UniProtKB - P46734 (MP2K3_HUMAN)
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Protein
Dual specificity mitogen-activated protein kinase kinase 3
Gene
MAP2K3
Organism
Homo sapiens (Human)
Status
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 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: ProtInc
- 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: Reactome
- activation of protein kinase activity Source: GO_Central
- cardiac muscle contraction Source: Ensembl
- inflammatory response Source: Ensembl
- positive regulation of protein kinase activity Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- proteolysis in other organism Source: Reactome
- regulation of apoptotic process Source: GO_Central
- regulation of cytokine biosynthetic process Source: Ensembl
- regulation of mitotic cell cycle Source: GO_Central
- signal transduction Source: ProtInc
- signal transduction by protein phosphorylation Source: GO_Central
- stress-activated protein kinase signaling cascade 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. |
| 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. |
Subcellular locationi
GO - Cellular componenti
- cytoplasm Source: GO_Central
- cytosol Source: Reactome
- membrane Source: UniProtKB
- nucleoplasm Source: Reactome
Pathology & Biotechi
Involvement in diseasei
Defects in MAP2K3 may be involved in colon cancer.
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. |
Chemistry databases
| ChEMBLi | CHEMBL2109. |
| 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
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, PhosphoproteinProteomic databases
| EPDi | P46734. |
| PaxDbi | P46734. |
| PeptideAtlasi | P46734. |
| PRIDEi | P46734. |
PTM databases
| iPTMneti | P46734. |
| PhosphoSitePlusi | P46734. |
Miscellaneous databases
| PMAP-CutDBi | P46734. |
Expressioni
Tissue specificityi
Abundant expression is seen in the skeletal muscle. It is also widely expressed in other tissues.
Gene expression databases
| Bgeei | ENSG00000034152. |
| CleanExi | HS_MAP2K3. |
| 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 Publications
Binary interactionsi
GO - Molecular functioni
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
| BioGridi | 111592. 33 interactors. |
| DIPi | DIP-34242N. |
| IntActi | P46734. 19 interactors. |
| MINTi | MINT-4300215. |
| STRINGi | 9606.ENSP00000345083. |
Chemistry databases
| BindingDBi | P46734. |
Structurei
3D structure databases
| ProteinModelPortali | P46734. |
| SMRi | P46734. |
| ModBasei | Search... |
| MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 64 – 325 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 262 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.Curated
Phylogenomic databases
| eggNOGi | KOG0984. Eukaryota. ENOG410XT3F. LUCA. |
| GeneTreei | ENSGT00760000119199. |
| HOGENOMi | HOG000234206. |
| HOVERGENi | HBG108518. |
| InParanoidi | P46734. |
| KOi | K04432. |
| OMAi | ACVTIGD. |
| OrthoDBi | EOG091G0A9H. |
| PhylomeDBi | P46734. |
| TreeFami | TF350701. |
Family and domain databases
| InterProi | View protein in InterPro IPR011009. Kinase-like_dom. 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. |
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.
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
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 Publication | 1 | |
| Natural variantiVAR_014209 | 215 | L → V in colon cancer. 1 Publication | 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] |
| UniGenei | Hs.514012. |
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
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. |
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: | July 5, 2017 | |
| This is version 183 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 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 - Human and mouse protein kinases
Human and mouse protein kinases: classification and index - SIMILARITY comments
Index of protein domains and families
