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Details on Person UniProt:P51610 HCFC1

Class:IdReferenceGeneProduct:56478
_chainChangeLoginitiator methionine:1 added on Sat February 7 2015;chain:2-1423 added on Sat February 7 2015;chain:2-1323 added on Sat February 7 2015;chain:2-1295 added on Sat February 7 2015;chain:2-1110 added on Sat February 7 2015;chain:2-1081 added on Sat February 7 2015;chain:2-1019 added on Sat February 7 2015;chain:1020-2035 added on Sat February 7 2015;chain:1082-2035 added on Sat February 7 2015;chain:1111-2035 added on Sat February 7 2015;chain:1296-2035 added on Sat February 7 2015;chain:1324-2035 added on Sat February 7 2015;chain:1424-2035 added on Sat February 7 2015;initiator methionine:1 for 56478 removed on Fri Nov 03 2023;initiator methionine: for 56478 added on Fri Nov 03 2023;initiator methionine: for 56478 removed on Fri Aug 15 2025;initiator methionine:1 for 56478 added on Fri Aug 15 2025
_displayNameUniProt:P51610 HCFC1
_timestamp2025-08-15 21:23:09
chaininitiator methionine:1
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chain:2-1323
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checksum0B0C581E2454631E
commentFUNCTION Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337, PubMed:12244100). Coactivator for EGR2 and GABP2 (PubMed:12244100, PubMed:14532282). 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 (PubMed:12670868). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852). Recruits KMT2E/MLL5 to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (PubMed:23629655). Modulates expression of homeobox protein PDX1, perhaps acting in concert with transcription factor E2F1, thereby regulating pancreatic beta-cell growth and glucose-stimulated insulin secretion (By similarity). May negatively modulate transcriptional activity of FOXO3 (By similarity).FUNCTION (Microbial infection) 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 (PubMed:10920196). The majority of N- and C-terminal cleavage products remain tightly, albeit non-covalently, associated (PubMed:10920196). Interacts with POU2F1, CREB3, ZBTB17, EGR2, E2F4, CREBZF, SP1, GABP2, Sin3 HDAC complex (SIN3A, HDAC1, HDAC2, SUDS3), SAP30, SIN3B and FHL2 (PubMed:10629049, PubMed:10675337, PubMed:10871379, PubMed:10976766, PubMed:10984507, PubMed:12244100, PubMed:12670868, PubMed:14532282, PubMed:15705566, PubMed:16624878, PubMed:9271389, PubMed:9389645). Component of a MLL1 complex, composed of at least the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BACC1, 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 (PubMed:15199122, PubMed:15960975). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). Interacts directly with THAP3 (via its HBM) (PubMed:20200153). Interacts (via the Kelch-repeat domain) with THAP1 (via the HBM); the interaction recruits HCHC1 to the RRM1 (PubMed:20200153). Interacts with THAP7 and THAP11 (via the HMB) (PubMed:31905202). 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 (PubMed:12670868, PubMed:21285374, PubMed:23353889). Component of the SET1 complex, at least composed of the catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, ASH2L, CXXC1, HCFC1 and DPY30 (PubMed:17998332, PubMed:18838538). Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 (PubMed:20018852). Component of a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5; the complex is formed as a result of interactions between components of a nuclear receptor-mediated transcription complex and a histone methylation complex (PubMed:19131338). Within the complex interacts with ZNF335 (PubMed:19131338). Interacts with TET2 and TET3 (PubMed:23353889). Interacts with HCFC1R1 (PubMed:12235138). Interacts with THAP11 (By similarity). Interacts (via Kelch domain) with KMT2E/MLL5 isoform 3 (via HBM motif) (PubMed:23629655). Interacts with E2F1 (PubMed:23629655). Accessory scaffold component of the polycomb repressive deubiquitinase (PR-DUB) complex, at least composed of BAP1, one of ASXL1, ASXL2 or (probably) ASXL3 and one of MBD5 or MBD6; the PR-DUB core associates with a number of accessory proteins, including FOXK1, FOXK2, KDM1B, HCFC1, YY1 and OGT (PubMed:20805357, PubMed:30664650). Interacts with YY1 (via Gly-rich region); the interaction is direct (PubMed:20805357). Interacts with BAP1 (via HBM-like motif) (PubMed:19188440, PubMed:19815555, PubMed:20805357).SUBUNIT (Microbial infection) 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 (PubMed:10629049). Interacts with the viral transactivator protein VP16 (PubMed:10629049, PubMed:9271389, PubMed:9389645).INTERACTION HCFC1R1 modulates its subcellular localization and overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm (PubMed:12235138). Non-processed HCFC1 associates with chromatin. Colocalizes with CREB3 and CANX in the ER.ALTERNATIVE PRODUCTS 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 (PubMed:10920196, PubMed:21285374, PubMed:7590226). 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 (PubMed:21285374, PubMed:28302723, PubMed:28584052).PTM O-glycosylated. GlcNAcylation by OGT 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS The N- and the C-terminal fragments fail to associate.CAUTION Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).SEQUENCE CAUTION Truncated N-terminus.
descriptionrecommendedName: fullName evidence="47"Host cell factor 1 shortName evidence="52"HCF shortName evidence="47"HCF-1 alternativeName: fullName evidence="51"C1 factor alternativeName: fullName evidence="53"CFF alternativeName: fullName evidence="53"VCAF alternativeName: fullName evidence="50"VP16 accessory protein component recommendedName: fullName evidence="49"HCF N-terminal chain 1 /component component recommendedName: fullName evidence="49"HCF N-terminal chain 2 /component component recommendedName: fullName evidence="49"HCF N-terminal chain 3 /component component recommendedName: fullName evidence="49"HCF N-terminal chain 4 /component component recommendedName: fullName evidence="49"HCF N-terminal chain 5 /component component recommendedName: fullName evidence="49"HCF N-terminal chain 6 /component component recommendedName: fullName evidence="49"HCF C-terminal chain 1 /component component recommendedName: fullName evidence="49"HCF C-terminal chain 2 /component component recommendedName: fullName evidence="49"HCF C-terminal chain 3 /component component recommendedName: fullName evidence="49"HCF C-terminal chain 4 /component component recommendedName: fullName evidence="49"HCF C-terminal chain 5 /component component recommendedName: fullName evidence="49"HCF C-terminal chain 6 /component
geneNameHCFC1
HCF1
HFC1
identifierP51610
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Alternative splicing
Autocatalytic cleavage
Cell cycle
Chromatin regulator
Cytoplasm
Direct protein sequencing
Disease variant
Glycoprotein
Host-virus interaction
Intellectual disability
Isopeptide bond
Kelch repeat
Methylation
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameHCFC1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8994256] ENSEMBL:ENSG00000172534 HCFC1 [Homo sapiens]
secondaryIdentifierHCFC1_HUMAN
Q6P4G5
sequenceLength2035
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:148368] UniProt:P51610-2 HCFC1 [Homo sapiens]
[ReferenceIsoform:231565] UniProt:P51610-3 HCFC1 [Homo sapiens]
[ReferenceIsoform:404287] UniProt:P51610-1 HCFC1 [Homo sapiens]
[ReferenceIsoform:8965181] UniProt:P51610-4 HCFC1 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:1592209] HCFC1 [nucleoplasm] [Homo sapiens]
[EntityWithAccessionedSequence:5690821] K48polyUb,K63polyUb-HCFC1 [nucleoplasm] [Homo sapiens]
(referenceSequence)[GroupModifiedResidue:6782534] ubiquitinylated lysine (K48-polyUb, K63-polyUb [nucleoplasm]) at 1807
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