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Reviewed, UniProtKB/Swiss-Prot O15264 (MK13_HUMAN)

Last modified February 9, 2010. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Mitogen-activated protein kinase 13
      Short name=MAP kinase 13
      Short name=MAPK 13
    EC=2.7.11.24
Alternative name(s):
    Stress-activated protein kinase 4
    Mitogen-activated protein kinase p38 delta
      Short name=MAP kinase p38 delta
Gene names
Name: MAPK13
Synonyms: PRKM13, SAPK4
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length365 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating downstream targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Ref.13

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated by phosphorylation on threonine and tyrosine by either of two dual specificity kinases, MAP2K3 and MAP2K6. Ref.13 Ref.1 Ref.2

Tissue specificity

Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells. Ref.2 Ref.12

Domain

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

Post-translational modification

Dually phosphorylated on Thr-180 and Tyr-182, which activates the enzyme. Ref.2 Ref.14 Ref.15

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ATF2P153361EBI-2116951,EBI-1170906
Pkd1Q9ERV01EBI-2116951,EBI-2255297From a different organism.
PRKD1Q151392EBI-2116951,EBI-1181072

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 365365Mitogen-activated protein kinase 13
PRO_0000186286

Regions

Domain25 – 308284Protein kinase
Nucleotide binding31 – 399ATP By similarity
Motif180 – 1823TXY

Sites

Active site1501Proton acceptor By similarity
Binding site541ATP By similarity

Amino acid modifications

Modified residue471Phosphoserine Ref.15
Modified residue1801Phosphothreonine Ref.2
Modified residue1821Phosphotyrosine Ref.2 Ref.14
Modified residue3501Phosphoserine

Natural variations

Natural variant411S → L: dbSNP rs55776345. Ref.17
VAR_042267
Natural variant2821A → V: dbSNP rs55990045. Ref.17
VAR_042268
Natural variant3001A → T: dbSNP rs41270090. Ref.17
VAR_042269

Experimental info

Mutagenesis1801T → A: Loss of kinase activity. Ref.2
Mutagenesis1821Y → A: Loss of kinase activity. Ref.2
Sequence conflict13 – 142DV → EL in AAC51374. Ref.4
Sequence conflict391V → W in AAC51374. Ref.4
Sequence conflict561L → P in AAC51758. Ref.3
Sequence conflict1661I → V in AAC51758. Ref.3
Sequence conflict2241K → R Ref.3
Sequence conflict2241K → R Ref.5

Secondary structure

............................................................. 365
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O15264-1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 52E749EDB2973DDF

FASTA36542,090
        10         20         30         40         50         60 
MSLIRKKGFY KQDVNKTAWE LPKTYVSPTH VGSGAYGSVC SAIDKRSGEK VAIKKLSRPF 

        70         80         90        100        110        120 
QSEIFAKRAY RELLLLKHMQ HENVIGLLDV FTPASSLRNF YDFYLVMPFM QTDLQKIMGM 

       130        140        150        160        170        180 
EFSEEKIQYL VYQMLKGLKY IHSAGVVHRD LKPGNLAVNE DCELKILDFG LARHADAEMT 

       190        200        210        220        230        240 
GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG 

       250        260        270        280        290        300 
VPGTEFVQKL NDKAAKSYIQ SLPQTPRKDF TQLFPRASPQ AADLLEKMLE LDVDKRLTAA 

       310        320        330        340        350        360 
QALTHPFFEP FRDPEEETEA QQPFDDSLEH EKLTVDEWKQ HIYKEIVNFS PIARKDSRRR 


