FAN1_MOUSE
ID FAN1_MOUSE Reviewed; 1020 AA.
AC Q69ZT1; Q14B88; Q8BVK2;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Fanconi-associated nuclease 1 {ECO:0000250|UniProtKB:Q9Y2M0};
DE EC=3.1.21.- {ECO:0000269|PubMed:24981866};
DE EC=3.1.4.1 {ECO:0000269|PubMed:24981866};
DE AltName: Full=FANCD2/FANCI-associated nuclease 1 {ECO:0000250|UniProtKB:Q9Y2M0};
DE Short=mFAN1 {ECO:0000303|PubMed:24981866};
DE AltName: Full=Myotubularin-related protein 15;
GN Name=Fan1 {ECO:0000312|MGI:MGI:3045266};
GN Synonyms=Kiaa1018 {ECO:0000303|PubMed:15368895}, Mtmr15;
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] (ISOFORM 3).
RC STRAIN=C57BL/6J; TISSUE=Testis;
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].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 45-1020 (ISOFORM 2).
RC TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
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).
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 (By similarity).
CC Not involved in DNA double-strand breaks resection. Acts as a 5'-3'
CC exonuclease that anchors at a cut end of DNA and cleaves DNA
CC successively at every third nucleotide, allowing to excise an ICL from
CC one strand through flanking incisions (PubMed:24981866). Probably keeps
CC excising with 3'-flap annealing until it reaches and unhooks the ICL.
CC Acts at sites that have a 5'-terminal phosphate anchor at a nick or a
CC 1- or 2-nucleotide flap and is augmented by a 3' flap (By similarity).
CC Also has endonuclease activity toward 5'-flaps (PubMed:24981866).
CC {ECO:0000250|UniProtKB:Q9Y2M0, ECO:0000269|PubMed:24981866}.
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:24981866};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9Y2M0};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9Y2M0};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000250|UniProtKB:Q9I2N0, ECO:0000250|UniProtKB:Q9Y2M0};
CC -!- SUBUNIT: Interacts with FANCD2 (when monoubiquitinated). Interacts with
CC FANCI, MLH1, MLH3 and PMS2. {ECO:0000250|UniProtKB:Q9Y2M0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y2M0}.
CC Note=Localizes at sites of DNA damage following recruitment by
CC monoubiquitinated FANCD2. Localizes to stalled replication forks via
CC its UBZ4-type zinc finger. {ECO:0000250|UniProtKB:Q9Y2M0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q69ZT1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q69ZT1-2; Sequence=VSP_029435, VSP_029436;
CC Name=3;
CC IsoId=Q69ZT1-3; Sequence=VSP_029432, VSP_029433;
CC Name=4;
CC IsoId=Q69ZT1-4; Sequence=VSP_029431, VSP_029434;
CC -!- DOMAIN: The UBZ4-type zinc finger specifically binds monoubiquitinated
CC FANCD2. {ECO:0000250|UniProtKB:Q9Y2M0}.
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:0000250|UniProtKB:Q9Y2M0}.
CC -!- PTM: Ubiquitinated and degraded during mitotic exit by the APC/C-Cdh1
CC complex. {ECO:0000250|UniProtKB:Q9Y2M0}.
CC -!- SIMILARITY: Belongs to the FAN1 family. {ECO:0000305}.
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DR EMBL; AK077918; BAC37062.1; -; mRNA.
DR EMBL; AC129199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC116270; AAI16271.1; -; mRNA.
DR EMBL; BC116271; AAI16272.1; -; mRNA.
DR EMBL; AK173087; BAD32365.1; -; mRNA.
DR CCDS; CCDS52265.1; -. [Q69ZT1-1]
DR RefSeq; NP_808561.2; NM_177893.3. [Q69ZT1-1]
DR RefSeq; XP_006541021.1; XM_006540958.3. [Q69ZT1-1]
DR AlphaFoldDB; Q69ZT1; -.
DR SMR; Q69ZT1; -.
DR BioGRID; 236987; 1.
DR STRING; 10090.ENSMUSP00000130012; -.
DR iPTMnet; Q69ZT1; -.
DR PhosphoSitePlus; Q69ZT1; -.
DR EPD; Q69ZT1; -.
DR MaxQB; Q69ZT1; -.
DR PaxDb; Q69ZT1; -.
DR PeptideAtlas; Q69ZT1; -.
DR PRIDE; Q69ZT1; -.
DR ProteomicsDB; 267566; -. [Q69ZT1-1]
DR ProteomicsDB; 267567; -. [Q69ZT1-2]
DR ProteomicsDB; 267568; -. [Q69ZT1-3]
DR ProteomicsDB; 267569; -. [Q69ZT1-4]
DR Antibodypedia; 22515; 126 antibodies from 22 providers.
DR Ensembl; ENSMUST00000163289; ENSMUSP00000130012; ENSMUSG00000033458. [Q69ZT1-1]
DR GeneID; 330554; -.
DR KEGG; mmu:330554; -.
DR UCSC; uc009hge.1; mouse. [Q69ZT1-2]
DR UCSC; uc009hgf.2; mouse. [Q69ZT1-3]
DR UCSC; uc012fmp.1; mouse. [Q69ZT1-1]
DR UCSC; uc029wgg.1; mouse. [Q69ZT1-4]
DR CTD; 22909; -.
