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Reviewed, UniProtKB/Swiss-Prot P49137 (MAPK2_HUMAN)

Last modified July 7, 2009. Version 97. 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 · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    MAP kinase-activated protein kinase 2
      Short name=MAPK-activated protein kinase 2
      Short name=MAPKAP kinase 2
      Short name=MAPKAPK-2
      Short name=MK2
    EC=2.7.11.1
Gene names
Name: MAPKAPK2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length400 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Its physiological substrate seems to be the small heat shock protein (HSP27/HSP25). In vitro can phosphorylate glycogen synthase at 'Ser-7' and tyrosine hydroxylase (on 'Ser-19' and 'Ser-40'). This kinase phosphorylates Ser in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue By similarity. Mediates both ERK and p38 MAPK/MAPK14 dependent neutrophil responses. Participates in TNF alpha-stimulated exocytosis of secretory vesicles in neutrophils. Plays a role in phagocytosis-induced respiratory burst activity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Seems to be activated by two distinct pathways: the first involves the stimulation of p42/p44 MAPK by growth factors, the second, triggered by stress and heat shock, depends on the activation of MPK2 and upstream MAPKK/MAPKKK.

Subunit structure

Interacts with PHC2. Ref.5

Tissue specificity

Expressed in all tissues examined.

Post-translational modification

Phosphorylated and activated by MAP kinase. Ref.6

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

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Binary interactions

With

Entry

#Exp.

IntAct

Notes

CDC25AP303041EBI-993299,EBI-747671
HSF1Q006134EBI-993299,EBI-719620
MAPK14Q165391EBI-993299,EBI-73946

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49137-1)

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.
Note: Has a nuclear localization signal.
Isoform 2 (identifier: P49137-2)

The sequence of this isoform differs from the canonical sequence as follows:
     354-400: EEMTSALATMRVDYEQIKIKKIEDASNPLLLKRRKKARALEAAALAH → GCLHDKNSDQATWLTRL

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 400400MAP kinase-activated protein kinase 2
PRO_0000086288

Regions

Domain64 – 325262Protein kinase
Nucleotide binding70 – 789ATP By similarity
Compositional bias10 – 4031Pro-rich
Compositional bias35 – 406Poly-Pro

Sites

Active site1861Proton acceptor
Binding site931ATP By similarity

Amino acid modifications

Modified residue631Phosphotyrosine Ref.6
Modified residue3281Phosphoserine; by autocatalysis By similarity
Modified residue3341Phosphothreonine; by MAPK By similarity
Modified residue3381Phosphothreonine By similarity

Natural variations

Alternative sequence354 – 40047EEMTS…AALAH → GCLHDKNSDQATWLTRL in isoform 2.
VSP_004910
Natural variant1731A → G Ref.8
VAR_040753
Natural variant3611A → S Ref.8
VAR_040754

Experimental info

Sequence conflict1161H → D in CAA53094. Ref.3
Sequence conflict247 – 2482WS → LV in CAA53094. Ref.3

Secondary structure

1 ....................................................... 400
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: E4EFFF11CCF288DC

FASTA40045,568
        10         20         30         40         50         60 
MLSNSQGQSP PVPFPAPAPP PQPPTPALPH PPAQPPPPPP QQFPQFHVKS GLQIKKNAII 

        70         80         90        100        110        120 
DDYKVTSQVL GLGINGKVLQ IFNKRTQEKF ALKMLQDCPK ARREVELHWR ASQCPHIVRI 

       130        140        150        160        170        180 
VDVYENLYAG RKCLLIVMEC LDGGELFSRI QDRGDQAFTE REASEIMKSI GEAIQYLHSI 

       190        200        210        220        230        240 
NIAHRDVKPE NLLYTSKRPN AILKLTDFGF AKETTSHNSL TTPCYTPYYV APEVLGPEKY 

       250        260        270        280        290        300 
DKSCDMWSLG VIMYILLCGY PPFYSNHGLA ISPGMKTRIR MGQYEFPNPE WSEVSEEVKM 

       310        320        330        340        350        360 
LIRNLLKTEP TQRMTITEFM NHPWIMQSTK VPQTPLHTSR VLKEDKERWE DVKEEMTSAL 

       370        380        390        400 
ATMRVDYEQI KIKKIEDASN PLLLKRRKKA RALEAAALAH

« Hide

Isoform 2.

