P51611 · HCFC1_MESAU

Function

function

Transcriptional coregulator (By similarity).
Involved in control of the cell cycle (PubMed:9087427).
Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (By similarity).
Coactivator for EGR2 and GABP2 (By similarity).
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 (By similarity).
As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues (By similarity).
Recruits KMT2E to E2F1 responsive promoters promoting transcriptional activation and thereby facilitates G1 to S phase transition (By similarity).
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).

Features

Showing features for site.

120902004006008001,0001,2001,4001,6001,8002,000
TypeIDPosition(s)Description
Site1019-1020Cleavage; by autolysis
Site1081-1082Cleavage; by autolysis
Site1110-1111Cleavage; by autolysis
Site1304-1305Cleavage; by autolysis
Site1332-1333Cleavage; by autolysis
Site1432-1433Cleavage; by autolysis

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componenthistone acetyltransferase complex
Cellular ComponentMLL1 complex
Cellular Componentneuronal cell body
Cellular Componentnucleus
Cellular ComponentSet1C/COMPASS complex
Molecular Functionchromatin binding
Molecular Functiontranscription coactivator activity
Biological Processchromatin organization
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processpositive regulation of mitotic cell cycle
Biological Processprotein stabilization

Keywords

Names & Taxonomy

Protein names

Gene names

    • Name
      HCFC1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Cricetidae > Cricetinae > Mesocricetus

Accessions

  • Primary accession
    P51611

Proteomes

Subcellular Location

Cytoplasm
Nucleus
Note: HCFC1R1 modulates its subcellular localization and overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm. Non-processed HCFC1 associates with chromatin. Colocalizes with CREB3 and CANX in the ER.

Keywords

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis134Causes temperature-sensitive cell cycle arrest in a Go-like state.

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, cross-link.

TypeIDPosition(s)Description
Initiator methionine1Removed
Modified residue2N-acetylalanine
ChainPRO_00000166282-1019HCF N-terminal chain 1
ChainPRO_00000166272-1081HCF N-terminal chain 2
ChainPRO_00000166262-1110HCF N-terminal chain 3
ChainPRO_00000166252-1304HCF N-terminal chain 4
ChainPRO_00000166242-1332HCF N-terminal chain 5
ChainPRO_00000166232-1432HCF N-terminal chain 6
Modified residue6Phosphoserine
Cross-link105Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link244Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link282Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue288N6-acetyllysine
Cross-link363Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue411Phosphoserine
Modified residue504Omega-N-methylarginine
Modified residue524Omega-N-methylarginine
Modified residue598Phosphoserine
Modified residue666Phosphoserine
Modified residue669Phosphoserine
Modified residue813N6-acetyllysine
ChainPRO_00000166291020-2090HCF C-terminal chain 1
ChainPRO_00000166301082-2090HCF C-terminal chain 2
ChainPRO_00000166311111-2090HCF C-terminal chain 3
Modified residue1204Phosphoserine
Modified residue1216Asymmetric dimethylarginine
Modified residue1223Phosphoserine
ChainPRO_00000166321305-2090HCF C-terminal chain 4
ChainPRO_00000166331333-2090HCF C-terminal chain 5
ChainPRO_00000166341433-2090HCF C-terminal chain 6
Modified residue1500Phosphothreonine
Modified residue1506Phosphoserine
Modified residue1559Phosphoserine
Modified residue1826Phosphoserine
Cross-link1862Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross-link1863Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue1893Phosphoserine
Modified residue2060N6-acetyllysine
Cross-link2079Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Post-translational modification

Proteolytically cleaved at one or several PPCE--THET sites within the HCF repeats. Cleavage is promoted by O-glycosylation (By similarity).
Further cleavage of the primary N- and C-terminal chains results in a 'trimming' and accumulation of the smaller chains (By similarity).
Cleavage is promoted by O-glycosylation (By similarity).
O-glycosylated. GlcNAcylation by OGT promotes proteolytic processing.
Ubiquitinated. Lys-1862 and Lys-1863 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.

Keywords

Interaction

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, SUDS3), SAP30, SIN3B and FHL2. 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 BAP18, 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 a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. 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 directly with OGT; the interaction, which requires the HCFC1 cleavage site domain, glycosylates and promotes the proteolytic processing of HCFC1 and retains OGT in the nucleus. 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. 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 (By similarity).
Within the complex interacts with ZNF335 (By similarity).
Interacts with TET2 and TET3. Interacts with HCFC1R1. Interacts with THAP11. Interacts (via Kelch domain) with KMT2E (via HBM motif). Interacts with E2F1. 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 (By similarity).
Interacts with YY1 (via Gly-rich region); the interaction is direct (By similarity).
Interacts with BAP1 (via HBM-like motif) (By similarity).

Protein-protein interaction databases

Family & Domains

Features

Showing features for repeat, domain, region, compositional bias.

TypeIDPosition(s)Description
Repeat44-89Kelch 1
Repeat93-140Kelch 2
Repeat148-194Kelch 3
Repeat217-265Kelch 4
Repeat266-313Kelch 5
Domain366-469Fibronectin type-III 1
Region407-434Disordered
Compositional bias414-432Pro residues
Region500-550Required for interaction with OGT
Region610-722Interaction with SIN3A
Region750-902Interaction with ZBTB17
Region813-912Interaction with GABP2
Repeat1010-1035HCF repeat 1
Repeat1072-1097HCF repeat 2
Region1098-1140Disordered
Repeat1101-1126HCF repeat 3
Repeat1157-1182HCF repeat 4; degenerate
Repeat1295-1320HCF repeat 5
Compositional bias1302-1354Polar residues
Region1302-1374Disordered
Repeat1323-1348HCF repeat 6
Repeat1358-1383HCF repeat 7; degenerate
Repeat1423-1448HCF repeat 8
Region1444-1486Disordered
Domain1853-1943Fibronectin type-III 2
Domain1945-2061Fibronectin type-III 3
Region2049-2090Disordered
Compositional bias2052-2070Polar residues

Domain

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.

