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P31152 (MK04_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mitogen-activated protein kinase 4

Short name=MAP kinase 4
Short name=MAPK 4
EC=2.7.11.24
Alternative name(s):
Extracellular signal-regulated kinase 4
Short name=ERK-4
MAP kinase isoform p63
Short name=p63-MAPK
Gene names
Name:MAPK4
Synonyms:ERK4, PRKM4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length587 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Atypical MAPK protein. Phosphorylates microtubule-associated protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed with MAPKAPK5 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPKAPK5, ERK4/MAPK4 is phosphorylated at Ser-186 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK4/MAPK4. May promote entry in the cell cycle By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Activated by phosphorylation at Ser-186.

Subunit structure

Homodimer. Heterodimer with ERK3/MAPK6. Interacts with (via FRIEDE motif) MAPKAPK5 By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: Translocates to the cytoplasm following interaction with MAPKAPK5 By similarity.

Tissue specificity

High expression in heart and brain.

Domain

The FRIEDE motif is required for docking MAPKAPK5 By similarity.

In contrast to classical MAPKs, the TXY motif within the activation loop is replaced by the SEG motif, whose phosphorylation activates the MAP kinases.

Post-translational modification

Phosphorylated at Ser-186 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites. Ref.5

Sequence similarities

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

Contains 1 protein kinase domain.

Sequence caution

The sequence CAA42411.1 differs from that shown. Reason: Frameshift at several positions.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HSP90AB1P082382EBI-3906061,EBI-352572

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 587587Mitogen-activated protein kinase 4
PRO_0000186254

Regions

Domain20 – 312293Protein kinase
Nucleotide binding26 – 349ATP By similarity
Motif186 – 1883SEG motif
Motif328 – 3336FRIEDE motif

Sites

Active site1491Proton acceptor By similarity
Binding site491ATP By similarity

Amino acid modifications

Modified residue1861Phosphoserine; by PAK1, PAK2 and PAK3 Ref.4 Ref.5

Natural variations

Natural variant381V → M. Ref.6
Corresponds to variant rs3752087 [ dbSNP | Ensembl ].
VAR_042254
Natural variant3711R → P. Ref.6
Corresponds to variant rs3752089 [ dbSNP | Ensembl ].
VAR_042255

Sequences

Sequence LengthMass (Da)Tools
P31152 [UniParc].

Last modified November 25, 2008. Version 2.
Checksum: 71DB32D1E63EF8EE

FASTA58765,922
        10         20         30         40         50         60 
MAEKGDCIAS VYGYDLGGRF VDFQPLGFGV NGLVLSAVDS RACRKVAVKK IALSDARSMK 

        70         80         90        100        110        120 
HALREIKIIR RLDHDNIVKV YEVLGPKGTD LQGELFKFSV AYIVQEYMET DLARLLEQGT 

       130        140        150        160        170        180 
LAEEHAKLFM YQLLRGLKYI HSANVLHRDL KPANIFISTE DLVLKIGDFG LARIVDQHYS 

       190        200        210        220        230        240 
HKGYLSEGLV TKWYRSPRLL LSPNNYTKAI DMWAAGCILA EMLTGRMLFA GAHELEQMQL 

       250        260        270        280        290        300 
ILETIPVIRE EDKDELLRVM PSFVSSTWEV KRPLRKLLPE VNSEAIDFLE KILTFNPMDR 

       310        320        330        340        350        360 
LTAEMGLQHP YMSPYSCPED EPTSQHPFRI EDEIDDIVLM AANQSQLSNW DTCSSRYPVS 

       370        380        390        400        410        420 
LSSDLEWRPD RCQDASEVQR DPRAGSAPLA EDVQVDPRKD SHSSSERFLE QSHSSMERAF 

       430        440        450        460        470        480 
EADYGRSCDY KVGSPSYLDK LLWRDNKPHH YSEPKLILDL SHWKQAAGAP PTATGLADTG 

       490        500        510        520        530        540 
AREDEPASLF LEIAQWVKST QGGPEHASPP ADDPERRLSA SPPGRPAPVD GGASPQFDLD 

       550        560        570        580 
VFISRALKLC TKPEDLPDNK LGDLNGACIP EHPGDLVQTE AFSKERW 

« Hide

References

« Hide 'large scale' references
[1]"Heterogeneous expression of four MAP kinase isoforms in human tissues."
Gonzalez F.A., Raden D.L., Rigby M.R., Davis R.J.
FEBS Lett. 304:170-178(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway."
Deleris P., Trost M., Topisirovic I., Tanguay P.L., Borden K.L., Thibault P., Meloche S.
J. Biol. Chem. 286:6470-6478(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-186.
[6]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] MET-38 AND PRO-371.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X59727 mRNA. Translation: CAA42411.1. Frameshift.
AK295058 mRNA. No translation available.
AC012433 Genomic DNA. No translation available.
AC090395 Genomic DNA. No translation available.
PIRS23429.
RefSeqNP_002738.2. NM_002747.3.
XP_005258356.1. XM_005258299.1.
UniGeneHs.433728.

3D structure databases

ProteinModelPortalP31152.
SMRP31152. Positions 13-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111582. 15 interactions.
IntActP31152. 11 interactions.
STRING9606.ENSP00000383234.

Chemistry

BindingDBP31152.
ChEMBLCHEMBL5759.
GuidetoPHARMACOLOGY2091.

PTM databases

PhosphoSiteP31152.

Polymorphism databases

DMDM215274102.

Proteomic databases

PaxDbP31152.
PRIDEP31152.

Protocols and materials databases

DNASU5596.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000400384; ENSP00000383234; ENSG00000141639.
ENST00000576626; ENSP00000459073; ENSG00000262673.
GeneID5596.
KEGGhsa:5596.
UCSCuc002lev.3. human.

Organism-specific databases

CTD5596.
GeneCardsGC18P048125.
H-InvDBHIX0027373.
HGNCHGNC:6878. MAPK4.
HPACAB025868.
HPA007461.
MIM176949. gene.
neXtProtNX_P31152.
PharmGKBPA30623.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233020.
HOVERGENHBG104376.
InParanoidP31152.
KOK06855.
OMARCQDASE.
PhylomeDBP31152.
TreeFamTF105098.

Enzyme and pathway databases

BRENDA2.7.11.24. 2681.
SignaLinkP31152.

Gene expression databases

ArrayExpressP31152.
BgeeP31152.
CleanExHS_MAPK4.
GenevestigatorP31152.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR008350. MAPK_ERK3/4.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSPR01771. ERK3ERK4MAPK.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMAPK4.
GenomeRNAi5596.
NextBio21720.
PROP31152.
SOURCESearch...

Entry information

Entry nameMK04_HUMAN
AccessionPrimary (citable) accession number: P31152
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: November 25, 2008
Last modified: April 16, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM