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Protein

Mitogen-activated protein kinase 1

Gene

MAPK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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. Mediates phosphorylation of TPR in respons to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).4 PublicationsBy similarity25 Publications
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.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Activity 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 DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei54ATPPROSITE-ProRule annotation1
Binding sitei54Inhibitor6 Publications1
Binding sitei108Inhibitor; via amide nitrogen and carbonyl oxygen6 Publications1
Binding sitei114Inhibitor6 Publications1
Active sitei149Proton acceptorPROSITE-ProRule annotation1
Binding sitei154Inhibitor6 Publications1
Binding sitei166Inhibitor6 Publications1
Binding sitei167Inhibitor6 Publications1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi31 – 39ATPPROSITE-ProRule annotation9
DNA bindingi259 – 277Add BLAST19

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Kinase, Repressor, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, Host-virus interaction, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-111995 phospho-PLA2 pathway
R-HSA-112409 RAF-independent MAPK1/3 activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-437239 Recycling pathway of L1
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-444257 RSK activation
R-HSA-445144 Signal transduction by L1
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5674499 Negative feedback regulation of MAPK pathway
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6798695 Neutrophil degranulation
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74749 Signal attenuation
R-HSA-879415 Advanced glycosylation endproduct receptor signaling
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-8939211 ESR-mediated signaling
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiP28482
SIGNORiP28482

Protein family/group databases

MoonDBiP28482 Predicted
MoonProtiP28482

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
MAP kinase isoform p42
Short name:
p42-MAPK
Mitogen-activated protein kinase 2
Short name:
MAP kinase 2
Short name:
MAPK 2
Gene namesi
Name:MAPK1
Synonyms:ERK2, PRKM1, PRKM2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100030.14
HGNCiHGNC:6871 MAPK1
MIMi176948 gene
neXtProtiNX_P28482

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi54K → R: Does not inhibit interaction with MAP2K1. 1 Publication1
Mutagenesisi176 – 179Missing : Inhibits homodimerization and interaction with TPR. 1 Publication4
Mutagenesisi185T → A: Inhibits interaction with TPR; when associated with A-187. 1 Publication1
Mutagenesisi187Y → A: Inhibits interaction with TPR; when associated with A-185. 1 Publication1
Mutagenesisi234L → A: Inhibits interaction with TPR. 1 Publication1
Mutagenesisi318D → A: Loss of dephosphorylation by PTPRJ. 2 Publications1
Mutagenesisi318D → N: Inhibits interaction with MAP2K1 but not with TPR; when associated with N-321. 2 Publications1
Mutagenesisi321D → N: Inhibits interaction with MAP2K1 but not with TPR; when associated with N-318. 1 Publication1

Organism-specific databases

DisGeNETi5594
MalaCardsiMAPK1
OpenTargetsiENSG00000100030
Orphaneti261330 Distal 22q11.2 microdeletion syndrome
PharmGKBiPA30616

Chemistry databases

ChEMBLiCHEMBL4040
DrugBankiDB07264 (S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDE
DB08521 4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE
DB08513 [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID
DB01169 Arsenic trioxide
DB01064 Isoprenaline
DB07010 N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDE
DB02116 Olomoucine
DB02482 Phosphonothreonine
DB02733 Purvalanol
DB04338 SB220025
DB11120 Turpentine
GuidetoPHARMACOLOGYi1495

Polymorphism and mutation databases

BioMutaiMAPK1
DMDMi119554

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001862472 – 360Mitogen-activated protein kinase 1Add BLAST359

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei29Phosphoserine; by SGK11 Publication1
Modified residuei185Phosphothreonine; by MAP2K1 and MAP2K2Combined sources1
Modified residuei187Phosphotyrosine; by MAP2K1 and MAP2K2Combined sources2 Publications1
Modified residuei190Phosphothreonine; by autocatalysis1 Publication1
Modified residuei246Phosphoserine1 Publication1
Modified residuei248Phosphoserine1 Publication1
Modified residuei284PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-185 and Tyr-187, which activates the enzyme. Undergoes regulatory phosphorylation on additional residues such as Ser-246 and Ser-248 in the kinase insert domain (KID) These phosphorylations, which are probably mediated by more than one kinase, are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its nuclear translocation. In addition, autophosphorylation of Thr-190 was shown to affect the subcellular localization of MAPK1/ERK2 as well. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2 and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs. Dephosphorylated by DUSP1 at Thr-185 and Tyr-187.By similarity7 Publications
ISGylated.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP28482
PaxDbiP28482
PeptideAtlasiP28482
PRIDEiP28482
ProteomicsDBi54488

