CHFR_MOUSE
ID CHFR_MOUSE Reviewed; 664 AA.
AC Q810L3; Q3TFD8; Q3U233; Q3U4U9; Q3UGJ9; Q8BJZ9; Q8BWH4;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=E3 ubiquitin-protein ligase CHFR;
DE EC=2.3.2.27 {ECO:0000269|PubMed:15793587};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Kidney, Lung, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15793587; DOI=10.1038/ng1538;
RA Yu X., Minter-Dykhouse K., Malureanu L., Zhao W.-M., Zhang D., Merkle C.J.,
RA Ward I.M., Saya H., Fang G., van Deursen J., Chen J.;
RT "Chfr is required for tumor suppression and Aurora A regulation.";
RL Nat. Genet. 37:401-406(2005).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-385, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q96EP1, ECO:0000269|PubMed:15793587}.
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:0000269|PubMed:15793587};
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q810L3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q810L3-2; Sequence=VSP_009351;
CC Name=3;
CC IsoId=Q810L3-3; Sequence=VSP_038129;
CC Name=4;
CC IsoId=Q810L3-4; Sequence=VSP_038128;
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 -!- DISRUPTION PHENOTYPE: Mice are viable and have no obvious developmental
CC defects. They are however cancer-prone and develop spontaneous tumors.
CC They also display increased skin tumor incidence after treatment with
CC dimethylbenz(a)anthracene. {ECO:0000269|PubMed:15793587}.
CC -!- SIMILARITY: Belongs to the CHFR family. {ECO:0000305}.
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DR EMBL; AK052473; BAC35008.2; -; mRNA.
DR EMBL; AK077629; BAC36912.1; -; mRNA.
DR EMBL; AK147892; BAE28209.1; -; mRNA.
DR EMBL; AK154038; BAE32331.1; -; mRNA.
DR EMBL; AK155295; BAE33172.1; -; mRNA.
DR EMBL; AK155525; BAE33309.1; -; mRNA.
DR EMBL; AK169182; BAE40960.1; -; mRNA.
DR EMBL; AK169193; BAE40969.1; -; mRNA.
DR EMBL; CH466529; EDL20040.1; -; Genomic_DNA.
DR EMBL; BC049792; AAH49792.1; -; mRNA.
DR CCDS; CCDS19522.1; -. [Q810L3-2]
DR CCDS; CCDS71637.1; -. [Q810L3-1]
DR CCDS; CCDS80358.1; -. [Q810L3-3]
DR RefSeq; NP_001276506.1; NM_001289577.1. [Q810L3-1]
DR RefSeq; NP_001276507.1; NM_001289578.1. [Q810L3-3]
DR RefSeq; NP_001276508.1; NM_001289579.1. [Q810L3-4]
DR RefSeq; NP_001276509.1; NM_001289580.1.
DR RefSeq; NP_766305.2; NM_172717.4. [Q810L3-2]
DR RefSeq; XP_011247747.1; XM_011249445.2. [Q810L3-4]
DR RefSeq; XP_011247748.1; XM_011249446.2. [Q810L3-4]
DR AlphaFoldDB; Q810L3; -.
DR SMR; Q810L3; -.
DR BioGRID; 231141; 6.
DR STRING; 10090.ENSMUSP00000108138; -.
DR iPTMnet; Q810L3; -.
DR PhosphoSitePlus; Q810L3; -.
DR EPD; Q810L3; -.
DR jPOST; Q810L3; -.
DR MaxQB; Q810L3; -.
DR PaxDb; Q810L3; -.
DR PeptideAtlas; Q810L3; -.
DR PRIDE; Q810L3; -.
DR ProteomicsDB; 281613; -. [Q810L3-1]
DR ProteomicsDB; 281614; -. [Q810L3-2]
DR ProteomicsDB; 281615; -. [Q810L3-3]
DR ProteomicsDB; 281616; -. [Q810L3-4]
DR Antibodypedia; 32145; 304 antibodies from 35 providers.
DR DNASU; 231600; -.
DR Ensembl; ENSMUST00000014812; ENSMUSP00000014812; ENSMUSG00000014668. [Q810L3-2]
DR Ensembl; ENSMUST00000112519; ENSMUSP00000108138; ENSMUSG00000014668. [Q810L3-1]
DR Ensembl; ENSMUST00000198633; ENSMUSP00000143480; ENSMUSG00000014668. [Q810L3-3]
DR GeneID; 231600; -.
