UniProtKB - Q8IW41 (MAPK5_HUMAN)
MAP kinase-activated protein kinase 5
MAPKAPK5
Functioni
Caution
Catalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 51 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 148 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 28 – 36 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium-dependent protein serine/threonine kinase activity Source: GO_Central
- calmodulin binding Source: GO_Central
- MAP kinase kinase activity Source: ProtInc
- mitogen-activated protein kinase binding Source: GO_Central
- p53 binding Source: UniProtKB
- protein serine/threonine kinase activity Source: UniProtKB
GO - Biological processi
- intracellular signal transduction Source: GO_Central
- negative regulation of TOR signaling Source: UniProtKB
- peptidyl-serine phosphorylation Source: GO_Central
- positive regulation of telomerase activity Source: BHF-UCL
- positive regulation of telomere capping Source: BHF-UCL
- positive regulation of telomere maintenance via telomerase Source: BHF-UCL
- protein autophosphorylation Source: UniProtKB
- Ras protein signal transduction Source: UniProtKB
- regulation of signal transduction by p53 class mediator Source: Reactome
- regulation of translation Source: UniProtKB
- signal transduction Source: ProtInc
- stress-induced premature senescence Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
PathwayCommonsi | Q8IW41 |
Reactomei | R-HSA-2559580, Oxidative Stress Induced Senescence R-HSA-5687128, MAPK6/MAPK4 signaling R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation |
SignaLinki | Q8IW41 |
SIGNORi | Q8IW41 |
Names & Taxonomyi
Protein namesi | Recommended name: MAP kinase-activated protein kinase 5 (EC:2.7.11.1)Short name: MAPK-activated protein kinase 5 Short name: MAPKAP kinase 5 Short name: MAPKAP-K5 Short name: MAPKAPK-5 Short name: MK-5 Short name: MK5 Alternative name(s): p38-regulated/activated protein kinase Short name: PRAK |
Gene namesi | Name:MAPKAPK5 Synonyms:PRAK |
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
EuPathDBi | HostDB:ENSG00000089022.13 |
HGNCi | HGNC:6889, MAPKAPK5 |
MIMi | 606723, gene |
neXtProti | NX_Q8IW41 |
Subcellular locationi
Nucleus
Other locations
Note: Translocates to the cytoplasm following phosphorylation and activation. Interaction with ERK3/MAPK6 or ERK4/MAPK4 and phosphorylation at Thr-182, activates the protein kinase activity, followed by translocation to the cytoplasm. Phosphorylation by PKA/PRKACA at Ser-115 also induces nuclear export.
Cytosol
- cytosol Source: HPA
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 51 | K → M: Kinase defective mutant, abolishes activity. 1 Publication | 1 | |
Mutagenesisi | 182 | T → A: No p38-beta/MAPK11-induced activation. 3 Publications | 1 | |
Mutagenesisi | 182 | T → D: Mimicks phosphorylation state and induces constitutive protein kinase activity. 3 Publications | 1 | |
Mutagenesisi | 212 | S → D: Mimicks phosphorylation state and displays a slightly higher protein kinase activity. 1 Publication | 1 | |
Mutagenesisi | 337 | L → G: Induces constitutive protein kinase activity. 1 Publication | 1 |
Keywords - Diseasei
Tumor suppressorOrganism-specific databases
DisGeNETi | 8550 |
OpenTargetsi | ENSG00000089022 |
PharmGKBi | PA30633 |
Miscellaneous databases
Pharosi | Q8IW41, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3094 |
DrugBanki | DB12010, Fostamatinib |
GuidetoPHARMACOLOGYi | 2096 |
Polymorphism and mutation databases
BioMutai | MAPKAPK5 |
DMDMi | 52000829 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086296 | 1 – 473 | MAP kinase-activated protein kinase 5Add BLAST | 473 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 115 | Phosphoserine; by PKABy similarity | 1 | |
Modified residuei | 182 | Phosphothreonine; by MAPK11, MAPK14, MAPK4, MAPK6 and PKACombined sources1 Publication | 1 | |
Modified residuei | 212 | Phosphoserine1 Publication | 1 | |
Modified residuei | 354 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q8IW41 |
jPOSTi | Q8IW41 |
MassIVEi | Q8IW41 |
MaxQBi | Q8IW41 |
PaxDbi | Q8IW41 |
PeptideAtlasi | Q8IW41 |
PRIDEi | Q8IW41 |
ProteomicsDBi | 70805 [Q8IW41-1] 70806 [Q8IW41-2] |
PTM databases
iPTMneti | Q8IW41 |
PhosphoSitePlusi | Q8IW41 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000089022, Expressed in corpus callosum and 220 other tissues |
ExpressionAtlasi | Q8IW41, baseline and differential |
Genevisiblei | Q8IW41, HS |
Organism-specific databases
HPAi | ENSG00000089022, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with ERK3/MAPK6 and ERK4/MAPK4 (via FRIEDE motif); the interaction is direct (By similarity).
