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Protein

Transcription factor AP-1

Gene

JUN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. Promotes activity of NR5A1 when phosphorylated by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation. Involved in activated KRAS-mediated transcriptional activation of USP28 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the USP28 promoter in colorectal cancer (CRC) cells (PubMed:24623306).3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei272Necessary for synergistic transcriptional activity with SMAD31

GO - Molecular functioni

  • cAMP response element binding Source: BHF-UCL
  • chromatin binding Source: Ensembl
  • DNA binding Source: ProtInc
  • DNA binding transcription factor activity Source: BHF-UCL
  • enzyme binding Source: UniProtKB
  • GTPase activator activity Source: UniProtKB
  • HMG box domain binding Source: Ensembl
  • identical protein binding Source: IntAct
  • protein heterodimerization activity Source: CAFA
  • protein homodimerization activity Source: CAFA
  • RNA binding Source: UniProtKB
  • RNA polymerase II activating transcription factor binding Source: CAFA
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: GO_Central
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • R-SMAD binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: Ensembl
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription coactivator activity Source: UniProtKB
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: UniProtKB
  • transcription factor activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1912408 Pre-NOTCH Transcription and Translation
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559582 Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-450341 Activation of the AP-1 family of transcription factors
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
R-HSA-8943724 Regulation of PTEN gene transcription
R-HSA-9018519 Estrogen-dependent gene expression
SignaLinkiP05412
SIGNORiP05412

Names & Taxonomyi

Protein namesi
Recommended name:
Transcription factor AP-1
Alternative name(s):
Activator protein 1
Short name:
AP1
Proto-oncogene c-Jun
V-jun avian sarcoma virus 17 oncogene homolog
p39
Gene namesi
Name:JUN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000177606.6
HGNCiHGNC:6204 JUN
MIMi165160 gene
neXtProtiNX_P05412

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-8; A-89; A-93; and A-286. 1 Publication1
Mutagenesisi8T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-89; A-93; and A-286. 1 Publication1
Mutagenesisi63S → A: Greatly reduced ATF7-mediated transcriptional activity; when associated with A-73. Abolishes interaction with FBXW7; when associated with A-73; A-91 and A-93. 2 Publications1
Mutagenesisi73S → A: Greatly reduced ATF7-mediated transcriptional activity; when associated with A-63. Abolishes interaction with FBXW7; when associated with A-63; A-91 and A-93. 2 Publications1
Mutagenesisi89T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-93; and A-286. 1 Publication1
Mutagenesisi91T → A: Abolishes interaction with FBXW7; when associated with A-63; A-73 and A-93. 1 Publication1
Mutagenesisi93T → A: Abolishes interaction with FBXW7; when associated with A-63; A-73 and A-91. 1 Publication1
Mutagenesisi93T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-89; and A-286. 1 Publication1
Mutagenesisi243S → A: Abolishes phosphorylation by DYRK2. Abolishes phosphorylation by GSK3B at Thr-239. 1 Publication1
Mutagenesisi272R → V: Abolishes the synergistic activity with SMAD3 to activate TGF-beta-mediated transcription. 1 Publication1
Mutagenesisi286T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-89; and A-93. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi3725
OpenTargetsiENSG00000177606
PharmGKBiPA30006

Chemistry databases

ChEMBLiCHEMBL4977
DrugBankiDB01169 Arsenic trioxide
DB01029 Irbesartan
DB05785 LGD-1550
DB00852 Pseudoephedrine
DB00570 Vinblastine

Polymorphism and mutation databases

BioMutaiJUN
DMDMi135298

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000764291 – 331Transcription factor AP-1Add BLAST331

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2Phosphothreonine; by PAK21 Publication1
Modified residuei8Phosphothreonine; by PAK21 Publication1
Cross-linki35Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki50Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei56N6-acetyllysine; alternateBy similarity1
Cross-linki56Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei58PhosphoserineCombined sources1
Modified residuei63Phosphoserine; by MAPK8 and PLK3Combined sources3 Publications1
Cross-linki70Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei73Phosphoserine; by MAPK8 and PLK33 Publications1
Modified residuei89Phosphothreonine; by PAK21 Publication1
Modified residuei91Phosphothreonine1 Publication1
Modified residuei93Phosphothreonine; by PAK22 Publications1
Cross-linki226Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei239Phosphothreonine; by GSK3-betaCombined sources1 Publication1
Modified residuei243Phosphoserine; by DYRK2 and GSK3-betaCombined sources2 Publications1
Modified residuei249Phosphoserine; by GSK3-beta2 Publications1
Modified residuei271N6-acetyllysine1 Publication1
Modified residuei286Phosphothreonine; by PAK21 Publication1

