FAN1_HUMAN
ID FAN1_HUMAN Reviewed; 1017 AA.
AC Q9Y2M0; A8K4M2; Q86WU8;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 4.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Fanconi-associated nuclease 1 {ECO:0000303|PubMed:20603015, ECO:0000303|PubMed:20603016, ECO:0000303|PubMed:20671156};
DE EC=3.1.21.- {ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20671156};
DE EC=3.1.4.1 {ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016};
DE AltName: Full=FANCD2/FANCI-associated nuclease 1 {ECO:0000303|PubMed:20603015, ECO:0000303|PubMed:20603016, ECO:0000303|PubMed:20671156};
DE Short=hFAN1 {ECO:0000303|PubMed:24981866};
DE AltName: Full=Myotubularin-related protein 15;
GN Name=FAN1 {ECO:0000303|PubMed:20603015};
GN Synonyms=KIAA1018 {ECO:0000303|PubMed:10231032}, MTMR15;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10231032; DOI=10.1093/dnares/6.1.63;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:63-70(1999).
RN [2]
RP SEQUENCE REVISION.
RA Ohara O., Nagase T., Kikuno R.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Teratocarcinoma;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLU-233.
RC TISSUE=Lung;
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN UBZ-TYPE,
RP INTERACTION WITH FANCD2 AND FANCI, AND MUTAGENESIS OF 981-ASP-ARG-982.
RX PubMed=20603015; DOI=10.1016/j.cell.2010.06.021;
RA MacKay C., Declais A.C., Lundin C., Agostinho A., Deans A.J.,
RA MacArtney T.J., Hofmann K., Gartner A., West S.C., Helleday T.,
RA Lilley D.M., Rouse J.;
RT "Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA
RT damage by monoubiquitinated FANCD2.";
RL Cell 142:65-76(2010).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, COFACTOR, DOMAIN
RP UBZ-TYPE, INTERACTION WITH FANCD2, AND MUTAGENESIS OF CYS-44; CYS-47 AND
RP ASP-960.
RX PubMed=20603016; DOI=10.1016/j.cell.2010.06.022;
RA Kratz K., Schopf B., Kaden S., Sendoel A., Eberhard R., Lademann C.,
RA Cannavo E., Sartori A.A., Hengartner M.O., Jiricny J.;
RT "Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to
RT interstrand crosslinking agents.";
RL Cell 142:77-88(2010).
RN [8]
RP SUBCELLULAR LOCATION, AND DOMAIN UBZ-TYPE.
RX PubMed=20935496; DOI=10.4161/cc.9.19.13207;
RA Shereda R.D., Machida Y., Machida Y.J.;
RT "Human KIAA1018/FAN1 localizes to stalled replication forks via its
RT ubiquitin-binding domain.";
RL Cell Cycle 9:3977-3983(2010).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH FANCD2; MLH1; MLH3 AND
RP PMS2, AND MUTAGENESIS OF CYS-44; CYS-47; LEU-477; GLN-864; ASP-960; GLU-975
RP AND LYS-977.
RX PubMed=20603073; DOI=10.1016/j.molcel.2010.06.023;
RA Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P.,
RA Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P.,
RA Elledge S.J.;
RT "A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease
RT necessary for DNA interstrand crosslink repair.";
RL Mol. Cell 39:36-47(2010).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DOMAIN UBZ-TYPE,
RP INTERACTION WITH FANCD2 AND FANCI, AND MUTAGENESIS OF CYS-44; ASP-960 AND
RP LYS-977.
RX PubMed=20671156; DOI=10.1126/science.1192656;
RA Liu T., Ghosal G., Yuan J., Chen J., Huang J.;
RT "FAN1 acts with FANCI-FANCD2 to promote DNA interstrand cross-link
RT repair.";
RL Science 329:693-696(2010).
RN [11]
RP FUNCTION.
RX PubMed=21115814; DOI=10.1073/pnas.1011081107;
RA Yoshikiyo K., Kratz K., Hirota K., Nishihara K., Takata M., Kurumizaka H.,
RA Horimoto S., Takeda S., Jiricny J.;
RT "KIAA1018/FAN1 nuclease protects cells against genomic instability induced
RT by interstrand cross-linking agents.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:21553-21557(2010).
