Reviewed, UniProtKB/Swiss-Prot P21708 (MK03_RAT)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase 3
    EC=2.7.11.24
Alternative name(s):
    Extracellular signal-regulated kinase 1
      Short name=ERK-1
    Insulin-stimulated MAP2 kinase
    MAP kinase 1
      Short name=MAPK 1
    p44-ERK1
    ERT2
    p44-MAPK
    Microtubule-associated protein 2 kinase
    MNK1

Gene names

Name:	Mapk3
Synonyms:	Erk1, Prkm3

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	380 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 ELK-1. Phosphorylates EIF4EBP1; required for initiation of translation. Phosphorylates microtubule-associated protein 2 (MAP2). Phosphorylates SPZ1. Phosphorylates heat shock factor protein 4 (HSF4) By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated and tyrosine phosphorylated in response to insulin and NGF.
Subunit structure	Interacts with NISCH, MORG1 and HSF4 By similarity.
Subcellular location	Isoform 2: Nucleus.
Tissue specificity	Highest levels within the nervous system, expressed in different tissues, mostly in intestine, placenta and lung.
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-203 and Tyr-205, which activates the enzyme. Ref.3 Ref.9 Ref.10 Ref.11
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
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	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 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 protein complex assembly Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: RGD insoluble fraction Inferred from direct assay. Source: RGD nucleoplasm Inferred from direct assay. Source: UniProtKB 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 protein binding Inferred from direct assay. Source: RGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P21708-1)

Also known as: A;

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: P21708-2)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     340-340: E → EVSRPPAAGRGISVPSVRPVPYCLCPQ

