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Protein

Mitogen-activated protein kinase 13

Gene

MAPK13

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei54 – 541ATPPROSITE-ProRule annotation
Active sitei150 – 1501Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi31 – 399ATPPROSITE-ProRule annotation

GO - Molecular functioni

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

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • intracellular signal transduction Source: UniProtKB
  • peptidyl-serine phosphorylation Source: BHF-UCL
  • positive regulation of inflammatory response Source: BHF-UCL
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to osmotic stress Source: UniProtKB
  • response to stress Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • vascular endothelial growth factor receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

ATP-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

HGNCiHGNC:6875. MAPK13.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi180 – 1801T → A: Loss of kinase activity. 1 Publication
Mutagenesisi182 – 1821Y → A: Loss of kinase activity. 1 Publication

Organism-specific databases

PharmGKBiPA30620.

Chemistry

ChEMBLiCHEMBL2094115.
GuidetoPHARMACOLOGYi1502.

Polymorphism and mutation databases

BioMutaiMAPK13.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 365365Mitogen-activated protein kinase 13PRO_0000186286Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei47 – 471PhosphoserineCombined sources
Modified residuei180 – 1801Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K71 Publication
Modified residuei182 – 1821Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and MAP2K71 Publication
Modified residuei350 – 3501PhosphoserineCombined sources

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.

PTM databases

iPTMnetiO15264.
PhosphoSiteiO15264.

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.
CleanExiHS_MAPK13.
ExpressionAtlasiO15264. baseline and differential.
GenevisibleiO15264. HS.

Organism-specific databases

HPAiCAB025854.
HPA007667.

Interactioni

Subunit structurei

Interacts with MAPK8IP2.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
FPR1P214623EBI-2116951,EBI-2869495
PRKD1Q151396EBI-2116951,EBI-1181072

Protein-protein interaction databases

BioGridi111589. 17 interactions.
IntActiO15264. 90 interactions.
MINTiMINT-1183220.
STRINGi9606.ENSP00000211287.

Chemistry

BindingDBiO15264.

Structurei

Secondary structure

1
365
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 85Combined sources
Beta strandi9 – 146Combined sources
Beta strandi17 – 226Combined sources
Beta strandi25 – 339Combined sources
Beta strandi35 – 4410Combined sources
Turni45 – 473Combined sources
Beta strandi50 – 567Combined sources
Helixi63 – 7816Combined sources
Beta strandi88 – 914Combined sources
Beta strandi95 – 973Combined sources
Beta strandi104 – 1085Combined sources
Beta strandi111 – 1133Combined sources
Helixi114 – 1174Combined sources
Helixi124 – 14320Combined sources
Helixi153 – 1553Combined sources
Beta strandi156 – 1583Combined sources
Beta strandi164 – 1663Combined sources
Helixi186 – 1883Combined sources
Helixi191 – 1955Combined sources
Turni196 – 1983Combined sources
Helixi204 – 21815Combined sources
Beta strandi222 – 2265Combined sources
Helixi228 – 23912Combined sources
Helixi244 – 2474Combined sources
Helixi253 – 2619Combined sources
Helixi270 – 2734Combined sources
Helixi279 – 28810Combined sources
Turni293 – 2953Combined sources
Helixi299 – 3035Combined sources
Helixi306 – 3083Combined sources
Turni309 – 3113Combined sources
Helixi314 – 3163Combined sources
Helixi327 – 3293Combined sources
Helixi335 – 34713Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3COIX-ray2.09A2-352[»]
4EYJX-ray2.10A1-352[»]
4EYMX-ray2.35A1-352[»]
4MYGX-ray2.59A/B1-352[»]
4YNOX-ray1.70A1-352[»]
ProteinModelPortaliO15264.
SMRiO15264. Positions 15-351.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15264.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 308284Protein kinasePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi180 – 1823TXY

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

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

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01773. P38MAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 142DV → EL in AAC51374 (PubMed:9207191).Curated
Sequence conflicti39 – 391V → W in AAC51374 (PubMed:9207191).Curated
Sequence conflicti56 – 561L → P in AAC51758 (PubMed:9295308).Curated
Sequence conflicti166 – 1661I → V in AAC51758 (PubMed:9295308).Curated
Sequence conflicti224 – 2241K → R in AAC51758 (PubMed:9295308).Curated
Sequence conflicti224 – 2241K → R in AAD23377 (PubMed:10066767).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411S → L.1 Publication
Corresponds to variant rs55776345 [ dbSNP | Ensembl ].
VAR_042267
Natural varianti282 – 2821A → V.1 Publication
Corresponds to variant rs55990045 [ dbSNP | Ensembl ].
VAR_042268
Natural varianti300 – 3001A → T.1 Publication
Corresponds to variant rs41270090 [ dbSNP | Ensembl ].
VAR_042269

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei204 – 25653VDIWS…DKAAK → GQILHPVPATDPQEGFHSAV PTGQPPGCGPAGEDAGARRG QAPDGRAGPHPSL in isoform 2. 1 PublicationVSP_056558Add
BLAST
Alternative sequencei257 – 364108Missing in isoform 2. 1 PublicationVSP_056559Add
BLAST

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. Translation: CAB08438.1.
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

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. Translation: CAB08438.1.
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
EntryMethodResolution (Å)ChainPositionsPDBsum
3COIX-ray2.09A2-352[»]
4EYJX-ray2.10A1-352[»]
4EYMX-ray2.35A1-352[»]
4MYGX-ray2.59A/B1-352[»]
4YNOX-ray1.70A1-352[»]
ProteinModelPortaliO15264.
SMRiO15264. Positions 15-351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111589. 17 interactions.
IntActiO15264. 90 interactions.
MINTiMINT-1183220.
STRINGi9606.ENSP00000211287.

Chemistry

BindingDBiO15264.
ChEMBLiCHEMBL2094115.
GuidetoPHARMACOLOGYi1502.

PTM databases

iPTMnetiO15264.
PhosphoSiteiO15264.

Polymorphism and mutation databases

BioMutaiMAPK13.

Proteomic databases

EPDiO15264.
MaxQBiO15264.
PaxDbiO15264.
PeptideAtlasiO15264.
PRIDEiO15264.

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.
GeneCardsiMAPK13.
HGNCiHGNC:6875. MAPK13.
HPAiCAB025854.
HPA007667.
MIMi602899. gene.
neXtProtiNX_O15264.
PharmGKBiPA30620.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074271.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiO15264.
KOiK04441.
OMAiEHPYFDN.
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.
PROiO15264.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156711.
CleanExiHS_MAPK13.
ExpressionAtlasiO15264. baseline and differential.
GenevisibleiO15264. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01773. P38MAPKINASE.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMK13_HUMAN
AccessioniPrimary (citable) accession number: O15264
Secondary accession number(s): O14739
, O15124, Q5U4A5, Q6FI46, Q9UNU0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: September 7, 2016
This is version 174 of the entry and version 1 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 6
    Human chromosome 6: 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.