FOS_PHOCM
ID FOS_PHOCM Reviewed; 381 AA.
AC Q56TT7;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 25-MAY-2022, entry version 66.
DE RecName: Full=Protein c-Fos {ECO:0000305};
DE AltName: Full=Cellular oncogene fos;
DE AltName: Full=Transcription factor AP-1 subunit c-Fos {ECO:0000305};
GN Name=FOS;
OS Phodopus campbelli (Campbell's dwarf Russian hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Phodopus.
OX NCBI_TaxID=47665;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Weiler E.;
RT "Expression of c-FOS in dwarf hamster Phodopus campbelli.";
RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Nuclear phosphoprotein which forms a tight but non-covalently
CC linked complex with the JUN/AP-1 transcription factor. On TGF-beta
CC activation, forms a multimeric SMAD3/SMAD4/JUN/FOS complex, at the
CC AP1/SMAD-binding site to regulate TGF-beta-mediated signaling. Has a
CC critical function in regulating the development of cells destined to
CC form and maintain the skeleton. It is thought to have an important role
CC in signal transduction, cell proliferation and differentiation (By
CC similarity). In growing cells, activates phospholipid synthesis,
CC possibly by activating CDS1 and PI4K2A. This activity requires Tyr-
CC dephosphorylation and association with the endoplasmic reticulum (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Heterodimer; with JUN (By similarity). Component of the
CC SMAD3/SMAD4/JUN/FOS complex required for synergistic TGF-beta-mediated
CC transcription at the AP1-binding site (By similarity). Interacts with
CC SMAD3; the interaction is weak even on TGF-beta activation (By
CC similarity). Interacts with MAFB (By similarity). Interacts with DSIPI;
CC this interaction inhibits the binding of active AP1 to its target DNA
CC (By similarity). Interacts with CDS1 and PI4K2A (By similarity).
CC Interacts (via bZIP domain and leucine-zipper region) with the
CC multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF)
CC subunits SMARCB1, SMARCC2 and SMARCD1 (By similarity). Interacts (via
CC bZIP domain and leucine-zipper region) with ARID1A (By similarity).
CC {ECO:0000250|UniProtKB:P01100, ECO:0000250|UniProtKB:P01101,
CC ECO:0000250|UniProtKB:P12841}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00978}.
CC Endoplasmic reticulum {ECO:0000250}. Cytoplasm, cytosol {ECO:0000250}.
CC Note=In quiescent cells, present in very small amounts in the cytosol.
CC Following induction of cell growth, first localizes to the endoplasmic
CC reticulum and only later to the nucleus. Localization at the
CC endoplasmic reticulum requires dephosphorylation at Tyr-10 and Tyr-30
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated in the C-terminal upon stimulation by nerve growth
CC factor (NGF) and epidermal growth factor (EGF). Phosphorylated, in
CC vitro, by MAPK and RSK1. Phosphorylation on both Ser-363 and Ser-375 by
CC MAPK1/2 and RSK1/2 leads to protein stabilization with phosphorylation
CC on Ser-375 being the major site for protein stabilization on NGF
CC stimulation. Phosphorylation on Ser-363 and Ser-375 primes further
CC phosphorylations on Thr-326 and Thr-332 through promoting docking of
CC MAPK to the DEF domain. Phosphorylation on Thr-232, induced by HA-RAS,
CC activates the transcriptional activity and antagonizes sumoylation.
CC Phosphorylation on Ser-363 by RSK2 in osteoblasts contributes to
CC osteoblast transformation (By similarity). {ECO:0000250}.
CC -!- PTM: Constitutively sumoylated with SUMO1, SUMO2 and SUMO3.
CC Desumoylated by SENP2. Sumoylation requires heterodimerization with JUN
CC and is enhanced by mitogen stimulation. Sumoylation inhibits the AP-1
CC transcriptional activity and is, itself, inhibited by Ras-activated
CC phosphorylation on Thr-232 (By similarity). {ECO:0000250}.
CC -!- PTM: In quiescent cells, the small amount of FOS present is
CC phosphorylated at Tyr-10 and Tyr-30 by SRC. This Tyr-phosphorylated
CC form is cytosolic. In growing cells, dephosphorylated by PTPN2.
CC Dephosphorylation leads to the association with endoplasmic reticulum
CC membranes and activation of phospholipid synthesis (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the bZIP family. Fos subfamily. {ECO:0000305}.
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DR EMBL; AY585680; AAU00056.1; -; Genomic_DNA.
DR AlphaFoldDB; Q56TT7; -.
DR SMR; Q56TT7; -.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IEA:InterPro.
DR InterPro; IPR000837; AP-1.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR029816; c-Fos/v-Fos.
DR PANTHER; PTHR23351; PTHR23351; 1.
DR PANTHER; PTHR23351:SF4; PTHR23351:SF4; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR PRINTS; PR00042; LEUZIPPRFOS.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 3: Inferred from homology;
KW Cytoplasm; DNA-binding; Endoplasmic reticulum; Isopeptide bond; Nucleus;
KW Phosphoprotein; Proto-oncogene; Ubl conjugation.
FT CHAIN 1..381
FT /note="Protein c-Fos"
FT /id="PRO_0000254957"
FT DOMAIN 137..200
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 139..159
FT /note="Basic motif; required for the activation of
FT phospholipid synthesis, but not for CDS1-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 165..193
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 223..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 355..381
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 358..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 10
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT MOD_RES 30
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT MOD_RES 232
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P01101"
FT MOD_RES 326
FT /note="Phosphothreonine; by MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT MOD_RES 332
FT /note="Phosphothreonine; by MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT MOD_RES 363
FT /note="Phosphoserine; by MAPK1, MAPK3 and RPS6KA3"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT MOD_RES 375
FT /note="Phosphoserine; by MAPK1 and MAPK3"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT CROSSLNK 113
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT CROSSLNK 128
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P01100"
FT CROSSLNK 265
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 265
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P01100"
SQ SEQUENCE 381 AA; 40957 MW; 291E080393C0CBFB CRC64;
MMFSGFNAEY EASSSRCSSA SPAGDSLSYY HSPADSFSSM GSPVNAQDFC ADLSVSSANF
IPTVTAISTS PDLQWLVQPT LVSSVAPSQT RAPHPYGVPT PPTGAYSRAG MVKTVSGGRA
QSIGRRGKVE QLSPEEEEKR RIRRERNKMA AAKCRNRRRE LTDTLQAETD HLEDEKSALQ
TEIANLLKEK EKLEFILAAH RPACKIPDDL GFPEDMSVAS LDLTGGLPEA TTPESEEAFS
LPLLNDPEPK TSLEPVKSIS NMELKAEPFD DFLFPASSRP SGSETTARSV PDMDLSGSFY
AADWEPLHSS SLGMGPMATE LEPLCTPVVT CTPSCTTYTS SFVFTYPEAD SFPSCAAAHR
KGSSSNEPSS DSLSSPTLLA L