RN [12]
RP UBIQUITINATION, PROTEASOMAL DEGRADATION, AND IDENTIFICATION OF D-BOX AND
RP KEN BOX MOTIFS.
RX PubMed=22854063; DOI=10.5732/cjc.012.10144;
RA Lai F., Hu K., Wu Y., Tang J., Sang Y., Cao J., Kang T.;
RT "Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1).";
RL Ai Zheng 31:440-448(2012).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-180, 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 [14]
RP FUNCTION.
RX PubMed=24981866; DOI=10.1016/j.celrep.2014.06.001;
RA Pennell S., Declais A.C., Li J., Haire L.F., Berg W., Saldanha J.W.,
RA Taylor I.A., Rouse J., Lilley D.M., Smerdon S.J.;
RT "FAN1 activity on asymmetric repair intermediates is mediated by an
RT atypical monomeric virus-type replication-repair nuclease domain.";
RL Cell Rep. 8:84-93(2014).
RN [15]
RP FUNCTION.
RX PubMed=25135477; DOI=10.1128/mcb.00457-14;
RA Chaudhury I., Stroik D.R., Sobeck A.;
RT "FANCD2-controlled chromatin access of the Fanconi-associated nuclease FAN1
RT is crucial for the recovery of stalled replication forks.";
RL Mol. Cell. Biol. 34:3939-3954(2014).
RN [16]
RP POSSIBLE INVOLVEMENT IN SCHIZOPHRENIA AND AUTISM.
RX PubMed=24344280; DOI=10.1073/pnas.1309475110;
RA Ionita-Laza I., Xu B., Makarov V., Buxbaum J.D., Roos J.L., Gogos J.A.,
RA Karayiorgou M.;
RT "Scan statistic-based analysis of exome sequencing data identifies FAN1 at
RT 15q13.3 as a susceptibility gene for schizophrenia and autism.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:343-348(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 364-1017 IN COMPLEX WITH TARGET
RP DNA AND CALCIUM, FUNCTION, AND MUTAGENESIS OF ARG-706 AND ARG-952.
RX PubMed=25430771; DOI=10.1126/science.1258973;
RA Wang R., Persky N.S., Yoo B., Ouerfelli O., Smogorzewska A., Elledge S.J.,
RA Pavletich N.P.;
RT "DNA repair. Mechanism of DNA interstrand cross-link processing by repair
RT nuclease FAN1.";
RL Science 346:1127-1130(2014).
RN [18]
RP VARIANTS KMIN ARG-871; PRO-929; ASP-937 AND ASN-960.
RX PubMed=22772369; DOI=10.1038/ng.2347;
RA Zhou W., Otto E.A., Cluckey A., Airik R., Hurd T.W., Chaki M., Diaz K.,
RA Lach F.P., Bennett G.R., Gee H.Y., Ghosh A.K., Natarajan S., Thongthip S.,
RA Veturi U., Allen S.J., Janssen S., Ramaswami G., Dixon J., Burkhalter F.,
RA Spoendlin M., Moch H., Mihatsch M.J., Verine J., Reade R., Soliman H.,
RA Godin M., Kiss D., Monga G., Mazzucco G., Amann K., Artunc F.,
RA Newland R.C., Wiech T., Zschiedrich S., Huber T.B., Friedl A., Slaats G.G.,
RA Joles J.A., Goldschmeding R., Washburn J., Giles R.H., Levy S.,
RA Smogorzewska A., Hildebrandt F.;
RT "FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic
RT kidney failure to defective DNA damage repair.";
RL Nat. Genet. 44:910-915(2012).
