CHFR_HUMAN
ID CHFR_HUMAN Reviewed; 664 AA.
AC Q96EP1; A6NEN5; B4DZ77; B4E2L6; Q96SL3; Q9NRT4; Q9NT32; Q9NVD5;
DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot.
DT 02-FEB-2004, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=E3 ubiquitin-protein ligase CHFR;
DE EC=2.3.2.27 {ECO:0000269|PubMed:11807090, ECO:0000269|PubMed:11912157, ECO:0000269|PubMed:14562038, ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19182791};
DE AltName: Full=Checkpoint with forkhead and RING finger domains protein;
DE AltName: Full=RING finger protein 196;
DE AltName: Full=RING-type E3 ubiquitin transferase CHFR {ECO:0000305};
GN Name=CHFR; Synonyms=RNF196;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP VARIANT MET-580.
RX PubMed=10935642; DOI=10.1038/35019108;
RA Scolnick D.M., Halazonetis T.D.;
RT "Chfr defines a mitotic stress checkpoint that delays entry into
RT metaphase.";
RL Nature 406:430-435(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 4), AND VARIANT
RP MET-580.
RC TISSUE=Teratocarcinoma, Testis, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-497.
RC TISSUE=Placenta;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-664.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOUBIQUITINATION, AND MUTAGENESIS OF
RP ILE-306 AND TRP-332.
RX PubMed=11807090; DOI=10.1083/jcb.200108016;
RA Kang D., Chen J., Wong J., Fang G.;
RT "The checkpoint protein Chfr is a ligase that ubiquitinates Plk1 and
RT inhibits Cdc2 at the G2 to M transition.";
RL J. Cell Biol. 156:249-259(2002).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AUTOUBIQUITINATION, SUBCELLULAR LOCATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11912157;
RA Chaturvedi P., Sudakin V., Bobiak M.L., Fisher P.W., Mattern M.R.,
RA Jablonski S.A., Hurle M.R., Zhu Y., Yen T.J., Zhou B.-B.;
RT "Chfr regulates a mitotic stress pathway through its RING-finger domain
RT with ubiquitin ligase activity.";
RL Cancer Res. 62:1797-1801(2002).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP VARIANTS ARG-270; VAL-497 AND MET-580, AND SILENCING IN PRIMARY CANCERS.
RX PubMed=11948416; DOI=10.1038/sj.onc.1205402;
RA Mizuno K., Osada H., Konishi H., Tatematsu Y., Yatabe Y., Mitsudomi T.,
RA Fujii Y., Takahashi T.;
RT "Aberrant hypermethylation of the CHFR prophase checkpoint gene in human
RT lung cancers.";
RL Oncogene 21:2328-2333(2002).
RN [10]
RP SILENCING IN PRIMARY CANCERS.
RX PubMed=12538348; DOI=10.1093/carcin/24.1.47;
RA Corn P.G., Summers M.K., Fogt F., Virmani A.K., Gazdar A.F.,
RA Halazonetis T.D., El-Deiry W.S.;
RT "Frequent hypermethylation of the 5' CpG island of the mitotic stress
RT checkpoint gene Chfr in colorectal and non-small cell lung cancer.";
RL Carcinogenesis 24:47-51(2003).
RN [11]
RP SILENCING IN PRIMARY CANCERS.
RX PubMed=12810945; DOI=10.1073/pnas.1337066100;
RA Toyota M., Sasaki Y., Satoh A., Ogi K., Kikuchi T., Suzuki H., Mita H.,
RA Tanaka N., Itoh F., Issa J.-P.J., Jair K.-W., Schuebel K.E., Imai K.,
RA Tokino T.;
RT "Epigenetic inactivation of CHFR in human tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7818-7823(2003).
RN [12]
RP SILENCING IN PRIMARY CANCERS.
RX PubMed=14695171;
RA Satoh A., Toyota M., Itoh F., Sasaki Y., Suzuki H., Ogi K., Kikuchi T.,
RA Mita H., Yamashita T., Kojima T., Kusano M., Fujita M., Hosokawa M.,
RA Endo T., Tokino T., Imai K.;
RT "Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors
RT in gastric cancer.";
RL Cancer Res. 63:8606-8613(2003).