Interacts with YWHAE; the interaction prevents phosphorylation of HSP27/HSPB1 leading to disrupt F-actin polymerization.
Interacts with SQSTM1.
By similarity2 PublicationsBinary interactionsi
Hide detailsQ8IW41
With | #Exp. | IntAct |
---|---|---|
AGER [Q15109] | 6 | EBI-1201460,EBI-1646426 |
HSPB1 [P04792] | 2 | EBI-1201460,EBI-352682 |
MAPK6 [Q16659] | 7 | EBI-1201460,EBI-1384105 |
TP53 [P04637] | 2 | EBI-1201460,EBI-366083 |
Isoform 2 [Q8IW41-2]
With | #Exp. | IntAct |
---|---|---|
MAPK6 [Q16659] | 6 | EBI-11958803,EBI-1384105 |
GO - Molecular functioni
- calmodulin binding Source: GO_Central
- mitogen-activated protein kinase binding Source: GO_Central
- p53 binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 114120, 24 interactors |
CORUMi | Q8IW41 |
IntActi | Q8IW41, 21 interactors |
MINTi | Q8IW41 |
STRINGi | 9606.ENSP00000449381 |
Chemistry databases
BindingDBi | Q8IW41 |
Miscellaneous databases
RNActi | Q8IW41, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 22 – 304 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 283 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 409 – 440 | Sequence analysisAdd BLAST | 32 |
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0604, Eukaryota |
GeneTreei | ENSGT00940000154089 |
HOGENOMi | CLU_000288_63_0_1 |
InParanoidi | Q8IW41 |
OMAi | GFFIHDP |
OrthoDBi | 843707at2759 |
PhylomeDBi | Q8IW41 |
TreeFami | TF312891 |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom 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 PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 3 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
MSEESDMDKA IKETSILEEY SINWTQKLGA GISGPVRVCV KKSTQERFAL
60 70 80 90 100
KILLDRPKAR NEVRLHMMCA THPNIVQIIE VFANSVQFPH ESSPRARLLI
110 120 130 140 150
VMEMMEGGEL FHRISQHRHF TEKQASQVTK QIALALRHCH LLNIAHRDLK
160 170 180 190 200
PENLLFKDNS LDAPVKLCDF GFAKIDQGDL MTPQFTPYYV APQVLEAQRR
210 220 230 240 250
HQKEKSGIIP TSPTPYTYNK SCDLWSLGVI IYVMLCGYPP FYSKHHSRTI
260 270 280 290 300
PKDMRRKIMT GSFEFPEEEW SQISEMAKDV VRKLLKVKPE ERLTIEGVLD
310 320 330 340 350
HPWLNSTEAL DNVLPSAQLM MDKAVVAGIQ QAHAEQLANM RIQDLKVSLK
360 370 380 390 400
PLHSVNNPIL RKRKLLGTKP KDSVYIHDHE NGAEDSNVAL EKLRDVIAQC
410 420 430 440 450
ILPQAGKGEN EDEKLNEVMQ EAWKYNRECK LLRDTLQSFS WNGRGFTDKV
460 470
DRLKLAEIVK QVIEEQTTSH ESQ
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketR4GN33 | R4GN33_HUMAN | MAP kinase-activated protein kinase... | MAPKAPK5 | 324 | Annotation score: | ||
F8VRP2 | F8VRP2_HUMAN | MAP kinase-activated protein kinase... | MAPKAPK5 | 74 | Annotation score: | ||
R4GN93 | R4GN93_HUMAN | MAP kinase-activated protein kinase... | MAPKAPK5 | 51 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 273 | I → T in CAB53747 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 291 | E → R in AAC39863 (PubMed:9628874).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_040758 | 67 | M → I1 PublicationCorresponds to variant dbSNP:rs34132040Ensembl. | 1 | |
Natural variantiVAR_040759 | 282 | R → K1 PublicationCorresponds to variant dbSNP:rs34843470Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_011597 | 407 – 408 | Missing in isoform 2. 3 Publications | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF032437 Genomic DNA Translation: AAC39863.1 AK122767 mRNA Translation: BAG53717.1 CH471054 Genomic DNA Translation: EAW97981.1 BC000833 mRNA Translation: AAH00833.1 BC041049 mRNA Translation: AAH41049.1 BC047284 mRNA Translation: AAH47284.2 AL110301 mRNA Translation: CAB53747.1 |
CCDSi | CCDS44975.1 [Q8IW41-1] CCDS44976.1 [Q8IW41-2] |
PIRi | T34519 |
RefSeqi | NP_003659.2, NM_003668.3 [Q8IW41-2] NP_620777.1, NM_139078.2 [Q8IW41-1] |
Genome annotation databases