CC -!- FUNCTION: Nuclease required for the repair of DNA interstrand cross-
CC links (ICL) recruited at sites of DNA damage by monoubiquitinated
CC FANCD2. Specifically involved in repair of ICL-induced DNA breaks by
CC being required for efficient homologous recombination, probably in the
CC resolution of homologous recombination intermediates (PubMed:20603015,
CC PubMed:20603016, PubMed:20603073, PubMed:20671156, PubMed:24981866,
CC PubMed:25430771). Not involved in DNA double-strand breaks resection
CC (PubMed:20603015, PubMed:20603016). Acts as a 5'-3' exonuclease that
CC anchors at a cut end of DNA and cleaves DNA successively at every third
CC nucleotide, allowing to excise an ICL from one strand through flanking
CC incisions. Probably keeps excising with 3'-flap annealing until it
CC reaches and unhooks the ICL (PubMed:25430771). Acts at sites that have
CC a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide flap
CC and is augmented by a 3' flap (PubMed:25430771). Also has endonuclease
CC activity toward 5'-flaps (PubMed:20603015, PubMed:20603016,
CC PubMed:24981866). {ECO:0000269|PubMed:20603015,
CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073,
CC ECO:0000269|PubMed:20671156, ECO:0000269|PubMed:24981866,
CC ECO:0000269|PubMed:25135477, ECO:0000269|PubMed:25430771}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolytically removes 5'-nucleotides successively from the
CC 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides.;
CC EC=3.1.4.1; Evidence={ECO:0000269|PubMed:20603015,
CC ECO:0000269|PubMed:20603016};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:20603016};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20603016};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000250|UniProtKB:Q9I2N0, ECO:0000269|PubMed:20603016};
CC -!- SUBUNIT: Interacts with FANCD2 (when monoubiquitinated). Interacts with
CC FANCI, MLH1, MLH3 and PMS2. {ECO:0000269|PubMed:20603015,
CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073,
CC ECO:0000269|PubMed:20671156}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20603015,
CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073,
CC ECO:0000269|PubMed:20671156, ECO:0000269|PubMed:20935496}.
CC Note=Localizes at sites of DNA damage following recruitment by
CC monoubiquitinated FANCD2 (PubMed:20603015, PubMed:20603016). Localizes
CC to stalled replication forks via its UBZ4-type zinc finger
CC (PubMed:20935496). {ECO:0000269|PubMed:20603015,
CC ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20935496}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9Y2M0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Y2M0-2; Sequence=VSP_029429, VSP_029430;
CC -!- DOMAIN: The UBZ4-type zinc finger specifically binds monoubiquitinated
CC FANCD2. {ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016,
CC ECO:0000269|PubMed:20671156, ECO:0000269|PubMed:20935496}.
CC -!- DOMAIN: The KEN box and D-box are required for interaction with
CC FZR1/CDH1 and essential for APC(CDH1)-mediated ubiquitination.
CC {ECO:0000269|PubMed:22854063}.
CC -!- PTM: Ubiquitinated and degraded during mitotic exit by the APC/C-Cdh1
CC complex. {ECO:0000269|PubMed:22854063}.
CC -!- DISEASE: Interstitial nephritis, karyomegalic (KMIN) [MIM:614817]: A
CC rare kidney disease characterized by chronic tubulointerstitial
CC nephritis associated with massively enlarged tubular epithelial cell
CC nuclei. The clinical picture is associated with recurrent upper
CC respiratory tract infections in addition to chronic kidney disease
CC beginning in the third decade of life. {ECO:0000269|PubMed:22772369}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Note=Schizophrenia and autism. Schizophrenia is a severe
CC psychiatric disorder characterized by positive, negative, and cognitive
CC symptoms, and it is associated with increased mortality and severely
CC reduced fecundity. Autim is a complex multifactorial, pervasive
CC developmental disorder characterized by impairments in reciprocal
CC social interaction and communication, restricted and stereotyped
CC patterns of interests and activities, and the presence of developmental
CC abnormalities by 3 years of age. Most individuals with autism also
CC manifest moderate intellectual disability. Disease susceptibility may
CC be associated with variants affecting the gene represented in this
CC entry. {ECO:0000269|PubMed:24344280}.
CC -!- SIMILARITY: Belongs to the FAN1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH47882.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA76862.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB023235; BAA76862.3; ALT_INIT; mRNA.
DR EMBL; AK290987; BAF83676.1; -; mRNA.