RN [13]
RP PHOSPHORYLATION, AND MUTAGENESIS OF THR-39 AND SER-205.
RX PubMed=14638868;
RA Shtivelman E.;
RT "Promotion of mitosis by activated protein kinase B after DNA damage
RT involves polo-like kinase 1 and checkpoint protein CHFR.";
RL Mol. Cancer Res. 1:959-969(2003).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH UBE2V2, AND PHOSPHORYLATION.
RX PubMed=14562038; DOI=10.1038/sj.onc.1206831;
RA Bothos J., Summers M.K., Venere M., Scolnick D.M., Halazonetis T.D.;
RT "The Chfr mitotic checkpoint protein functions with Ubc13-Mms2 to form
RT Lys63-linked polyubiquitin chains.";
RL Oncogene 22:7101-7107(2003).
RN [15]
RP FUNCTION.
RX PubMed=14694445; DOI=10.1002/mc.10161;
RA Erson A.E., Petty E.M.;
RT "CHFR-associated early G2/M checkpoint defects in breast cancer cells.";
RL Mol. Carcinog. 39:26-33(2004).
RN [16]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=15467728; DOI=10.1038/nsmb837;
RA Daniels M.J., Marson A., Venkitaraman A.R.;
RT "PML bodies control the nuclear dynamics and function of the CHFR mitotic
RT checkpoint protein.";
RL Nat. Struct. Mol. Biol. 11:1114-1121(2004).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN PBZ-TYPE,
RP POLY-ADP-RIBOSYLATION, ADP-RIBOSE-BINDING, AND MUTAGENESIS OF ARG-632;
RP CYS-635; CYS-641; ARG-642 AND GLN-644.
RX PubMed=18172500; DOI=10.1038/nature06420;
RA Ahel I., Ahel D., Matsusaka T., Clark A.J., Pines J., Boulton S.J.,
RA West S.C.;
RT "Poly(ADP-ribose)-binding zinc finger motifs in DNA repair/checkpoint
RT proteins.";
RL Nature 451:81-85(2008).
RN [18]
RP DOMAIN FHA.
RX PubMed=18335050; DOI=10.1371/journal.pone.0001776;
RA Fukuda T., Kondo Y., Nakagama H.;
RT "The anti-proliferative effects of the CHFR depend on the forkhead
RT associated domain, but not E3 ligase activity mediated by ring finger
RT domain.";
RL PLoS ONE 3:E1776-E1776(2008).
RN [19]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH HDAC1 AND HDAC2,
RP AUTOUBIQUITINATION, AND MUTAGENESIS OF ILE-306.
RX PubMed=19182791; DOI=10.1038/ncb1837;
RA Oh Y.M., Kwon Y.E., Kim J.M., Bae S.J., Lee B.K., Yoo S.J., Chung C.H.,
RA Deshaies R.J., Seol J.H.;
RT "Chfr is linked to tumour metastasis through the downregulation of HDAC1.";
RL Nat. Cell Biol. 11:295-302(2009).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 14-128.
RX PubMed=12121644; DOI=10.1016/s0969-2126(02)00776-1;
RA Stavridi E.S., Huyen Y., Loreto I.R., Scolnick D.M., Halazonetis T.D.,
RA Pavletich N.P., Jeffrey P.D.;
RT "Crystal structure of the FHA domain of the Chfr mitotic checkpoint protein
RT and its complex with tungstate.";
RL Structure 10:891-899(2002).
RN [21]
RP VARIANTS LEU-166; PRO-202 AND SER-536.
RX PubMed=14612512;
RA Mariatos G., Bothos J., Zacharatos P., Summers M.K., Scolnick D.M.,
RA Kittas C., Halazonetis T.D., Gorgoulis V.G.;
RT "Inactivating mutations targeting the chfr mitotic checkpoint gene in human
RT lung cancer.";
RL Cancer Res. 63:7185-7189(2003).
