host cell factor; HCF; HCF-1; C1 factor; VP16 accessory protein; VCAF; CFF (HCFC1, HCF1)

Function: 1) control of the cell cycle 2) upon lytic infection of permissive cells a) HSV transactivator protein VP16 associates with HCFC1 b) binding to HCFC1 activates VP16 for association with POU2F1 c) forms multiprotein-DNA complex responsible for activating transcription of the HSV immediate early genes 3) antagonizes transactivation by ZBTB17 & GABP2 4) represses ZBTB17 activation of the p15(INK4b) promote 5) coactivator for EGR2 & GABP2 6) tethers chromatin a) modifies Set1/Ash2 histone H3-K4 methyltrasferase (transcriptional activation) b) Sin3 histone deacetylase complexes (transcriptional repression) 7) proteolytically cleaved at one or several PPCE-THET sites within HCF repeats; further cleavage of the primary N- & C-terminal chains results in a 'trimming' & accumulation of the smaller chains 8) cleaved to form 6 polypeptides 110-150 kD & a minor 300 kD polypeptide; the majority of N- & C-terminal cleavage products remain noncovalently associated 9) interacts with POU2F1, VP16, CREB3, ZBTB17, EGR2, E2F4, ZF, SP1, GABP2, Sin3 HDAC complex, Set1/Ash2 HMT complex, SAP30, SIN3B, OGT1 10) component of MLL1 complex 11) component of MLL5-L complex 12) component of the SET1 complex 13) component of the NSL complex 14) component of a THAP1/THAP3-HCFC1-OGT complex required for regulation of transcriptional activity of RRM1 a) interacts directly with OGT - the interaction, which requires the HCFC1 cleavage site domain, glycosylates & promotes the proteolytic processing of HCFC1, retains OGT in the nucleus & impacts the expression of HSV immediate early viral genes b) interacts directly with THAP3 (via its HBM) c) interacts (via the kelch-repeat domain) with THAP1 (via the HBM) - the interaction recruits HCHC1 to the RRM1 d) interacts with HCFC1R1 & THAP11 Structure: - O-glycosylated - the HCF repeat is a highly specific proteolytic cleavage signal - the kelch repeats fold into a 6-bladed kelch beta-propeller called the beta-propeller domain which mediates interaction with HCFC1R1 Compartment: - cytoplasm, nucleus - HCFC1R1 modulates its subcellular localization - overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm - nuclear in general - uniquely cytoplasmic in trigeminal ganglia, becoming nuclear upon HSV reactivation from the latent state - non-processed HCFC1 associates with chromatin - colocalizes with CREB3 & CANX in the endoplasmic reticulum Alternative splicing: named isoforms=3 Expression: - highly expressed in fetal tissues, adult kidney - expressed in all tissues

Properties

SIZE: MW = 209 kD entity length = 2035 aa COMPARTMENT: cell nucleus MOTIF: kelch repeat {44-313} (5) binding site SITE: 610-722 FOR-BINDING-OF: paired amphipathic helix protein sin3a binding site SITE: 750-902 FOR-BINDING-OF: zinc finger & BTB domain-containing protein 17 binding site SITE: 813-912 FOR-BINDING-OF: GABP2 HCF {1010-1035} MOTIF: proteolytic site {1019-1020} HCF {1072-1097} MOTIF: proteolytic site {1081-1082} HCF {1101-1126} MOTIF: proteolytic site {1110-1111} HCF {1158-1183} HCF {1286-1311} MOTIF: proteolytic site {1295-1296} HCF {1314-1339} MOTIF: proteolytic site {1323-1324} HCF {1349-1374} HCF {1414-1439} MOTIF: proteolytic site {1423-1424}

Database Correlations

OMIM 300019 UniProt P51610 Pfam PF01344 Entrez Gene 3054 Kegg hsa:3054

References

UniProt :accession P51610