DR EMBL; AC087481; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047882; AAH47882.1; ALT_INIT; mRNA.
DR CCDS; CCDS32186.1; -. [Q9Y2M0-1]
DR CCDS; CCDS58344.1; -. [Q9Y2M0-2]
DR RefSeq; NP_001139566.1; NM_001146094.1. [Q9Y2M0-2]
DR RefSeq; NP_001139567.1; NM_001146095.1. [Q9Y2M0-2]
DR RefSeq; NP_001139568.1; NM_001146096.1. [Q9Y2M0-2]
DR RefSeq; NP_055782.3; NM_014967.4. [Q9Y2M0-1]
DR RefSeq; XP_005254289.1; XM_005254232.4. [Q9Y2M0-1]
DR RefSeq; XP_005254291.1; XM_005254234.4. [Q9Y2M0-1]
DR RefSeq; XP_005254292.1; XM_005254235.3. [Q9Y2M0-1]
DR PDB; 4REA; X-ray; 3.81 A; A/B=373-1017.
DR PDB; 4REB; X-ray; 4.20 A; A/H=373-1017.
DR PDB; 4REC; X-ray; 2.20 A; A=373-1017.
DR PDB; 4RI8; X-ray; 2.90 A; A/B=370-1017.
DR PDB; 4RI9; X-ray; 2.90 A; A/B=370-1017.
DR PDB; 4RIA; X-ray; 3.00 A; A/B=370-1017.
DR PDB; 4RIB; X-ray; 3.25 A; A/B=364-1017.
DR PDB; 4RIC; X-ray; 2.80 A; A/B=370-1009.
DR PDB; 4RID; X-ray; 3.30 A; A/B=370-1009.
DR PDB; 4RY3; X-ray; 2.80 A; A=371-1010.
DR PDBsum; 4REA; -.
DR PDBsum; 4REB; -.
DR PDBsum; 4REC; -.
DR PDBsum; 4RI8; -.
DR PDBsum; 4RI9; -.
DR PDBsum; 4RIA; -.
DR PDBsum; 4RIB; -.
DR PDBsum; 4RIC; -.
DR PDBsum; 4RID; -.
DR PDBsum; 4RY3; -.
DR AlphaFoldDB; Q9Y2M0; -.
DR SMR; Q9Y2M0; -.
DR BioGRID; 116573; 55.
DR IntAct; Q9Y2M0; 26.
DR MINT; Q9Y2M0; -.
DR STRING; 9606.ENSP00000354497; -.
DR DEPOD; FAN1; -.
DR iPTMnet; Q9Y2M0; -.
DR PhosphoSitePlus; Q9Y2M0; -.
DR BioMuta; FAN1; -.
DR DMDM; 160410012; -.
DR EPD; Q9Y2M0; -.
DR jPOST; Q9Y2M0; -.
DR MassIVE; Q9Y2M0; -.
DR MaxQB; Q9Y2M0; -.
DR PaxDb; Q9Y2M0; -.
DR PeptideAtlas; Q9Y2M0; -.
DR PRIDE; Q9Y2M0; -.
DR ProteomicsDB; 85841; -. [Q9Y2M0-1]
DR ProteomicsDB; 85842; -. [Q9Y2M0-2]
DR Antibodypedia; 22515; 126 antibodies from 22 providers.
DR DNASU; 22909; -.
DR Ensembl; ENST00000362065.9; ENSP00000354497.4; ENSG00000198690.10. [Q9Y2M0-1]
DR Ensembl; ENST00000561594.5; ENSP00000455983.1; ENSG00000198690.10. [Q9Y2M0-2]
DR Ensembl; ENST00000561607.6; ENSP00000454223.1; ENSG00000198690.10. [Q9Y2M0-2]
DR Ensembl; ENST00000565466.5; ENSP00000454544.1; ENSG00000198690.10. [Q9Y2M0-2]
DR Ensembl; ENST00000621063.1; ENSP00000484956.1; ENSG00000276787.1. [Q9Y2M0-1]
DR Ensembl; ENST00000656435.1; ENSP00000499534.1; ENSG00000198690.10. [Q9Y2M0-1]
DR Ensembl; ENST00000657391.1; ENSP00000499703.1; ENSG00000198690.10. [Q9Y2M0-1]
DR Ensembl; ENST00000658773.1; ENSP00000499742.1; ENSG00000198690.10. [Q9Y2M0-2]
DR Ensembl; ENST00000670849.1; ENSP00000499638.1; ENSG00000198690.10. [Q9Y2M0-1]
DR GeneID; 22909; -.