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.3
	Chain	2 – 380	379	Mitogen-activated protein kinase 3		PRO_0000186253
Regions
	Domain	43 – 331	289	Protein kinase
	Nucleotide binding	49 – 57	9	ATP By similarity
	Motif	203 – 205	3	TXY
Sites
	Active site	167	1	Proton acceptor By similarity
	Binding site	72	1	ATP By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.3
	Modified residue	203	1	Phosphothreonine Ref.3 Ref.11
	Modified residue	205	1	Phosphotyrosine Ref.3 Ref.11
Natural variations
	Alternative sequence	340	1	E → EVSRPPAAGRGISVPSVRPV PYCLCPQ in isoform 2.		VSP_004830
Experimental info
	Sequence conflict	95	1	R → G Ref.1
	Sequence conflict	95	1	R → G Ref.4
	Sequence conflict	95	1	R → G Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (A) [UniParc]. Last modified January 23, 2007. Version 5. Checksum: 49C4EA95B627237F	FASTA	380	43,081
	10 20 30 40 50 60 MAAAAAAPGG GGGEPRGTAG VVPVVPGEVE VVKGQPFDVG PRYTQLQYIG EGAYGMVSSA 70 80 90 100 110 120 YDHVRKTRVA IKKISPFEHQ TYCQRTLREI QILLRFRHEN VIGIRDILRA PTLEAMRDVY 130 140 150 160 170 180 IVQDLMETDL YKLLKSQQLS NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLINTTCD 190 200 210 220 230 240 LKICDFGLAR IADPEHDHTG FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML 250 260 270 280 290 300 SNRPIFPGKH YLDQLNHILG ILGSPSQEDL NCIINMKARN YLQSLPSKTK VAWAKLFPKS 310 320 330 340 350 360 DSKALDLLDR MLTFNPNKRI TVEEALAHPY LEQYYDPTDE PVAEEPFTFD MELDDLPKER 370 380 LKELIFQETA RFQPGAPEAP
	Isoform 2 (B). Checksum: 2F40B2DFA5A116B0	FASTA	406	45,770
	10 20 30 40 50 60 MAAAAAAPGG GGGEPRGTAG VVPVVPGEVE VVKGQPFDVG PRYTQLQYIG EGAYGMVSSA 70 80 90 100 110 120 YDHVRKTRVA IKKISPFEHQ TYCQRTLREI QILLRFRHEN VIGIRDILRA PTLEAMRDVY 130 140 150 160 170 180 IVQDLMETDL YKLLKSQQLS NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLINTTCD 190 200 210 220 230 240 LKICDFGLAR IADPEHDHTG FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML 250 260 270 280 290 300 SNRPIFPGKH YLDQLNHILG ILGSPSQEDL NCIINMKARN YLQSLPSKTK VAWAKLFPKS 310 320 330 340 350 360 DSKALDLLDR MLTFNPNKRI TVEEALAHPY LEQYYDPTDE VSRPPAAGRG ISVPSVRPVP 370 380 390 400 YCLCPQPVAE EPFTFDMELD DLPKERLKEL IFQETARFQP GAPEAP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of a rat cDNA encoding the ERK1-MAP kinase." Marquardt B., Stabel S. Gene 120:297-299(1992) [PubMed: 1327976] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: Sprague-Dawley. Tissue: Brain.
[2]	"ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK." Yung Y., Yao Z., Hanoch T., Seger R. J. Biol. Chem. 275:15799-15808(2000) [PubMed: 10748187] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]	Bienvenut W.V., von Kriegsheim A.F., Kolch W. Submitted (AUG-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-65; 96-132; 157-209; 213-221; 280-357 AND 361-380 (ISOFORM 2), CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, PHOSPHORYLATION AT THR-203 AND TYR-205, MASS SPECTROMETRY. Tissue: Pheochromocytoma.
[4]	Maisonpierre P.C., le Beau M.M., Espinosa R. III, Ip N.Y., Belluscio L., la Monte S.M., Squinto S., Furth M.E., Yancopoulos G.D. Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-380 (ISOFORM 1).
[5]	Lubec G., Afjehi-Sadat L., Kang S.U. Submitted (JUL-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 73-84 AND 183-190, MASS SPECTROMETRY. Strain: Sprague-Dawley. Tissue: Brain and Spinal cord.
[6]	"An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control." Boulton T.G., Yancopoulos G.D., Gregory J.S., Slaughter C., Moomaw C., Hsu J., Cobb M.H. Science 249:64-67(1990) [PubMed: 2164259] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-380 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[7]	"Molecular analysis of microtubule-associated protein-2 kinase cDNA from mouse and rat brain." de Miguel C., Kligman D., Patel J., Detera-Wadleigh S.D. DNA Cell Biol. 10:505-514(1991) [PubMed: 1716439] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-380 (ISOFORM 1). Tissue: Brain cortex.
[8]	"Purification and properties of extracellular signal-regulated kinase 1, an insulin-stimulated microtubule-associated protein 2 kinase." Boulton T.G., Gregory J.S., Cobb M.H. Biochemistry 30:278-286(1991) [PubMed: 1846291] [Abstract] Cited for: PROTEIN SEQUENCE OF 43-64 AND 167-185, CHARACTERIZATION.
[9]	"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.
[10]	"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.
[11]	"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-203 AND TYR-205, MASS SPECTROMETRY. Tissue: Kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	S46779 mRNA. Translation: AAA11604.1. X65198 mRNA. Translation: CAA46318.1. AF155236 mRNA. Translation: AAF71666.1. M61177 mRNA. Translation: AAA63486.1. M38194 mRNA. Translation: AAA41123.1. U12008 mRNA. Translation: AAA20009.1.
IPI	IPI00206172. IPI00231081.
PIR	JC1451.
RefSeq	NP_059043.1.
UniGene	Rn.2592
3D structure databases
HSSP	HSSP built from PDB template 1PME based on UniProtKB P28482.
SMR	P21708. Positions 30-374.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:487N.
STRING	P21708.
PTM databases
PhosphoSite	P21708.
Genome annotation databases
Ensembl	ENSRNOT00000026627; ENSRNOP00000026627; ENSRNOG00000019601; Rattus norvegicus. [Genome view]
GeneID	50689.
KEGG	rno:50689.
NMPDR	fig|10116.3.peg.2990.
UCSC	NM_017347. rat.
Organism-specific databases
CTD	50689.
RGD	3046. Mapk3.
Phylogenomic databases
HOVERGEN	P21708.
OMA	EALETEP.
Enzyme and pathway databases
BRENDA	2.7.11.24. 248.
Gene expression databases
ArrayExpress	P21708.
Genevestigator	P21708.
GermOnline	ENSRNOG00000019601. 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	610550.

Entry information

Entry name

MK03_RAT

Accession

Primary (citable) accession number: P21708
Secondary accession number(s): Q4PIY8, Q62686, Q9JJ13

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 1991
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 115 of the entry and version 5 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)