Reviewed, UniProtKB/Swiss-Prot P63086 (MK01_RAT)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 1
    EC=2.7.11.24
Alternative name(s):
    Extracellular signal-regulated kinase 2
      Short name=ERK-2
    Mitogen-activated protein kinase 2
      Short name=MAP kinase 2
      Short name=MAPK 2
    p42-MAPK
    ERT1

Gene names

Name:	Mapk1
Synonyms:	Erk2, Mapk, Prkm1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	358 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Involved in both the initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors such as ELK1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1. Phosphorylates heat shock factor protein 4 (HSF4) and ARHGEF2 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by phosphorylation on tyrosine and threonine in response to insulin and NGF. Both phosphorylations are required for activity.
Subunit structure	Interacts with ARHGEF2, NISCH, MORG1 and HSF4 By similarity. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads stlto nuclear location and MAPK1 activation.
Tissue specificity	Highest levels within the nervous system, expressed in different tissues, mostly in muscle, thymus and heart.
Developmental stage	Increased expression during development.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme By similarity. Autophosphorylated on threonine and tyrosine residues in vitro, which correlates with a slow and low level of activation.
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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW nuclear translocation of MAPK Inferred from direct assay. Source: RGD positive regulation of cell migration Inferred from expression pattern. Source: RGD positive regulation of cell proliferation Inferred from expression pattern. Source: RGD positive regulation of transcription Inferred from expression pattern. Source: RGD positive regulation of translation Inferred from mutant phenotype. Source: RGD protein amino acid phosphorylation Inferred from direct assay. Source: RGD response to estrogen stimulus Inferred from direct assay. Source: RGD sensory perception of pain Inferred from mutant phenotype. Source: UniProtKB
Cellular component	axon part Inferred from direct assay. Source: RGD cytosol Inferred from direct assay. Source: RGD dendrite cytoplasm Inferred from direct assay. Source: RGD insoluble fraction Inferred from direct assay. Source: RGD nucleoplasm Inferred from direct assay. Source: UniProtKB perikaryon Inferred from direct assay. Source: RGD protein complex Inferred from direct assay. Source: RGD soluble fraction Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from direct assay. Source: RGD MAP kinase activity Inferred from direct assay. Source: UniProtKB mitogen-activated protein kinase kinase kinase binding Inferred from physical interaction. Source: RGD transcription factor binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2

Chain

2 – 358

357

Mitogen-activated protein kinase 1

PRO_0000186249

Regions

Domain

23 – 311

289

Protein kinase

Nucleotide binding

29 – 37

9

ATP

Motif

183 – 185

3

TXY

Compositional bias

2 – 7

6

Poly-Ala

Sites

Active site

147

1

Proton acceptor

Binding site

52

1

ATP

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.2

Modified residue

183

1

Phosphothreonine By similarity

Modified residue

185

1

Phosphotyrosine By similarity

Modified residue

188

1

Phosphothreonine Ref.6

Modified residue

200

1

Phosphoserine By similarity

Secondary structure

1

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358

Helix Strand Turn

Details...

