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P46196

- MK01_BOVIN

UniProt

P46196 - MK01_BOVIN

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Protein
Mitogen-activated protein kinase 1
Gene
MAPK1, ERK2, PRKM1
Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

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 activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium By similarity.

Enzyme regulationi

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei54 – 541ATP By similarity
Binding sitei54 – 541Inhibitor By similarity
Binding sitei108 – 1081Inhibitor; via amide nitrogen and carbonyl oxygen By similarity
Binding sitei114 – 1141Inhibitor By similarity
Active sitei149 – 1491Proton acceptor By similarity
Binding sitei154 – 1541Inhibitor By similarity
Binding sitei166 – 1661Inhibitor By similarity
Binding sitei167 – 1671Inhibitor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi31 – 399ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. MAP kinase activity Source: UniProtKB-EC
  3. RNA polymerase II carboxy-terminal domain kinase activity Source: Ensembl
  4. protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  1. B cell receptor signaling pathway Source: Ensembl
  2. ERBB signaling pathway Source: Ensembl
  3. ERK1 and ERK2 cascade Source: Ensembl
  4. T cell receptor signaling pathway Source: Ensembl
  5. apoptotic process Source: UniProtKB-KW
  6. cell cycle Source: UniProtKB-KW
  7. cellular response to DNA damage stimulus Source: Ensembl
  8. cytosine metabolic process Source: Ensembl
  9. labyrinthine layer blood vessel development Source: Ensembl
  10. lipopolysaccharide-mediated signaling pathway Source: Ensembl
  11. mammary gland epithelial cell proliferation Source: Ensembl
  12. negative regulation of cell differentiation Source: Ensembl
  13. organ morphogenesis Source: Ensembl
  14. peptidyl-serine phosphorylation Source: UniProtKB
  15. peptidyl-threonine phosphorylation Source: UniProtKB
  16. positive regulation of peptidyl-threonine phosphorylation Source: Ensembl
  17. regulation of protein stability Source: UniProtKB
  18. response to epidermal growth factor Source: UniProtKB
  19. response to exogenous dsRNA Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_202074. FCERI mediated MAPK activation.
REACT_202837. Signaling by FGFR.
REACT_203126. phospho-PLA2 pathway.
REACT_203215. Senescence-Associated Secretory Phenotype (SASP).
REACT_204725. Advanced glycosylation endproduct receptor signaling.
REACT_205036. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_207562. Negative regulation of FGFR signaling.
REACT_209393. Growth hormone receptor signaling.
REACT_210032. ERK2 activation.
REACT_211475. Regulation of actin dynamics for phagocytic cup formation.
REACT_215912. Thrombin signalling through proteinase activated receptors (PARs).
REACT_216684. Signal transduction by L1.
REACT_217282. NCAM signaling for neurite out-growth.
REACT_217767. Oncogene Induced Senescence.
REACT_218305. CREB phosphorylation through the activation of Ras.
REACT_218726. Regulation of HSF1-mediated heat shock response.
REACT_220172. Golgi Cisternae Pericentriolar Stack Reorganization.
REACT_220398. ERKs are inactivated.
REACT_221197. Activation of the AP-1 family of transcription factors.
REACT_222627. RSK activation.
REACT_223433. Recycling pathway of L1.
REACT_225657. Oxidative Stress Induced Senescence.
REACT_226850. ERK/MAPK targets.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 1 (EC:2.7.11.24)
Short name:
MAP kinase 1
Short name:
MAPK 1
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 namesi
Name:MAPK1
Synonyms:ERK2, PRKM1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Unplaced

Subcellular locationi

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.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Ensembl
  3. microtubule organizing center Source: UniProtKB-SubCell
  4. mitochondrion Source: Ensembl
  5. mitotic spindle Source: UniProtKB
  6. nucleus Source: UniProtKB
  7. pseudopodium Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed By similarity
Chaini2 – 360359Mitogen-activated protein kinase 1
PRO_0000186246Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanine By similarity
Modified residuei29 – 291Phosphoserine; by SGK1 By similarity
Modified residuei185 – 1851Phosphothreonine; by MAP2K1 and MAP2K2 By similarity
Modified residuei187 – 1871Phosphotyrosine; by MAP2K1 and MAP2K2 By similarity
Modified residuei190 – 1901Phosphothreonine; by autocatalysis By similarity
Modified residuei246 – 2461Phosphoserine By similarity
Modified residuei248 – 2481Phosphoserine By similarity
Modified residuei284 – 2841Phosphoserine By similarity

Post-translational modificationi

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.

