Reviewed, UniProtKB/Swiss-Prot O15264 (MK13_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	365 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Cell cycle
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome cell cycle Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro protein kinase cascade Ref.1 Inferred from direct assay. Source: UniProtKB response to stress Ref.1 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MP kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATF2	P15336	1	EBI-2116951,EBI-1170906
Pkd1	Q9ERV0	1	EBI-2116951,EBI-2255297	From a different organism.
PRKD1	Q15139	2	EBI-2116951,EBI-1181072

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 365

365

Mitogen-activated protein kinase 13

PRO_0000186286

Regions

Domain

25 – 308

284

Protein kinase

Nucleotide binding

31 – 39

9

ATP By similarity

Motif

180 – 182

3

TXY

Sites

Active site

150

1

Proton acceptor By similarity

Binding site

54

1

ATP By similarity

Amino acid modifications

Modified residue

47

1

Phosphoserine Ref.15

Modified residue

180

1

Phosphothreonine Ref.2

Modified residue

182

1

Phosphotyrosine Ref.2 Ref.14

Modified residue

350

1

Phosphoserine

Natural variations

Natural variant

41

1

S → L: dbSNP rs55776345. Ref.17

VAR_042267

Natural variant

282

1

A → V: dbSNP rs55990045. Ref.17

VAR_042268

Natural variant

300

1

A → T: dbSNP rs41270090. Ref.17

VAR_042269

Experimental info

Mutagenesis

180

1

T → A: Loss of kinase activity. Ref.2

Mutagenesis

182

1

Y → A: Loss of kinase activity. Ref.2

Sequence conflict

13 – 14

2

DV → EL in AAC51374. Ref.4

Sequence conflict

39

1

V → W in AAC51374. Ref.4

Sequence conflict

56

1

L → P in AAC51758. Ref.3

Sequence conflict

166

1

I → V in AAC51758. Ref.3

Sequence conflict

224

1

K → R Ref.3

Sequence conflict

224

1

K → R Ref.5

Secondary structure

1

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365

Helix Strand Turn

Details...

Helix

4 – 8

5

Beta strand

9 – 14

6

Beta strand

17 – 22

6

Beta strand

25 – 33

9

Beta strand

35 – 44

10

Turn

45 – 47

3

Beta strand

50 – 58

9

Helix

63 – 78

16

Beta strand

88 – 91

4

Helix

97 – 99

3

Beta strand

104 – 108

5

Beta strand

111 – 113

3

Helix

114 – 116

3

Turn

117 – 119

3

Helix

124 – 143

20

Helix

153 – 155

3

Beta strand

156 – 158

3

Beta strand

164 – 166

3

Helix

191 – 194

4

Helix

204 – 218

15

Beta strand

222 – 226

5

Helix

228 – 239

12

Helix

244 – 247

4

Helix

253 – 260

8

Turn

270 – 273

4

Helix

279 – 288

10

Turn

293 – 295

3

Helix

299 – 303

5

Helix

306 – 308

3

Turn

309 – 311

3

Helix

314 – 316

3

Turn

327 – 330

4

Helix

335 – 347

13

Sequences

	Sequence		Length	Mass (Da)
	O15264-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 52E749EDB2973DDF	FASTA	365	42,090
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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. , 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.

IPI

IPI00005741.

PIR

JC5528.

RefSeq

NP_002745.1.

UniGene

Hs.178695

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3COI	X-ray	2.09	A	2-352	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O15264. 85 interactions.

STRING

O15264.

PTM databases

PhosphoSite

O15264.

Proteomic databases

PRIDE

O15264.

Genome annotation databases

Ensembl

ENST00000211287; ENSP00000211287; ENSG00000156711; Homo sapiens. [Genome view]

GeneID

5603.

KEGG

hsa:5603.

UCSC

uc003ols.1. human.

Organism-specific databases

CTD

5603.

GeneCards

GC06P036129.

H-InvDB

HIX0022365.

HGNC

HGNC:6875. MAPK13.

HPA

HPA007667.

MIM

602899. gene.

PharmGKB

PA30620.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13426.

HOGENOM

HBG755340.

HOVERGEN

O15264.

InParanoid

O15264.

OMA

EWKQHIY.

OrthoDB

EOG94F8VP.

PhylomeDB

O15264.

Enzyme and pathway databases

BRENDA

2.7.11.24. 247.

Pathway_Interaction_DB

p38gammadeltapathway. Signaling mediated by p38-gamma and p38-delta.

Reactome

REACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpress

O15264.

Bgee

O15264.

CleanEx

HS_MAPK13.

Genevestigator

O15264.

GermOnline

ENSG00000156711. Homo sapiens.

Family and domain databases

InterPro

IPR011009. 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]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR01773. P38MAPKINASE.

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

21772.

SOURCE

Search...

Entry information

Entry name

MK13_HUMAN

Accession

Primary (citable) accession number: O15264
Secondary accession number(s): O14739 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.