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Protein

Mitogen-activated protein kinase 3

Gene

MAPK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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, 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.12 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-202 and Tyr-204 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. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei71ATPPROSITE-ProRule annotation1
Active sitei166Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi48 – 56ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: Reactome
  • MAP kinase activity Source: UniProtKB
  • phosphatase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: Reactome

GO - Biological processi

  • activation of MAPK activity Source: Reactome
  • apoptotic process Source: UniProtKB-KW
  • arachidonic acid metabolic process Source: Ensembl
  • axon guidance Source: Reactome
  • Bergmann glial cell differentiation Source: Ensembl
  • BMP signaling pathway Source: BHF-UCL
  • cardiac neural crest cell development involved in heart development Source: Ensembl
  • cartilage development Source: Ensembl
  • caveolin-mediated endocytosis Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cellular response to mechanical stimulus Source: UniProtKB
  • DNA damage induced protein phosphorylation Source: UniProtKB
  • ERK1 and ERK2 cascade Source: Ensembl
  • face development Source: Ensembl
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • Fc-gamma receptor signaling pathway involved in phagocytosis Source: Reactome
  • fibroblast growth factor receptor signaling pathway Source: Reactome
  • interleukin-1-mediated signaling pathway Source: BHF-UCL
  • JAK-STAT cascade involved in growth hormone signaling pathway Source: Reactome
  • lipopolysaccharide-mediated signaling pathway Source: Ensembl
  • lung morphogenesis Source: Ensembl
  • MAPK cascade Source: BHF-UCL
  • MAPK import into nucleus Source: Ensembl
  • negative regulation of apolipoprotein binding Source: Ensembl
  • outer ear morphogenesis Source: Ensembl
  • peptidyl-serine phosphorylation Source: Ensembl
  • peptidyl-tyrosine autophosphorylation Source: UniProtKB
  • phosphorylation Source: UniProtKB
  • platelet activation Source: Reactome
  • positive regulation of cyclase activity Source: CACAO
  • positive regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • positive regulation of histone acetylation Source: BHF-UCL
  • positive regulation of histone phosphorylation Source: BHF-UCL
  • positive regulation of protein phosphorylation Source: BHF-UCL
  • positive regulation of telomerase activity Source: BHF-UCL
  • positive regulation of telomere capping Source: BHF-UCL
  • positive regulation of telomere maintenance via telomerase Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of translation Source: Ensembl
  • positive regulation of xenophagy Source: Ensembl
  • protein complex assembly Source: Ensembl
  • protein phosphorylation Source: UniProtKB
  • regulation of cellular response to heat Source: Reactome
  • regulation of cytoskeleton organization Source: UniProtKB
  • regulation of early endosome to late endosome transport Source: UniProtKB
  • regulation of Golgi inheritance Source: UniProtKB
  • regulation of ossification Source: Ensembl
  • regulation of phosphatidylinositol 3-kinase signaling Source: Reactome
  • regulation of sequence-specific DNA binding transcription factor activity Source: Reactome
  • regulation of stress-activated MAPK cascade Source: UniProtKB
  • response to epidermal growth factor Source: UniProtKB
  • response to exogenous dsRNA Source: Ensembl
  • response to toxic substance Source: Ensembl
  • sensory perception of pain Source: Ensembl
  • thymus development Source: Ensembl
  • thyroid gland development Source: Ensembl
  • trachea formation Source: Ensembl
  • transcription initiation from RNA polymerase I promoter Source: Reactome
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis, Cell cycle, Host-virus interaction

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02421-MONOMER.
BRENDAi2.7.11.24. 2681.
ReactomeiR-HSA-110056. MAPK3 (ERK1) activation.
R-HSA-112409. RAF-independent MAPK1/3 activation.
R-HSA-1169408. ISG15 antiviral mechanism.
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-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-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-73728. RNA Polymerase I Promoter Opening.
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-982772. Growth hormone receptor signaling.
SignaLinkiP27361.
SIGNORiP27361.

Names & Taxonomyi

Protein namesi
Recommended name:
Mitogen-activated protein kinase 3 (EC:2.7.11.24)
Short name:
MAP kinase 3
Short name:
MAPK 3
Alternative name(s):
ERT2
Extracellular signal-regulated kinase 1
Short name:
ERK-1
Insulin-stimulated MAP2 kinase
MAP kinase isoform p44
Short name:
p44-MAPK
Microtubule-associated protein 2 kinase
p44-ERK1
Gene namesi
Name:MAPK3
Synonyms:ERK1, PRKM3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:6877. MAPK3.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Autophosphorylation at Thr-207 promotes nuclear localization.

