs36047035Ensembl. | 1 | |
Natural variantiVAR_046063 | 68 | S → P1 PublicationCorresponds to variant dbSNP:rs34105301Ensembl. | 1 | |
Natural variantiVAR_046064 | 84 | A → T1 PublicationCorresponds to variant dbSNP:rs2305873Ensembl. | 1 | |
Natural variantiVAR_046065 | 90 | M → I1 PublicationCorresponds to variant dbSNP:rs36076766Ensembl. | 1 | |
Natural variantiVAR_046066 | 94 | R → L1 PublicationCorresponds to variant dbSNP:rs56067280Ensembl. | 1 | |
Natural variantiVAR_046067 | 96 | R → W1 PublicationCorresponds to variant dbSNP:rs56216806Ensembl. | 1 | |
Natural variantiVAR_014208 | 175 | R → W in colon cancer. 1 PublicationCorresponds to variant dbSNP:rs1339756947Ensembl. | 1 | |
Natural variantiVAR_014209 | 215 | L → V in colon cancer. 1 PublicationCorresponds to variant dbSNP:rs989026404Ensembl. | 1 | |
Natural variantiVAR_046068 | 293 | R → H1 PublicationCorresponds to variant dbSNP:rs35206134Ensembl. | 1 | |
Natural variantiVAR_046069 | 339 | V → M1 PublicationCorresponds to variant dbSNP:rs2363198Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_004878 | 1 – 29 | Missing in isoform 1. 2 PublicationsAdd BLAST | 29 | |
Alternative sequenceiVSP_004877 | 1 – 16 | MESPA…MPQSK → MGVQGTLMSRDSQTPHLLSI L in isoform 2. CuratedAdd BLAST | 16 |
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 |
CCDSi | CCDS11217.1 [P46734-1] CCDS11218.1 [P46734-2] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000316920; ENSP00000319139; ENSG00000034152 [P46734-2] ENST00000342679; ENSP00000345083; ENSG00000034152 [P46734-1] ENST00000361818; ENSP00000355081; ENSG00000034152 [P46734-2] ENST00000613338; ENSP00000478619; ENSG00000034152 [P46734-2] |
GeneIDi | 5606 |
KEGGi | hsa:5606 |
UCSCi | uc021tsq.2 human [P46734-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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 |
CCDSi | CCDS11217.1 [P46734-1] CCDS11218.1 [P46734-2] |
RefSeqi | NP_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] |
3D structure databases
SMRi | P46734 |
ModBasei | Search... |
Protein-protein interaction databases
BioGridi | 111592, 122 interactors |
CORUMi | P46734 |
DIPi | DIP-34242N |
IntActi | P46734, 22 interactors |
MINTi | P46734 |
STRINGi | 9606.ENSP00000345083 |
Chemistry databases
BindingDBi | P46734 |
ChEMBLi | CHEMBL2109 |
DrugBanki | DB12010 Fostamatinib |
DrugCentrali | P46734 |
GuidetoPHARMACOLOGYi | 2064 |
PTM databases
iPTMneti | P46734 |
PhosphoSitePlusi | P46734 |
Polymorphism and mutation databases
BioMutai | MAP2K3 |
DMDMi | 24638466 |
Proteomic databases
CPTACi | CPTAC-814 CPTAC-815 |
EPDi | P46734 |
jPOSTi | P46734 |
MassIVEi | P46734 |
PaxDbi | P46734 |
PeptideAtlasi | P46734 |
PRIDEi | P46734 |
ProteomicsDBi | 55750 [P46734-1] 55751 [P46734-2] 55752 [P46734-3] |
Protocols and materials databases
DNASUi | 5606 |
Genome annotation databases
Ensembli | ENST00000316920; ENSP00000319139; ENSG00000034152 [P46734-2] ENST00000342679; ENSP00000345083; ENSG00000034152 [P46734-1] ENST00000361818; ENSP00000355081; ENSG00000034152 [P46734-2] ENST00000613338; ENSP00000478619; ENSG00000034152 [P46734-2] |
GeneIDi | 5606 |
KEGGi | hsa:5606 |
UCSCi | uc021tsq.2 human [P46734-1] |
Organism-specific databases
CTDi | 5606 |
DisGeNETi | 5606 |
GeneCardsi | MAP2K3 |
HGNCi | HGNC:6843 MAP2K3 |
HPAi | CAB018548 |
MIMi | 602315 gene |
neXtProti | NX_P46734 |
OpenTargetsi | ENSG00000034152 |
PharmGKBi | PA30588 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0984 Eukaryota ENOG410XT3F LUCA |
GeneTreei | ENSGT00940000160875 |
HOGENOMi | HOG000234206 |
InParanoidi | P46734 |
KOi | K04432 |
OMAi | ETDMASF |
OrthoDBi | 81952at2759 |
PhylomeDBi | P46734 |
TreeFami | TF350701 |
Enzyme and pathway databases
BRENDAi | 2.7.12.2 2681 |
Reactomei | R-HSA-2559580 Oxidative Stress Induced Senescence R-HSA-450302 activated TAK1 mediates p38 MAPK activation R-HSA-5210891 Uptake and function of anthrax toxins [P46734-3] |
SignaLinki | P46734 |
SIGNORi | P46734 |
Miscellaneous databases
ChiTaRSi | MAP2K3 human |
GeneWikii | MAP2K3 |
GenomeRNAii | 5606 |
Pharosi | P46734 |
PMAP-CutDBi | P46734 |
PROi | PR:P46734 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000034152 Expressed in 241 organ(s), highest expression level in buccal mucosa cell |
ExpressionAtlasi | P46734 baseline and differential |
Genevisiblei | P46734 HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069 Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MP2K3_HUMAN | |
Accessioni | P46734Primary (citable) accession number: P46734 Secondary accession number(s): B3KSK7 Q9UE72 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
Last sequence update: | November 1, 2002 | |
Last modified: | October 16, 2019 | |
This is version 202 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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 proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot