HCF1_CAEEL
ID HCF1_CAEEL Reviewed; 782 AA.
AC G5EC23;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Host cell factor homolog hcf-1 {ECO:0000303|PubMed:9858614};
DE Short=HCF homolog {ECO:0000303|PubMed:9858614};
GN Name=hcf-1 {ECO:0000312|WormBase:C46A5.9};
GN ORFNames=C46A5.9 {ECO:0000312|WormBase:C46A5.9};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAD12580.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=9858614; DOI=10.1128/mcb.19.1.909;
RA Liu Y., Hengartner M.O., Herr W.;
RT "Selected elements of herpes simplex virus accessory factor HCF are highly
RT conserved in Caenorhabditis elegans.";
RL Mol. Cell. Biol. 19:909-915(1999).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP DEVELOPMENTAL STAGE, PHOSPHORYLATION AT SER-423; SER-431; SER-449 AND
RP SER-498, AND MUTAGENESIS OF SER-449.
RX PubMed=11341844; DOI=10.1021/bi010086o;
RA Wysocka J., Liu Y., Kobayashi R., Herr W.;
RT "Developmental and cell-cycle regulation of Caenorhabditis elegans HCF
RT phosphorylation.";
RL Biochemistry 40:5786-5794(2001).
RN [4] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=14629117; DOI=10.1078/0171-9335-00341;
RA Izeta A., Malcomber S., O'Rourke D., Hodgkin J., O'Hare P.;
RT "A C-terminal targeting signal controls differential compartmentalisation
RT of Caenorhabditis elegans host cell factor (HCF) to the nucleus or
RT mitochondria.";
RL Eur. J. Cell Biol. 82:495-504(2003).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=18043729; DOI=10.1371/journal.pone.0001213;
RA Lee S., Horn V., Julien E., Liu Y., Wysocka J., Bowerman B.,
RA Hengartner M.O., Herr W.;
RT "Epigenetic regulation of histone H3 serine 10 phosphorylation status by
RT HCF-1 proteins in C. elegans and mammalian cells.";
RL PLoS ONE 2:e1213-e1213(2007).
RN [6] {ECO:0000305}
RP FUNCTION, INTERACTION WITH DAF-16, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=18828672; DOI=10.1371/journal.pbio.0060233;
RA Li J., Ebata A., Dong Y., Rizki G., Iwata T., Lee S.S.;
RT "Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-
RT 16 regulator.";
RL PLoS Biol. 6:e233-e233(2008).
RN [7] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19521497; DOI=10.1371/journal.pgen.1000510;
RA Mani K., Fay D.S.;
RT "A mechanistic basis for the coordinated regulation of pharyngeal
RT morphogenesis in Caenorhabditis elegans by LIN-35/Rb and UBC-18-ARI-1.";
RL PLoS Genet. 5:E1000510-E1000510(2009).
RN [8] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH SIR-2.1; FTT-2 AND PAR-5.
RX PubMed=21909281; DOI=10.1371/journal.pgen.1002235;
RA Rizki G., Iwata T.N., Li J., Riedel C.G., Picard C.L., Jan M., Murphy C.T.,
RA Lee S.S.;
RT "The evolutionarily conserved longevity determinants HCF-1 and SIR-
RT 2.1/SIRT1 collaborate to regulate DAF-16/FOXO.";
RL PLoS Genet. 7:E1002235-E1002235(2011).
RN [9] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22568582; DOI=10.1111/j.1474-9726.2012.00831.x;
RA Rizki G., Picard C.L., Pereyra C., Lee S.S.;
RT "Host cell factor 1 inhibits SKN-1 to modulate oxidative stress responses
RT in Caenorhabditis elegans.";
RL Aging Cell 11:717-721(2012).
CC -!- FUNCTION: Transcriptional coregulator (PubMed:18828672). Involved in
CC control of the cell cycle and in modulating mitotic histone
CC phosphorylation (PubMed:18043729). Plays a role in modulating lifespan
CC by regulating the transcriptional activity of daf-16/Forkhead box
CC protein O, in concert with protein deacetylase sir-2.1/SIRT1, and
CC perhaps acting independently of the Insulin/IGF-1-like signaling (IIS)
CC mediated pathway (PubMed:18828672, PubMed:21909281). Negatively
CC modulates responses to environmental stresses, including oxidative
CC stress, heat stress, and exposure to heavy metals; acting via
CC regulation of the transcription factors daf-16 and skn-1
CC (PubMed:18828672, PubMed:21909281, PubMed:22568582). May play a role in
CC pharyngeal development via positive modulation of expression of sup-35
CC (PubMed:19521497). {ECO:0000269|PubMed:18043729,
CC ECO:0000269|PubMed:18828672, ECO:0000269|PubMed:19521497,
CC ECO:0000269|PubMed:21909281, ECO:0000269|PubMed:22568582}.