Post-translational modificationi

Ubiquitinated by the SCF(FBXW7), leading to its degradation (PubMed:14739463, PubMed:27458189). Ubiquitination takes place following phosphorylation, that promotes interaction with FBXW7 (PubMed:14739463).2 Publications
Phosphorylated by CaMK4 and PRKDC; phosphorylation enhances the transcriptional activity. Phosphorylated by HIPK3. Phosphorylated by DYRK2 at Ser-243; this primes the protein for subsequent phosphorylation by GSK3B at Thr-239. Phosphorylated at Thr-239, Ser-243 and Ser-249 by GSK3B; phosphorylation reduces its ability to bind DNA. Phosphorylated by PAK2 at Thr-2, Thr-8, Thr-89, Thr-93 and Thr-286 thereby promoting JUN-mediated cell proliferation and transformation. Phosphorylated by PLK3 following hypoxia or UV irradiation, leading to increase DNA-binding activity.9 Publications
Acetylated at Lys-271 by EP300.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP05412
MaxQBiP05412
PaxDbiP05412
PeptideAtlasiP05412
PRIDEiP05412
ProteomicsDBi51836

PTM databases

iPTMnetiP05412
PhosphoSitePlusiP05412

Expressioni

Gene expression databases

BgeeiENSG00000177606
CleanExiHS_JUN
GenevisibleiP05412 HS

Organism-specific databases

HPAiCAB003801
CAB007780
HPA059474

Interactioni

Subunit structurei

Heterodimer with either FOS or BATF3 or ATF7 (PubMed:10376527, PubMed:12087103, PubMed:15467742). The ATF7/JUN heterodimer is essential for ATF7 transactivation activity (PubMed:10376527). Interacts with DSIPI; the interaction inhibits the binding of active AP1 to its target DNA (By similarity). Interacts with HIVEP3 and MYBBP1A (By similarity). Interacts with SP1, SPIB and TCF20 (PubMed:10196196, PubMed:16478997, PubMed:8663478). Interacts with COPS5; the interaction leads indirectly to its phosphorylation (PubMed:8837781). Component of the SMAD3/SMAD4/JUN/FOS/complex which forms at the AP1 promoter site (PubMed:10995748). The SMAD3/SMAD4 heterodimer acts synergistically with the JUN/FOS heterodimer to activate transcription in response to TGF-beta (PubMed:9732876). Interacts (via its basic DNA binding and leucine zipper domains) with SMAD3 (via an N-terminal domain); the interaction is required for TGF-beta-mediated transactivation of the SMAD3/SMAD4/JUN/FOS/complex (PubMed:10995748). Interacts with methylated RNF187 (PubMed:20852630, PubMed:23624934). Binds to HIPK3. Interacts (when phosphorylated) with FBXW7 (PubMed:14739463). Found in a complex with PRR7 and FBXW7 (PubMed:27458189). Interacts with PRR7 and FBXW7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (PubMed:27458189).By similarity13 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • HMG box domain binding Source: Ensembl
  • identical protein binding Source: IntAct
  • protein heterodimerization activity Source: CAFA
  • protein homodimerization activity Source: CAFA
  • RNA polymerase II activating transcription factor binding Source: CAFA
  • R-SMAD binding Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi109928, 247 interactors
ComplexPortaliCPX-480 AP-1 transcription factor complex FOS-JUN-NFATC2
CPX-486 AP-1 transcription factor complex FOS-JUN
CPX-490 AP-1 transcription factor complex JUN dimer
CORUMiP05412
DIPiDIP-5961N
ELMiP05412
IntActiP05412, 1378 interactors
MINTiP05412
STRINGi9606.ENSP00000360266

Chemistry databases

BindingDBiP05412

Structurei

Secondary structure

1331
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi255 – 310Combined sources56

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A02X-ray2.70J253-308[»]
1FOSX-ray3.05F/H254-315[»]
1JNMX-ray2.20A/B254-315[»]
1JUNNMR-A/B276-314[»]
1S9KX-ray3.10E257-308[»]
1T2KX-ray3.00C254-314[»]
5FV8X-ray1.99D/E277-308[»]
5T01X-ray1.89A/B254-315[»]
ProteinModelPortaliP05412
SMRiP05412
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP05412

