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Protein

Dual specificity mitogen-activated protein kinase kinase 5

Gene

MAP2K5

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

Caution

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

Keywordsi

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

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000137764.19
HGNCiHGNC:6845 MAP2K5
MIMi602520 gene
neXtProtiNX_Q13163

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

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

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

Show more details

Protein-protein interaction databases

BioGridi11159324 interactors.
CORUMiQ13163
DIPiDIP-27558N
IntActiQ13163 18 interactors.
MINTiQ13163
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

Phylogenomic databases

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

Family and domain databases

CDDicd06395 PB1_Map2k5, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000270 PB1_dom
IPR034851 PB1_MAP2K5
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00564 PB1, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00666 PB1, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51745 PB1, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

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 → R1 PublicationCorresponds to variant dbSNP:rs56241934Ensembl.1
Natural variantiVAR_040824427A → V1 Publication1
Natural variantiVAR_046070428A → T1 PublicationCorresponds to variant dbSNP:rs55811347Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiMP2K5_HUMAN
AccessioniPrimary (citable) accession number: Q13163
Secondary accession number(s): B4DE43, Q92961, Q92962
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 28, 2006
Last modified: March 28, 2018
This is version 183 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

3D-structure, Complete proteome, Reference proteome