DR KEGG; mmu:231600; -.
DR UCSC; uc008ypv.3; mouse. [Q810L3-1]
DR UCSC; uc008ypw.3; mouse. [Q810L3-2]
DR UCSC; uc008ypz.3; mouse. [Q810L3-3]
DR CTD; 55743; -.
DR MGI; MGI:2444898; Chfr.
DR VEuPathDB; HostDB:ENSMUSG00000014668; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00400000022306; -.
DR InParanoid; Q810L3; -.
DR OMA; DEDTCPN; -.
DR OrthoDB; 1506037at2759; -.
DR PhylomeDB; Q810L3; -.
DR TreeFam; TF330957; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 231600; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Chfr; mouse.
DR PRO; PR:Q810L3; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q810L3; protein.
DR Bgee; ENSMUSG00000014668; Expressed in spermatocyte and 246 other tissues.
DR ExpressionAtlas; Q810L3; baseline and differential.
DR Genevisible; Q810L3; MM.
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:0061630; F:ubiquitin protein ligase activity; IMP:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISO:MGI.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0044779; P:meiotic spindle checkpoint signaling; ISO:MGI.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:MGI.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; ISS:UniProtKB.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:MGI.
DR GO; GO:0031648; P:protein destabilization; IDA:MGI.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:MGI.
DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:MGI.
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 1: Evidence at protein level;
KW ADP-ribosylation; Alternative splicing; Cell cycle; Cell division;
KW Metal-binding; Mitosis; Nucleus; Phosphoprotein; Reference proteome;
KW Transferase; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..664
FT /note="E3 ubiquitin-protein ligase CHFR"
FT /id="PRO_0000055873"
FT DOMAIN 38..89
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT ZN_FING 303..342
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 633..655
FT /note="PBZ-type"
FT REGION 170..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 245..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 385
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT VAR_SEQ 1..140
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038128"
FT VAR_SEQ 135..206
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_038129"
FT VAR_SEQ 470
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_009351"
FT CONFLICT 98
FT /note="Q -> H (in Ref. 1; BAC36912)"
FT /evidence="ECO:0000305"
FT CONFLICT 230
FT /note="L -> F (in Ref. 1; BAE32331)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="E -> V (in Ref. 1; BAE28209)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="G -> C (in Ref. 1; BAC36912)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 664 AA; 73871 MW; D651BE3E463DEBB6 CRC64;
MELHGEEQPP PPQEPWGRLL RLGAEEDEPQ ILLWKREWTI GRRRGCDLSF PSNKLVSGDH
CKLTVDEISG EVTLEDTSTN GTVINKLQVV KKQTYPLQSG DIIYLVYRKN EPEHNVAYLY
ESLSGKQSLT QDSLEANKEN MFHVTKDCSG PGQGDDPQVP LLSPMAQTCL EEPQPSTSTS
DLLPTASTSS TEPELTSAGQ KHSSSSGPGN TSISPKGRSS LVANGELSSL SPVFQDKEAS
FSLLESKDHE ELEPAKKKMK GDGELDTNLQ LLVSGQRGNA QTSSEDVKDA SVKPDKMEET
LTCIICQDLL HDCVSLQPCM HTFCAACYSG WMERSSLCPT CRCPVERICK NHILNNLVEA
YLIQHPDKSR SEEDVRSMDA RNKITQDMLQ PKVRRSFSDE EGSSEDLLEL SDVDSESSDI
SQPYIVCRQC PEYRRQAVQS LPCPVPESEL GATLALGGEA PSTSASLPTA APDYMCPLQG
SHAICTCCFQ PMPDRRAERE QDPRVAPQQC AVCLQPFCHL YWGCTRTGCF GCLAPFCELN
LGDKCLDGVL NNNNYESDIL KNYLATRGLT WKSVLTESLL ALQRGVFMLS DYRITGNTVL
CYCCGLRSFR ELTYQYRQNI PASELPVTVT SRPDCYWGRN CRTQVKAHHA MKFNHICEQT
RFKN