2D gel databases

OGPiP28482

PTM databases

iPTMnetiP28482
PhosphoSitePlusiP28482
SwissPalmiP28482

Expressioni

Gene expression databases

BgeeiENSG00000100030 Expressed in 241 organ(s), highest expression level in putamen
CleanExiHS_MAPK1
ExpressionAtlasiP28482 baseline and differential
GenevisibleiP28482 HS

Organism-specific databases

HPAiCAB004229
HPA003995
HPA005700
HPA030069

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, DUSP6, NISCH, SGK1, and isoform 1 of NEK2. Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with MORG1, PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with DCC (By similarity). The phosphorylated form interacts with PML (isoform PML-4). Interacts with STYX. Interacts with CDK2AP2. Interacts with CAVIN4 (By similarity). Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity (PubMed:9788880).By similarity22 Publications
(Microbial infection) Interacts with HIV-1 Nef through its SH3 domain.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111580, 251 interactors
CORUMiP28482
DIPiDIP-519N
ELMiP28482
IntActiP28482, 101 interactors
MINTiP28482
STRINGi9606.ENSP00000215832

Chemistry databases

BindingDBiP28482

Structurei

Secondary structure

1360
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP28482
SMRiP28482
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP28482

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 313Protein kinasePROSITE-ProRule annotationAdd BLAST289

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni105 – 108Inhibitor-binding4
Regioni153 – 154Inhibitor-binding2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi185 – 187TXY1 Publication3
Motifi318 – 322Cytoplasmic retention motif1 Publication5
Motifi327 – 333Nuclear translocation motif1 Publication7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 9Poly-Ala8

Domaini

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

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP28482
KOiK04371
OMAiDIYIVQC
OrthoDBiEOG091G08QL
PhylomeDBiP28482
TreeFamiTF105097

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P28482-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR
60 70 80 90 100
VAIKKISPFE HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD
110 120 130 140 150
VYIVQDLMET DLYKLLKTQH LSNDHICYFL YQILRGLKYI HSANVLHRDL
160 170 180 190 200
KPSNLLLNTT CDLKICDFGL ARVADPDHDH TGFLTEYVAT RWYRAPEIML
210 220 230 240 250
NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI LGILGSPSQE
260 270 280 290 300
DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK
310 320 330 340 350
RIEVEQALAH PYLEQYYDPS DEPIAEAPFK FDMELDDLPK EKLKELIFEE
360
TARFQPGYRS
Length:360
Mass (Da):41,390
Last modified:January 23, 2007 - v3
Checksum:iE85D0B2A5D2D724E
GO
Isoform 2 (identifier: P28482-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     242-285: Missing.

Show »
Length:316
Mass (Da):36,432
Checksum:i6076E1767B603945
GO

Sequence cautioni

The sequence CAA77753 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti91R → Q in CAA77752 (PubMed:1319925).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_047815242 – 285Missing in isoform 2. 1 PublicationAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84489 mRNA Translation: AAA58459.1
Z11694 mRNA Translation: CAA77752.1
Z11695 mRNA Translation: CAA77753.1 Different initiation.
DQ399292 mRNA Translation: ABD60303.1
AP000553 Genomic DNA No translation available.
AP000554 Genomic DNA No translation available.
AP000555 Genomic DNA No translation available.
BC017832 mRNA Translation: AAH17832.1
CCDSiCCDS13795.1 [P28482-1]
PIRiJQ1400
RefSeqiNP_002736.3, NM_002745.4 [P28482-1]
NP_620407.1, NM_138957.3 [P28482-1]
UniGeneiHs.431850

Genome annotation databases

EnsembliENST00000215832; ENSP00000215832; ENSG00000100030 [P28482-1]
ENST00000398822; ENSP00000381803; ENSG00000100030 [P28482-1]
ENST00000544786; ENSP00000440842; ENSG00000100030 [P28482-2]
GeneIDi5594
KEGGihsa:5594
UCSCiuc010gtk.2 human [P28482-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Wikipedia

Extracellular signal-regulated kinase entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M84489 mRNA Translation: AAA58459.1
Z11694 mRNA Translation: CAA77752.1
Z11695 mRNA Translation: CAA77753.1 Different initiation.
DQ399292 mRNA Translation: ABD60303.1
AP000553 Genomic DNA No translation available.
AP000554 Genomic DNA No translation available.
AP000555 Genomic DNA No translation available.
BC017832 mRNA Translation: AAH17832.1
CCDSiCCDS13795.1 [P28482-1]
PIRiJQ1400
RefSeqiNP_002736.3, NM_002745.4 [P28482-1]
NP_620407.1, NM_138957.3 [P28482-1]
UniGeneiHs.431850

