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Q16659 (MK06_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | 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 6

Short name=MAP kinase 6
Short name=MAPK 6
EC=2.7.11.24
Alternative name(s):
Extracellular signal-regulated kinase 3
Short name=ERK-3
MAP kinase isoform p97
Short name=p97-MAPK
Gene names
Name:MAPK6
Synonyms:ERK3, PRKM6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length721 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, ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6. 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-189.

Subunit structure

Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif) MAPKAPK5 By similarity. Interacts with UBE3A; this interaction may be indirect and mediated by HERC2, possibly via HERC2 interaction with NEURL4. Ref.13

Subcellular location

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

Tissue specificity

Highest expression in the skeletal muscle, followed by the brain. Also found in heart, placenta, lung, liver, pancreas, kidney and skin fibroblasts.

Domain

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

Post-translational modification

Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in catalytic activation. Phosphorylated by MAPKAPK5 at other sites. Ref.12

Ubiquitination at Met-1 leads to degradation by the proteasome pathway.

Sequence similarities

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

Contains 1 protein kinase domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAPKAPK5Q8IW413EBI-1384105,EBI-1201460
vifP125042EBI-1384105,EBI-779991From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 721721Mitogen-activated protein kinase 6
PRO_0000186257

Regions

Domain20 – 316297Protein kinase
Nucleotide binding26 – 349ATP By similarity
Motif189 – 1913SEG motif
Motif332 – 3376FRIEDE motif

Sites

Active site1521Proton acceptor By similarity
Binding site491ATP By similarity

Amino acid modifications

Modified residue1891Phosphoserine; by PAK1, PAK2 and PAK3 Ref.9 Ref.10 Ref.12
Cross-link1Peptide (Met-Gly) (interchain with G-Cter in ubiquitin)

Natural variations

Natural variant2901L → V. Ref.7 Ref.14
Corresponds to variant rs35697691 [ dbSNP | Ensembl ].
VAR_042256

Experimental info

Sequence conflict2291K → R in BAG36392. Ref.4
Sequence conflict5271F → L in BAG70115. Ref.4

Secondary structure

................................................ 721
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16659 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: DAA3AAA9B98BB31F

FASTA72182,681
        10         20         30         40         50         60 
MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK IVLTDPQSVK 

        70         80         90        100        110        120 
HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE LNSVYIVQEY METDLANVLE 

       130        140        150        160        170        180 
QGPLLEEHAR LFMYQLLRGL KYIHSANVLH RDLKPANLFI NTEDLVLKIG DFGLARIMDP 

       190        200        210        220        230        240 
HYSHKGHLSE GLVTKWYRSP RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ 

       250        260        270        280        290        300 
MQLILESIPV VHEEDRQELL SVIPVYIRND MTEPHKPLTQ LLPGISREAL DFLEQILTFS 

       310        320        330        340        350        360 
PMDRLTAEEA LSHPYMSIYS FPMDEPISSH PFHIEDEVDD ILLMDETHSH IYNWERYHDC 

       370        380        390        400        410        420 
QFSEHDWPVH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK YLDGDREKYL EDPAFDTNYS 

       430        440        450        460        470        480 
TEPCWQYSDH HENKYCDLEC SHTCNYKTRS SSYLDNLVWR ESEVNHYYEP KLIIDLSNWK 

       490        500        510        520        530        540 
EQSKEKSDKK GKSKCERNGL VKAQIALEEA SQQLAGKERE KNQGFDFDSF IAGTIQLSSQ 

       550        560        570        580        590        600 
HEPTDVVDKL NDLNSSVSQL ELKSLISKSV SQEKQEKGMA NLAQLEALYQ SSWDSQFVSG 

       610        620        630        640        650        660 
GEDCFFINQF CEVRKDEQVE KENTYTSYLD KFFSRKEDTE MLETEPVEDG KLGERGHEEG 

       670        680        690        700        710        720 
FLNNSGEFLF NKQLESIGIP QFHSPVGSPL KSIQATLTPS AMKSSPQIPH QTYSSILKHL 


