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Protein

Dual specificity mitogen-activated protein kinase kinase 5

Gene

MAP2K5

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

Functioni

Acts as a scaffold for the formation of a ternary MAP3K2/MAP3K3-MAP3K5-MAPK7 signaling complex. Activation of this pathway appears to play a critical role in protecting cells from stress-induced apoptosis, neuronal survival and cardiac development and angiogenesis.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei195ATP1
Active sitei283Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi172 – 180ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • activation of MAPK activity Source: BHF-UCL
  • cellular response to growth factor stimulus Source: BHF-UCL
  • cellular response to laminar fluid shear stress Source: BHF-UCL
  • ERK5 cascade Source: Ensembl
  • heart development Source: Ensembl
  • negative regulation of cell migration involved in sprouting angiogenesis Source: BHF-UCL
  • negative regulation of chemokine (C-X-C motif) ligand 2 production Source: BHF-UCL
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: BHF-UCL
  • negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
  • negative regulation of interleukin-8 biosynthetic process Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: BHF-UCL
  • negative regulation of response to cytokine stimulus Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of cell growth Source: Ensembl
  • positive regulation of epithelial cell proliferation Source: Ensembl
  • positive regulation of protein metabolic process Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

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

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS06391-MONOMER.
BRENDAi2.7.12.2. 2681.
ReactomeiR-HSA-198765. Signalling to ERK5.
SignaLinkiQ13163.
SIGNORiQ13163.

Names & Taxonomyi

Protein namesi
Recommended name:
Dual specificity mitogen-activated protein kinase kinase 5 (EC:2.7.12.2)
Short name:
MAP kinase kinase 5
Short name:
MAPKK 5
Alternative name(s):
MAPK/ERK kinase 5
Short name:
MEK 5
Gene namesi
Name:MAP2K5
Synonyms:MEK5, MKK5, PRKMK5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:6845. MAP2K5.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi195K → M: Inactivation. 1 Publication1
Mutagenesisi311S → A: Inactivation. 1 Publication1
Mutagenesisi315T → A: Inactivation. 1 Publication1

Organism-specific databases

DisGeNETi5607.
OpenTargetsiENSG00000137764.
PharmGKBiPA30590.

Chemistry databases

ChEMBLiCHEMBL4948.
GuidetoPHARMACOLOGYi2066.

Polymorphism and mutation databases

BioMutaiMAP2K5.
DMDMi118572669.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863831 – 448Dual specificity mitogen-activated protein kinase kinase 5Add BLAST448

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei311PhosphoserineCombined sources1 Publication1
Modified residuei315Phosphothreonine1 Publication1

Post-translational modificationi

Activated by phosphorylation on Ser/Thr by MAP kinase kinase kinases.By similarity
Yersinia yopJ may acetylate Ser/Thr residues, preventing phosphorylation and activation, thus blocking the MAPK signaling pathway.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13163.
MaxQBiQ13163.
PaxDbiQ13163.
PeptideAtlasiQ13163.
PRIDEiQ13163.

PTM databases

iPTMnetiQ13163.
PhosphoSitePlusiQ13163.

Expressioni

Tissue specificityi

Expressed in many adult tissues. Abundant in heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000137764.
CleanExiHS_MAP2K5.
ExpressionAtlasiQ13163. baseline and differential.
GenevisibleiQ13163. HS.

Organism-specific databases

HPAiCAB022094.
HPA027347.
HPA027755.

Interactioni

Subunit structurei

Interacts with PARD6A, MAP3K3 and MAPK7. Forms a complex with SQSTM1 and PRKCZ or PRKCI (By similarity). Interacts with Yersinia yopJ.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GRB2P629932EBI-307294,EBI-401755
MAP3K3Q997592EBI-307294,EBI-307281
MAPK7Q131644EBI-307294,EBI-1213983

Protein-protein interaction databases

BioGridi111593. 24 interactors.
DIPiDIP-27558N.
IntActiQ13163. 14 interactors.
MINTiMINT-1155433.
STRINGi9606.ENSP00000178640.

Chemistry databases

BindingDBiQ13163.

