UniProtKB - P05412 (JUN_HUMAN)
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Protein
Transcription factor AP-1
Gene
JUN
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 272 | Necessary for synergistic transcriptional activity with SMAD3 | 1 |
GO - Molecular functioni
- cAMP response element binding Source: BHF-UCL
- chromatin binding Source: Ensembl
- DNA binding Source: ProtInc
- 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 core promoter proximal region sequence-specific DNA binding Source: GO_Central
- RNA polymerase II distal enhancer sequence-specific DNA binding Source: BHF-UCL
- RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: ParkinsonsUK-UCL
- R-SMAD binding Source: BHF-UCL
- transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific 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 core promoter proximal region sequence-specific binding Source: BHF-UCL
- transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: UniProtKB
- transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
- transcription factor binding Source: BHF-UCL
- transcription regulatory region DNA binding Source: UniProtKB
GO - Biological processi
- aging Source: Ensembl
- angiogenesis Source: Ensembl
- axon regeneration Source: Ensembl
- cellular response to cadmium ion Source: CAFA
- cellular response to calcium ion Source: Ensembl
- cellular response to hormone stimulus Source: GO_Central
- cellular response to potassium ion starvation Source: Ensembl
- cellular response to reactive oxygen species Source: CAFA
- circadian rhythm Source: Ensembl
- eyelid development in camera-type eye Source: Ensembl
- Fc-epsilon receptor signaling pathway Source: Reactome
- leading edge cell differentiation Source: Ensembl
- learning Source: Ensembl
- liver development Source: Ensembl
- membrane depolarization Source: Ensembl
- microglial cell activation Source: Ensembl
- monocyte differentiation Source: Ensembl
- negative regulation by host of viral transcription Source: UniProtKB
- negative regulation of cell proliferation Source: Ensembl
- negative regulation of DNA binding Source: UniProtKB
- negative regulation of neuron apoptotic process Source: Ensembl
- negative regulation of protein autophosphorylation Source: Ensembl
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
- outflow tract morphogenesis Source: Ensembl
- positive regulation by host of viral transcription Source: UniProtKB
- positive regulation of apoptotic process Source: CAFA
- positive regulation of cell differentiation Source: GO_Central
- positive regulation of DNA replication Source: Ensembl
- positive regulation of DNA-templated transcription, initiation Source: CACAO
- positive regulation of endothelial cell proliferation Source: Ensembl
- positive regulation of epithelial cell migration Source: Ensembl
- positive regulation of ERK1 and ERK2 cascade Source: Ensembl
- positive regulation of fibroblast proliferation Source: Ensembl
- positive regulation of monocyte differentiation Source: Ensembl
- positive regulation of neuron apoptotic process Source: Ensembl
- positive regulation of pri-miRNA transcription from RNA polymerase II promoter Source: BHF-UCL
- positive regulation of smooth muscle cell proliferation Source: Ensembl
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
- Ras protein signal transduction Source: UniProtKB
- regulation of cell cycle Source: GO_Central
- regulation of cell proliferation Source: GO_Central
- regulation of sequence-specific DNA binding transcription factor activity Source: Reactome
- release of cytochrome c from mitochondria Source: Ensembl
- response to cAMP Source: GO_Central
- response to cytokine Source: GO_Central
- response to drug Source: GO_Central
- response to hydrogen peroxide Source: Ensembl
- response to lipopolysaccharide Source: GO_Central
- response to mechanical stimulus Source: GO_Central
- response to muscle stretch Source: Ensembl
- response to radiation Source: GO_Central
- SMAD protein import into nucleus Source: BHF-UCL
- SMAD protein signal transduction Source: BHF-UCL
- transforming growth factor beta receptor signaling pathway Source: BHF-UCL
Keywordsi
| Molecular function | Activator, DNA-binding |
| Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
| Reactomei | R-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. |
