Q8TD08 (MK15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 15
Short name=MAP kinase 15
Short name=MAPK 15
EC=2.7.11.24

Alternative name(s):
Extracellular signal-regulated kinase 7
Short name=ERK-7
Extracellular signal-regulated kinase 8
Short name=ERK-8

Gene names

Name:	MAPK15
Synonyms:	ERK7, ERK8

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	544 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In vitro, phosphorylates MBP. Ref.1 Ref.2
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by threonine and tyrosine phosphorylation. Inhibited by dual specificity phosphatases, such as DUSP1 By similarity.
Subunit structure	Interacts with CSK/c-Src, ABL1, RET and TGFB1I1. Ref.1 Ref.2 Ref.4
Tissue specificity	Widely expressed with a maximal expression in lung and kidney. Ref.1 Ref.2
Domain	The N-terminal region (1-20) is the minimal region necessary for ubiquitination and further proteasomal degradation By similarity. The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-175 and Tyr-177, which activates the enzyme. Autophosphorylated on threonine and tyrosine residues in vitro. Ref.1 Ubiquitinated. Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of DNA replication Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of protein catabolic process Inferred from electronic annotation. Source: Compara positive regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara positive regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay Ref.1. Source: UniProtKB response to estradiol stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Non-traceable author statement Ref.1. Source: UniProtKB intracellular Non-traceable author statement Ref.1. Source: UniProtKB nucleus Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Inferred from direct assay Ref.1. Source: UniProtKB SH3 domain binding Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8TD08-1)

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.

Isoform 2 (identifier: Q8TD08-2)

Also known as: Erk8 delta;

The sequence of this isoform differs from the canonical sequence as follows:
     241-254: DLLALGSGCRASVL → GAQTACRSGTGAST
     255-544: Missing.

Note: Appears not to be a CSK- and RET-dependent activated kinase.

Isoform 3 (identifier: Q8TD08-3)

