UniProtKB - Q13163 (MP2K5_HUMAN)
Dual specificity mitogen-activated protein kinase kinase 5
MAP2K5
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 PublicationsCatalytic activityi
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 195 | ATP | 1 | |
Active sitei | 283 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 172 – 180 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- MAP kinase kinase activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
- protein kinase activity Source: ProtInc
- protein serine/threonine kinase activity Source: UniProtKB-KW
- protein serine kinase activity Source: RHEA
- protein tyrosine kinase activity Source: UniProtKB-KW
GO - Biological processi
- 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
- MAPK cascade Source: GO_Central
- 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 production 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 by RNA polymerase II Source: BHF-UCL
- positive regulation of cell growth Source: Ensembl
- positive regulation of epithelial cell proliferation Source: Ensembl
- positive regulation of MAP kinase activity Source: BHF-UCL
- positive regulation of protein metabolic process Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- signal transduction Source: ProtInc
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase, Tyrosine-protein kinase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.12.2, 2681 |
PathwayCommonsi | Q13163 |
Reactomei | R-HSA-198765, Signalling to ERK5 |
SignaLinki | Q13163 |
SIGNORi | Q13163 |
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 |
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:6845, MAP2K5 |
MIMi | 602520, gene |
neXtProti | NX_Q13163 |
VEuPathDBi | HostDB:ENSG00000137764 |
Subcellular locationi
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 195 | K → M: Inactivation. 1 Publication | 1 | |
Mutagenesisi | 311 | S → A: Inactivation. 1 Publication | 1 | |
Mutagenesisi | 315 | T → A: Inactivation. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 5607 |
OpenTargetsi | ENSG00000137764 |
PharmGKBi | PA30590 |
Miscellaneous databases
Pharosi | Q13163, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4948 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q13163 |
GuidetoPHARMACOLOGYi | 2066 |
Genetic variation databases
BioMutai | MAP2K5 |
DMDMi | 118572669 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086383 | 1 – 448 | Dual specificity mitogen-activated protein kinase kinase 5Add BLAST | 448 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 311 | PhosphoserineCombined sources1 Publication | 1 | |
Modified residuei | 315 | Phosphothreonine1 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
CPTACi | CPTAC-818 CPTAC-819 |
EPDi | Q13163 |
jPOSTi | Q13163 |
MassIVEi | Q13163 |
MaxQBi | Q13163 |
PaxDbi | Q13163 |
PeptideAtlasi | Q13163 |
PRIDEi | Q13163 |
ProteomicsDBi | 59199 [Q13163-1] 59200 [Q13163-2] 59201 [Q13163-3] 59202 [Q13163-4] |
PTM databases
iPTMneti | Q13163 |
PhosphoSitePlusi | Q13163 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000137764, Expressed in frontal cortex and 230 other tissues |
ExpressionAtlasi | Q13163, baseline and differential |
Genevisiblei | Q13163, HS |
Organism-specific databases
HPAi | ENSG00000137764, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with PARD6A, MAP3K3 and MAPK7.
Forms a complex with SQSTM1 and PRKCZ or PRKCI (By similarity).
By similarity3 Publications(Microbial infection) Interacts with Yersinia YopJ.
1 PublicationBinary interactionsi
Q13163
Protein-protein interaction databases
BioGRIDi | 111593, 99 interactors |
CORUMi | Q13163 |
DIPi | DIP-27558N |
IntActi | Q13163, 54 interactors |
MINTi | Q13163 |
STRINGi | 9606.ENSP00000178640 |
Chemistry databases
BindingDBi | Q13163 |
Miscellaneous databases
RNActi | Q13163, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q13163 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q13163 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 18 – 109 | PB1PROSITE-ProRule annotationAdd BLAST | 92 | |
Domaini | 166 – 409 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 244 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 18 – 25 | Interaction with MAPK7By similarity | 8 | |
Regioni | 64 – 68 | Interaction with MAP3K2/MAP3K3By similarity | 5 | |
Regioni | 116 – 144 | DisorderedSequence analysisAdd BLAST | 29 | |
Regioni | 117 – 131 | Interaction with MAPK7By similarityAdd BLAST | 15 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 123 – 144 | Polar residuesSequence analysisAdd BLAST | 22 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0581, Eukaryota |
GeneTreei | ENSGT00940000157505 |
HOGENOMi | CLU_000288_2_0_1 |
InParanoidi | Q13163 |
OMAi | LQIFPRX |
OrthoDBi | 81952at2759 |
PhylomeDBi | Q13163 |
TreeFami | TF106468 |
Family and domain databases
CDDi | cd06395, PB1_Map2k5, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00564, PB1, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00666, PB1, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 4 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
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH7BZL1 | H7BZL1_HUMAN | Dual-specificity mitogen-activated ... | MAP2K5 | 128 | Annotation score: | ||