| SignaLinki | P05412. |
| SIGNORi | P05412. |
Names & Taxonomyi
| Protein namesi | Recommended name: Transcription factor AP-1Alternative 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 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:6204. JUN. |
Subcellular locationi
GO - Cellular componenti
- cytosol Source: Ensembl
- nuclear chromosome Source: ProtInc
- nuclear euchromatin Source: BHF-UCL
- nucleoplasm Source: HPA
- nucleus Source: ParkinsonsUK-UCL
- transcriptional repressor complex Source: Ensembl
- transcription factor AP-1 complex Source: CAFA
Keywords - Cellular componenti
NucleusPathology & Biotechi
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 2 | T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-8; A-89; A-93; and A-286. 1 Publication | 1 | |
| Mutagenesisi | 8 | T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-89; A-93; and A-286. 1 Publication | 1 | |
| Mutagenesisi | 63 | S → 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 Publications | 1 | |
| Mutagenesisi | 73 | S → 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 Publications | 1 | |
| Mutagenesisi | 89 | T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-93; and A-286. 1 Publication | 1 | |
| Mutagenesisi | 91 | T → A: Abolishes interaction with FBXW7; when associated with A-63; A-73 and A-93. 1 Publication | 1 | |
| Mutagenesisi | 93 | T → A: Abolishes interaction with FBXW7; when associated with A-63; A-73 and A-91. 1 Publication | 1 | |
| Mutagenesisi | 93 | T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-89; and A-286. 1 Publication | 1 | |
| Mutagenesisi | 243 | S → A: Abolishes phosphorylation by DYRK2. Abolishes phosphorylation by GSK3B at Thr-239. 1 Publication | 1 | |
| Mutagenesisi | 272 | R → V: Abolishes the synergistic activity with SMAD3 to activate TGF-beta-mediated transcription. 1 Publication | 1 | |
| Mutagenesisi | 286 | T → A: Complete loss of PAK2-mediated phosphorylation; when associated with A-2; A-8; A-89; and A-93. 1 Publication | 1 |
Keywords - Diseasei
Proto-oncogeneOrganism-specific databases
| DisGeNETi | 3725. |
| OpenTargetsi | ENSG00000177606. |
| PharmGKBi | PA30006. |
Chemistry databases
| ChEMBLi | CHEMBL4977. |
| DrugBanki | DB01169. Arsenic trioxide. DB01029. Irbesartan. DB05785. LGD-1550. DB00852. Pseudoephedrine. DB00570. Vinblastine. |
Polymorphism and mutation databases
| BioMutai | JUN. |
| DMDMi | 135298. |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000076429 | 1 – 331 | Transcription factor AP-1Add BLAST | 331 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 2 | Phosphothreonine; by PAK21 Publication | 1 | |
| Modified residuei | 8 | Phosphothreonine; by PAK21 Publication | 1 | |
| Modified residuei | 56 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 58 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 63 | Phosphoserine; by MAPK8 and PLK3Combined sources3 Publications | 1 | |
| Modified residuei | 73 | Phosphoserine; by MAPK8 and PLK33 Publications | 1 | |
| Modified residuei | 89 | Phosphothreonine; by PAK21 Publication | 1 | |
| Modified residuei | 91 | Phosphothreonine1 Publication | 1 | |
| Modified residuei | 93 | Phosphothreonine; by PAK22 Publications | 1 | |
| Modified residuei | 239 | Phosphothreonine; by GSK3-betaCombined sources1 Publication | 1 | |
| Modified residuei | 243 | Phosphoserine; by DYRK2 and GSK3-betaCombined sources2 Publications | 1 | |
| Modified residuei | 249 | Phosphoserine; by GSK3-beta2 Publications | 1 | |
| Modified residuei | 271 | N6-acetyllysine1 Publication | 1 | |
| Modified residuei | 286 | Phosphothreonine; by PAK21 Publication | 1 |
Post-translational modificationi
Ubiquitinated by the SCF(FBXW7), leading to its degradation. Ubiquitination takes place following phosphorylation, that promotes interaction with FBXW7.1 Publication
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, Phosphoprotein, Ubl conjugationProteomic databases
| EPDi | P05412. |
| MaxQBi | P05412. |
| PaxDbi | P05412. |
| PeptideAtlasi | P05412. |
| PRIDEi | P05412. |
PTM databases
| iPTMneti | P05412. |
| PhosphoSitePlusi | P05412. |
Expressioni
Gene expression databases
| Bgeei | ENSG00000177606. |
| CleanExi | HS_JUN. |
| Genevisiblei | P05412. HS. |
Organism-specific databases
| HPAi | CAB003801. CAB007780. HPA059474. |