GO - Cellular componenti

  • caveola Source: UniProtKB
  • cytoskeleton Source: UniProtKB
  • cytosol Source: UniProtKB
  • early endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • focal adhesion Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • late endosome Source: UniProtKB
  • microtubule cytoskeleton Source: HPA
  • mitochondrion Source: UniProtKB
  • nuclear envelope Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • protein complex Source: Ensembl
  • pseudopodium Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi5595.
OpenTargetsiENSG00000102882.
PharmGKBiPA30622.

Chemistry databases

ChEMBLiCHEMBL3385.
DrugBankiDB01169. Arsenic trioxide.
DB00605. Sulindac.
GuidetoPHARMACOLOGYi1494.

Polymorphism and mutation databases

BioMutaiMAPK3.
DMDMi232066.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00001862512 – 379Mitogen-activated protein kinase 3Add BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei198PhosphothreonineCombined sources1
Modified residuei202Phosphothreonine; by MAP2K1 and MAP2K2Combined sources1
Modified residuei204Phosphotyrosine; by MAP2K1 and MAP2K2Combined sources2 Publications1
Modified residuei207Phosphothreonine; by autocatalysis1 Publication1
Modified residuei263PhosphoserineBy similarity1
Modified residuei265PhosphoserineBy similarity1
Modified residuei301PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually phosphorylated on Thr-202 and Tyr-204, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated by PTPRJ at Tyr-204.By similarity5 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP27361.
MaxQBiP27361.
PaxDbiP27361.
PeptideAtlasiP27361.
PRIDEiP27361.

PTM databases

iPTMnetiP27361.
PhosphoSitePlusiP27361.

Expressioni

Gene expression databases

BgeeiENSG00000102882.
CleanExiHS_MAPK3.
ExpressionAtlasiP27361. baseline and differential.
GenevisibleiP27361. HS.

Organism-specific databases

HPAiCAB002683.
HPA003995.
HPA005700.
HPA030069.

Interactioni

Subunit structurei

Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Binds to HIV-1 Nef through its SH3 domain. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1, NISCH, and SGK1. Interacts with PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (By similarity). Interacts with TPR. Interacts with CDKN2AIP.By similarity13 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DAPK1P533555EBI-73995,EBI-358616
DHPSP493663EBI-73995,EBI-741925
DUSP1P285623EBI-73995,EBI-975493
ELK1P194192EBI-73995,EBI-726632
MAP2K1Q027502EBI-73995,EBI-492564
MAPK1P284823EBI-73995,EBI-959949
MAPK14Q165395EBI-73995,EBI-73946
NsmfQ9EPI62EBI-73995,EBI-6899705From a different organism.
PKMP14618-13EBI-73995,EBI-4304679
PNKDQ8N4904EBI-73995,EBI-746368
PTPRBP234672EBI-73995,EBI-1265766
PTPRJQ129135EBI-73995,EBI-2264500
PtprrQ621323EBI-73995,EBI-6954051From a different organism.
RPS6KA2Q153492EBI-73995,EBI-1384149
SCRIBQ141602EBI-73995,EBI-357345

GO - Molecular functioni

  • phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111581. 187 interactors.
DIPiDIP-30985N.
IntActiP27361. 89 interactors.
MINTiMINT-99599.
STRINGi9606.ENSP00000263025.

Chemistry databases

BindingDBiP27361.