DR KEGG; hsa:22909; -.
DR MANE-Select; ENST00000362065.9; ENSP00000354497.4; NM_014967.5; NP_055782.3.
DR UCSC; uc001zfc.3; human. [Q9Y2M0-1]
DR CTD; 22909; -.
DR DisGeNET; 22909; -.
DR GeneCards; FAN1; -.
DR HGNC; HGNC:29170; FAN1.
DR HPA; ENSG00000198690; Low tissue specificity.
DR MalaCards; FAN1; -.
DR MIM; 613534; gene.
DR MIM; 614817; phenotype.
DR neXtProt; NX_Q9Y2M0; -.
DR OpenTargets; ENSG00000198690; -.
DR Orphanet; 401996; Karyomegalic interstitial nephritis.
DR Orphanet; 144; Lynch syndrome.
DR PharmGKB; PA165478601; -.
DR VEuPathDB; HostDB:ENSG00000198690; -.
DR eggNOG; KOG2143; Eukaryota.
DR GeneTree; ENSGT00390000018637; -.
DR HOGENOM; CLU_005116_4_0_1; -.
DR InParanoid; Q9Y2M0; -.
DR OMA; LEEHYMW; -.
DR OrthoDB; 1003565at2759; -.
DR PhylomeDB; Q9Y2M0; -.
DR TreeFam; TF312870; -.
DR PathwayCommons; Q9Y2M0; -.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; Q9Y2M0; -.
DR BioGRID-ORCS; 22909; 11 hits in 1082 CRISPR screens.
DR ChiTaRS; FAN1; human.
DR GenomeRNAi; 22909; -.
DR Pharos; Q9Y2M0; Tbio.
DR PRO; PR:Q9Y2M0; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9Y2M0; protein.
DR Bgee; ENSG00000198690; Expressed in right hemisphere of cerebellum and 148 other tissues.
DR ExpressionAtlas; Q9Y2M0; baseline and differential.
DR Genevisible; Q9Y2M0; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045171; C:intercellular bridge; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB.
DR GO; GO:0070336; F:flap-structured DNA binding; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; TAS:UniProtKB.
DR GO; GO:0004528; F:phosphodiesterase I activity; IEA:UniProtKB-EC.
DR GO; GO:0140036; F:ubiquitin-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; IDA:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB.
DR Gene3D; 3.40.1350.10; -; 1.
DR InterPro; IPR033315; Fan1-like.
DR InterPro; IPR006642; Rad18_UBZ4.
DR InterPro; IPR011856; tRNA_endonuc-like_dom_sf.
DR InterPro; IPR014883; VRR_NUC.
DR PANTHER; PTHR15749; PTHR15749; 1.
DR Pfam; PF08774; VRR_NUC; 1.
DR SMART; SM00990; VRR_NUC; 1.
DR SMART; SM00734; ZnF_Rad18; 1.