Structurei

Secondary structure

1448
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi17 – 23Combined sources7
Turni24 – 26Combined sources3
Beta strandi27 – 33Combined sources7
Helixi41 – 51Combined sources11
Beta strandi58 – 63Combined sources6
Beta strandi65 – 67Combined sources3
Beta strandi69 – 72Combined sources4
Helixi75 – 93Combined sources19
Turni94 – 96Combined sources3
Beta strandi102 – 107Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NPTX-ray1.75A/C5-108[»]
2O2VX-ray1.83A5-108[»]
4IC7X-ray2.60B/E16-130[»]
ProteinModelPortaliQ13163.
SMRiQ13163.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13163.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini18 – 109PB1PROSITE-ProRule annotationAdd BLAST92
Domaini166 – 409Protein kinasePROSITE-ProRule annotationAdd BLAST244

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni18 – 25Interaction with MAPK7By similarity8
Regioni64 – 68Interaction with MAP3K2/MAP3K3By similarity5
Regioni117 – 131Interaction with MAPK7By similarityAdd BLAST15

Domaini

Binds MAP3K2/MAP3K3 and MAPK7 via non-overlapping residues of the PB1 domain. This domain also mediates interactions with SQSTM1 and PARD6A (By similarity).By similarity

Sequence similaritiesi

Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ13163.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG091G06I7.
PhylomeDBiQ13163.
TreeFamiTF106468.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B (identifier: Q13163-1) [UniParc]FASTAAdd to basket

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
MLWLALGPFP AMENQVLVIR IKIPNSGAVD WTVHSGPQLL FRDVLDVIGQ
60 70 80 90 100
VLPEATTTAF EYEDEDGDRI TVRSDEEMKA MLSYYYSTVM EQQVNGQLIE
110 120 130 140 150
PLQIFPRACK PPGERNIHGL KVNTRAGPSQ HSSPAVSDSL PSNSLKKSSA
160 170 180 190 200
ELKKILANGQ MNEQDIRYRD TLGHGNGGTV YKAYHVPSGK ILAVKVILLD
210 220 230 240 250
ITLELQKQIM SELEILYKCD SSYIIGFYGA FFVENRISIC TEFMDGGSLD
260 270 280 290 300
VYRKMPEHVL GRIAVAVVKG LTYLWSLKIL HRDVKPSNML VNTRGQVKLC
310 320 330 340 350
DFGVSTQLVN SIAKTYVGTN AYMAPERISG EQYGIHSDVW SLGISFMELA
360 370 380 390 400
LGRFPYPQIQ KNQGSLMPLQ LLQCIVDEDS PVLPVGEFSE PFVHFITQCM
410 420 430 440
RKQPKERPAP EELMGHPFIV QFNDGNAAVV SMWVCRALEE RRSQQGPP
Length:448
Mass (Da):50,112
Last modified:November 28, 2006 - v2
Checksum:iF23BB327E2A9C7DC
GO
Isoform A (identifier: Q13163-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     349-358: Missing.

Show »
Length:438
Mass (Da):48,968
Checksum:i21246312F1640EE2
GO
Isoform C (identifier: Q13163-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     349-358: Missing.
     444-448: QQGPP → LASLPSPSPSV

Note: Incomplete sequence.
Show »
Length:444
Mass (Da):49,497
Checksum:i574D15B06FD49134
GO
Isoform 4 (identifier: Q13163-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-45: MLWLALGPFPAMENQVLVIRIKIPNSGAVDWTVHSGPQLLFRDVL → MMEGHFPQS

Note: No experimental confirmation available.
Show »
Length:412
Mass (Da):46,131
Checksum:i7B00956329FCAEDB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_040823118H → R.1 PublicationCorresponds to variant rs56241934dbSNPEnsembl.1
Natural variantiVAR_040824427A → V.1 Publication1
Natural variantiVAR_046070428A → T.1 PublicationCorresponds to variant rs55811347dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0433331 – 45MLWLA…FRDVL → MMEGHFPQS in isoform 4. 1 PublicationAdd BLAST45
Alternative sequenceiVSP_021825349 – 358Missing in isoform A and isoform C. 2 Publications10
Alternative sequenceiVSP_021826444 – 448QQGPP → LASLPSPSPSV in isoform C. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25265 mRNA. Translation: AAA96146.1.
U71087 mRNA. Translation: AAB16851.1.
U71088 mRNA. Translation: AAB16852.2.
BT006780 mRNA. Translation: AAP35426.1.
AK293459 mRNA. Translation: BAG56954.1.
CR542229 mRNA. Translation: CAG47025.1.
AC009292 Genomic DNA. No translation available.
AC016355 Genomic DNA. No translation available.
AC103753 Genomic DNA. No translation available.
BC008838 mRNA. Translation: AAH08838.1.
CCDSiCCDS10224.1. [Q13163-1]
CCDS42051.1. [Q13163-2]
CCDS55970.1. [Q13163-4]
RefSeqiNP_001193733.1. NM_001206804.1. [Q13163-4]
NP_002748.1. NM_002757.3. [Q13163-2]
NP_660143.1. NM_145160.2. [Q13163-1]
UniGeneiHs.114198.