DR MGI; MGI:3045266; Fan1.
DR VEuPathDB; HostDB:ENSMUSG00000033458; -.
DR eggNOG; KOG2143; Eukaryota.
DR GeneTree; ENSGT00390000018637; -.
DR HOGENOM; CLU_005116_3_0_1; -.
DR InParanoid; Q69ZT1; -.
DR OMA; LEEHYMW; -.
DR OrthoDB; 1003565at2759; -.
DR PhylomeDB; Q69ZT1; -.
DR TreeFam; TF312870; -.
DR Reactome; R-MMU-6783310; Fanconi Anemia Pathway.
DR BioGRID-ORCS; 330554; 6 hits in 106 CRISPR screens.
DR PRO; PR:Q69ZT1; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q69ZT1; protein.
DR Bgee; ENSMUSG00000033458; Expressed in quadriceps femoris and 60 other tissues.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0017108; F:5'-flap endonuclease activity; ISS:UniProtKB.
DR GO; GO:0070336; F:flap-structured DNA binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004528; F:phosphodiesterase I activity; IEA:UniProtKB-EC.
DR GO; GO:0140036; F:ubiquitin-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0036297; P:interstrand cross-link repair; ISS:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS: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 PROSITE; PS51908; ZF_UBZ4; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Coiled coil; DNA damage; DNA repair; Endonuclease;
KW Exonuclease; Hydrolase; Magnesium; Manganese; Metal-binding; Nuclease;
KW Nucleus; Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1020
FT /note="Fanconi-associated nuclease 1"
FT /id="PRO_0000311225"
FT DOMAIN 898..1010
FT /note="VRR-NUC"
FT ZN_FING 41..69
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 173..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 224..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 673..737
FT /evidence="ECO:0000255"
FT MOTIF 14..22
FT /note="D-box"
FT MOTIF 212..214
FT /note="KEN box"
FT COMPBIAS 176..195
FT /note="Polar 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 837
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 963
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 963
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 978
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 979
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT VAR_SEQ 415..469
FT /note="ASGQKLYVRLFQRKLTWIKMSKLEYEEIASDLTPVVEELKDSGFLQTESELQ
FT ELS -> GTFGLLAFRASSSGLCAMGGPVSSLMTTTRSHCGSTAGWLSVSRRGPFKTSS
FT CAW (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029431"
FT VAR_SEQ 462..468
FT /note="ESELQEL -> GTVRRRT (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029432"
FT VAR_SEQ 469..1020
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_029433"
FT VAR_SEQ 470..1020
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029434"
FT VAR_SEQ 728..743
FT /note="AIRCIREGLADPHVRT -> VLAAYPAAYLVLNGKL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_029435"
FT VAR_SEQ 744..1020
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15368895"
FT /id="VSP_029436"
SQ SEQUENCE 1020 AA; 112925 MW; A887731CD19DBF93 CRC64;
MPSQRKSPDQ KRPRRSLSTS KTAKSQCHSI TSYFNSAPPA KLACSTCHKM VPRYDLIRHL
DESCANNGVG DDVQVEPAQA GLMSPTVPTS DLPSGPLENV TPQKLSPPKR SLISVQCGSK
LGIQQQTSPY FKDALVSKDQ NELPNQSVEI MPLGSLTSKL SRRYLNAKKS LAKNEGLASQ
CPQTSPSTPG TSLTDNCPEM EDKDEVLNSS QKENIYSCAP LKEENASEQK VKNNKITGDE
SQKASCGEPA LTPASAEHAS ILLSSDSTLV SNTKSSPGDT LVKQESARRA DVGLAEPLEV
RSHKEVQMTF DAAAKTLVSG EAESNGPTDV DMSDMTTWSN NQELVREAGS VLHCPLEQGS
SCGGPSETAQ LALSHPYYLR SFLVVLQALL GNEEDMKLFD EQEKAIITRF YQLSASGQKL
YVRLFQRKLT WIKMSKLEYE EIASDLTPVV EELKDSGFLQ TESELQELSD VLELLSAPEL
KALAKTFHLV SPGGQKQQLV DAFHKLAKQR SVCTWGKTQP GIRAVILKRA KDLAGRSLRV
CKGPRAVFAR ILLLFSLTDS MEDEEAACGG QGQLSTVLLV NLGRMEFPQY TICRKTQIFR
DREDLIRYAA AAHMLSDISA AMASGNWEDA KELARSAKRD WEQLKSHPSL RYHEALPPFL
RCFTVGWIYT RISSRAVEVL ERLHMYEEAV KELENLLSQK IYCPDSRGRW WDRLALNLHQ
HLKRLEEAIR CIREGLADPH VRTGHRLSLY QRAVRLRESP SCRKYKHLFS RLPEVAVGDV
KHVTITGRLC PQHGMGKSVF VMESGDGANP TTVLCSVEEL ALGYYRQSGF DQGIHGEGST
FSTLCGLLLW DIIFMDGIPD VFRNAYQASP LDLLTDSFFA SREQALEARL QLIHSAPAES
LRAWVGEAWQ AQQGRVASLV SWDRFTSLQQ AQDLVSCLGG PVLSGVCRRL AADFRHCRGG
LPDLVVWNSQ SHHCKLVEVK GPSDRLSCKQ MIWLYELQKL GADVEVCHVV AVGAKSKGLG