DR PROSITE; PS51908; ZF_UBZ4; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Disease variant;
KW DNA damage; DNA repair; Endonuclease; Exonuclease; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1017
FT /note="Fanconi-associated nuclease 1"
FT /id="PRO_0000311224"
FT DOMAIN 895..1007
FT /note="VRR-NUC"
FT ZN_FING 41..69
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 170..189
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 671..696
FT /evidence="ECO:0000255"
FT MOTIF 14..22
FT /note="D-box"
FT /evidence="ECO:0000305"
FT MOTIF 212..214
FT /note="KEN box"
FT /evidence="ECO:0000305"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 47
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 59
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 834
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 960
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 960
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 975
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 976
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 527..533
FT /note="AKALAGQ -> FCWLLLQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_029429"
FT VAR_SEQ 534..1017
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_029430"
FT VARIANT 233
FT /note="G -> E (in dbSNP:rs4779794)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_037167"
FT VARIANT 871
FT /note="C -> R (in KMIN; partially complement cell survival
FT upon exposure to mitomycin C)"
FT /evidence="ECO:0000269|PubMed:22772369"
FT /id="VAR_068958"
FT VARIANT 929
FT /note="Q -> P (in KMIN)"
FT /evidence="ECO:0000269|PubMed:22772369"
FT /id="VAR_068959"
FT VARIANT 937
FT /note="G -> D (in KMIN; dbSNP:rs1270571213)"
FT /evidence="ECO:0000269|PubMed:22772369"
FT /id="VAR_068960"
FT VARIANT 960
FT /note="D -> N (in KMIN; dbSNP:rs751703979)"
FT /evidence="ECO:0000269|PubMed:22772369"
FT /id="VAR_068961"
FT MUTAGEN 44
FT /note="C->A: Abolishes interaction with monoubiquitinated
FT FANCD2; when associated with A-47."
FT /evidence="ECO:0000269|PubMed:20603016,
FT ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:20671156"
FT MUTAGEN 47
FT /note="C->A: Abolishes interaction with monoubiquitinated
FT FANCD2; when associated with A-44."
FT /evidence="ECO:0000269|PubMed:20603016,
FT ECO:0000269|PubMed:20603073"
FT MUTAGEN 477
FT /note="L->P: Still localized to sites of DNA damage but the
FT strength of the signal is diminished."
FT /evidence="ECO:0000269|PubMed:20603073"
FT MUTAGEN 706
FT /note="R->A: Strongly reduced affinity for sites that have
FT a 5'-terminal phosphate anchor at a flap of 1 nucleotide;
FT when associated with A-952."
FT /evidence="ECO:0000269|PubMed:25430771"
FT MUTAGEN 864
FT /note="Q->A: Loss of nuclease activity; when associated
FT with A-960; A-975 and A-977."
FT /evidence="ECO:0000269|PubMed:20603073"
FT MUTAGEN 952
FT /note="R->A: Strongly reduced affinity for sites that have
FT a 5'-terminal phosphate anchor at a flap of 1 nucleotide;
FT when associated with A-706."
FT /evidence="ECO:0000269|PubMed:25430771"
FT MUTAGEN 960
FT /note="D->A: Loss of nuclease activity. Loss of nuclease
FT activity; when associated with A-864; A-975 and A-977."
FT /evidence="ECO:0000269|PubMed:20603016,
FT ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:20671156"
FT MUTAGEN 975
FT /note="E->A: Loss of nuclease activity; when associated
FT with A-864; A-960 and A-977."
FT /evidence="ECO:0000269|PubMed:20603073"
FT MUTAGEN 977
FT /note="K->A: Loss of nuclease activity; when associated
FT with A-864; A-960 and A-975."
FT /evidence="ECO:0000269|PubMed:20603073,
FT ECO:0000269|PubMed:20671156"
FT MUTAGEN 981..982
FT /note="DR->AA: Loss of nuclease activity."