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:0000269|PubMed:10935642, ECO:0000269|PubMed:11807090,
CC ECO:0000269|PubMed:11912157, ECO:0000269|PubMed:14562038,
CC ECO:0000269|PubMed:14694445, ECO:0000269|PubMed:18172500,
CC ECO:0000269|PubMed:19182791}.
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:11807090,
CC ECO:0000269|PubMed:11912157, ECO:0000269|PubMed:14562038,
CC ECO:0000269|PubMed:18172500, ECO:0000269|PubMed:19182791};
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Interacts with HDAC1 and HDAC2. Interacts with PML (with
CC sumoylated form of PML). {ECO:0000269|PubMed:14562038,
CC ECO:0000269|PubMed:15467728, ECO:0000269|PubMed:19182791}.
CC -!- INTERACTION:
CC Q96EP1-2; P51668: UBE2D1; NbExp=3; IntAct=EBI-12344389, EBI-743540;
CC Q96EP1-2; P62837: UBE2D2; NbExp=3; IntAct=EBI-12344389, EBI-347677;
CC Q96EP1-2; Q96LR5: UBE2E2; NbExp=3; IntAct=EBI-12344389, EBI-2129763;
CC Q96EP1-2; Q969T4: UBE2E3; NbExp=3; IntAct=EBI-12344389, EBI-348496;
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000269|PubMed:11912157,
CC ECO:0000269|PubMed:15467728, ECO:0000269|PubMed:18172500}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q96EP1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96EP1-2; Sequence=VSP_009349;
CC Name=3;
CC IsoId=Q96EP1-3; Sequence=VSP_009350;
CC Name=4;
CC IsoId=Q96EP1-4; Sequence=VSP_038127;
CC Name=5;
CC IsoId=Q96EP1-5; Sequence=VSP_038126;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:10935642}.
CC -!- DEVELOPMENTAL STAGE: Weakly expressed in G1 phase, and highly expressed
CC during S phase. {ECO:0000269|PubMed:11912157}.
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.
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.
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 -!- PTM: Autoubiquitinated; may regulate its cellular level.
CC {ECO:0000269|PubMed:11807090, ECO:0000269|PubMed:11912157,
CC ECO:0000269|PubMed:19182791}.
CC -!- PTM: Phosphorylated by PKB. Phosphorylation may affect its E3 ligase
CC activity. {ECO:0000269|PubMed:14562038, ECO:0000269|PubMed:14638868}.
CC -!- MISCELLANEOUS: CHFR is silenced in many primary cancers because of CpG
CC methylation and deacetylated histones on its promoter region. This
CC however raises the question of whether CHFR silencing is a consequence
CC or a cause of primary cancers.
CC -!- SIMILARITY: Belongs to the CHFR family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CHFRID526.html";
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DR EMBL; AF170724; AAF91084.1; -; mRNA.
DR EMBL; AK001658; BAA91817.1; -; mRNA.
DR EMBL; AK027687; BAB55297.1; -; mRNA.
DR EMBL; AK302785; BAG63989.1; -; mRNA.
DR EMBL; AK304333; BAG65178.1; -; mRNA.
DR EMBL; AC127070; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012072; AAH12072.1; -; mRNA.
DR EMBL; AL137561; CAB70812.1; -; mRNA.
DR CCDS; CCDS31937.1; -. [Q96EP1-3]
DR CCDS; CCDS53847.1; -. [Q96EP1-5]
DR CCDS; CCDS53848.1; -. [Q96EP1-2]
DR CCDS; CCDS53849.1; -. [Q96EP1-1]
DR PIR; T46399; T46399.
DR RefSeq; NP_001154816.1; NM_001161344.1. [Q96EP1-1]
DR RefSeq; NP_001154817.1; NM_001161345.1. [Q96EP1-4]
DR RefSeq; NP_001154818.1; NM_001161346.1. [Q96EP1-2]
DR RefSeq; NP_001154819.1; NM_001161347.1. [Q96EP1-5]
DR RefSeq; NP_060693.2; NM_018223.2. [Q96EP1-3]
DR PDB; 1LGP; X-ray; 2.00 A; A=14-128.