CC -!- SUBUNIT: Interacts with daf-16/FOXO (PubMed:18828672). Interacts with
CC deacetylase sir-2.1 (PubMed:21909281). Interacts with the 14-3-3 family
CC proteins ftt-2 and par-5 (PubMed:21909281).
CC {ECO:0000269|PubMed:18828672, ECO:0000269|PubMed:21909281}.
CC -!- INTERACTION:
CC G5EC23; Q20655: ftt-2; NbExp=2; IntAct=EBI-4480523, EBI-966073;
CC G5EC23; P41932: par-5; NbExp=2; IntAct=EBI-4480523, EBI-318108;
CC G5EC23; D3YT50: sir-2.1; NbExp=2; IntAct=EBI-4480523, EBI-4480509;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14629117,
CC ECO:0000269|PubMed:18043729, ECO:0000269|PubMed:18828672}.
CC Note=Localizes to nucleus, except for nucleolus.
CC {ECO:0000269|PubMed:14629117}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos and the L1 larval stage (at
CC protein level) (PubMed:11341844, PubMed:18828672). Expressed in embryos
CC and adults, with lower levels in L1-L4 larvae (PubMed:9858614,
CC PubMed:14629117). {ECO:0000269|PubMed:11341844,
CC ECO:0000269|PubMed:14629117, ECO:0000269|PubMed:18828672,
CC ECO:0000269|PubMed:9858614}.
CC -!- PTM: Phosphorylated at multiple serine residues (PubMed:11341844).
CC Phosphorylation is developmentally regulated, occurring in embryos but
CC not L1 larvae (PubMed:11341844). Phosphorylation may be cell-cycle-
CC regulated (PubMed:11341844). {ECO:0000269|PubMed:11341844}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes 20-30% increase in
CC lifespan (PubMed:18828672). Causes smaller brood size (50% of wild
CC type) and lower hatching rate (21% vs. 99%) at 12 degrees Celsius
CC (PubMed:18043729). Increases intestinal expression of skn-1 target
CC genes, including gcs-1, gst-4 and gst-7; increase abolished in an skn-1
CC mutant background (PubMed:22568582). Substantially reduces enrichment
CC of hcf-1 on the efl-1 promoter and enhances enrichment of daf-16 at
CC sod-3 and mtl-1 promoters (PubMed:18828672). Two-fold reduction in the
CC level of embryonic expression of sup-35 in a lin-35 mutant background
CC (PubMed:19521497). Partial suppression of larval lethality in both lin-
CC 35;ubc-18 and lin-35;pha-1 mutant backgrounds and suppression of
CC pharynx-unattached phenotypes in a pha-1 mutant background
CC (PubMed:19521497). {ECO:0000269|PubMed:18043729,
CC ECO:0000269|PubMed:18828672, ECO:0000269|PubMed:19521497,
CC ECO:0000269|PubMed:22568582}.
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DR EMBL; AF072907; AAD12580.1; -; mRNA.
DR EMBL; BX284604; CCD66593.1; -; Genomic_DNA.
DR PIR; T29816; T29816.
DR PIR; T43277; T43277.
DR RefSeq; NP_501279.1; NM_068878.4.
DR AlphaFoldDB; G5EC23; -.
DR SMR; G5EC23; -.
DR IntAct; G5EC23; 3.
DR STRING; 6239.C46A5.9; -.
DR EPD; G5EC23; -.
DR PaxDb; G5EC23; -.
DR PeptideAtlas; G5EC23; -.
DR EnsemblMetazoa; C46A5.9.1; C46A5.9.1; WBGene00001827.
DR GeneID; 177560; -.
DR KEGG; cel:CELE_C46A5.9; -.
DR CTD; 177560; -.
DR WormBase; C46A5.9; CE26914; WBGene00001827; hcf-1.
DR eggNOG; KOG4152; Eukaryota.
DR GeneTree; ENSGT00940000166952; -.