Structurei

Secondary structure

1379
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi29 – 31Combined sources3
Beta strandi34 – 36Combined sources3
Turni39 – 41Combined sources3
Beta strandi42 – 51Combined sources10
Beta strandi54 – 61Combined sources8
Turni62 – 65Combined sources4
Beta strandi66 – 73Combined sources8
Helixi79 – 94Combined sources16
Beta strandi105 – 107Combined sources3
Turni112 – 114Combined sources3
Beta strandi118 – 122Combined sources5
Beta strandi126 – 128Combined sources3
Helixi129 – 135Combined sources7
Helixi140 – 159Combined sources20
Helixi169 – 171Combined sources3
Beta strandi172 – 174Combined sources3
Beta strandi180 – 182Combined sources3
Helixi193 – 195Combined sources3
Helixi208 – 210Combined sources3
Helixi213 – 215Combined sources3
Turni216 – 218Combined sources3
Helixi225 – 240Combined sources16
Helixi250 – 261Combined sources12
Helixi266 – 269Combined sources4
Helixi275 – 282Combined sources8
Helixi292 – 295Combined sources4
Helixi301 – 310Combined sources10
Helixi315 – 317Combined sources3
Helixi321 – 325Combined sources5
Helixi328 – 330Combined sources3
Turni331 – 333Combined sources3
Helixi336 – 338Combined sources3
Helixi350 – 354Combined sources5
Helixi357 – 368Combined sources12
Helixi369 – 371Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZOQX-ray2.39A/B1-379[»]
4QTBX-ray1.40A/B1-379[»]
ProteinModelPortaliP27361.
SMRiP27361.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27361.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 330Protein kinasePROSITE-ProRule annotationAdd BLAST289

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi202 – 204TXY3

Domaini

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.1 Publication

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP27361.
KOiK04371.
OMAiRAPCADS.
OrthoDBiEOG091G08QL.
PhylomeDBiP27361.
TreeFamiTF105097.

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.
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]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P27361-1) [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
MAAAAAQGGG GGEPRRTEGV GPGVPGEVEM VKGQPFDVGP RYTQLQYIGE
60 70 80 90 100
GAYGMVSSAY DHVRKTRVAI KKISPFEHQT YCQRTLREIQ ILLRFRHENV
110 120 130 140 150
IGIRDILRAS TLEAMRDVYI VQDLMETDLY KLLKSQQLSN DHICYFLYQI
160 170 180 190 200
LRGLKYIHSA NVLHRDLKPS NLLINTTCDL KICDFGLARI ADPEHDHTGF
210 220 230 240 250
LTEYVATRWY RAPEIMLNSK GYTKSIDIWS VGCILAEMLS NRPIFPGKHY
260 270 280 290 300
LDQLNHILGI LGSPSQEDLN CIINMKARNY LQSLPSKTKV AWAKLFPKSD
310 320 330 340 350
SKALDLLDRM LTFNPNKRIT VEEALAHPYL EQYYDPTDEP VAEEPFTFAM
360 370
ELDDLPKERL KELIFQETAR FQPGVLEAP
Length:379
Mass (Da):43,136
Last modified:January 23, 2007 - v4
Checksum:iE6020CE413EC41F7
GO
Isoform 2 (identifier: P27361-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     259-302: Missing.

Show »
Length:335
Mass (Da):38,275
Checksum:i54DA760A09F1F2F5
GO
Isoform 3 (identifier: P27361-3) [UniParc]FASTAAdd to basket
Also known as: ERK1b

The sequence of this isoform differs from the canonical sequence as follows:
     340-379: PVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP → VGQSPAAVGLGAGEQGGT

Show »
Length:357
Mass (Da):40,088
Checksum:iF2C6D29C623AC072
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti174I → S in CAA42744 (PubMed:7687743).Curated1
Sequence conflicti174I → S in AAK52329 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042253323E → K.1 PublicationCorresponds to variant rs55859133dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_041906259 – 302Missing in isoform 2. 1 PublicationAdd BLAST44
Alternative sequenceiVSP_041907340 – 379PVAEE…VLEAP → VGQSPAAVGLGAGEQGGT in isoform 3. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60188 mRNA. Translation: CAA42744.1.
AY033607 mRNA. Translation: AAK52329.1.
DQ399291 mRNA. Translation: ABD60302.1.
EU332853 Genomic DNA. Translation: ABY87542.1.
AC012645 Genomic DNA. No translation available.
CH471238 Genomic DNA. Translation: EAW79912.1.
CH471238 Genomic DNA. Translation: EAW79915.1.
BC013992 mRNA. Translation: AAH13992.1.
M84490 mRNA. Translation: AAA36142.1.
Z11696 mRNA. Translation: CAA77754.1.
CCDSiCCDS10672.1. [P27361-1]
CCDS42148.1. [P27361-2]
CCDS42149.1. [P27361-3]
PIRiA48082.
RefSeqiNP_001035145.1. NM_001040056.2. [P27361-3]
NP_001103361.1. NM_001109891.1. [P27361-2]
NP_002737.2. NM_002746.2. [P27361-1]
UniGeneiHs.861.