Checksum: FF09AD93D4F73BDB
Show »

FASTA37042,203

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References

« Hide 'large scale' references
[1]"The primary structure of a human MAP kinase activated protein kinase 2."
Zu Y.-L., Wu F., Gilchrist A., Ai Y., Labadia M.E., Huang C.K.
Biochem. Biophys. Res. Commun. 200:1118-1124(1994) [PubMed: 8179591] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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] (ISOFORM 1).
Tissue: Skin and Testis.
[3]"The substrate specificity and structure of mitogen-activated protein (MAP) kinase-activated protein kinase-2."
Stokoe D., Caudwell B., Cohen P.T.W., Cohen P.
Biochem. J. 296:843-849(1993) [PubMed: 8280084] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-400.
[4]"MAPK-activated protein kinase-2 participates in p38 MAPK-dependent and ERK-dependent functions in human neutrophils."
Coxon P.Y., Rane M.J., Uriarte S., Powell D.W., Singh S., Butt W., Chen Q., McLeish K.R.
Cell. Signal. 15:993-1001(2003) [PubMed: 14499342] [Abstract]
Cited for: FUNCTION.
[5]"P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity."
Yannoni Y.M., Gaestel M., Lin L.L.
FEBS Lett. 564:205-211(2004) [PubMed: 15094067] [Abstract]
Cited for: INTERACTION WITH PHC2.
[6]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-63, MASS SPECTROMETRY.
[7]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]"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] GLY-173 AND SER-361.
+Additional computationally mapped references.

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Cross-references

Sequence databases

U12779 mRNA. Translation: AAA20851.1.
BC036060 mRNA. Translation: AAH36060.2.
BC052584 mRNA. Translation: AAH52584.1.
X75346 mRNA. Translation: CAA53094.1.
IPIIPI00026054.
IPI00215763.
PIRJC2204.
S39793.
RefSeqNP_004750.1.
NP_116584.2.
UniGeneHs.643566

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1KWPX-ray2.80A/B1-400[»]
1NXKX-ray2.70A/B/C/D1-400[»]
1NY3X-ray3.00A1-400[»]
2JBOX-ray3.10A41-364[»]
2JBPX-ray3.31A/B/C/D/E/F/G/H/I/J/K/L41-364[»]
2OKRX-ray2.00C/F370-393[»]
2ONLX-ray4.00C/D1-400[»]
2OZAX-ray2.70A47-400[»]
2P3GX-ray3.80X45-371[»]
2PZYX-ray2.90A/B/C/D41-364[»]
3FPMX-ray3.30A41-364[»]
3FYJX-ray3.80X45-371[»]
3FYKX-ray3.50X45-371[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP49137. 7 interactions.

PTM databases

PhosphoSiteP49137.

Proteomic databases

PRIDEP49137.

Genome annotation databases

EnsemblENSG00000162889. Homo sapiens. [Contig view]
GeneID9261.
KEGGhsa:9261.
UCSCuc001hem.1. human.

Organism-specific databases

GeneCardsGC01P204924.
H-InvDBHIX0023634.
HGNCHGNC:6887. MAPKAPK2.
HPACAB010297.
MIM602006. gene.
PharmGKBPA30631.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP49137.
HOVERGENP49137.
OMAP49137. SLATPCY.

Enzyme and pathway databases

BRENDA2.7.11.1. 247.
Pathway_Interaction_DBil2_1pathway. IL2-mediated signaling events.
p38_mk2pathway. p38 signaling mediated by MAPKAP kinases.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
ReactomeREACT_11061. Signalling by NGF.

Gene expression databases

ArrayExpressP49137.
BgeeP49137.
CleanExHS_MAPKAPK2.
GermOnlineENSG00000162889. Homo sapiens.

Family and domain databases

InterProIPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
ProDomPD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio34715.
SOURCESearch...

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Entry information

Entry nameMAPK2_HUMAN
AccessionPrimary (citable) accession number: P49137
Secondary accession number(s): Q8IYD6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: July 7, 2009
This is version 97 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

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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

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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 · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents