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Q8TD08

- MK15_HUMAN

UniProt

Q8TD08 - MK15_HUMAN

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Protein
Mitogen-activated protein kinase 15
Gene
MAPK15, ERK7, ERK8
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

In vitro, phosphorylates MBP.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Activated by threonine and tyrosine phosphorylation. Inhibited by dual specificity phosphatases, such as DUSP1 By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei42 – 421ATP By similarity
Active sitei137 – 1371Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi19 – 279ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: UniProtKB
  3. SH3 domain binding Source: UniProtKB

GO - Biological processi

  1. MAPK cascade Source: GOC
  2. negative regulation of DNA replication Source: Ensembl
  3. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  4. positive regulation of protein catabolic process Source: Ensembl
  5. positive regulation of protein phosphorylation Source: Ensembl
  6. positive regulation of protein ubiquitination Source: Ensembl
  7. protein autophosphorylation Source: UniProtKB
  8. response to estradiol Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ8TD08.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 15 (EC:2.7.11.24)
Short name:
MAP kinase 15
Short name:
MAPK 15
Alternative name(s):
Extracellular signal-regulated kinase 7
Short name:
ERK-7
Extracellular signal-regulated kinase 8
Short name:
ERK-8
Gene namesi
Name:MAPK15
Synonyms:ERK7, ERK8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:24667. MAPK15.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: UniProtKB
  2. intracellular Source: UniProtKB
  3. nucleus Source: Ensembl
Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi42 – 421K → R: Loss of autophosphorylation and activity. 1 Publication
Mutagenesisi175 – 1751T → A: Loss of autophosphorylation and activity. 1 Publication
Mutagenesisi177 – 1771Y → A: Loss of autophosphorylation and activity. 1 Publication

Organism-specific databases

PharmGKBiPA142671478.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 544544Mitogen-activated protein kinase 15
PRO_0000232637Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei175 – 1751Phosphothreonine1 Publication
Modified residuei177 – 1771Phosphotyrosine1 Publication
Modified residuei415 – 4151Phosphoserine1 Publication

Post-translational modificationi

Dually phosphorylated on Thr-175 and Tyr-177, which activates the enzyme. Autophosphorylated on threonine and tyrosine residues in vitro.1 Publication
Ubiquitinated. Ubiquitination may allow its tight kinase activity regulation and rapid turnover. May be ubiquitinated by a SCF E3 ligase By similarity.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ8TD08.
PaxDbiQ8TD08.
PRIDEiQ8TD08.

PTM databases

PhosphoSiteiQ8TD08.

Expressioni

Tissue specificityi

Widely expressed with a maximal expression in lung and kidney.2 Publications

Gene expression databases

BgeeiQ8TD08.
CleanExiHS_MAPK15.
GenevestigatoriQ8TD08.

Organism-specific databases

HPAiHPA002704.

Interactioni

Subunit structurei

Interacts with CSK/c-Src, ABL1, RET and TGFB1I1.3 Publications

Protein-protein interaction databases

BioGridi128827. 18 interactions.
IntActiQ8TD08. 9 interactions.
STRINGi9606.ENSP00000337691.

Structurei

3D structure databases

ProteinModelPortaliQ8TD08.
SMRiQ8TD08. Positions 5-402.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini13 – 304292Protein kinase
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi175 – 1773TXY

Domaini

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.

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
KOiK08293.
OMAiCTVKLCD.
OrthoDBiEOG7VDXPC.
PhylomeDBiQ8TD08.
TreeFamiTF105101.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8TD08-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MCTVVDPRIV RRYLLRRQLG QGAYGIVWKA VDRRTGEVVA IKKIFDAFRD    50
KTDAQRTFRE ITLLQEFGDH PNIISLLDVI RAENDRDIYL VFEFMDTDLN 100
AVIRKGGLLQ DVHVRSIFYQ LLRATRFLHS GHVVHRDQKP SNVLLDANCT 150
VKLCDFGLAR SLGDLPEGPE DQAVTEYVAT RWYRAPEVLL SSHRYTLGVD 200
MWSLGCILGE MLRGRPLFPG TSTLHQLELI LETIPPPSEE DLLALGSGCR 250
ASVLHQLGSR PRQTLDALLP PDTSPEALDL LRRLLVFAPD KRLSATQALQ 300
HPYVQRFHCP SDEWAREADV RPRAHEGVQL SVPEYRSRVY QMILECGGSS 350
GTSREKGPEG VSPSQAHLHK PRADPQLPSR TPVQGPRPRP QSSPGHDPAE 400
HESPRAAKNV PRQNSAPLLQ TALLGNGERP PGAKEAPPLT LSLVKPSGRG 450
AAPSLTSQAA AQVANQALIR GDWNRGGGVR VASVQQVPPR LPPEARPGRR 500
MFSTSALQGA QGGARALLGG YSQAYGTVCH SALGHLPLLE GHHV 544
Length:544
Mass (Da):59,832
Last modified:June 1, 2002 - v1
Checksum:i758E0E3B9654AAC5
GO
Isoform 2 (identifier: Q8TD08-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:254
Mass (Da):28,696
Checksum:i88FC081FFB15644A
GO
Isoform 3 (identifier: Q8TD08-3) [UniParc]FASTAAdd to Basket

