Reviewed, UniProtKB/Swiss-Prot P31152 (MK04_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 4
    EC=2.7.11.24
Alternative name(s):
    Extracellular signal-regulated kinase 4
      Short name=ERK-4
    MAP kinase isoform p63
    p63-MAPK

Gene names

Name:	MAPK4
Synonyms:	ERK4, PRKM4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	587 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphorylates microtubule-associated protein 2 (MAP2). May promote entry in the cell cycle.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Tissue specificity	High expression in heart and brain.
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.

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
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 587	587	Mitogen-activated protein kinase 4		PRO_0000186254
Regions
	Domain	20 – 312	293	Protein kinase
	Nucleotide binding	26 – 34	9	ATP By similarity
Sites
	Active site	149	1	Proton acceptor By similarity
	Binding site	49	1	ATP By similarity
Amino acid modifications
	Modified residue	186	1	Phosphoserine Ref.4
Natural variations
	Natural variant	38	1	V → M: dbSNP rs3752087. Ref.5		VAR_042254
	Natural variant	371	1	R → P Ref.5		VAR_042255

Sequences

	Sequence		Length	Mass (Da)
	P31152-1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: 71DB32D1E63EF8EE	FASTA	587	65,922
	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

References

	« Hide 'large scale' referencesShow '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: 1319925] [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. , 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: 14702039] [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. , 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: 16177791] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, MASS SPECTROMETRY.
[5]	"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] MET-38 AND PRO-371.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBLGenBankDDBJ	X59727 mRNA. Translation: CAA42411.1. Frameshift. AK295058 mRNA. No translation available. AC012433 Genomic DNA. No translation available. AC090395 Genomic DNA. No translation available.
IPI	IPI00010156.
PIR	S23429.
RefSeq	NP_002738.2.
UniGene	Hs.433728
3D structure databases
HSSP	HSSP built from PDB template 1KV1 based on UniProtKB Q16539.
ModBase	Search...
PTM databases
PhosphoSite	P31152.
Genome annotation databases
Ensembl	ENSG00000141639. Homo sapiens. [Contig view]
GeneID	5596.
KEGG	hsa:5596.
Organism-specific databases
GeneCards	GC18P046340.
HGNC	HGNC:6878. MAPK4.
HPA	HPA007461.
MIM	176949. gene.
PharmGKB	PA30623.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P31152.
OMA	P31152. PDRCQDA.
Enzyme and pathway databases
BRENDA	2.7.11.24. 247.
Gene expression databases
ArrayExpress	P31152.
Bgee	P31152.
CleanEx	HS_MAPK4.
GermOnline	ENSG00000141639. Homo sapiens.
Family and domain databases
InterPro	IPR008350. Erk_3_4_MAPK. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01771. ERK3ERK4MAPK.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

MK04_HUMAN

Accession

Primary (citable) accession number: P31152

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	November 25, 2008
Last modified:	June 16, 2009
This is version 87 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)