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Q8TD08 (MK15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length544 AA.
Sequence statusComplete.
Protein existenceEvidence 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 diversityAlternative splicing
Polymorphism
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMAPK cascade

Inferred from direct assay Ref.1. Source: GOC

negative regulation of DNA replication

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay Ref.1. Source: UniProtKB

response to estradiol

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular region

Non-traceable author statement Ref.1. Source: UniProtKB

intracellular

Non-traceable author statement Ref.1. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP 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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 544544Mitogen-activated protein kinase 15
PRO_0000232637

Regions

Domain13 – 304292Protein kinase
Nucleotide binding19 – 279ATP By similarity
Motif175 – 1773TXY

Sites

Active site1371Proton acceptor By similarity
Binding site421ATP By similarity

Amino acid modifications

Modified residue1751Phosphothreonine Ref.1
Modified residue1771Phosphotyrosine Ref.1
Modified residue4151Phosphoserine Ref.5

Natural variations

Alternative sequence951M → MGCPPSPPPPTAVRTLSA in isoform 3.
VSP_017918
Alternative sequence241 – 25414DLLAL…RASVL → GAQTACRSGTGAST in isoform 2.
VSP_017919
Alternative sequence255 – 544290Missing in isoform 2.
VSP_017920
Alternative sequence261 – 544284Missing in isoform 3.
VSP_017921
Natural variant2211T → K.
Corresponds to variant rs60732298 [ dbSNP | Ensembl ].
VAR_061535
Natural variant5051S → P.
Corresponds to variant rs56038219 [ dbSNP | Ensembl ].
VAR_061536

Experimental info

Mutagenesis421K → R: Loss of autophosphorylation and activity. Ref.1
Mutagenesis1751T → A: Loss of autophosphorylation and activity. Ref.1
Mutagenesis1771Y → A: Loss of autophosphorylation and activity. Ref.1
Sequence conflict1131H → R in AAY44299. Ref.2

Sequences

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

Last modified June 1, 2002. Version 1.
Checksum: 758E0E3B9654AAC5

FASTA54459,832
        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 

« Hide

Isoform 2 (Erk8 delta) [UniParc].

Checksum: 88FC081FFB15644A
Show »

FASTA25428,696
Isoform 3 [UniParc].

Checksum: 07B9D39A696701D0
Show »

FASTA27731,112

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+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.
CCDSCCDS6409.2. [Q8TD08-1]
RefSeqNP_620590.2. NM_139021.2. [Q8TD08-1]
UniGeneHs.493169.

3D structure databases

ProteinModelPortalQ8TD08.
SMRQ8TD08. Positions 5-402.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid128827. 18 interactions.
IntActQ8TD08. 9 interactions.
STRING9606.ENSP00000337691.

Chemistry

BindingDBQ8TD08.
ChEMBLCHEMBL5198.
GuidetoPHARMACOLOGY2090.

PTM databases

PhosphoSiteQ8TD08.

Polymorphism databases

DMDM74760462.

Proteomic databases

MaxQBQ8TD08.
PaxDbQ8TD08.
PRIDEQ8TD08.

Protocols and materials databases

DNASU225689.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338033; ENSP00000337691; ENSG00000181085. [Q8TD08-1]
ENST00000395107; ENSP00000378539; ENSG00000181085. [Q8TD08-3]
ENST00000395108; ENSP00000378540; ENSG00000181085. [Q8TD08-2]
ENST00000565147; ENSP00000457917; ENSG00000260463. [Q8TD08-1]
ENST00000566107; ENSP00000456140; ENSG00000260463. [Q8TD08-2]
ENST00000567917; ENSP00000455873; ENSG00000260463. [Q8TD08-3]
GeneID225689.
KEGGhsa:225689.
UCSCuc003yzj.3. human. [Q8TD08-1]

Organism-specific databases

CTD225689.
GeneCardsGC08P144798.
HGNCHGNC:24667. MAPK15.
HPAHPA002704.
neXtProtNX_Q8TD08.
PharmGKBPA142671478.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
KOK08293.
OMACTVKLCD.
OrthoDBEOG7VDXPC.
PhylomeDBQ8TD08.
TreeFamTF105101.

Enzyme and pathway databases

SignaLinkQ8TD08.

Gene expression databases

BgeeQ8TD08.
CleanExHS_MAPK15.
GenevestigatorQ8TD08.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMAPK15.
GenomeRNAi225689.
NextBio91718.
PROQ8TD08.

Entry information

Entry nameMK15_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 109 of the entry and version 1 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

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 8

Human chromosome 8: entries, gene names and cross-references to MIM