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    2,090
  • Mass (Da)
    214,942
  • Last updated
    1996-10-01 v1
  • Checksum
    E495E8B1F2385E17
MASAVSPANLPAVLLQPRWKRVVGWSGPVPRPRHGHRAVAIKELIVVFGGGNEGIVDELHVYNTATNQWFIPAVRGDIPPGCAAYGFVCDGTRLLVFGGMVEYGKYSNDLYELQASRWEWKRLKAKTPKNGPPPCPRLGHSFSLVGNKCYLFGGLANDSEDPKNNIPRYLNDLYILELRPGSGVVAWDIPITYGVLPPPRESHTAVVYTEKDNKKSKLVIYGGMSGCRLGDLWTLDIETLTWNKPSLSGVAPLPRSLHSATTIGNKMYVFGGWVPLVMDDVKVATHEKEWKCTNTLACLNLDTMAWETILMDTLEDNIPRARAGHCAVAINTRLYIWSGRDGYRKAWNNQVCCKDLWYLETEKPPPPARVQLVRANTNSLEVSWGAVATADSYLLQLQKYDIPATAATATSPTPNPVPSVPANPPKSPAPAAAAPAVQPLTQVGITLVPQAAAAPPSTTTIQVLPTVPGSSISVPTAARAQGVPAVLKVTGPQATTGTPLVTMRPAGQAGKAPVTVTSLPASVRMVVPTQSAQGTVIGSNPQMSGMAALAAAAAATQKIPPSSAPTVLSVPAGTTIVKTVAVTPGTTTLPATVKVASSPVMVSNPATRMLKTAAAQVGTSVSSAANTSTRPIITVHKSGTVTVAQQAQVVTTVVGGVTKTITLVKSPISVPGGSALISNLGKVMSVVQTKPVQTSAVTGQASTGPVTQIIQTKGPLPAGTILKLVTSADGKPTTIITTTQASGAGSKPTILGISSVSPSTTKPGTTTIIKTIPMSAIITQAGATGVTSTPGIKSPITIITTKVMTSGTGAPAKIITAVPKIATGHGQQGVTQVVLKGAPGQPGAILRTVPMSGVRLVTPVTVSAVKPAVTTLVVKGTTGVTTLGTVTGTVSTSLAGAGAHSTSASLATPITTLGTIATLSSQVINPTAITVSAAQTTLTAAGGLTTPTITMQPVSQPTQVTLITAPSGVEAQPVHDLPVSILASPTTEQPTATVTIADSGQGDVQPGTVTLVCSNPPCETHETGTTNTATTTVVANLGGHPQPTQVQFVCDRQEAAASLVTSAVGQQNGNVVRVCSNPPCETHETGTTNTATTATSNMAGQHGCSNPPCETHETGTTSTATTAMSSMGTGQQRDTRHTSSNPTVVRITVAPGALERTQGTVKPQCQTQQANMTNTTMTVQATRSPCPAGPLLRPSVALEAGNHSPAFVQLALPSVRVGLSGPSNKDMPTGHQLETYHTYTTNTPTTALSIMGAGELGTARLIPTSTYESLQASSPSSTMTMTALEALLCPSATVTQVCSNPPCETHETGTTNTATTSNAGSAQRVCSNPPCETHETGTTHTATTATSNGGAGQPEGGQQPAGGRPCETHQTTSTGTTMSVSVGALLPDATPSHGTLESGLEVVAVSTVTSQAGATLLASFPTQRVCSNPPCETHETGTTHTATTVTSNMSSNQDPPPAASDQGEVVSTQGDSANITSSSGITTTVSSTLPRAVTTVTQSTPVPGPSVPNISSLTETPGALTSEVPIPATITVTIANTETSDMPFSAVDILQPPEELQVSPGPRQQLPPRQLLQSASTPLMGESSEVLSASQTPELQAAVDLSSTGDPSSGQEPTSSAVVATVVVQPPPPTQSEVDQLSLPQELMAEAQAGTTTLMVTGLTPEELAVTAAAEAAAQAAATEEAQALAIQAVLQAAQQAVMAGTGEPMDTSEAAAAVTQAELGHLSAEGQEGQATTIPIVLTQQELAALVQQQQQLQEVQAQAQQQHHLPTEALAPADSLNDPSIESNCLNELASAVPSTVALLPSTATESLAPSNTFVAPQPVVVASPAKMQAAATLTEVDNGIESLGVKPDLPPPPSKAPVKKENQWFDVGVIKGTSVMVTHYFLPPDDAVQSDDDSGTIPDYNQLKKQELQPGTAYKFRVAGINACGRGPFSEISAFKTCLPGFPGAPCAIKISKSPDGAHLTWEPPSVTSGKIIEYSVYLAIQSSQAGGEPKSSTPAQLAFMRVYCGPSPSCLVQSSSLSNAHIDYTTKPAIIFRIAARNEKGYGPATQVRWLQETSKDSSGTKPASKRPMSSPEMKSAPKKSKADGQ

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias414-432Pro residues
Compositional bias1302-1354Polar residues
Compositional bias2052-2070Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
D45419
EMBL· GenBank· DDBJ
BAA08258.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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