FT /evidence="ECO:0000269|PubMed:20603015"
FT CONFLICT 9
FT /note="D -> DK (in Ref. 5; AAH47882)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="S -> P (in Ref. 3; BAF83676)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="V -> A (in Ref. 1; BAA76862)"
FT /evidence="ECO:0000305"
FT HELIX 374..388
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 398..408
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 412..422
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 431..433
FT /evidence="ECO:0007829|PDB:4REC"
FT TURN 437..439
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 444..452
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 455..458
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 459..461
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 465..471
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 474..483
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 493..503
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 520..531
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 533..537
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 539..552
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:4REC"
FT TURN 557..559
FT /evidence="ECO:0007829|PDB:4RIC"
FT TURN 563..565
FT /evidence="ECO:0007829|PDB:4RI8"
FT HELIX 566..568
FT /evidence="ECO:0007829|PDB:4RIC"
FT HELIX 573..575
FT /evidence="ECO:0007829|PDB:4RY3"
FT HELIX 577..580
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 595..598
FT /evidence="ECO:0007829|PDB:4RIC"
FT HELIX 599..620
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 624..639
FT /evidence="ECO:0007829|PDB:4REC"
FT TURN 640..643
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 645..651
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 655..658
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 662..679
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 683..695
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 697..699
FT /evidence="ECO:0007829|PDB:4RI8"
FT HELIX 701..703
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 704..716
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 722..734
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 740..754
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 757..759
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 761..765
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 778..783
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 786..788
FT /evidence="ECO:0007829|PDB:4RIB"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:4RI9"
FT STRAND 804..806
FT /evidence="ECO:0007829|PDB:4RIC"
FT STRAND 811..813
FT /evidence="ECO:0007829|PDB:4RI9"
FT HELIX 814..824
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 829..832
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 835..850
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 861..863
FT /evidence="ECO:0007829|PDB:4RID"
FT TURN 868..871
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 874..877
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 880..891
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 895..909
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 921..924
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 925..949
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 951..955
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 960..964
FT /evidence="ECO:0007829|PDB:4REC"
FT TURN 966..968
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 971..977
FT /evidence="ECO:0007829|PDB:4REC"
FT HELIX 985..996
FT /evidence="ECO:0007829|PDB:4REC"
FT STRAND 1001..1007
FT /evidence="ECO:0007829|PDB:4REC"
SQ SEQUENCE 1017 AA; 114225 MW; 5E4E0A8A1A158F50 CRC64;
MMSEGKPPDK KRPRRSLSIS KNKKKASNSI ISCFNNAPPA KLACPVCSKM VPRYDLNRHL
DEMCANNDFV QVDPGQVGLI NSNVSMVDLT SVTLEDVTPK KSPPPKTNLT PGQSDSAKRE
VKQKISPYFK SNDVVCKNQD ELRNRSVKVI CLGSLASKLS RKYVKAKKSI DKDEEFAGSS
PQSSKSTVVK SLIDNSSEIE DEDQILENSS QKENVFKCDS LKEECIPEHM VRGSKIMEAE
SQKATRECEK SALTPGFSDN AIMLFSPDFT LRNTLKSTSE DSLVKQECIK EVVEKREACH
CEEVKMTVAS EAKIQLSDSE AKSHSSADDA SAWSNIQEAP LQDDSCLNND IPHSIPLEQG
SSCNGPGQTT GHPYYLRSFL VVLKTVLENE DDMLLFDEQE KGIVTKFYQL SATGQKLYVR
LFQRKLSWIK MTKLEYEEIA LDLTPVIEEL TNAGFLQTES ELQELSEVLE LLSAPELKSL
AKTFHLVNPN GQKQQLVDAF LKLAKQRSVC TWGKNKPGIG AVILKRAKAL AGQSVRICKG
PRAVFSRILL LFSLTDSMED EDAACGGQGQ LSTVLLVNLG RMEFPSYTIN RKTHIFQDRD
DLIRYAAATH MLSDISSAMA NGNWEEAKEL AQCAKRDWNR LKNHPSLRCH EDLPLFLRCF
TVGWIYTRIL SRFVEILQRL HMYEEAVREL ESLLSQRIYC PDSRGRWWDR LALNLHQHLK
RLEPTIKCIT EGLADPEVRT GHRLSLYQRA VRLRESPSCK KFKHLFQQLP EMAVQDVKHV
TITGRLCPQR GMCKSVFVME AGEAADPTTV LCSVEELALA HYRRSGFDQG IHGEGSTFST
LYGLLLWDII FMDGIPDVFR NACQAFPLDL CTDSFFTSRR PALEARLQLI HDAPEESLRA
WVAATWHEQE GRVASLVSWD RFTSLQQAQD LVSCLGGPVL SGVCRHLAAD FRHCRGGLPD
LVVWNSQSRH FKLVEVKGPN DRLSHKQMIW LAELQKLGAE VEVCHVVAVG AKSQSLS