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

Note: No experimental confirmation available.

Show »
Length:277
Mass (Da):31,112
Checksum:i07B9D39A696701D0
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti221 – 2211T → K.
Corresponds to variant rs60732298 [ dbSNP | Ensembl ].
VAR_061535
Natural varianti505 – 5051S → P.
Corresponds to variant rs56038219 [ dbSNP | Ensembl ].
VAR_061536

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei95 – 951M → MGCPPSPPPPTAVRTLSA in isoform 3.
VSP_017918
Alternative sequencei241 – 25414DLLAL…RASVL → GAQTACRSGTGAST in isoform 2.
VSP_017919Add
BLAST
Alternative sequencei255 – 544290Missing in isoform 2.
VSP_017920Add
BLAST
Alternative sequencei261 – 544284Missing in isoform 3.
VSP_017921Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti113 – 1131H → R in AAY44299. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY065978 mRNA. Translation: AAL40897.1.
AY994058 mRNA. Translation: AAY44299.1.
BC028034 mRNA. Translation: AAH28034.1.
CCDSiCCDS6409.2. [Q8TD08-1]
RefSeqiNP_620590.2. NM_139021.2. [Q8TD08-1]
UniGeneiHs.493169.

Genome annotation databases

EnsembliENST00000338033; 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]
GeneIDi225689.
KEGGihsa:225689.
UCSCiuc003yzj.3. human. [Q8TD08-1]

Polymorphism databases

DMDMi74760462.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AY065978 mRNA. Translation: AAL40897.1 .
AY994058 mRNA. Translation: AAY44299.1 .
BC028034 mRNA. Translation: AAH28034.1 .
CCDSi CCDS6409.2. [Q8TD08-1 ]
RefSeqi NP_620590.2. NM_139021.2. [Q8TD08-1 ]
UniGenei Hs.493169.

3D structure databases

ProteinModelPortali Q8TD08.
SMRi Q8TD08. Positions 5-402.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 128827. 18 interactions.
IntActi Q8TD08. 9 interactions.
STRINGi 9606.ENSP00000337691.

Chemistry

BindingDBi Q8TD08.
ChEMBLi CHEMBL5198.
GuidetoPHARMACOLOGYi 2090.

PTM databases

PhosphoSitei Q8TD08.

Polymorphism databases

DMDMi 74760462.

Proteomic databases

MaxQBi Q8TD08.
PaxDbi Q8TD08.
PRIDEi Q8TD08.

Protocols and materials databases

DNASUi 225689.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000338033 ; 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 ]
GeneIDi 225689.
KEGGi hsa:225689.
UCSCi uc003yzj.3. human. [Q8TD08-1 ]

Organism-specific databases

CTDi 225689.
GeneCardsi GC08P144798.
HGNCi HGNC:24667. MAPK15.
HPAi HPA002704.
neXtProti NX_Q8TD08.
PharmGKBi PA142671478.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
KOi K08293.
OMAi CTVKLCD.
OrthoDBi EOG7VDXPC.
PhylomeDBi Q8TD08.
TreeFami TF105101.

Enzyme and pathway databases

SignaLinki Q8TD08.

Miscellaneous databases

GeneWikii MAPK15.
GenomeRNAii 225689.
NextBioi 91718.
PROi Q8TD08.

Gene expression databases

Bgeei Q8TD08.
CleanExi HS_MAPK15.
Genevestigatori Q8TD08.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiMK15_HUMAN
AccessioniPrimary (citable) accession number: Q8TD08
Secondary accession number(s): Q2TCF9, Q8N362
Entry historyi
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 statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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