Helix

20 – 22

3

Beta strand

23 – 31

9

Beta strand

36 – 42

7

Turn

43 – 46

4

Beta strand

47 – 54

8

Helix

60 – 75

16

Beta strand

84 – 88

5

Turn

93 – 95

3

Beta strand

99 – 104

6

Beta strand

107 – 109

3

Helix

110 – 114

5

Helix

121 – 140

20

Helix

150 – 152

3

Beta strand

153 – 155

3

Beta strand

161 – 163

3

Helix

174 – 176

3

Helix

189 – 191

3

Helix

194 – 196

3

Turn

197 – 199

3

Helix

206 – 221

16

Helix

231 – 242

12

Helix

247 – 250

4

Helix

256 – 263

8

Helix

273 – 276

4

Helix

282 – 291

10

Turn

296 – 298

3

Helix

302 – 306

5

Helix

309 – 311

3

Turn

312 – 314

3

Helix

317 – 319

3

Helix

338 – 349

12

Sequences

	Sequence		Length	Mass (Da)
	P63086-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3BBCF22471EDBA0B	FASTA	358	41,276
	10 20 30 40 50 60 MAAAAAAGPE MVRGQVFDVG PRYTNLSYIG EGAYGMVCSA YDNLNKVRVA IKKISPFEHQ 70 80 90 100 110 120 TYCQRTLREI KILLRFRHEN IIGINDIIRA PTIEQMKDVY IVQDLMETDL YKLLKTQHLS 130 140 150 160 170 180 NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLLNTTCD LKICDFGLAR VADPDHDHTG 190 200 210 220 230 240 FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML SNRPIFPGKH YLDQLNHILG 250 260 270 280 290 300 ILGSPSQEDL NCIINLKARN YLLSLPHKNK VPWNRLFPNA DSKALDLLDK MLTFNPHKRI 310 320 330 340 350 EVEQALAHPY LEQYYDPSDE PIAEAPFKFD MELDDLPKEK LKELIFEETA RFQPGYRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylated in response to insulin and NGF." Boulton T.G., Nye S.H., Robbins D.J., Ip N.Y., Radziejewska E., Morgenbesser S.D., DePinho R.A., Panayotatos N., Cobb M.H., Yancopoulos G.D. Cell 65:663-675(1991) [PubMed: 2032290] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Brain.
[2]	Bienvenut W.V., von Kriegsheim A.F., Kolch W. Submitted (AUG-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 69-75; 137-170; 193-201 AND 341-351, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Pheochromocytoma.
[3]	Lubec G., Kang S.U. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 163-170, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain.
[4]	"Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation." Seger R., Ahn N.G., Boulton T.G., Yancopoulos G.D., Panayotatos N., Radziejewska E., Ericsson L., Bratlien R.L., Cobb M.H., Krebs E.G. Proc. Natl. Acad. Sci. U.S.A. 88:6142-6146(1991) [PubMed: 1712480] [Abstract] Cited for: AUTOPHOSPHORYLATION.
[5]	"PHAS-I as a link between mitogen-activated protein kinase and translation initiation." Lin T.-A., Kong X., Haystead T.A.J., Pause A., Belsham G.J., Sonenberg N., Lawrence J.C. Jr. Science 266:653-656(1994) [PubMed: 7939721] [Abstract] Cited for: PHOSPHORYLATION OF EIF4EBP1.
[6]	"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites." Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A. Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed: 16641100] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183; TYR-185 AND THR-188, MASS SPECTROMETRY. Tissue: Kidney.
[7]	"Identification of pY19-Caveolin-2 as a positive regulator of insulin-stimulated actin cytoskeleton-dependent mitogenesis." Kwon H., Jeong K., Pak Y. J. Cell. Mol. Med. 0:0-0(2008) [PubMed: 18624764] [Abstract] Cited for: INTERACTION WITH CAV2.
[8]	"Caveolin-2 regulation of STAT3 transcriptional activation in response to insulin." Kwon H., Jeong K., Hwang E.M., Park J.-Y., Hong S.-G., Choi W.-S., Pak Y. Biochim. Biophys. Acta 1793:1325-1333(2009) [PubMed: 19427337] [Abstract] Cited for: INTERACTION WITH CAV2.
[9]	"Atomic structure of the MAP kinase ERK2 at 2.3-A resolution." Zhang F., Strand A., Robbins D., Cobb M.H., Goldsmith E.J. Nature 367:704-710(1994) [PubMed: 8107865] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[10]	"Activation mechanism of the MAP kinase ERK2 by dual phosphorylation." Canagarajah B.J., Khokhlatchev A., Cobb M.H., Goldsmith E.J. Cell 90:859-869(1997) [PubMed: 9298898] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M64300 mRNA. Translation: AAA41124.1.

IPI

IPI00199688.

PIR

A40033.

RefSeq

NP_446294.1.

UniGene

Rn.34914

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ERK	X-ray	2.30	A	1-358	[»]
1GOL	X-ray	2.80	A	1-358	[»]
2ERK	X-ray	2.40	A	1-358	[»]
2FYS	X-ray	2.50	A/B	2-357	[»]
2GPH	X-ray	1.90	A	2-357	[»]
2Z7L	X-ray	2.41	A	1-358	[»]
3C9W	X-ray	2.50	A/B	2-358	[»]
3ERK	X-ray	2.10	A	1-358	[»]
4ERK	X-ray	2.20	A	1-358	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:29117N.

STRING

P63086.

PTM databases

PhosphoSite

P63086.

Proteomic databases

PRIDE

P63086.

Genome annotation databases

Ensembl

ENSRNOT00000002533; ENSRNOP00000002533; ENSRNOG00000001849; Rattus norvegicus. [Genome view]

GeneID

116590.

KEGG

rno:116590.

Organism-specific databases

CTD

116590.

RGD

70500. Mapk1.

Phylogenomic databases

HOVERGEN

P63086.

Enzyme and pathway databases

BRENDA

2.7.11.24. 248.

Gene expression databases

ArrayExpress

P63086.

Genevestigator

P63086.

GermOnline

ENSRNOG00000001849. Rattus norvegicus.

Family and domain databases

InterPro

IPR008349. Erk_1_2_MAPK.
IPR003527. MAP_kinase_CS.
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

PR01770. ERK1ERK2MAPK.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS01351. MAPK. 1 hit.
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

619269.

Entry information

Entry name

MK01_RAT

Accession

Primary (citable) accession number: P63086
Secondary accession number(s): P27703

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	January 23, 2007
Last modified:	October 13, 2009
This is version 73 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)