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Protein

Mitogen-activated protein kinase 13

Gene

MAPK13

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

Functioni

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Activity regulationi

Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei54ATPPROSITE-ProRule annotation1
Active sitei150Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 39ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • MAP kinase activity Source: UniProtKB
  • protein serine/threonine kinase activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Stress response, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-171007 p38MAPK events
R-HSA-376172 DSCAM interactions
R-HSA-4420097 VEGFA-VEGFR2 Pathway
SignaLinkiO15264
SIGNORiO15264

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 13 (EC:2.7.11.24)
Short name:
MAP kinase 13
Short name:
MAPK 13
Alternative name(s):
Mitogen-activated protein kinase p38 delta
Short name:
MAP kinase p38 delta
Stress-activated protein kinase 4
Gene namesi
Name:MAPK13
Synonyms:PRKM13, SAPK4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000156711.16
HGNCiHGNC:6875 MAPK13
MIMi602899 gene
neXtProtiNX_O15264

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
Mutagenesisi180T → A: Loss of kinase activity. 1 Publication1
Mutagenesisi182Y → A: Loss of kinase activity. 1 Publication1

Organism-specific databases

DisGeNETi5603
OpenTargetsiENSG00000156711
PharmGKBiPA30620

Chemistry databases

ChEMBLiCHEMBL2939
DrugBankiDB05157 KC706
GuidetoPHARMACOLOGYi1502

Polymorphism and mutation databases

BioMutaiMAPK13

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001862861 – 365Mitogen-activated protein kinase 13Add BLAST365

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei47PhosphoserineCombined sources1
Modified residuei180Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K71 Publication1
Modified residuei182Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K71 Publication1
Modified residuei350PhosphoserineCombined sources1

Post-translational modificationi

Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO15264
MaxQBiO15264
PaxDbiO15264
PeptideAtlasiO15264
PRIDEiO15264
ProteomicsDBi48552

PTM databases

iPTMnetiO15264
PhosphoSitePlusiO15264

Expressioni

Tissue specificityi

Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells.2 Publications

Gene expression databases

BgeeiENSG00000156711 Expressed in 187 organ(s), highest expression level in left adrenal gland
CleanExiHS_MAPK13
ExpressionAtlasiO15264 baseline and differential
GenevisibleiO15264 HS

Organism-specific databases

HPAiCAB025854
HPA007667

Interactioni

Subunit structurei

Interacts with MAPK8IP2.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi111589, 17 interactors
IntActiO15264, 90 interactors
MINTiO15264
STRINGi9606.ENSP00000211287

Chemistry databases

BindingDBiO15264

Structurei

Secondary structure

1365
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO15264
SMRiO15264
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15264

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 308Protein kinasePROSITE-ProRule annotationAdd BLAST284

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi180 – 182TXY3

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00550000074271
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiO15264
KOiK04441
OMAiWELPRRY
OrthoDBiEOG091G08QL
PhylomeDBiO15264
TreeFamiTF105100

Family and domain databases

CDDicd07879 STKc_p38delta, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008352 MAPK_p38-like
IPR038785 p38delta
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01773 P38MAPKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O15264-1) [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
MSLIRKKGFY KQDVNKTAWE LPKTYVSPTH VGSGAYGSVC SAIDKRSGEK
60 70 80 90 100
VAIKKLSRPF QSEIFAKRAY RELLLLKHMQ HENVIGLLDV FTPASSLRNF
110 120 130 140 150
YDFYLVMPFM QTDLQKIMGM EFSEEKIQYL VYQMLKGLKY IHSAGVVHRD
160 170 180 190 200
LKPGNLAVNE DCELKILDFG LARHADAEMT GYVVTRWYRA PEVILSWMHY
210 220 230 240 250
NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG VPGTEFVQKL
260 270 280 290 300
NDKAAKSYIQ SLPQTPRKDF TQLFPRASPQ AADLLEKMLE LDVDKRLTAA
310 320 330 340 350
QALTHPFFEP FRDPEEETEA QQPFDDSLEH EKLTVDEWKQ HIYKEIVNFS
360
PIARKDSRRR SGMKL
Length:365
Mass (Da):42,090
Last modified:January 1, 1998 - v1
Checksum:i52E749EDB2973DDF
GO
Isoform 2 (identifier: O15264-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     204-256: VDIWSVGCIM...VQKLNDKAAK → GQILHPVPAT...DGRAGPHPSL
     257-364: Missing.

Note: No experimental confirmation available.
Show »
Length:257
Mass (Da):28,779
Checksum:iBDCA13CF80344118
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5R3E6Q5R3E6_HUMAN
Mitogen-activated protein kinase 13
MAPK13
152Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13 – 14DV → EL in AAC51374 (PubMed:9207191).Curated2
Sequence conflicti39V → W in AAC51374 (PubMed:9207191).Curated1
Sequence conflicti56L → P in AAC51758 (PubMed:9295308).Curated1
Sequence conflicti166I → V in AAC51758 (PubMed:9295308).Curated1
Sequence conflicti224K → R in AAC51758 (PubMed:9295308).Curated1
Sequence conflicti224K → R in AAD23377 (PubMed:10066767).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04226741S → L1 PublicationCorresponds to variant dbSNP:rs55776345Ensembl.1
Natural variantiVAR_042268282A → V1 PublicationCorresponds to variant dbSNP:rs55990045Ensembl.1
Natural variantiVAR_042269300A → T1 PublicationCorresponds to variant dbSNP:rs41270090Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056558204 – 256VDIWS…DKAAK → GQILHPVPATDPQEGFHSAV PTGQPPGCGPAGEDAGARRG QAPDGRAGPHPSL in isoform 2. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_056559257 – 364Missing in isoform 2. 1 PublicationAdd BLAST108