Genome annotation databases

EnsembliENST00000178640; ENSP00000178640; ENSG00000137764. [Q13163-1]
ENST00000354498; ENSP00000346493; ENSG00000137764. [Q13163-4]
ENST00000395476; ENSP00000378859; ENSG00000137764. [Q13163-2]
GeneIDi5607.
KEGGihsa:5607.
UCSCiuc002aqu.4. human. [Q13163-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U25265 mRNA. Translation: AAA96146.1.
U71087 mRNA. Translation: AAB16851.1.
U71088 mRNA. Translation: AAB16852.2.
BT006780 mRNA. Translation: AAP35426.1.
AK293459 mRNA. Translation: BAG56954.1.
CR542229 mRNA. Translation: CAG47025.1.
AC009292 Genomic DNA. No translation available.
AC016355 Genomic DNA. No translation available.
AC103753 Genomic DNA. No translation available.
BC008838 mRNA. Translation: AAH08838.1.
CCDSiCCDS10224.1. [Q13163-1]
CCDS42051.1. [Q13163-2]
CCDS55970.1. [Q13163-4]
RefSeqiNP_001193733.1. NM_001206804.1. [Q13163-4]
NP_002748.1. NM_002757.3. [Q13163-2]
NP_660143.1. NM_145160.2. [Q13163-1]
UniGeneiHs.114198.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NPTX-ray1.75A/C5-108[»]
2O2VX-ray1.83A5-108[»]
4IC7X-ray2.60B/E16-130[»]
ProteinModelPortaliQ13163.
SMRiQ13163.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111593. 24 interactors.
DIPiDIP-27558N.
IntActiQ13163. 14 interactors.
MINTiMINT-1155433.
STRINGi9606.ENSP00000178640.

Chemistry databases

BindingDBiQ13163.
ChEMBLiCHEMBL4948.
GuidetoPHARMACOLOGYi2066.

PTM databases

iPTMnetiQ13163.
PhosphoSitePlusiQ13163.

Polymorphism and mutation databases

BioMutaiMAP2K5.
DMDMi118572669.

Proteomic databases

EPDiQ13163.
MaxQBiQ13163.
PaxDbiQ13163.
PeptideAtlasiQ13163.
PRIDEiQ13163.

Protocols and materials databases

DNASUi5607.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000178640; ENSP00000178640; ENSG00000137764. [Q13163-1]
ENST00000354498; ENSP00000346493; ENSG00000137764. [Q13163-4]
ENST00000395476; ENSP00000378859; ENSG00000137764. [Q13163-2]
GeneIDi5607.
KEGGihsa:5607.
UCSCiuc002aqu.4. human. [Q13163-1]

Organism-specific databases

CTDi5607.
DisGeNETi5607.
GeneCardsiMAP2K5.
HGNCiHGNC:6845. MAP2K5.
HPAiCAB022094.
HPA027347.
HPA027755.
MIMi602520. gene.
neXtProtiNX_Q13163.
OpenTargetsiENSG00000137764.
PharmGKBiPA30590.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0581. Eukaryota.
ENOG410XQ5A. LUCA.
GeneTreeiENSGT00760000119199.
HOGENOMiHOG000234206.
HOVERGENiHBG108518.
InParanoidiQ13163.
KOiK04463.
OMAiEVVSMWV.
OrthoDBiEOG091G06I7.
PhylomeDBiQ13163.
TreeFamiTF106468.

Enzyme and pathway databases

BioCyciZFISH:HS06391-MONOMER.
BRENDAi2.7.12.2. 2681.
ReactomeiR-HSA-198765. Signalling to ERK5.
SignaLinkiQ13163.
SIGNORiQ13163.

Miscellaneous databases

ChiTaRSiMAP2K5. human.
EvolutionaryTraceiQ13163.
GeneWikiiMAP2K5.
GenomeRNAii5607.
PROiQ13163.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000137764.
CleanExiHS_MAP2K5.
ExpressionAtlasiQ13163. baseline and differential.
GenevisibleiQ13163. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00666. PB1. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMP2K5_HUMAN
AccessioniPrimary (citable) accession number: Q13163
Secondary accession number(s): B4DE43, Q92961, Q92962
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 28, 2006
Last modified: November 30, 2016
This is version 172 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.