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

Function

• control of the cell cycle
• upon lytic infection of permissive cells
  • HSV transactivator protein VP16 associates with HCFC1
  • binding to HCFC1 activates VP16 for association with POU2F1
  • forms multiprotein-DNA complex responsible for activating transcription of the HSV immediate early genes
• antagonizes transactivation by ZBTB17 & GABP2
• represses ZBTB17 activation of the p15(INK4b) promote
• coactivator for EGR2 & GABP2
• tethers chromatin
  • modifies Set1/Ash2 histone H3-K4 methyltrasferase (transcriptional activation)
  • Sin3 histone deacetylase complexes (transcriptional repression)
• 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
• cleaved to form 6 polypeptides 110-150 kD & a minor 300 kD polypeptide; the majority of N- & C-terminal cleavage products remain noncovalently associated
• interacts with POU2F1, VP16, CREB3, ZBTB17, EGR2, E2F4, ZF, SP1, GABP2, Sin3 HDAC complex, Set1/Ash2 HMT complex, SAP30, SIN3B, OGT1
• component of MLL1 complex
• component of MLL5-L complex
• component of the SET1 complex
• component of the NSL complex
• component of a THAP1/THAP3-HCFC1-OGT complex required for regulation of transcriptional activity of RRM1
  • 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
  • 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 & 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

More general terms

• nuclear protein

Component of

• MLL1 complex
• MLL5-L complex
• Set1/Ash2 histone methyltransferase (HMT) complex
• NSL complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=3054
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:3054
• OMIM: https://mirror.omim.org/entry/300019
• UniProt: http://www.uniprot.org/uniprot/P51610.html