DR PDB; 1LGQ; X-ray; 2.10 A; A/B=14-124.
DR PDB; 2XOC; X-ray; 1.89 A; A/B=407-664.
DR PDB; 2XOY; X-ray; 2.60 A; A/B=407-664.
DR PDB; 2XOZ; X-ray; 2.37 A; A/B=407-664.
DR PDB; 2XP0; X-ray; 1.98 A; A/B=394-664.
DR PDBsum; 1LGP; -.
DR PDBsum; 1LGQ; -.
DR PDBsum; 2XOC; -.
DR PDBsum; 2XOY; -.
DR PDBsum; 2XOZ; -.
DR PDBsum; 2XP0; -.
DR AlphaFoldDB; Q96EP1; -.
DR SMR; Q96EP1; -.
DR BioGRID; 120861; 52.
DR DIP; DIP-40098N; -.
DR IntAct; Q96EP1; 22.
DR STRING; 9606.ENSP00000392395; -.
DR iPTMnet; Q96EP1; -.
DR PhosphoSitePlus; Q96EP1; -.
DR BioMuta; CHFR; -.
DR DMDM; 41688511; -.
DR EPD; Q96EP1; -.
DR jPOST; Q96EP1; -.
DR MassIVE; Q96EP1; -.
DR MaxQB; Q96EP1; -.
DR PaxDb; Q96EP1; -.
DR PeptideAtlas; Q96EP1; -.
DR PRIDE; Q96EP1; -.
DR ProteomicsDB; 76432; -. [Q96EP1-1]
DR ProteomicsDB; 76433; -. [Q96EP1-2]
DR ProteomicsDB; 76434; -. [Q96EP1-3]
DR ProteomicsDB; 76435; -. [Q96EP1-4]
DR ProteomicsDB; 76436; -. [Q96EP1-5]
DR Antibodypedia; 32145; 304 antibodies from 35 providers.
DR DNASU; 55743; -.
DR Ensembl; ENST00000266880.11; ENSP00000266880.8; ENSG00000072609.18. [Q96EP1-3]
DR Ensembl; ENST00000432561.6; ENSP00000392395.2; ENSG00000072609.18. [Q96EP1-1]
DR Ensembl; ENST00000443047.6; ENSP00000416431.2; ENSG00000072609.18. [Q96EP1-5]
DR Ensembl; ENST00000450056.7; ENSP00000398735.2; ENSG00000072609.18. [Q96EP1-2]
DR GeneID; 55743; -.
DR KEGG; hsa:55743; -.
DR MANE-Select; ENST00000450056.7; ENSP00000398735.2; NM_001161346.2; NP_001154818.1. [Q96EP1-2]
DR UCSC; uc001uld.3; human. [Q96EP1-1]
DR CTD; 55743; -.
DR DisGeNET; 55743; -.
DR GeneCards; CHFR; -.
DR HGNC; HGNC:20455; CHFR.
DR HPA; ENSG00000072609; Low tissue specificity.
DR MIM; 605209; gene.
DR neXtProt; NX_Q96EP1; -.
DR OpenTargets; ENSG00000072609; -.
DR PharmGKB; PA134898949; -.
DR VEuPathDB; HostDB:ENSG00000072609; -.
DR eggNOG; KOG0802; Eukaryota.
DR GeneTree; ENSGT00400000022306; -.
DR HOGENOM; CLU_032966_0_0_1; -.
DR InParanoid; Q96EP1; -.
DR OMA; DEDTCPN; -.
DR OrthoDB; 1506037at2759; -.
DR PhylomeDB; Q96EP1; -.
DR TreeFam; TF330957; -.
DR PathwayCommons; Q96EP1; -.
DR SignaLink; Q96EP1; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 55743; 6 hits in 1118 CRISPR screens.
DR ChiTaRS; CHFR; human.