Interactioni
Subunit structurei
Heterodimer with either FOS or BATF3 or ATF7. The ATF7/JUN heterodimer is essential for ATF7 transactivation activity. 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. Interacts with COPS5; the interaction leads indirectly to its phosphorylation. Component of the SMAD3/SMAD4/JUN/FOS/complex which forms at the AP1 promoter site. The SMAD3/SMAD4 heterodimer acts synergistically with the JUN/FOS heterodimer to activate transcription in response to TGF-beta. 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. Interacts with methylated RNF187. Binds to HIPK3. Interacts (when phosphorylated) with FBXW7 (PubMed:14739463).By similarity12 Publications
Binary interactionsi
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
Protein-protein interaction databases
| BioGridi | 109928. 230 interactors. |
| DIPi | DIP-5961N. |
| IntActi | P05412. 1376 interactors. |
| MINTi | MINT-105756. |
| STRINGi | 9606.ENSP00000360266. |
Chemistry databases
| BindingDBi | P05412. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Helixi | 255 – 310 | Combined sources | 56 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 1A02 | X-ray | 2.70 | J | 253-308 | [»] | |
| 1FOS | X-ray | 3.05 | F/H | 254-315 | [»] | |
| 1JNM | X-ray | 2.20 | A/B | 254-315 | [»] | |
| 1JUN | NMR | - | A/B | 276-314 | [»] | |
| 1S9K | X-ray | 3.10 | E | 257-308 | [»] | |
| 1T2K | X-ray | 3.00 | C | 254-314 | [»] | |
| 5T01 | X-ray | 1.89 | A/B | 254-315 | [»] | |
| ProteinModelPortali | P05412. | |||||
| SMRi | P05412. | |||||
| ModBasei | Search... | |||||
| MobiDBi | Search... | |||||
Miscellaneous databases
| EvolutionaryTracei | P05412. |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 252 – 315 | bZIPPROSITE-ProRule annotationAdd BLAST | 64 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 252 – 279 | Basic motifPROSITE-ProRule annotationAdd BLAST | 28 | |
| Regioni | 280 – 308 | Leucine-zipperPROSITE-ProRule annotationAdd BLAST | 29 |
Sequence similaritiesi
Phylogenomic databases
| eggNOGi | KOG0837. Eukaryota. ENOG410XRWH. LUCA. |
| GeneTreei | ENSGT00390000009929. |
| HOGENOMi | HOG000006648. |
| HOVERGENi | HBG001722. |
| InParanoidi | P05412. |
| KOi | K04448. |
| OMAi | KDHVAQL. |
| OrthoDBi | EOG091G0N0L. |
| PhylomeDBi | P05412. |
| TreeFami | TF323952. |
Family and domain databases
| InterProi | View protein in InterPro IPR004827. bZIP. IPR015558. C_Jun/v-Jun. IPR005643. JNK. IPR002112. Leuzip_Jun. IPR008917. TF_DNA-bd. |
| PANTHERi | PTHR11462:SF43. PTHR11462:SF43. 1 hit. |
| Pfami | View protein in Pfam PF00170. bZIP_1. 1 hit. PF03957. Jun. 1 hit. |
| PRINTSi | PR00043. LEUZIPPRJUN. |
| SMARTi | View protein in SMART SM00338. BRLZ. 1 hit. |
| SUPFAMi | SSF47454. SSF47454. 1 hit. |
| PROSITEi | View protein in PROSITE PS50217. BZIP. 1 hit. PS00036. BZIP_BASIC. 1 hit. |
Sequencei
Sequence statusi: Complete.
P05412-1 [UniParc]FASTAAdd to basket
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
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 11 | D → G AA sequence (PubMed:2825349).Curated | 1 | |
| Sequence conflicti | 14 | L → F AA sequence (PubMed:2825349).Curated | 1 | |
| Sequence conflicti | 80 | I → V AA sequence (PubMed:2825349).Curated | 1 | |
| Sequence conflicti | 151 | A → S in CAG46525 (Ref. 3) Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_012070 | 297 | T → 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. |
| CCDSi | CCDS610.1. |
| PIRi | A31264. TVHUJN. |
| RefSeqi | NP_002219.1. NM_002228.3. |
| UniGenei | Hs.696684. |
Genome annotation databases
| Ensembli | ENST00000371222; ENSP00000360266; ENSG00000177606. |
| GeneIDi | 3725. |
| KEGGi | hsa:3725. |
| UCSCi | uc001cze.4. human. |
Keywords - Coding sequence diversityi
PolymorphismSimilar 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. |
Entry informationi
| Entry namei | JUN_HUMAN | |
| Accessioni | P05412Primary (citable) accession number: P05412 Secondary accession number(s): Q6FHM7, Q96G93 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1988 |
| Last sequence update: | October 1, 1989 | |
| Last modified: | July 5, 2017 | |
| This is version 224 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any 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 proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