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1PMEX-ray2.00A1-360[»]
1TVOX-ray2.50A1-360[»]
1WZYX-ray2.50A1-360[»]
2OJGX-ray2.00A2-360[»]
2OJIX-ray2.60A2-360[»]
2OJJX-ray2.40A2-360[»]
2Y9QX-ray1.55A1-360[»]
3D42X-ray2.46B184-191[»]
3D44X-ray1.90B184-191[»]
3I5ZX-ray2.20A1-360[»]
3I60X-ray2.50A1-360[»]
3SA0X-ray1.59A1-360[»]
3TEIX-ray2.40A1-360[»]
3W55X-ray3.00A1-360[»]
4FMQX-ray2.10A1-360[»]
4FUXX-ray2.20A1-360[»]
4FUYX-ray2.00A1-360[»]
4FV0X-ray2.10A1-360[»]
4FV1X-ray1.99A1-360[»]
4FV2X-ray2.00A1-360[»]
4FV3X-ray2.20A1-360[»]
4FV4X-ray2.50A1-360[»]
4FV5X-ray2.40A1-360[»]
4FV6X-ray2.50A1-360[»]
4FV7X-ray1.90A1-360[»]
4FV8X-ray2.00A1-360[»]
4FV9X-ray2.11A1-360[»]
4G6NX-ray2.00A1-360[»]
4G6OX-ray2.20A1-360[»]
4H3PX-ray2.30A/D1-360[»]
4H3QX-ray2.20A1-360[»]
4IZ5X-ray3.19A/B/C/D8-360[»]
4IZ7X-ray1.80A/C8-360[»]
4IZAX-ray1.93A/C8-360[»]
4N0SX-ray1.80A1-360[»]
4NIFX-ray2.15B/E1-360[»]
4O6EX-ray1.95A13-360[»]
4QP1X-ray2.70A/B1-360[»]
4QP2X-ray2.23A/B1-360[»]
4QP3X-ray2.60A/B1-360[»]
4QP4X-ray2.20A/B1-360[»]
4QP6X-ray3.10A/B1-360[»]
4QP7X-ray2.25A/B1-360[»]
4QP8X-ray2.45A/B1-360[»]
4QP9X-ray2.00A1-360[»]
4QPAX-ray2.85A/B1-360[»]
4QTAX-ray1.45A1-360[»]
4QTEX-ray1.50A1-360[»]
4XJ0X-ray2.58A/B12-360[»]
4ZXTX-ray2.00A1-360[»]
4ZZMX-ray1.89A11-360[»]
4ZZNX-ray1.33A11-360[»]
4ZZOX-ray1.63A11-360[»]
5AX3X-ray2.98A1-360[»]
5BUEX-ray2.40A2-360[»]
5BUIX-ray2.12A2-360[»]
5BUJX-ray1.85A2-360[»]
5BVDX-ray1.90A2-360[»]
5BVEX-ray2.00A2-360[»]
5BVFX-ray1.90A2-360[»]
5K4IX-ray1.76A9-360[»]
5LCJX-ray1.78A1-360[»]
5LCKX-ray1.89A1-360[»]
5NGUX-ray2.74A1-360[»]
5NHFX-ray2.14A1-360[»]
5NHHX-ray1.94A1-360[»]
5NHJX-ray2.12A1-360[»]
5NHLX-ray2.07A1-360[»]
5NHOX-ray2.24A1-360[»]
5NHPX-ray1.99A1-360[»]
5NHVX-ray2.00A1-360[»]
5V60X-ray2.18A8-360[»]
5V61X-ray2.20A8-360[»]
5V62X-ray1.90A10-360[»]
5WP1X-ray1.40A4-360[»]
6G8XX-ray1.76A1-360[»]
6G91X-ray1.80A1-360[»]
6G92X-ray1.99A1-360[»]
6G93X-ray1.67A1-360[»]
6G97X-ray1.90A1-360[»]
6G9AX-ray1.91A1-360[»]
6G9DX-ray1.80A1-360[»]
6G9HX-ray1.73A1-360[»]
6G9JX-ray1.98A1-360[»]
6G9KX-ray1.94A1-360[»]
6G9MX-ray1.86A1-360[»]
6G9NX-ray1.76A1-360[»]
6GDMX-ray1.91A1-360[»]
6GDQX-ray1.86A1-360[»]
6GE0X-ray1.82A1-360[»]
ProteinModelPortaliP28482
SMRiP28482
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111580, 251 interactors
CORUMiP28482
DIPiDIP-519N
ELMiP28482
IntActiP28482, 101 interactors
MINTiP28482
STRINGi9606.ENSP00000215832