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10488 mRNA Translation: CAA71512.1
U93232 mRNA Translation: AAB87639.1
AF015256 mRNA Translation: AAC51758.1
AF004709 mRNA Translation: AAC51374.1
AF092535 mRNA Translation: AAD23377.1
AF100546 mRNA Translation: AAF36772.1
BT007221 mRNA Translation: AAP35885.1
CR536490 mRNA Translation: CAG38729.1
Z95152 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03874.1
CH471081 Genomic DNA Translation: EAX03875.1
BC000433 mRNA Translation: AAH00433.1
BC001641 mRNA Translation: AAH01641.1
BC004428 mRNA Translation: AAH04428.1
BC085196 mRNA Translation: AAH85196.1
CCDSiCCDS4818.1 [O15264-1]
PIRiJC5528
RefSeqiNP_002745.1, NM_002754.4 [O15264-1]
UniGeneiHs.178695

Genome annotation databases

EnsembliENST00000211287; ENSP00000211287; ENSG00000156711 [O15264-1]
ENST00000373766; ENSP00000362871; ENSG00000156711 [O15264-2]
GeneIDi5603
KEGGihsa:5603
UCSCiuc003ols.5 human [O15264-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y10488 mRNA Translation: CAA71512.1
U93232 mRNA Translation: AAB87639.1
AF015256 mRNA Translation: AAC51758.1
AF004709 mRNA Translation: AAC51374.1
AF092535 mRNA Translation: AAD23377.1
AF100546 mRNA Translation: AAF36772.1
BT007221 mRNA Translation: AAP35885.1
CR536490 mRNA Translation: CAG38729.1
Z95152 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03874.1
CH471081 Genomic DNA Translation: EAX03875.1
BC000433 mRNA Translation: AAH00433.1
BC001641 mRNA Translation: AAH01641.1
BC004428 mRNA Translation: AAH04428.1
BC085196 mRNA Translation: AAH85196.1
CCDSiCCDS4818.1 [O15264-1]
PIRiJC5528
RefSeqiNP_002745.1, NM_002754.4 [O15264-1]
UniGeneiHs.178695

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3COIX-ray2.09A2-352[»]
4EYJX-ray2.10A1-352[»]
4EYMX-ray2.35A1-352[»]
4MYGX-ray2.59A/B1-352[»]
4YNOX-ray1.70A1-352[»]
5EKNX-ray2.59A1-352[»]
5EKOX-ray2.00A1-352[»]
ProteinModelPortaliO15264
SMRiO15264
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111589, 17 interactors
IntActiO15264, 90 interactors
MINTiO15264
STRINGi9606.ENSP00000211287

Chemistry databases

BindingDBiO15264
ChEMBLiCHEMBL2939
DrugBankiDB05157 KC706
GuidetoPHARMACOLOGYi1502

PTM databases

iPTMnetiO15264
PhosphoSitePlusiO15264

Polymorphism and mutation databases

BioMutaiMAPK13

Proteomic databases

EPDiO15264
MaxQBiO15264
PaxDbiO15264
PeptideAtlasiO15264
PRIDEiO15264
ProteomicsDBi48552

Protocols and materials databases

DNASUi5603
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000211287; ENSP00000211287; ENSG00000156711 [O15264-1]
ENST00000373766; ENSP00000362871; ENSG00000156711 [O15264-2]
GeneIDi5603
KEGGihsa:5603
UCSCiuc003ols.5 human [O15264-1]

Organism-specific databases

CTDi5603
DisGeNETi5603
EuPathDBiHostDB:ENSG00000156711.16
GeneCardsiMAPK13
HGNCiHGNC:6875 MAPK13
HPAiCAB025854
HPA007667
MIMi602899 gene
neXtProtiNX_O15264
OpenTargetsiENSG00000156711
PharmGKBiPA30620
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00550000074271
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiO15264
KOiK04441
OMAiWELPRRY
OrthoDBiEOG091G08QL
PhylomeDBiO15264
TreeFamiTF105100

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-168638 NOD1/2 Signaling Pathway
R-HSA-171007 p38MAPK events
R-HSA-376172 DSCAM interactions
R-HSA-4420097 VEGFA-VEGFR2 Pathway
SignaLinkiO15264
SIGNORiO15264

Miscellaneous databases

EvolutionaryTraceiO15264
GeneWikiiMAPK13
GenomeRNAii5603
PROiPR:O15264
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156711 Expressed in 187 organ(s), highest expression level in left adrenal gland
CleanExiHS_MAPK13
ExpressionAtlasiO15264 baseline and differential
GenevisibleiO15264 HS

Family and domain databases

CDDicd07879 STKc_p38delta, 1 hit
InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008352 MAPK_p38-like
IPR038785 p38delta
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01773 P38MAPKINASE
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMK13_HUMAN
AccessioniPrimary (citable) accession number: O15264
Secondary accession number(s): O14739
, O15124, Q5U4A5, Q6FI46, Q9UNU0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: November 7, 2018
This is version 187 of the entry and version 1 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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 chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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