Ensembli | ENST00000550735; ENSP00000449667; ENSG00000089022 [Q8IW41-2] ENST00000551404; ENSP00000449381; ENSG00000089022 [Q8IW41-1] |
GeneIDi | 8550 |
KEGGi | hsa:8550 |
UCSCi | uc001tta.5, human [Q8IW41-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF032437 Genomic DNA Translation: AAC39863.1 AK122767 mRNA Translation: BAG53717.1 CH471054 Genomic DNA Translation: EAW97981.1 BC000833 mRNA Translation: AAH00833.1 BC041049 mRNA Translation: AAH41049.1 BC047284 mRNA Translation: AAH47284.2 AL110301 mRNA Translation: CAB53747.1 |
CCDSi | CCDS44975.1 [Q8IW41-1] CCDS44976.1 [Q8IW41-2] |
PIRi | T34519 |
RefSeqi | NP_003659.2, NM_003668.3 [Q8IW41-2] NP_620777.1, NM_139078.2 [Q8IW41-1] |
3D structure databases
SMRi | Q8IW41 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114120, 24 interactors |
CORUMi | Q8IW41 |
IntActi | Q8IW41, 21 interactors |
MINTi | Q8IW41 |
STRINGi | 9606.ENSP00000449381 |
Chemistry databases
BindingDBi | Q8IW41 |
ChEMBLi | CHEMBL3094 |
DrugBanki | DB12010, Fostamatinib |
GuidetoPHARMACOLOGYi | 2096 |
PTM databases
iPTMneti | Q8IW41 |
PhosphoSitePlusi | Q8IW41 |
Polymorphism and mutation databases
BioMutai | MAPKAPK5 |
DMDMi | 52000829 |
Proteomic databases
EPDi | Q8IW41 |
jPOSTi | Q8IW41 |
MassIVEi | Q8IW41 |
MaxQBi | Q8IW41 |
PaxDbi | Q8IW41 |
PeptideAtlasi | Q8IW41 |
PRIDEi | Q8IW41 |
ProteomicsDBi | 70805 [Q8IW41-1] 70806 [Q8IW41-2] |
Protocols and materials databases
Antibodypediai | 3873, 602 antibodies |
DNASUi | 8550 |
Genome annotation databases
Ensembli | ENST00000550735; ENSP00000449667; ENSG00000089022 [Q8IW41-2] ENST00000551404; ENSP00000449381; ENSG00000089022 [Q8IW41-1] |
GeneIDi | 8550 |
KEGGi | hsa:8550 |
UCSCi | uc001tta.5, human [Q8IW41-1] |
Organism-specific databases
CTDi | 8550 |
DisGeNETi | 8550 |
EuPathDBi | HostDB:ENSG00000089022.13 |
GeneCardsi | MAPKAPK5 |
HGNCi | HGNC:6889, MAPKAPK5 |
HPAi | ENSG00000089022, Low tissue specificity |
MIMi | 606723, gene |
neXtProti | NX_Q8IW41 |
OpenTargetsi | ENSG00000089022 |
PharmGKBi | PA30633 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0604, Eukaryota |
GeneTreei | ENSGT00940000154089 |
HOGENOMi | CLU_000288_63_0_1 |
InParanoidi | Q8IW41 |
OMAi | GFFIHDP |
OrthoDBi | 843707at2759 |
PhylomeDBi | Q8IW41 |
TreeFami | TF312891 |
Enzyme and pathway databases
PathwayCommonsi | Q8IW41 |
Reactomei | R-HSA-2559580, Oxidative Stress Induced Senescence R-HSA-5687128, MAPK6/MAPK4 signaling R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation |
SignaLinki | Q8IW41 |
SIGNORi | Q8IW41 |
Miscellaneous databases
BioGRID-ORCSi | 8550, 14 hits in 878 CRISPR screens |
ChiTaRSi | MAPKAPK5, human |
GeneWikii | MAPKAPK5 |
GenomeRNAii | 8550 |
Pharosi | Q8IW41, Tchem |
PROi | PR:Q8IW41 |
RNActi | Q8IW41, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000089022, Expressed in corpus callosum and 220 other tissues |
ExpressionAtlasi | Q8IW41, baseline and differential |
Genevisiblei | Q8IW41, HS |
Family and domain databases
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom 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 PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MAPK5_HUMAN | |
Accessioni | Q8IW41Primary (citable) accession number: Q8IW41 Secondary accession number(s): B3KVA5 Q9UG86 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 13, 2004 |
Last sequence update: | September 13, 2004 | |
Last modified: | December 2, 2020 | |
This is version 174 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
Reference proteomeDocuments
- 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 - SIMILARITY comments
Index of protein domains and families - Human chromosome 12
Human chromosome 12: 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