DR EvolutionaryTrace; Q96EP1; -.
DR GeneWiki; CHFR; -.
DR GenomeRNAi; 55743; -.
DR Pharos; Q96EP1; Tbio.
DR PRO; PR:Q96EP1; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96EP1; protein.
DR Bgee; ENSG00000072609; Expressed in granulocyte and 182 other tissues.
DR ExpressionAtlas; Q96EP1; baseline and differential.
DR Genevisible; Q96EP1; HS.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0044779; P:meiotic spindle checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IMP:UniProtKB.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IEA:Ensembl.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IDA: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 DisProt; DP02729; -.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00097; -.
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 1: Evidence at protein level;
KW 3D-structure; ADP-ribosylation; Alternative splicing; Cell cycle;
KW Cell division; Metal-binding; Mitosis; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..664
FT /note="E3 ubiquitin-protein ligase CHFR"
FT /id="PRO_0000055872"
FT DOMAIN 38..89
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT ZN_FING 304..343
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 633..655
FT /note="PBZ-type"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 142..267
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 388..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 439..461
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..211
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 250..265
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 386
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q810L3"
FT VAR_SEQ 115..207
FT /note="NVAYLYESLSEKQGMTQESFEANKENVFHGTKDTSGAGAGRGADPRVPPSSP
FT ATQVCFEEPQPSTSTSDLFPTASASSTEPSPAGRERSSSCG -> R (in isoform
FT 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_038126"
FT VAR_SEQ 135..146
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_009349"
FT VAR_SEQ 136..206
FT /note="ANKENVFHGTKDTSGAGAGRGADPRVPPSSPATQVCFEEPQPSTSTSDLFPT
FT ASASSTEPSPAGRERSSSC -> MVPCCVAQAGLKLLGSSDPPTLASQSIVIT (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_009350"
FT VAR_SEQ 470
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038127"
FT VARIANT 166
FT /note="P -> L (in a patient with non small cell lung
FT carcinomas; homozygous; dbSNP:rs1176037831)"
FT /evidence="ECO:0000269|PubMed:14612512"
FT /id="VAR_017582"
FT VARIANT 202
FT /note="R -> P (in a patient with non small cell lung
FT carcinomas)"
FT /evidence="ECO:0000269|PubMed:14612512"
FT /id="VAR_017583"
FT VARIANT 270
FT /note="G -> R (in dbSNP:rs115096950)"
FT /evidence="ECO:0000269|PubMed:11948416"
FT /id="VAR_017584"
FT VARIANT 497
FT /note="A -> V (in dbSNP:rs2306541)"
FT /evidence="ECO:0000269|PubMed:11948416,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_017585"
FT VARIANT 536
FT /note="F -> S (in a patient with non small cell lung
FT carcinomas)"
FT /evidence="ECO:0000269|PubMed:14612512"
FT /id="VAR_017586"
FT VARIANT 580
FT /note="V -> M (in dbSNP:rs2306536)"
FT /evidence="ECO:0000269|PubMed:10935642,
FT ECO:0000269|PubMed:11948416, ECO:0000269|PubMed:14702039"
FT /id="VAR_017587"
FT MUTAGEN 39
FT /note="T->A: Abolishes phosphorylation but not
FT autoubiquitination; when associated with A-205."
FT /evidence="ECO:0000269|PubMed:14638868"
FT MUTAGEN 205
FT /note="S->A: Abolishes phosphorylation but not
FT autoubiquitination; when associated with A-39."
FT /evidence="ECO:0000269|PubMed:14638868"
FT MUTAGEN 306
FT /note="I->A: Abolishes autoubiquitination. Does not affect
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:11807090,
FT ECO:0000269|PubMed:19182791"
FT MUTAGEN 332
FT /note="W->A: Abolishes autoubiquitination in vitro."
FT /evidence="ECO:0000269|PubMed:11807090"
FT MUTAGEN 632
FT /note="R->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 635
FT /note="C->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-641."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 641
FT /note="C->A: Abolishes poly(ADP-ribose)-binding and poly-
FT ADP-ribosylation by PARP1; when associated with A-635."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 642
FT /note="R->A: Impairs poly(ADP-ribose)-binding and poly-ADP-
FT ribosylation by PARP1."
