P46196 (MK01_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase 1
Short name=MAP kinase 1
Short name=MAPK 1
EC=2.7.11.24

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

Gene names

Name:	MAPK1
Synonyms:	ERK2, PRKM1

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	360 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The the MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additionnal cytosolic and nuclear targets, thereby extending the specificity of the cascade By similarity. Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-185 and Tyr-187 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephospphorylated and inactivated by DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors By similarity.
Subunit structure	Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, MKNK2, DUSP6, MORG1, NISCH, PEA15, SGK1, and isoform 1 of NEK2 By similarity. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation By similarity. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm › cytoskeleton › centrosome By similarity. Cytoplasm By similarity. Note: PEA15-binding and phosphorylated DAPK1 promote its cytoplasmic retention By similarity. Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization By similarity.
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Phosphorylated upon FLT3 and KIT signaling By similarity. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2 By similarity. Phosphorylation at Ser-246 and Ser-248 as well as autophosphorylation at Thr-190 promote nuclear localization. Ligand-activated ALK induces tyrosine phosphorylation By similarity. Dephosphorylated by PTPRJ at Tyr-187 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	Apoptosis Cell cycle
Cellular component	Cytoplasm Cytoskeleton Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell
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
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 360	359	Mitogen-activated protein kinase 1		PRO_0000186246
Regions
	Domain	25 – 313	289	Protein kinase
	Nucleotide binding	31 – 39	9	ATP By similarity
	Region	105 – 108	4	Inhibitor-binding By similarity
	Region	153 – 154	2	Inhibitor-binding By similarity
	Motif	185 – 187	3	TXY
	Compositional bias	2 – 9	8	Poly-Ala
Sites
	Active site	149	1	Proton acceptor By similarity
	Binding site	54	1	ATP By similarity
	Binding site	54	1	Inhibitor By similarity
	Binding site	108	1	Inhibitor; via amide nitrogen and carbonyl oxygen By similarity
	Binding site	114	1	Inhibitor By similarity
	Binding site	154	1	Inhibitor By similarity
	Binding site	166	1	Inhibitor By similarity
	Binding site	167	1	Inhibitor By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine By similarity
	Modified residue	29	1	Phosphoserine; by SGK1 By similarity
	Modified residue	63	1	Phosphothreonine By similarity
	Modified residue	181	1	Phosphothreonine By similarity
	Modified residue	185	1	Phosphothreonine; by MAP2K1 and MAP2K2 By similarity
	Modified residue	187	1	Phosphotyrosine; by MAP2K1 and MAP2K2 By similarity
	Modified residue	190	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	202	1	Phosphoserine By similarity
	Modified residue	246	1	Phosphoserine By similarity
	Modified residue	248	1	Phosphoserine By similarity
	Modified residue	284	1	Phosphoserine By similarity

Sequences

	Sequence		Length	Mass (Da)
	P46196 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: E85D0B2A4E9549DE	FASTA	360	41,376
	10 20 30 40 50 60 MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR VAIKKISPFE 70 80 90 100 110 120 HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD VYIVQDLMET DLYKLLKTQH 130 140 150 160 170 180 LSNDHICYFL YQILRGLKYI HSANVLHRDL KPSNLLLNTT CDLKICDFGL ARVADPDHDH 190 200 210 220 230 240 TGFLTEYVAT RWYRAPEIML NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI 250 260 270 280 290 300 LGILGSPSQE DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK 310 320 330 340 350 360 RIEVEQALAH PYLEQYYDPS DEPVAEAPFK FDMELDDLPK EKLKELIFEE TARFQPGYRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and sequencing of ERK2 from a bovine adrenal medulla cDNA library." Ely C.M., Cox M.E., Her J., Parsons S.J. Submitted (JUL-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal medulla.
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Hereford. Tissue: Fetal pons.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z14089 mRNA. Translation: CAA78467.1. BC133588 mRNA. Translation: AAI33589.2.
IPI	IPI00713672.
PIR	S25011.
RefSeq	NP_786987.1. NM_175793.2.
UniGene	Bt.167.
3D structure databases
ProteinModelPortal	P46196.
SMR	P46196. Positions 8-357.
ModBase	Search...
Protein-protein interaction databases
STRING	P46196.
Proteomic databases
PRIDE	P46196.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	327672.
KEGG	bta:327672.
Organism-specific databases
CTD	5594.
Phylogenomic databases
eggNOG	maNOG17378.
HOVERGEN	HBG014652.
PhylomeDB	P46196.
Family and domain databases
InterPro	IPR008349. Erk_1_2_MAPK. IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K04371.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR01770. ERK1ERK2MAPK.
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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...

Entry information

Entry name

MK01_BOVIN

Accession

Primary (citable) accession number: P46196
Secondary accession number(s): A2VE60

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 106 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program