Genome annotation databases

EnsembliENST00000263025; ENSP00000263025; ENSG00000102882. [P27361-1]
ENST00000322266; ENSP00000327293; ENSG00000102882. [P27361-2]
ENST00000395199; ENSP00000378625; ENSG00000102882. [P27361-3]
ENST00000395202; ENSP00000378628; ENSG00000102882. [P27361-2]
GeneIDi5595.
KEGGihsa:5595.
UCSCiuc002dws.4. human. [P27361-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X60188 mRNA. Translation: CAA42744.1.
AY033607 mRNA. Translation: AAK52329.1.
DQ399291 mRNA. Translation: ABD60302.1.
EU332853 Genomic DNA. Translation: ABY87542.1.
AC012645 Genomic DNA. No translation available.
CH471238 Genomic DNA. Translation: EAW79912.1.
CH471238 Genomic DNA. Translation: EAW79915.1.
BC013992 mRNA. Translation: AAH13992.1.
M84490 mRNA. Translation: AAA36142.1.
Z11696 mRNA. Translation: CAA77754.1.
CCDSiCCDS10672.1. [P27361-1]
CCDS42148.1. [P27361-2]
CCDS42149.1. [P27361-3]
PIRiA48082.
RefSeqiNP_001035145.1. NM_001040056.2. [P27361-3]
NP_001103361.1. NM_001109891.1. [P27361-2]
NP_002737.2. NM_002746.2. [P27361-1]
UniGeneiHs.861.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZOQX-ray2.39A/B1-379[»]
4QTBX-ray1.40A/B1-379[»]
ProteinModelPortaliP27361.
SMRiP27361.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111581. 187 interactors.
DIPiDIP-30985N.
IntActiP27361. 89 interactors.
MINTiMINT-99599.
STRINGi9606.ENSP00000263025.

Chemistry databases

BindingDBiP27361.
ChEMBLiCHEMBL3385.
DrugBankiDB01169. Arsenic trioxide.
DB00605. Sulindac.
GuidetoPHARMACOLOGYi1494.

PTM databases

iPTMnetiP27361.
PhosphoSitePlusiP27361.

Polymorphism and mutation databases

BioMutaiMAPK3.
DMDMi232066.

Proteomic databases

EPDiP27361.
MaxQBiP27361.
PaxDbiP27361.
PeptideAtlasiP27361.
PRIDEiP27361.

Protocols and materials databases

DNASUi5595.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263025; ENSP00000263025; ENSG00000102882. [P27361-1]
ENST00000322266; ENSP00000327293; ENSG00000102882. [P27361-2]
ENST00000395199; ENSP00000378625; ENSG00000102882. [P27361-3]
ENST00000395202; ENSP00000378628; ENSG00000102882. [P27361-2]
GeneIDi5595.
KEGGihsa:5595.
UCSCiuc002dws.4. human. [P27361-1]

Organism-specific databases

CTDi5595.
DisGeNETi5595.
GeneCardsiMAPK3.
HGNCiHGNC:6877. MAPK3.
HPAiCAB002683.
HPA003995.
HPA005700.
HPA030069.
MIMi601795. gene.
neXtProtiNX_P27361.
OpenTargetsiENSG00000102882.
PharmGKBiPA30622.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0660. Eukaryota.
ENOG410XNY0. LUCA.
GeneTreeiENSGT00550000074298.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP27361.
KOiK04371.
OMAiRAPCADS.
OrthoDBiEOG091G08QL.
PhylomeDBiP27361.
TreeFamiTF105097.

Enzyme and pathway databases

BioCyciZFISH:HS02421-MONOMER.
BRENDAi2.7.11.24. 2681.
ReactomeiR-HSA-110056. MAPK3 (ERK1) activation.
R-HSA-112409. RAF-independent MAPK1/3 activation.
R-HSA-1169408. ISG15 antiviral mechanism.
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-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-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-73728. RNA Polymerase I Promoter Opening.
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-982772. Growth hormone receptor signaling.
SignaLinkiP27361.
SIGNORiP27361.

Miscellaneous databases

EvolutionaryTraceiP27361.
GeneWikiiMAPK3.
GenomeRNAii5595.
PROiP27361.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102882.
CleanExiHS_MAPK3.
ExpressionAtlasiP27361. baseline and differential.
GenevisibleiP27361. HS.

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.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiMK03_HUMAN
AccessioniPrimary (citable) accession number: P27361
Secondary accession number(s): A8CZ58, B0LPG3, Q8NHX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 195 of the entry and version 4 of the sequence. [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. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.