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Protein

Proto-oncogene c-Fos

Gene

FOS

Organism
Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at transcript leveli

Functioni

Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. On TGF-beta activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation (By similarity). In growing cells, activates phospholipid synthesis, possibly by activating CDS1 and PI4K2A. This activity requires Tyr-dephosphorylation and association with the endoplasmic reticulum (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Proto-oncogene c-Fos
Alternative name(s):
Cellular oncogene fos
Gene namesi
Name:FOS
OrganismiCricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
Taxonomic identifieri10029 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaCricetidaeCricetinaeCricetulus

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation
  • Endoplasmic reticulum By similarity
  • Cytoplasmcytosol By similarity

  • Note: In quiescent cells, present in very small amounts in the cytosol. Following induction of cell growth, first localizes to the endoplasmic reticulum and only later to the nucleus. Localization at the endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30 (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 381381Proto-oncogene c-FosPRO_0000076463Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei10 – 101Phosphotyrosine; by SRCBy similarity
Modified residuei30 – 301Phosphotyrosine; by SRCBy similarity
Cross-linki113 – 113Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki128 – 128Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei232 – 2321PhosphothreonineBy similarity
Cross-linki265 – 265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternateBy similarity
Cross-linki265 – 265Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateBy similarity
Modified residuei326 – 3261Phosphothreonine; by MAPK1 and MAPK3By similarity
Modified residuei332 – 3321Phosphothreonine; by MAPK1 and MAPK3By similarity
Modified residuei363 – 3631Phosphoserine; by MAPK1, MAPK3 and RPS6KA3By similarity
Modified residuei375 – 3751Phosphoserine; by MAPK1 and MAPK3By similarity

Post-translational modificationi

Phosphorylated in the C-terminal upon stimulation by nerve growth factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in vitro, by MAPK and RSK1. Phosphorylation on both Ser-363 and Ser-375 by MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation on Ser-375 being the major site for protein stabilization on NGF stimulation. Phosphorylation on Ser-363 and Ser-375 primes further phosphorylations on Thr-326 and Thr-332 through promoting docking of MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS, activates the transcriptional activity and antagonizes sumoylation. Phosphorylation on Ser-363 by RSK2 in osteoblasts contributes to osteoblast transformation (By similarity).By similarity
Constitutively sumoylated with SUMO1, SUMO2 and SUMO3. Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1 transcriptional activity and is, itself, inhibited by Ras-activated phosphorylation on Thr-232 (By similarity).By similarity
In quiescent cells, the small amount of FOS present is phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated form is cytosolic. In growing cells, dephosphorylated by PTPN2. Dephosphorylation leads to the association with endoplasmic reticulum membranes and activation of phospholipid synthesis (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Heterodimer; with JUN (By similarity). Component of the SMAD3/SMAD4/JUN/FOS complex required for synergistic TGF-beta-mediated transcription at the AP1 promoter site. Interacts with SMAD3; the interaction is weak even on TGF-beta activation. Interacts with MAFB. Interacts with DSIPI; this interaction inhibits the binding of active AP1 to its target DNA. Interacts with MAFB (By similarity). Interacts with CDS1 and PI4K2A (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ9Z2Q8.
SMRiQ9Z2Q8. Positions 139-198.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini137 – 20064bZIPPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni139 – 15921Basic motif; required for the activation of phospholipid synthesis, but not for CDS1-bindingPROSITE-ProRule annotationAdd
BLAST
Regioni165 – 19329Leucine-zipperPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the bZIP family. Fos subfamily.Curated
Contains 1 bZIP (basic-leucine zipper) domain.PROSITE-ProRule annotation

Phylogenomic databases

HOVERGENiHBG005743.
KOiK04379.

Family and domain databases

InterProiIPR000837. AP-1.
IPR004827. bZIP.
IPR029816. c-Fos/v-Fos.
[Graphical view]
PANTHERiPTHR23351. PTHR23351. 1 hit.
PTHR23351:SF4. PTHR23351:SF4. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
PRINTSiPR00042. LEUZIPPRFOS.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z2Q8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMFSGFNADY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNAQDFC
60 70 80 90 100
ADLSGSSANF IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGVPT
110 120 130 140 150
PSAGAYSRAA MVKTVSGGRA QSISRRSKVE QLSPEEEEKR RIRRERNKMA
160 170 180 190 200
AAKCWNRRRE LTDTLQAETD QLEDEKSALQ TEIANLLKEK EKLEFILAAH
210 220 230 240 250
RPACKIPDDL GFPEEMSVAS LDLTGGLPEA TTPESEEAFS LPLLNDAEPK
260 270 280 290 300
TSLEPVKSIS NMELKAEPFD DFLFPPSSRP SGSETTARSV PDMDLSGSFY
310 320 330 340 350
AADWEPLHSS SLGMGPMVTE LEPLCTPVVT CTPSCTTYTS SFVFTYPEAD
360 370 380
SFPSCAAAHR KGSSSNEPSS DSLSSPTLLA L
Length:381
Mass (Da):40,998
Last modified:May 1, 1999 - v1
Checksum:iD65B8690926549A9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033012 mRNA. Translation: AAC83461.1.
RefSeqiNP_001233612.1. NM_001246683.1.

Genome annotation databases

GeneIDi100689418.
KEGGicge:100689418.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF033012 mRNA. Translation: AAC83461.1.
RefSeqiNP_001233612.1. NM_001246683.1.

3D structure databases

ProteinModelPortaliQ9Z2Q8.
SMRiQ9Z2Q8. Positions 139-198.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi100689418.
KEGGicge:100689418.

Organism-specific databases

CTDi2353.

Phylogenomic databases

HOVERGENiHBG005743.
KOiK04379.

Family and domain databases

InterProiIPR000837. AP-1.
IPR004827. bZIP.
IPR029816. c-Fos/v-Fos.
[Graphical view]
PANTHERiPTHR23351. PTHR23351. 1 hit.
PTHR23351:SF4. PTHR23351:SF4. 1 hit.
PfamiPF00170. bZIP_1. 1 hit.
[Graphical view]
PRINTSiPR00042. LEUZIPPRFOS.
SMARTiSM00338. BRLZ. 1 hit.
[Graphical view]
PROSITEiPS50217. BZIP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOS_CRIGR
AccessioniPrimary (citable) accession number: Q9Z2Q8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: July 6, 2016
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. 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.