Human Gene HCFC1 (uc004fjp.3) Description and Page Index
Description: Homo sapiens host cell factor C1 (VP16-accessory protein) (HCFC1), mRNA. RefSeq Summary (NM_005334): This gene is a member of the host cell factor family and encodes a protein with five Kelch repeats, a fibronectin-like motif, and six HCF repeats, each of which contains a highly specific cleavage signal. This nuclear coactivator is proteolytically cleaved at one of the six possible sites, resulting in the creation of an N-terminal chain and the corresponding C-terminal chain. The final form of this protein consists of noncovalently bound N- and C-terminal chains. The protein is involved in control of the cell cycle and transcriptional regulation during herpes simplex virus infection. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: L20010.1 [ECO:0000332] RNAseq introns :: mixed/partial sample support SAMEA1965299, SAMEA1966682 [ECO:0000350] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000310441.12/ ENSP00000309555.7 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg19 chrX:153,213,008-153,236,819 Size: 23,812 Total Exon Count: 26 Strand: - Coding Region Position: hg19 chrX:153,214,798-153,236,291 Size: 21,494 Coding Exon Count: 26
ID:HCFC1_HUMAN DESCRIPTION: RecName: Full=Host cell factor 1; Short=HCF; Short=HCF-1; AltName: Full=C1 factor; AltName: Full=CFF; AltName: Full=VCAF; AltName: Full=VP16 accessory protein; Contains: RecName: Full=HCF N-terminal chain 1; Contains: RecName: Full=HCF N-terminal chain 2; Contains: RecName: Full=HCF N-terminal chain 3; Contains: RecName: Full=HCF N-terminal chain 4; Contains: RecName: Full=HCF N-terminal chain 5; Contains: RecName: Full=HCF N-terminal chain 6; Contains: RecName: Full=HCF C-terminal chain 1; Contains: RecName: Full=HCF C-terminal chain 2; Contains: RecName: Full=HCF C-terminal chain 3; Contains: RecName: Full=HCF C-terminal chain 4; Contains: RecName: Full=HCF C-terminal chain 5; Contains: RecName: Full=HCF C-terminal chain 6; FUNCTION: Involved in control of the cell cycle. Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300. Coactivator for EGR2 and GABP2. Tethers the chromatin modifying Set1/Ash2 histone H3 'Lys-4' methyltransferase (H3K4me) and Sin3 histone deacetylase (HDAC) complexes (involved in the activation and repression of transcription, respectively) together. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. In case of human herpes simplex virus (HSV) infection, HCFC1 forms a multiprotein-DNA complex with the viral transactivator protein VP16 and POU2F1 thereby enabling the transcription of the viral immediate early genes. SUBUNIT: Composed predominantly of six polypeptides ranging from 110 to 150 kDa and a minor 300 kDa polypeptide. The majority of N- and C-terminal cleavage products remain tightly, albeit non- covalently, associated. Interacts with POU2F1, CREB3, ZBTB17, EGR2, E2F4, CREBZF, SP1, GABP2, Sin3 HDAC complex (SIN3A, HDAC1, HDAC2, SDS3), SAP30, SIN3B and FHL2. Component of a MLL1 complex, composed of at least the core components MLL, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components C17orf49, CHD8, DPY30, E2F6, HCFC2, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8, PELP1, PHF20,. PRP31, RING2, RUVBL1, RUVBL2, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the MLL5-L complex, composed of at least MLL5, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Interacts directly with OGT; the interaction, which requires the HCFC1 cleavage site domain, glycosylates and promotes the proteolytic processing of HCFC1, retains OGT in the nucleus and impacts the expression of herpes simplex virus immediate early viral genes. Interacts directly with THAP3 (via its HBM). Interacts (via the Kelch-repeat domain) with THAP1 (via the HBM); the interaction recruits HCHC1 to the RRM1. Interacts with HCFC1R1 and THAP11. Associates with the VP16-induced complex; binding to HCFC1 activates the viral transcriptional activator VP16 for association with POU2F1, to form a multiprotein-DNA complex responsible for activating transcription of the viral immediate early genes. Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L, CXXC1, HCFC1 and DPY30. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts with the viral transactivator protein VP16. INTERACTION: Self; NbExp=2; IntAct=EBI-396176, EBI-396176; Q9UBL3:ASH2L; NbExp=4; IntAct=EBI-396176, EBI-540797; O43889:CREB3; NbExp=5; IntAct=EBI-396176, EBI-625002; O43889-2:CREB3; NbExp=4; IntAct=EBI-396176, EBI-625022; Q9NS37:CREBZF; NbExp=8; IntAct=EBI-396176, EBI-632965; O43524:FOXO3; NbExp=2; IntAct=EBI-396176, EBI-1644164; Q06546:GABPA; NbExp=2; IntAct=EBI-396176, EBI-638925; Q06547:GABPB1; NbExp=3; IntAct=EBI-396176, EBI-618165; Q06547-2:GABPB1; NbExp=6; IntAct=EBI-396176, EBI-618189; Q13547:HDAC1; NbExp=2; IntAct=EBI-396176, EBI-301834; Q92769:HDAC2; NbExp=2; IntAct=EBI-396176, EBI-301821; O15294:OGT; NbExp=9; IntAct=EBI-396176, EBI-539828; O15047:SETD1A; NbExp=2; IntAct=EBI-396176, EBI-540779; Q96ST3:SIN3A; NbExp=6; IntAct=EBI-396176, EBI-347218; Q96EB6:SIRT1; NbExp=2; IntAct=EBI-396176, EBI-1802965; P08047:SP1; NbExp=4; IntAct=EBI-396176, EBI-298336; Q9H7L9:SUDS3; NbExp=2; IntAct=EBI-396176, EBI-540496; Q96EK4:THAP11; NbExp=2; IntAct=EBI-396176, EBI-1790529; P61964:WDR5; NbExp=4; IntAct=EBI-396176, EBI-540834; Q13105:ZBTB17; NbExp=9; IntAct=EBI-396176, EBI-372156; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=HCFC1R1 modulates its subcellular localization and overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm. Nuclear in general, but uniquely cytoplasmic in trigeminal ganglia, becoming nuclear upon HSV reactivation from the latent state. Non-processed HCFC1 associates with chromatin. Colocalizes with CREB3 and CANX in the ER. TISSUE SPECIFICITY: Highly expressed in fetal tissues and the adult kidney. Present in all tissues tested. DOMAIN: The HCF repeat is a highly specific proteolytic cleavage signal. DOMAIN: The kelch repeats fold into a 6-bladed kelch beta- propeller called the beta-propeller domain which mediates interaction with HCFC1R1. PTM: Proteolytically cleaved at one or several PPCE--THET sites within the HCF repeats. Further cleavage of the primary N- and C- terminal chains results in a 'trimming' and accumulation of the smaller chains. Cleavage is promoted by O-glycosylation. PTM: O-glycosylated. O-glycosylation promotes proteolytic processing. PTM: Ubiquitinated. Lys-1807 and Lys-1808 are ubiquitinated both via 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. BAP1 mediated deubiquitination of 'Lys-48'-linked polyubiquitin chains; deubiquitination by BAP1 does not seem to stabilize the protein. SIMILARITY: Contains 5 Kelch repeats. SEQUENCE CAUTION: Sequence=CAA55790.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): HCFC1 CDC HuGE Published Literature: HCFC1
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 49265 - Fibronectin type III 50965 - Galactose oxidase, central domain
ModBase Predicted Comparative 3D Structure on P51610
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.