CHFR_DANRE
ID CHFR_DANRE Reviewed; 637 AA.
AC A5WW08; A8E4S5;
DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=E3 ubiquitin-protein ligase CHFR;
DE EC=2.3.2.27 {ECO:0000250|UniProtKB:Q96EP1};
DE AltName: Full=Checkpoint with forkhead and RING finger domains protein;
DE AltName: Full=RING-type E3 ubiquitin transferase CHFR {ECO:0000305};
GN Name=chfr; ORFNames=si:dkey-69h6.7;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: E3 ubiquitin-protein ligase that functions in the antephase
CC checkpoint by actively delaying passage into mitosis in response to
CC microtubule poisons. Acts in early prophase before chromosome
CC condensation, when the centrosome move apart from each other along the
CC periphery of the nucleus. Probably involved in signaling the presence
CC of mitotic stress caused by microtubule poisons by mediating the 'Lys-
CC 48'-linked ubiquitination of target proteins, leading to their
CC degradation by the proteasome. May also promote the formation of 'Lys-
CC 63'-linked polyubiquitin chains and functions with the specific
CC ubiquitin-conjugating ubc13-mms2 (ube2n-ube2v2) heterodimer. Substrates
CC that are polyubiquitinated at 'Lys-63' are usually not targeted for
CC degradation, but are rather involved in signaling cellular stress.
CC {ECO:0000250|UniProtKB:Q96EP1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q96EP1};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EP1}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A5WW08-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A5WW08-2; Sequence=VSP_038139;
CC -!- DOMAIN: The PBZ-type zinc finger (also named CYR) mediates non-covalent
CC poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the
CC presence of zinc and is required for its function in antephase
CC checkpoint. {ECO:0000250|UniProtKB:Q96EP1}.
CC -!- DOMAIN: The FHA domain plays a key role in the anti-proliferative
CC properties of the protein and is involved in initiating a cell cycle
CC arrest at G2/M. {ECO:0000250|UniProtKB:Q96EP1}.
CC -!- SIMILARITY: Belongs to the CHFR family. {ECO:0000305}.
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DR EMBL; CT573109; CAN88580.1; -; Genomic_DNA.
DR EMBL; BC153311; AAI53312.1; -; mRNA.
DR RefSeq; NP_001093485.1; NM_001100015.1. [A5WW08-1]
DR RefSeq; XP_017211627.1; XM_017356138.1. [A5WW08-1]
DR RefSeq; XP_017211628.1; XM_017356139.1. [A5WW08-2]
DR AlphaFoldDB; A5WW08; -.
DR SMR; A5WW08; -.
DR STRING; 7955.ENSDARP00000099431; -.
DR PaxDb; A5WW08; -.
DR Ensembl; ENSDART00000110783; ENSDARP00000099431; ENSDARG00000075347. [A5WW08-1]
DR Ensembl; ENSDART00000115227; ENSDARP00000098332; ENSDARG00000075347. [A5WW08-2]
DR GeneID; 564271; -.
DR KEGG; dre:564271; -.
DR CTD; 55743; -.
DR ZFIN; ZDB-GENE-030131-3522; chfr.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00400000022306; -.
DR HOGENOM; CLU_032966_0_0_1; -.
DR InParanoid; A5WW08; -.
DR OMA; DEDTCPN; -.
DR OrthoDB; 1506037at2759; -.
DR PhylomeDB; A5WW08; -.
DR TreeFam; TF330957; -.
DR UniPathway; UPA00143; -.
DR PRO; PR:A5WW08; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000075347; Expressed in ovary and 33 other tissues.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; ISS:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; ISS:UniProtKB.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR019406; APLF_PBZ.
DR InterPro; IPR040909; CHFR_Znf-CRD.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF10283; zf-CCHH; 1.
DR Pfam; PF17979; zf-CRD; 1.
DR SMART; SM00240; FHA; 1.
DR SMART; SM00184; RING; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell cycle; Cell division; Metal-binding; Mitosis;
KW Nucleus; Reference proteome; Transferase; Ubl conjugation pathway; Zinc;
KW Zinc-finger.
FT CHAIN 1..637
FT /note="E3 ubiquitin-protein ligase CHFR"
FT /id="PRO_0000385302"
FT DOMAIN 31..82
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT ZN_FING 277..316
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 606..628
FT /note="PBZ-type"
FT REGION 120..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 193..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..447
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 193..214
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..242
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 443
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_038139"
FT CONFLICT 61
FT /note="N -> I (in Ref. 2; AAI53312)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="K -> Q (in Ref. 2; AAI53312)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="N -> I (in Ref. 2; AAI53312)"
FT /evidence="ECO:0000305"
FT CONFLICT 200
FT /note="G -> R (in Ref. 2; AAI53312)"
FT /evidence="ECO:0000305"
FT CONFLICT 204
FT /note="S -> P (in Ref. 2; AAI53312)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 637 AA; 71730 MW; 7193C3203671217E CRC64;
MTNQDSDQAW GKLVKVDASP GSEIVLINSE CTVGRKKDCD LSFPANKLVS GNHCKITHDQ
NSGKVWLEDM STNGTVINMS KVVKKQTHLL QNGDVIYFVY RKNEPEQNIA YVYQSITPQE
SASHDVEDAG REEDSDLTET ESEPAPVEPV IVKPLPQSGH EDPQPSTSSS SLHFYNMPLS
TCSDVSARKN PVSSSAVCKG DSTSSGSPAQ TRLKWTCWTD GEPEEEMQRK RRKTDRDDPG
FGSAHSDASA DIPLRGASGK EKTEGATTDK MEESLTCIIC QDLLYDCISV QPCMHTFCAA
CYSGWMERSS FCPTCRCPVE RIRKNHILNN LVEAYLLQHP EKCRTEDDLR SMDARNKITQ
DMLQPKVERS FSDEEASSDY LFELSDNDSD ISDMSQPYMM CRQCPGYRKE LSSALWICES
AQSESLAKTA GDGPSTSSDS TTAAPQEFRC PPQASHLICT CCLQPMPDRR FEHLPPQVSP
QHCLVCQKPF CHVYWGCPRI GCHGCLARFS ELNLNDKCLD GVFNGNQYES EVLQNYLSCR
GMSWRHLLQD SLQALQQGLY HLSDYRITAN SFLCYCCGLR TFRELAYKYR ERIPPSELPD
AVTNRPNCYW GRNCRTQVKA HHALKFNHIC EQTRFKN
