Reviewed, UniProtKB/Swiss-Prot Q16659 (MK06_HUMAN)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 6
    EC=2.7.11.24
Alternative name(s):
    Extracellular signal-regulated kinase 3
      Short name=ERK-3
    MAP kinase isoform p97
    p97-MAPK

Gene names

Name:	MAPK6
Synonyms:	ERK3, PRKM6

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	721 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 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by threonine and tyrosine phosphorylation 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	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-626 and Tyr-628, which activates the enzyme 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
Biological process	Cell cycle
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Traceable author statement. Source: ProtInc signal transduction Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 721

721

Mitogen-activated protein kinase 6

PRO_0000186257

Regions

Domain

20 – 316

297

Protein kinase

Nucleotide binding

26 – 34

9

ATP By similarity

Motif

626 – 628

3

TXY

Sites

Active site

152

1

Proton acceptor By similarity

Binding site

49

1

ATP By similarity

Amino acid modifications

Modified residue

189

1

Phosphoserine Ref.6

Modified residue

386

1

Phosphoserine Ref.6

Modified residue

389

1

Phosphothreonine Ref.6

Modified residue

626

1

Phosphothreonine By similarity

Modified residue

628

1

Phosphotyrosine By similarity

Modified residue

665

1

Phosphoserine Ref.6

Natural variations

Natural variant

290

1

L → V

VAR_042256

Secondary structure

1

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721

Helix Strand Turn

Details...

Beta strand

14 – 16

3

Turn

17 – 19

3

Beta strand

20 – 25

6

Beta strand

34 – 39

6

Turn

40 – 42

3

Beta strand

45 – 52

8

Helix

56 – 70

15

Beta strand

80 – 84

5

Beta strand

102 – 109

8

Beta strand

112 – 114

3

Helix

115 – 119

5

Helix

126 – 145

20

Helix

155 – 157

3

Beta strand

158 – 161

4

Turn

162 – 165

4

Beta strand

166 – 169

4

Helix

190 – 192

3

Helix

200 – 204

5

Helix

211 – 227

17

Helix

237 – 247

11

Helix

253 – 260

8

Helix

265 – 270

6

Helix

278 – 281

4

Helix

287 – 294

8

Helix

301 – 303

3

Helix

307 – 311

5

Helix

314 – 317

4

Sequences

	Sequence		Length	Mass (Da)
	Q16659-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: DAA3AAA9B98BB31F	FASTA	721	82,681
	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

References

	« Hide 'large scale' referencesShow '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: 7969157] [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: 8875998] [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]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Oesophageal carcinoma.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-290. Tissue: Placenta.
[6]	"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-189; SER-386; THR-389 AND SER-665, MASS SPECTROMETRY.
[7]	"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: VARIANT [LARGE SCALE ANALYSIS] VAL-290.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

X80692 mRNA. Translation: CAA56709.1.
L77964 mRNA. Translation: AAA98769.1.
AF420474 mRNA. Translation: AAL17605.1.
CR749401 mRNA. Translation: CAH18246.1.
BC035492 mRNA. Translation: AAH35492.1.

IPI

IPI00003431.

PIR

A56352.

RefSeq

NP_002739.1.

UniGene

Hs.411847

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2I6L	X-ray	2.25	A/B	9-327	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q16659.

PTM databases

PhosphoSite

Q16659.

Proteomic databases

PRIDE

Q16659.

Genome annotation databases

Ensembl

ENST00000261845; ENSP00000261845; ENSG00000069956; Homo sapiens. [Genome view]

GeneID

5597.

KEGG

hsa:5597.

NMPDR

fig|9606.3.peg.10716.

UCSC

uc002abp.1. human.

Organism-specific databases

CTD

5597.

GeneCards

GC15P050098.

H-InvDB

HIX0026784.
HIX0058579.
HIX0060074.

HGNC

HGNC:6879. MAPK6.

HPA

CAB005184.

MIM

602904. gene.

PharmGKB

PA30624.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q16659.

HOVERGEN

Q16659.

OMA

PAFDTSY.

Enzyme and pathway databases

BRENDA

2.7.11.24. 247.

Gene expression databases

ArrayExpress

Q16659.

Bgee

Q16659.

CleanEx

HS_MAPK6.

Genevestigator

Q16659.

GermOnline

ENSG00000069956. 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

NextBio

21724.

SOURCE

Search...

Entry information

Entry name

MK06_HUMAN

Accession

Primary (citable) accession number: Q16659
Secondary accession number(s): Q68DH4, Q8IYN8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	November 3, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.