DR HOGENOM; CLU_002603_1_0_1; -.
DR InParanoid; G5EC23; -.
DR OMA; RKAWSNQ; -.
DR OrthoDB; 416932at2759; -.
DR PhylomeDB; G5EC23; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00001827; Expressed in embryo and 4 other tissues.
DR GO; GO:0035097; C:histone methyltransferase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005667; C:transcription regulator complex; IMP:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:WormBase.
DR GO; GO:0003713; F:transcription coactivator activity; IMP:UniProtKB.
DR GO; GO:0001221; F:transcription coregulator binding; IPI:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; IBA:GO_Central.
DR GO; GO:0043054; P:dauer exit; IGI:WormBase.
DR GO; GO:0098542; P:defense response to other organism; IGI:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:WormBase.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0010621; P:negative regulation of transcription by transcription factor localization; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0046686; P:response to cadmium ion; IMP:WormBase.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IGI:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR CDD; cd00063; FN3; 2.
DR Gene3D; 2.120.10.80; -; 2.
DR Gene3D; 2.60.40.10; -; 2.
DR InterPro; IPR003961; FN3_dom.
DR InterPro; IPR036116; FN3_sf.
DR InterPro; IPR043536; HCF1/2.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR PANTHER; PTHR46003; PTHR46003; 1.
DR SMART; SM00060; FN3; 2.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF49265; SSF49265; 1.
PE 1: Evidence at protein level;
KW Kelch repeat; Nucleus; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..782
FT /note="Host cell factor homolog hcf-1"
FT /id="PRO_0000454327"
FT REPEAT 55..103
FT /note="Kelch 1"
FT /evidence="ECO:0000255"
FT REPEAT 105..151
FT /note="Kelch 2"
FT /evidence="ECO:0000255"
FT REPEAT 161..222
FT /note="Kelch 3"
FT /evidence="ECO:0000255"
FT REPEAT 227..271
FT /note="Kelch 4"
FT /evidence="ECO:0000255"
FT REPEAT 280..324
FT /note="Kelch 5"
FT /evidence="ECO:0000255"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 423..553
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..25
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..471
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 513..540
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 423
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11341844"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11341844"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11341844"
FT MOD_RES 498
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11341844"
FT MUTAGEN 449
FT /note="S->A: Drastically reduces phosphorylation in vitro."
FT /evidence="ECO:0000269|PubMed:11341844"
SQ SEQUENCE 782 AA; 87359 MW; 1DF7775CA82B8309 CRC64;
MDEDVGLEAT NYSRGDESRS EEQEKNVVRW RIVQQSTGPN PKPRHGHRAV VLKELIVIFG
GGNEGMIDEL HAYNTQKREW TAPQCCGDVP TPAAAFGAIS LGNKIYRFGG MTEYGKYTND
LYELQSTRWE WRRLNPRVHS NGHLPCPRIG HSFVVSQKSQ KAYVFGGLSN DLNDPKRNVP
HYLDDLYVIN LSGPQHLIWE KLNATGPGPI SRESHTAVIY EKDSISRMVV YGGMNGVRLG
DLWYLNLNTL HWTEIKFDDP RTGIPPMPRS LHSSVLIGDK MFVYGGWVPL LEHASTEQQT
EKEWKCTSSL GCWNITEDRW VPLHLYCSDE DTIPRGRAGH CAAAVGDRMY IWSGRDGYRK
AWSNQVCCRD MWLLDTILPE QPGKVQLGRA GFNSLEISWP IVQGASGYFL QIGFGDAKEQ
SVSPIKRATT SPRKQPSIVP PSQKETEQSP KKPQGTAPSI ISTQGTTYTA PADPKPATDE
GGLPQDLFED TEKNETASPK RSNDAQSADS STCEQKKTDE SGLEEDSEKD QKPSDAGETD
EMKEENGDDD LPWFDVGIID KATINVTHYF NDRQQSLEKQ LNDLIDHNAF KCVNDSVFTT
EDKIPLINGQ SYRFRVSAIN GLGKGAWSET ASCKTCVPGY PSAPSSIRIT KSHEGAQLTW
EPPSNTNISG KIIEYSVYLA VKNQSANSAD SQLAFMRVYC GPQADCQVLQ SNLGTAFVDQ
TNKPAIIFRI AARNEKGYGP ATQVRWLQDQ QKIPVRTNYP NNSGFIYQQH GGQQKRARFD
HQ