Chemistry databases

BindingDBiP28482
ChEMBLiCHEMBL4040
DrugBankiDB07264 (S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDE
DB08521 4-[5-(4-FLUORO-PHENYL)-2-(4-METHANESULFINYL-PHENYL)-3H-IMIDAZOL-4-YL]-PYRIDINE
DB08513 [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID
DB01169 Arsenic trioxide
DB01064 Isoprenaline
DB07010 N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDE
DB02116 Olomoucine
DB02482 Phosphonothreonine
DB02733 Purvalanol
DB04338 SB220025
DB11120 Turpentine
GuidetoPHARMACOLOGYi1495

Protein family/group databases

MoonDBiP28482 Predicted
MoonProtiP28482

PTM databases

iPTMnetiP28482
PhosphoSitePlusiP28482
SwissPalmiP28482

Polymorphism and mutation databases

BioMutaiMAPK1
DMDMi119554

2D gel databases

OGPiP28482

Proteomic databases

EPDiP28482
PaxDbiP28482
PeptideAtlasiP28482
PRIDEiP28482
ProteomicsDBi54488

Protocols and materials databases

DNASUi5594
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215832; ENSP00000215832; ENSG00000100030 [P28482-1]
ENST00000398822; ENSP00000381803; ENSG00000100030 [P28482-1]
ENST00000544786; ENSP00000440842; ENSG00000100030 [P28482-2]
GeneIDi5594
KEGGihsa:5594
UCSCiuc010gtk.2 human [P28482-1]

Organism-specific databases

CTDi5594
DisGeNETi5594
EuPathDBiHostDB:ENSG00000100030.14
GeneCardsiMAPK1
HGNCiHGNC:6871 MAPK1
HPAiCAB004229
HPA003995
HPA005700
HPA030069
MalaCardsiMAPK1
MIMi176948 gene
neXtProtiNX_P28482
OpenTargetsiENSG00000100030
Orphaneti261330 Distal 22q11.2 microdeletion syndrome
PharmGKBiPA30616
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660 Eukaryota
ENOG410XNY0 LUCA
GeneTreeiENSGT00910000144035
HOGENOMiHOG000233024
HOVERGENiHBG014652
InParanoidiP28482
KOiK04371
OMAiDIYIVQC
OrthoDBiEOG091G08QL
PhylomeDBiP28482
TreeFamiTF105097

Enzyme and pathway databases

BRENDAi2.7.11.24 2681
ReactomeiR-HSA-111995 phospho-PLA2 pathway
R-HSA-112409 RAF-independent MAPK1/3 activation
R-HSA-112411 MAPK1 (ERK2) activation
R-HSA-1295596 Spry regulation of FGF signaling
R-HSA-162658 Golgi Cisternae Pericentriolar Stack Reorganization
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2029482 Regulation of actin dynamics for phagocytic cup formation
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-3371453 Regulation of HSF1-mediated heat shock response
R-HSA-375165 NCAM signaling for neurite out-growth
R-HSA-437239 Recycling pathway of L1
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-444257 RSK activation
R-HSA-445144 Signal transduction by L1
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-456926 Thrombin signalling through proteinase activated receptors (PARs)
R-HSA-5654726 Negative regulation of FGFR1 signaling
R-HSA-5654727 Negative regulation of FGFR2 signaling
R-HSA-5654732 Negative regulation of FGFR3 signaling
R-HSA-5654733 Negative regulation of FGFR4 signaling
R-HSA-5663213 RHO GTPases Activate WASPs and WAVEs
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-5674135 MAP2K and MAPK activation
R-HSA-5674499 Negative feedback regulation of MAPK pathway
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6798695 Neutrophil degranulation
R-HSA-6802946 Signaling by moderate kinase activity BRAF mutants
R-HSA-6802948 Signaling by high-kinase activity BRAF mutants
R-HSA-6802949 Signaling by RAS mutants
R-HSA-6802952 Signaling by BRAF and RAF fusions
R-HSA-6802955 Paradoxical activation of RAF signaling by kinase inactive BRAF
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-74749 Signal attenuation
R-HSA-879415 Advanced glycosylation endproduct receptor signaling
R-HSA-881907 Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-8939211 ESR-mediated signaling
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-982772 Growth hormone receptor signaling
SignaLinkiP28482
SIGNORiP28482

Miscellaneous databases

ChiTaRSiMAPK1 human
EvolutionaryTraceiP28482
GeneWikiiMAPK1
GenomeRNAii5594
PROiPR:P28482
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100030 Expressed in 241 organ(s), highest expression level in putamen
CleanExiHS_MAPK1
ExpressionAtlasiP28482 baseline and differential
GenevisibleiP28482 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR003527 MAP_kinase_CS
IPR008349 MAPK_ERK1/2
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
PRINTSiPR01770 ERK1ERK2MAPK
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS01351 MAPK, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMK01_HUMAN
AccessioniPrimary (citable) accession number: P28482
Secondary accession number(s): A8CZ64
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: January 23, 2007
Last modified: November 7, 2018
This is version 219 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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