SGMKL 

« Hide

References

« Hide 'large scale' references
[1]"Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases."
Goedert M., Cuenda A., Craxton M., Jakes R., Cohen P.
EMBO J. 16:3563-3571(1997) [PubMed: 9218798] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION.
Tissue: Pituitary.
[2]"Characterization of the structure and function of the fourth member of p38 group mitogen-activated protein kinases, p38delta."
Jiang Y., Gram H., Zhao M., New L., Gu J., Feng L., Di Padova F., Ulevitch R.J., Han J.
J. Biol. Chem. 272:30122-30128(1997) [PubMed: 9374491] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-180 AND TYR-182, MUTAGENESIS OF THR-180 AND TYR-182, ENZYME REGULATION, TISSUE SPECIFICITY.
Tissue: Liver.
[3]"Molecular cloning and characterization of a novel p38 mitogen-activated protein kinase."
Wang X.S., Diener K., Manthey C.L., Wang S.-W., Rosenzweig B., Bray J., Delaney J., Cole C., Zukowski M., Yao Z.
J. Biol. Chem. 272:23668-23674(1997) [PubMed: 9295308] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity and sensitivity to inhibition by pyridinyl imidazoles."
Kumar S., McDonnell P.C., Gum R.J., Hand A.T., Lee J.C., Young P.R.
Biochem. Biophys. Res. Commun. 235:533-538(1997) [PubMed: 9207191] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Murine p38-delta mitogen-activated protein kinase, a developmentally regulated protein kinase that is activated by stress and proinflammatory cytokines."
Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R., Tan T.-H.
J. Biol. Chem. 274:7095-7102(1999) [PubMed: 10066767] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]"Structure and polymorphism of two stress-activated protein kinase genes centromeric of the MHC: SAPK2a and SAPK4."
Herbison C.E., Sayer D.C., Bellgard M., Allcock R.J.N., Christiansen F.T., Price P.
DNA Seq. 10:229-243(1999) [PubMed: 10727080] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed: 14574404] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[12]"Differential expression and activation of p38 mitogen-activated protein kinase alpha, beta, gamma, and delta in inflammatory cell lineages."
Hale K.K., Trollinger D., Rihanek M., Manthey C.L.
J. Immunol. 162:4246-4252(1999) [PubMed: 10201954] [Abstract]
Cited for: TISSUE SPECIFICITY.
[13]"A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta."
Knebel A., Morrice N., Cohen P.
EMBO J. 20:4360-4369(2001) [PubMed: 11500363] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION.
[14]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-182, MASS SPECTROMETRY.
[15]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, MASS SPECTROMETRY.
Tissue: Platelet.
[16]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, MASS SPECTROMETRY.
[17]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-41; VAL-282 AND THR-300.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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: EAX03875.1.
BC000433 mRNA. Translation: AAH00433.1.
BC001641 mRNA. Translation: AAH01641.1.
BC004428 mRNA. Translation: AAH04428.1.
IPIIPI00005741.
PIRJC5528.
RefSeqNP_002745.1.
UniGeneHs.178695

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3COIX-ray2.09A2-352[»]
ModBaseSearch...

Protein-protein interaction databases

IntActO15264. 85 interactions.
STRINGO15264.

PTM databases

PhosphoSiteO15264.

Proteomic databases

PRIDEO15264.

Genome annotation databases

EnsemblENST00000211287; ENSP00000211287; ENSG00000156711; Homo sapiens. [Genome view]
GeneID5603.
KEGGhsa:5603.
UCSCuc003ols.1. human.

Organism-specific databases

CTD5603.
GeneCardsGC06P036129.
H-InvDBHIX0022365.
HGNCHGNC:6875. MAPK13.
HPAHPA007667.
MIM602899. gene.
PharmGKBPA30620.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG13426.
HOGENOMHBG755340.
HOVERGENO15264.
InParanoidO15264.
OMAEWKQHIY.
OrthoDBEOG94F8VP.
PhylomeDBO15264.

Enzyme and pathway databases

BRENDA2.7.11.24. 247.
Pathway_Interaction_DBp38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.
ReactomeREACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpressO15264.
BgeeO15264.
CleanExHS_MAPK13.
GenevestigatorO15264.
GermOnlineENSG00000156711. Homo sapiens.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008352. MAPK_p38.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_prot_kinase-like_dom.
IPR002290. Ser/Thr_prot_kinase_dom.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01773. P38MAPKINASE.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio21772.
SOURCESearch...

Entry information

Entry nameMK13_HUMAN
AccessionPrimary (citable) accession number: O15264
Secondary accession number(s): O14739 expand/collapse secondary AC list , O15124, Q6FI46, Q9UNU0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: February 9, 2010
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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List of human entries with polymorphisms or disease mutations

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents