ID   CHFR_PONAB              Reviewed;         571 AA.
AC   Q5RF77;
DT   22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   25-MAY-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;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) 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. Promotes the ubiquitination and
CC       subsequent degradation of AURKA and PLK1. Probably acts as a tumor
CC       suppressor, possibly by mediating the polyubiquitination of HDAC1,
CC       leading to its degradation. May also promote the formation of 'Lys-63'-
CC       linked polyubiquitin chains and functions with the specific ubiquitin-
CC       conjugating UBC13-MMS2 (UBE2N-UBE2V2) heterodimer. Substrates that are
CC       polyubiquitinated at 'Lys-63' are usually not targeted for degradation,
CC       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   -!- SUBUNIT: Interacts with HDAC1 and HDAC2. Interacts with PML (with
CC       sumoylated form of PML). {ECO:0000250|UniProtKB:Q96EP1}.
CC   -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EP1}.
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. The FHA domain may be required to interact with
CC       phosphorylated proteins. {ECO:0000250|UniProtKB:Q96EP1}.
CC   -!- PTM: Poly-ADP-ribosylated. In addition to binding non covalently
CC       poly(ADP-ribose) via its PBZ-type zinc finger, the protein is also
CC       covalently poly-ADP-ribosylated by PARP1.
CC       {ECO:0000250|UniProtKB:Q96EP1}.
CC   -!- PTM: Autoubiquitinated; may regulate its cellular level.
CC       {ECO:0000250|UniProtKB:Q96EP1}.
CC   -!- PTM: Phosphorylated by PKB. Phosphorylation may affect its E3 ligase
CC       activity. {ECO:0000250|UniProtKB:Q96EP1}.
CC   -!- SIMILARITY: Belongs to the CHFR family. {ECO:0000305}.
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DR   EMBL; CR857284; CAH89580.1; -; mRNA.
DR   RefSeq; NP_001124696.1; NM_001131224.1.
DR   AlphaFoldDB; Q5RF77; -.
DR   SMR; Q5RF77; -.
DR   GeneID; 100171543; -.
DR   KEGG; pon:100171543; -.
DR   CTD; 55743; -.
DR   eggNOG; KOG0802; Eukaryota.
DR   InParanoid; Q5RF77; -.
DR   UniPathway; UPA00143; -.
DR   Proteomes; UP000001595; Unplaced.
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   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; 2.
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   ADP-ribosylation; Cell cycle; Cell division; Metal-binding; Mitosis;
KW   Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..571
FT                   /note="E3 ubiquitin-protein ligase CHFR"
FT                   /id="PRO_0000385301"
FT   DOMAIN          38..89
FT                   /note="FHA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT   ZN_FING         212..251
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   ZN_FING         540..562
FT                   /note="PBZ-type"
FT   REGION          1..21
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          113..138
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          297..325
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         152
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q96EP1"
FT   MOD_RES         294
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q810L3"
SQ   SEQUENCE   571 AA;  63873 MW;  D7FFA1F65121798A CRC64;
     MERPEEGKQS PPPQPWGRLL RLGAEEGEPY VLLRKREWTI GRRRGCDLSF PSNKLVSGDH
     CRIAVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHRSGGGG
     ISPKGSGPSV ASDEVSSFAT ALPDRKTASF SSLEPQDQED LEPMKKKMRG DGDLDLNGQL
     LVAQPRRNAQ TVHEDVRAAA GKPDKMEETL TCIICQDLLH DCVSLQPCMH TFCAACYSGW
     MERSSLCPTC RCPVERICKN HILNNLVEAY LIQHPDKSRS EEDVQSMDAR NKITQDMLQP
     KVRRSFSDEE GSSEDLLELS DVDSESSDIS QPYVVCRQCP EYRRQAAQPP PCPAPEGEPG
     VPQALVDAPS TSVSLTTVQD YVCPLQGSHA LCTCCFQPMP DRRAEREQNP RVAPQQCAVC
     LQPFCHLYWG CTRTGCFGCL APFCELNLGD KCLDGVLNNN SYESDILKNY LATRGLTWKN
     MLTESLVALQ RGVFLLSDYR VTGDTILCYC CGLRSFRELT YQYRQNIPAS ELPVAVTSRP
     DCYWGRNCRT QVKAHHAMKF NHICEQTRFK N