A0A087WWX7 | A0A087WWX7_HUMAN | Dual-specificity mitogen-activated ... | MAP2K5 | 182 | Annotation score: | ||
A6NK28 | A6NK28_HUMAN | Dual-specificity mitogen-activated ... | MAP2K5 | 258 | Annotation score: | ||
A0A087X0Z8 | A0A087X0Z8_HUMAN | Dual-specificity mitogen-activated ... | MAP2K5 | 49 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040823 | 118 | H → R1 PublicationCorresponds to variant dbSNP:rs56241934Ensembl. | 1 | |
Natural variantiVAR_040824 | 427 | A → V1 PublicationCorresponds to variant dbSNP:rs1226964455Ensembl. | 1 | |
Natural variantiVAR_046070 | 428 | A → T1 PublicationCorresponds to variant dbSNP:rs55811347Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_043333 | 1 – 45 | MLWLA…FRDVL → MMEGHFPQS in isoform 4. 1 PublicationAdd BLAST | 45 | |
Alternative sequenceiVSP_021825 | 349 – 358 | Missing in isoform A and isoform C. 2 Publications | 10 | |
Alternative sequenceiVSP_021826 | 444 – 448 | QQGPP → LASLPSPSPSV in isoform C. 1 Publication | 5 |
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 |
CCDSi | CCDS10224.1 [Q13163-1] CCDS42051.1 [Q13163-2] CCDS55970.1 [Q13163-4] |
RefSeqi | NP_001193733.1, NM_001206804.1 [Q13163-4] NP_002748.1, NM_002757.3 [Q13163-2] NP_660143.1, NM_145160.2 [Q13163-1] |
Genome annotation databases
Ensembli | ENST00000178640; ENSP00000178640; ENSG00000137764 ENST00000354498; ENSP00000346493; ENSG00000137764 [Q13163-4] ENST00000395476; ENSP00000378859; ENSG00000137764 [Q13163-2] |
GeneIDi | 5607 |
KEGGi | hsa:5607 |
MANE-Selecti | ENST00000178640.10; ENSP00000178640.5; NM_145160.3; NP_660143.1 |
UCSCi | uc002aqu.4, human [Q13163-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS10224.1 [Q13163-1] CCDS42051.1 [Q13163-2] CCDS55970.1 [Q13163-4] |
RefSeqi | NP_001193733.1, NM_001206804.1 [Q13163-4] NP_002748.1, NM_002757.3 [Q13163-2] NP_660143.1, NM_145160.2 [Q13163-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2NPT | X-ray | 1.75 | A/C | 5-108 | [»] | |
2O2V | X-ray | 1.83 | A | 5-108 | [»] | |
4IC7 | X-ray | 2.60 | B/E | 16-130 | [»] | |
SMRi | Q13163 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 111593, 99 interactors |
CORUMi | Q13163 |
DIPi | DIP-27558N |
IntActi | Q13163, 54 interactors |
MINTi | Q13163 |
STRINGi | 9606.ENSP00000178640 |
Chemistry databases
BindingDBi | Q13163 |
ChEMBLi | CHEMBL4948 |
DrugBanki | DB12010, Fostamatinib |
DrugCentrali | Q13163 |
GuidetoPHARMACOLOGYi | 2066 |
PTM databases
iPTMneti | Q13163 |
PhosphoSitePlusi | Q13163 |
Genetic variation databases
BioMutai | MAP2K5 |
DMDMi | 118572669 |
Proteomic databases
CPTACi | CPTAC-818 CPTAC-819 |
EPDi | Q13163 |
jPOSTi | Q13163 |
MassIVEi | Q13163 |
MaxQBi | Q13163 |
PaxDbi | Q13163 |
PeptideAtlasi | Q13163 |
PRIDEi | Q13163 |
ProteomicsDBi | 59199 [Q13163-1] 59200 [Q13163-2] 59201 [Q13163-3] 59202 [Q13163-4] |
Protocols and materials databases
Antibodypediai | 26267, 601 antibodies from 37 providers |
DNASUi | 5607 |
Genome annotation databases
Ensembli | ENST00000178640; ENSP00000178640; ENSG00000137764 ENST00000354498; ENSP00000346493; ENSG00000137764 [Q13163-4] ENST00000395476; ENSP00000378859; ENSG00000137764 [Q13163-2] |
GeneIDi | 5607 |
KEGGi | hsa:5607 |
MANE-Selecti | ENST00000178640.10; ENSP00000178640.5; NM_145160.3; NP_660143.1 |
UCSCi | uc002aqu.4, human [Q13163-1] |
Organism-specific databases
CTDi | 5607 |
DisGeNETi | 5607 |
GeneCardsi | MAP2K5 |
HGNCi | HGNC:6845, MAP2K5 |
HPAi | ENSG00000137764, Low tissue specificity |
MIMi | 602520, gene |
neXtProti | NX_Q13163 |
OpenTargetsi | ENSG00000137764 |
PharmGKBi | PA30590 |
VEuPathDBi | HostDB:ENSG00000137764 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0581, Eukaryota |
GeneTreei | ENSGT00940000157505 |
HOGENOMi | CLU_000288_2_0_1 |
InParanoidi | Q13163 |
OMAi | LQIFPRX |
OrthoDBi | 81952at2759 |
PhylomeDBi | Q13163 |
TreeFami | TF106468 |
Enzyme and pathway databases
BRENDAi | 2.7.12.2, 2681 |
PathwayCommonsi | Q13163 |
Reactomei | R-HSA-198765, Signalling to ERK5 |
SignaLinki | Q13163 |
SIGNORi | Q13163 |
Miscellaneous databases
BioGRID-ORCSi | 5607, 13 hits in 1079 CRISPR screens |
ChiTaRSi | MAP2K5, human |
EvolutionaryTracei | Q13163 |
GeneWikii | MAP2K5 |
GenomeRNAii | 5607 |
Pharosi | Q13163, Tchem |
PROi | PR:Q13163 |
RNActi | Q13163, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000137764, Expressed in frontal cortex and 230 other tissues |
ExpressionAtlasi | Q13163, baseline and differential |
Genevisiblei | Q13163, HS |
Family and domain databases
CDDi | cd06395, PB1_Map2k5, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00564, PB1, 1 hit PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00666, PB1, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | MP2K5_HUMAN | |
Accessioni | Q13163Primary (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: | February 23, 2022 | |
This is version 209 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
3D-structure, Reference proteomeDocuments
- Human and mouse protein kinases
Human and mouse protein kinases: classification and index - Human chromosome 15
Human chromosome 15: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families