The sequence of this isoform differs from the canonical sequence as follows:
     95-95: M → MGCPPSPPPPTAVRTLSA
     261-544: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 544	544	Mitogen-activated protein kinase 15		PRO_0000232637
Regions
	Domain	13 – 304	292	Protein kinase
	Nucleotide binding	19 – 27	9	ATP By similarity
	Motif	175 – 177	3	TXY
Sites
	Active site	137	1	Proton acceptor By similarity
	Binding site	42	1	ATP By similarity
Amino acid modifications
	Modified residue	175	1	Phosphothreonine Ref.1
	Modified residue	177	1	Phosphotyrosine Ref.1
	Modified residue	415	1	Phosphoserine Ref.5
Natural variations
	Alternative sequence	95	1	M → MGCPPSPPPPTAVRTLSA in isoform 3.		VSP_017918
	Alternative sequence	241 – 254	14	DLLAL…RASVL → GAQTACRSGTGAST in isoform 2.		VSP_017919
	Alternative sequence	255 – 544	290	Missing in isoform 2.		VSP_017920
	Alternative sequence	261 – 544	284	Missing in isoform 3.		VSP_017921
	Natural variant	221	1	T → K. Corresponds to variant rs60732298 [ dbSNP | Ensembl ].		VAR_061535
	Natural variant	505	1	S → P. Corresponds to variant rs56038219 [ dbSNP | Ensembl ].		VAR_061536
Experimental info
	Mutagenesis	42	1	K → R: Loss of autophosphorylation and activity. Ref.1
	Mutagenesis	175	1	T → A: Loss of autophosphorylation and activity. Ref.1
	Mutagenesis	177	1	Y → A: Loss of autophosphorylation and activity. Ref.1
	Sequence conflict	113	1	H → R in AAY44299. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 758E0E3B9654AAC5	FASTA	544	59,832
	10 20 30 40 50 60 MCTVVDPRIV RRYLLRRQLG QGAYGIVWKA VDRRTGEVVA IKKIFDAFRD KTDAQRTFRE 70 80 90 100 110 120 ITLLQEFGDH PNIISLLDVI RAENDRDIYL VFEFMDTDLN AVIRKGGLLQ DVHVRSIFYQ 130 140 150 160 170 180 LLRATRFLHS GHVVHRDQKP SNVLLDANCT VKLCDFGLAR SLGDLPEGPE DQAVTEYVAT 190 200 210 220 230 240 RWYRAPEVLL SSHRYTLGVD MWSLGCILGE MLRGRPLFPG TSTLHQLELI LETIPPPSEE 250 260 270 280 290 300 DLLALGSGCR ASVLHQLGSR PRQTLDALLP PDTSPEALDL LRRLLVFAPD KRLSATQALQ 310 320 330 340 350 360 HPYVQRFHCP SDEWAREADV RPRAHEGVQL SVPEYRSRVY QMILECGGSS GTSREKGPEG 370 380 390 400 410 420 VSPSQAHLHK PRADPQLPSR TPVQGPRPRP QSSPGHDPAE HESPRAAKNV PRQNSAPLLQ 430 440 450 460 470 480 TALLGNGERP PGAKEAPPLT LSLVKPSGRG AAPSLTSQAA AQVANQALIR GDWNRGGGVR 490 500 510 520 530 540 VASVQQVPPR LPPEARPGRR MFSTSALQGA QGGARALLGG YSQAYGTVCH SALGHLPLLE GHHV
	Isoform 2 (Erk8 delta) [UniParc]. Checksum: 88FC081FFB15644A	FASTA	254	28,696
	10 20 30 40 50 60 MCTVVDPRIV RRYLLRRQLG QGAYGIVWKA VDRRTGEVVA IKKIFDAFRD KTDAQRTFRE 70 80 90 100 110 120 ITLLQEFGDH PNIISLLDVI RAENDRDIYL VFEFMDTDLN AVIRKGGLLQ DVHVRSIFYQ 130 140 150 160 170 180 LLRATRFLHS GHVVHRDQKP SNVLLDANCT VKLCDFGLAR SLGDLPEGPE DQAVTEYVAT 190 200 210 220 230 240 RWYRAPEVLL SSHRYTLGVD MWSLGCILGE MLRGRPLFPG TSTLHQLELI LETIPPPSEE 250 GAQTACRSGT GAST
	Isoform 3 [UniParc]. Checksum: 07B9D39A696701D0	FASTA	277	31,112
	10 20 30 40 50 60 MCTVVDPRIV RRYLLRRQLG QGAYGIVWKA VDRRTGEVVA IKKIFDAFRD KTDAQRTFRE 70 80 90 100 110 120 ITLLQEFGDH PNIISLLDVI RAENDRDIYL VFEFMGCPPS PPPPTAVRTL SADTDLNAVI 130 140 150 160 170 180 RKGGLLQDVH VRSIFYQLLR ATRFLHSGHV VHRDQKPSNV LLDANCTVKL CDFGLARSLG 190 200 210 220 230 240 DLPEGPEDQA VTEYVATRWY RAPEVLLSSH RYTLGVDMWS LGCILGEMLR GRPLFPGTST 250 260 270 LHQLELILET IPPPSEEDLL ALGSGCRASV LHQLGSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ERK8, a new member of the mitogen-activated protein kinase family." Abe M.K., Saelzler M.P., Espinosa R. III, Kahle K.T., Hershenson M.B., Le Beau M.M., Rosner M.R. J. Biol. Chem. 277:16733-16743(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, INTERACTION WITH CSK, MUTAGENESIS OF LYS-42; THR-175 AND TYR-177, PHOSPHORYLATION AT THR-175 AND TYR-177, CHARACTERIZATION, FUNCTION. Tissue: Testis.
[2]	"Activation of the Erk8 mitogen-activated protein (MAP) kinase by RET/PTC3, a constitutively active form of the RET proto-oncogene." Iavarone C., Acunzo M., Carlomagno F., Catania A., Melillo R.M., Carlomagno S.M., Santoro M., Chiariello M. J. Biol. Chem. 281:10567-10576(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, FUNCTION, INTERACTION WITH ABL1 AND RET. Tissue: Medulla oblongata.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[4]	"ERK8 down-regulates transactivation of the glucocorticoid receptor through Hic-5." Saelzler M.P., Spackman C.C., Liu Y., Martinez L.C., Harris J.P., Abe M.K. J. Biol. Chem. 281:16821-16832(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TGFB1I1.
[5]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY065978 mRNA. Translation: AAL40897.1. AY994058 mRNA. Translation: AAY44299.1. BC028034 mRNA. Translation: AAH28034.1.
IPI	IPI00165955. IPI00747020. IPI00935477.
RefSeq	NP_620590.2. NM_139021.2.
UniGene	Hs.493169.
3D structure databases
ProteinModelPortal	Q8TD08.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8TD08. 2 interactions.
STRING	9606.ENSP00000337691.
PTM databases
PhosphoSite	Q8TD08.
Polymorphism databases
DMDM	74760462.
Proteomic databases
PaxDb	Q8TD08.
PRIDE	Q8TD08.
Protocols and materials databases
DNASU	225689.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338033; ENSP00000337691; ENSG00000181085. ENST00000395107; ENSP00000378539; ENSG00000181085. ENST00000395108; ENSP00000378540; ENSG00000181085. ENST00000565147; ENSP00000457917; ENSG00000260463. ENST00000566107; ENSP00000456140; ENSG00000260463. ENST00000567917; ENSP00000455873; ENSG00000260463.
GeneID	225689.
KEGG	hsa:225689.
UCSC	uc003yzj.3. human.
Organism-specific databases
CTD	225689.
GeneCards	GC08P144798.
HGNC	HGNC:24667. MAPK15.
HPA	HPA002704.
neXtProt	NX_Q8TD08.
PharmGKB	PA142671478.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233024.
HOVERGEN	HBG014652.
KO	K08293.
OMA	GEMLRGQ.
OrthoDB	EOG470THD.
PhylomeDB	Q8TD08.
Gene expression databases
Bgee	Q8TD08.
CleanEx	HS_MAPK15.
Genevestigator	Q8TD08.
GermOnline	ENSG00000181085. Homo sapiens.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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
BindingDB	Q8TD08.
ChEMBL	CHEMBL5198.
GenomeRNAi	225689.
NextBio	91718.

Entry information

Entry name

MK15_HUMAN

Accession

Primary (citable) accession number: Q8TD08
Secondary accession number(s): Q2TCF9, Q8N362

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 18, 2006
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.