FT /evidence="ECO:0000269|PubMed:18172500"
FT MUTAGEN 644
FT /note="Q->A: Impairs poly(ADP-ribose)-binding and poly-ADP-
FT ribosylation by PARP1."
FT /evidence="ECO:0000269|PubMed:18172500"
FT CONFLICT 256
FT /note="V -> E (in Ref. 2; BAA91817)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="S -> P (in Ref. 2; BAA91817)"
FT /evidence="ECO:0000305"
FT CONFLICT 599
FT /note="V -> A (in Ref. 2; BAG65178)"
FT /evidence="ECO:0000305"
FT CONFLICT 617
FT /note="R -> Q (in Ref. 2; BAA91817)"
FT /evidence="ECO:0000305"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 35..43
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:1LGP"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 72..76
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 82..90
FT /evidence="ECO:0007829|PDB:1LGQ"
FT STRAND 92..96
FT /evidence="ECO:0007829|PDB:1LGQ"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:1LGP"
FT HELIX 112..114
FT /evidence="ECO:0007829|PDB:1LGP"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:1LGP"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:2XOC"
FT STRAND 482..484
FT /evidence="ECO:0007829|PDB:2XOC"
FT TURN 486..488
FT /evidence="ECO:0007829|PDB:2XOC"
FT STRAND 491..493
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 496..500
FT /evidence="ECO:0007829|PDB:2XOC"
FT TURN 511..513
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 519..522
FT /evidence="ECO:0007829|PDB:2XOC"
FT STRAND 532..535
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 536..538
FT /evidence="ECO:0007829|PDB:2XOC"
FT TURN 543..552
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 554..566
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 571..583
FT /evidence="ECO:0007829|PDB:2XOC"
FT STRAND 599..601
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 602..618
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 622..624
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 627..630
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 638..640
FT /evidence="ECO:0007829|PDB:2XOC"
FT HELIX 643..645
FT /evidence="ECO:0007829|PDB:2XP0"
FT HELIX 647..652
FT /evidence="ECO:0007829|PDB:2XOC"
SQ SEQUENCE 664 AA; 73386 MW; 141A1E7FEFAE36A2 CRC64;
MERPEEGKQS PPPQPWGRLL RLGAEEGEPH VLLRKREWTI GRRRGCDLSF PSNKLVSGDH
CRIVVDEKSG QVTLEDTSTS GTVINKLKVV KKQTCPLQTG DVIYLVYRKN EPEHNVAYLY
ESLSEKQGMT QESFEANKEN VFHGTKDTSG AGAGRGADPR VPPSSPATQV CFEEPQPSTS
TSDLFPTASA SSTEPSPAGR ERSSSCGSGG GGISPKGSGP SVASDEVSSF ASALPDRKTA
SFSSLEPQDQ EDLEPVKKKM RGDGDLDLNG QLLVAQPRRN AQTVHEDVRA AAGKPDKMEE
TLTCIICQDL LHDCVSLQPC MHTFCAACYS GWMERSSLCP TCRCPVERIC KNHILNNLVE
AYLIQHPDKS RSEEDVQSMD ARNKITQDML QPKVRRSFSD EEGSSEDLLE LSDVDSESSD
ISQPYVVCRQ CPEYRRQAAQ PPHCPAPEGE PGAPQALGDA PSTSVSLTTA VQDYVCPLQG
SHALCTCCFQ PMPDRRAERE QDPRVAPQQC AVCLQPFCHL YWGCTRTGCY GCLAPFCELN
LGDKCLDGVL NNNSYESDIL KNYLATRGLT WKNMLTESLV ALQRGVFLLS DYRVTGDTVL
CYCCGLRSFR ELTYQYRQNI PASELPVAVT SRPDCYWGRN CRTQVKAHHA MKFNHICEQT
RFKN