N 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3."
Zhu A.X., Zhao Y., Moller D.E., Flier J.S.
Mol. Cell. Biol. 14:8202-8211(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal skeletal muscle.
[2]"Primary structure, expression and chromosomal locus of a human homolog of rat ERK3."
Meloche S., Beatty B.G., Pellerin J.
Oncogene 13:1575-1579(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Smooth muscle.
[3]"ERK-3 cDNA clone isolated from human oral cancer."
Saranath D., Mahale A., Rai R., Dedhia P.
Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Oral cancer.
[4]"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].
Tissue: Trachea.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Esophageal carcinoma.
[6]"Human protein factory for converting the transcriptome into an in vitro-expressed proteome."
Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B. expand/collapse author list , Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S., Nomura N.
Nat. Methods 5:1011-1017(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"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], VARIANT VAL-290.
Tissue: Placenta.
[8]"N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and p21 directs their degradation by the proteasome."
Coulombe P., Rodier G., Bonneil E., Thibault P., Meloche S.
Mol. Cell. Biol. 24:6140-6150(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT MET-1.
[9]"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-189, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"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-189, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[12]"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-189.
[13]"Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes."
Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M., Harper J.W., Howley P.M.
Mol. Cell. Biol. 32:3095-3106(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBE3A AND NEURL4.
[14]"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: VARIANT [LARGE SCALE ANALYSIS] VAL-290.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X80692 mRNA. Translation: CAA56709.1.
L77964 mRNA. Translation: AAA98769.1.
AF420474 mRNA. Translation: AAL17605.1.
AK313633 mRNA. Translation: BAG36392.1.
CR749401 mRNA. Translation: CAH18246.1.
AB451301 mRNA. Translation: BAG70115.1.
BC035492 mRNA. Translation: AAH35492.1.
CCDSCCDS10147.1.
PIRA56352.
RefSeqNP_002739.1. NM_002748.3.
XP_005254593.1. XM_005254536.2.
XP_005254594.1. XM_005254537.1.
XP_005254595.1. XM_005254538.1.
XP_005254596.1. XM_005254539.2.
UniGeneHs.411847.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2I6LX-ray2.25A/B9-327[»]
ProteinModelPortalQ16659.
SMRQ16659. Positions 13-358.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111583. 175 interactions.
IntActQ16659. 173 interactions.
MINTMINT-8247530.
STRING9606.ENSP00000261845.

Chemistry

BindingDBQ16659.
ChEMBLCHEMBL5121.
GuidetoPHARMACOLOGY2092.

PTM databases

PhosphoSiteQ16659.

Polymorphism databases

DMDM2499596.

Proteomic databases

MaxQBQ16659.
PaxDbQ16659.
PRIDEQ16659.

Protocols and materials databases

DNASU5597.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261845; ENSP00000261845; ENSG00000069956.
GeneID5597.
KEGGhsa:5597.
UCSCuc002abp.3. human.

Organism-specific databases

CTD5597.
GeneCardsGC15P052311.
HGNCHGNC:6879. MAPK6.
HPACAB005184.
HPA030262.
HPA047825.
MIM602904. gene.
neXtProtNX_Q16659.
PharmGKBPA30624.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233020.
HOVERGENHBG104376.
InParanoidQ16659.
KOK06855.
OMAEHDWPIH.
OrthoDBEOG780RKS.
PhylomeDBQ16659.
TreeFamTF105098.

Enzyme and pathway databases

BRENDA2.7.11.24. 2681.
SignaLinkQ16659.

Gene expression databases

BgeeQ16659.
CleanExHS_MAPK6.
GenevestigatorQ16659.

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

EvolutionaryTraceQ16659.
GeneWikiMAPK6.
GenomeRNAi5597.
NextBio21724.
PROQ16659.
SOURCESearch...

Entry information

Entry nameMK06_HUMAN
AccessionPrimary (citable) accession number: Q16659
Secondary accession number(s): B2R945 expand/collapse secondary AC list , B5BU65, Q68DH4, Q8IYN8
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 139 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 15

Human chromosome 15: entries, gene names and cross-references to MIM