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P46196 (MK01_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismBos taurus (Bovine) [Reference proteome]
Taxonomic identifier9913 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos

Protein attributes

Sequence length360 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 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, DCC, 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 additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. May play a role in the spindle assembly checkpoint By similarity. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation 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. Dephosphorylated 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 1of 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 1binding prevents from dephosphorylation and inactivation By similarity. Interacts with DCC By similarity. The phosphorylated form interacts with PML By similarity.

Subcellular location

Nucleus By similarity. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome By similarity. Cytoplasm By similarity. Cytoplasmcytoskeletonspindle 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. Associated with the spindle during prometaphase and metaphase 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.

ISGylated 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 processApoptosis
Cell cycle
   Cellular componentCytoplasm
Cytoskeleton
Nucleus
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

ERBB signaling pathway

Inferred from electronic annotation. Source: Ensembl

ERK1 and ERK2 cascade

Inferred from electronic annotation. Source: Ensembl

T cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

cytosine metabolic process

Inferred from electronic annotation. Source: Ensembl

labyrinthine layer blood vessel development

Inferred from electronic annotation. Source: Ensembl

lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

mammary gland epithelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell differentiation

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of protein stability

Inferred from sequence or structural similarity. Source: UniProtKB

response to epidermal growth factor

Inferred from sequence or structural similarity. Source: UniProtKB

response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from electronic annotation. Source: Ensembl

microtubule organizing center

Inferred from electronic annotation. Source: UniProtKB-SubCell

mitochondrion

Inferred from electronic annotation. Source: Ensembl

mitotic spindle

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

pseudopodium

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

RNA polymerase II carboxy-terminal domain kinase activity

Inferred from electronic annotation. Source: Ensembl

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 360359Mitogen-activated protein kinase 1
PRO_0000186246

Regions

Domain25 – 313289Protein kinase
Nucleotide binding31 – 399ATP By similarity
Region105 – 1084Inhibitor-binding By similarity
Region153 – 1542Inhibitor-binding By similarity
Motif185 – 1873TXY
Compositional bias2 – 98Poly-Ala

Sites

Active site1491Proton acceptor By similarity
Binding site541ATP By similarity
Binding site541Inhibitor By similarity
Binding site1081Inhibitor; via amide nitrogen and carbonyl oxygen By similarity
Binding site1141Inhibitor By similarity
Binding site1541Inhibitor By similarity
Binding site1661Inhibitor By similarity
Binding site1671Inhibitor By similarity

Amino acid modifications

Modified residue21N-acetylalanine By similarity
Modified residue291Phosphoserine; by SGK1 By similarity
Modified residue1851Phosphothreonine; by MAP2K1 and MAP2K2 By similarity
Modified residue1871Phosphotyrosine; by MAP2K1 and MAP2K2 By similarity
Modified residue1901Phosphothreonine; by autocatalysis By similarity
Modified residue2461Phosphoserine By similarity
Modified residue2481Phosphoserine By similarity
Modified residue2841Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P46196 [UniParc].

Last modified January 23, 2007. Version 3.
Checksum: E85D0B2A4E9549DE

FASTA36041,376
        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 

« Hide

References

« Hide '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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z14089 mRNA. Translation: CAA78467.1.
BC133588 mRNA. Translation: AAI33589.2.
PIRS25011.
RefSeqNP_786987.1. NM_175793.2.
UniGeneBt.109487.

3D structure databases

ProteinModelPortalP46196.
SMRP46196. Positions 8-357.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9913.ENSBTAP00000013623.

Proteomic databases

PRIDEP46196.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID327672.
KEGGbta:327672.

Organism-specific databases

CTD5594.

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG014652.
KOK04371.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR003527. MAP_kinase_CS.
IPR008349. MAPK_ERK1/2.
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]
PRINTSPR01770. ERK1ERK2MAPK.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio20810137.

Entry information

Entry nameMK01_BOVIN
AccessionPrimary (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: June 11, 2014
This is version 126 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families