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini252 – 315bZIPPROSITE-ProRule annotationAdd BLAST64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni252 – 279Basic motifPROSITE-ProRule annotationAdd BLAST28
Regioni280 – 308Leucine-zipperPROSITE-ProRule annotationAdd BLAST29

Sequence similaritiesi

Belongs to the bZIP family. Jun subfamily.Curated

Phylogenomic databases

eggNOGiKOG0837 Eukaryota
ENOG410XRWH LUCA
GeneTreeiENSGT00390000009929
HOGENOMiHOG000006648
HOVERGENiHBG001722
InParanoidiP05412
KOiK04448
OMAiTFTYANM
OrthoDBiEOG091G0N0L
PhylomeDBiP05412
TreeFamiTF323952

Family and domain databases

InterProiView protein in InterPro
IPR004827 bZIP
IPR015558 C_Jun/v-Jun
IPR005643 JNK
IPR002112 Leuzip_Jun
IPR008917 TF_DNA-bd_sf
PANTHERiPTHR11462:SF8 PTHR11462:SF8, 1 hit
PfamiView protein in Pfam
PF00170 bZIP_1, 1 hit
PF03957 Jun, 1 hit
PRINTSiPR00043 LEUZIPPRJUN
SMARTiView protein in SMART
SM00338 BRLZ, 1 hit
SUPFAMiSSF47454 SSF47454, 1 hit
PROSITEiView protein in PROSITE
PS50217 BZIP, 1 hit
PS00036 BZIP_BASIC, 1 hit

Sequencei

Sequence statusi: Complete.

P05412-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTAKMETTFY DDALNASFLP SESGPYGYSN PKILKQSMTL NLADPVGSLK
60 70 80 90 100
PHLRAKNSDL LTSPDVGLLK LASPELERLI IQSSNGHITT TPTPTQFLCP
110 120 130 140 150
KNVTDEQEGF AEGFVRALAE LHSQNTLPSV TSAAQPVNGA GMVAPAVASV
160 170 180 190 200
AGGSGSGGFS ASLHSEPPVY ANLSNFNPGA LSSGGGAPSY GAAGLAFPAQ
210 220 230 240 250
PQQQQQPPHH LPQQMPVQHP RLQALKEEPQ TVPEMPGETP PLSPIDMESQ
260 270 280 290 300
ERIKAERKRM RNRIAASKCR KRKLERIARL EEKVKTLKAQ NSELASTANM
310 320 330
LREQVAQLKQ KVMNHVNSGC QLMLTQQLQT F
Length:331
Mass (Da):35,676
Last modified:October 1, 1989 - v2
Checksum:i0695E23AC4D33561
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11D → G AA sequence (PubMed:2825349).Curated1
Sequence conflicti14L → F AA sequence (PubMed:2825349).Curated1
Sequence conflicti80I → V AA sequence (PubMed:2825349).Curated1
Sequence conflicti151A → S in CAG46525 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012070297T → M. Corresponds to variant dbSNP:rs9989Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J04111 Genomic DNA Translation: AAA59197.1
CR541724 mRNA Translation: CAG46525.1
BT019759 mRNA Translation: AAV38564.1
AY217548 Genomic DNA Translation: AAO22993.1
AL136985 Genomic DNA No translation available.
BC002646 mRNA No translation available.
BC006175 mRNA Translation: AAH06175.1
BC009874 mRNA Translation: AAH09874.2
BC068522 mRNA Translation: AAH68522.1
CCDSiCCDS610.1
PIRiA31264 TVHUJN
RefSeqiNP_002219.1, NM_002228.3
UniGeneiHs.696684

Genome annotation databases

EnsembliENST00000371222; ENSP00000360266; ENSG00000177606
GeneIDi3725
KEGGihsa:3725
UCSCiuc001cze.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiJUN_HUMAN
AccessioniPrimary (citable) accession number: P05412
Secondary accession number(s): Q6FHM7, Q96G93
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1988
Last sequence update: October 1, 1989
Last modified: June 20, 2018
This is version 234 of the entry and version 2 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. Human chromosome 1
    Human chromosome 1: 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. SIMILARITY comments
    Index of protein domains and families

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