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP46196.

Interactioni

Subunit structurei

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. Interacts with DCC By similarity. The phosphorylated form interacts with PML By similarity. Interacts with STYX By similarity.

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000013623.

Structurei

3D structure databases

ProteinModelPortaliP46196.
SMRiP46196. Positions 8-357.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini25 – 313289Protein kinase
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni105 – 1084Inhibitor-binding By similarity
Regioni153 – 1542Inhibitor-binding By similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi185 – 1873TXY

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi2 – 98Poly-Ala

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Sequence similaritiesi

Phylogenomic databases

eggNOGiCOG0515.
HOVERGENiHBG014652.
KOiK04371.

Family and domain databases

InterProiIPR011009. 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]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PRINTSiPR01770. ERK1ERK2MAPK.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P46196-1 [UniParc]FASTAAdd to Basket

« Hide

MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR    50
VAIKKISPFE HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD 100
VYIVQDLMET DLYKLLKTQH LSNDHICYFL YQILRGLKYI HSANVLHRDL 150
KPSNLLLNTT CDLKICDFGL ARVADPDHDH TGFLTEYVAT RWYRAPEIML 200
NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI LGILGSPSQE 250
DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK 300
RIEVEQALAH PYLEQYYDPS DEPVAEAPFK FDMELDDLPK EKLKELIFEE 350
TARFQPGYRS 360
Length:360
Mass (Da):41,376
Last modified:January 23, 2007 - v3
Checksum:iE85D0B2A4E9549DE
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z14089 mRNA. Translation: CAA78467.1.
BC133588 mRNA. Translation: AAI33589.2.
PIRiS25011.
RefSeqiNP_786987.1. NM_175793.2.
UniGeneiBt.109487.

Genome annotation databases

GeneIDi327672.
KEGGibta:327672.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z14089 mRNA. Translation: CAA78467.1 .
BC133588 mRNA. Translation: AAI33589.2 .
PIRi S25011.
RefSeqi NP_786987.1. NM_175793.2.
UniGenei Bt.109487.

3D structure databases

ProteinModelPortali P46196.
SMRi P46196. Positions 8-357.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9913.ENSBTAP00000013623.

Proteomic databases

PRIDEi P46196.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 327672.
KEGGi bta:327672.

Organism-specific databases

CTDi 5594.

Phylogenomic databases

eggNOGi COG0515.
HOVERGENi HBG014652.
KOi K04371.

Enzyme and pathway databases

Reactomei REACT_202074. FCERI mediated MAPK activation.
REACT_202837. Signaling by FGFR.
REACT_203126. phospho-PLA2 pathway.
REACT_203215. Senescence-Associated Secretory Phenotype (SASP).
REACT_204725. Advanced glycosylation endproduct receptor signaling.
REACT_205036. Gastrin-CREB signalling pathway via PKC and MAPK.
REACT_207562. Negative regulation of FGFR signaling.
REACT_209393. Growth hormone receptor signaling.
REACT_210032. ERK2 activation.
REACT_211475. Regulation of actin dynamics for phagocytic cup formation.
REACT_215912. Thrombin signalling through proteinase activated receptors (PARs).
REACT_216684. Signal transduction by L1.
REACT_217282. NCAM signaling for neurite out-growth.
REACT_217767. Oncogene Induced Senescence.
REACT_218305. CREB phosphorylation through the activation of Ras.
REACT_218726. Regulation of HSF1-mediated heat shock response.
REACT_220172. Golgi Cisternae Pericentriolar Stack Reorganization.
REACT_220398. ERKs are inactivated.
REACT_221197. Activation of the AP-1 family of transcription factors.
REACT_222627. RSK activation.
REACT_223433. Recycling pathway of L1.
REACT_225657. Oxidative Stress Induced Senescence.
REACT_226850. ERK/MAPK targets.

Miscellaneous databases

NextBioi 20810137.

Family and domain databases

InterProi IPR011009. 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 ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PRINTSi PR01770. ERK1ERK2MAPK.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS01351. MAPK. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiMK01_BOVIN
AccessioniPrimary (citable) accession number: P46196
Secondary accession number(s): A2VE60
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: January 23, 2007
Last modified: September 3, 2014
This is version 127 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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