FAN1_DANRE
ID FAN1_DANRE Reviewed; 988 AA.
AC Q1LWH4; A5WVQ6; A7MBL6; T1ECT2;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Fanconi-associated nuclease 1 {ECO:0000250|UniProtKB:Q9Y2M0};
DE EC=3.1.21.- {ECO:0000250|UniProtKB:Q9Y2M0};
DE EC=3.1.4.1 {ECO:0000250|UniProtKB:Q9Y2M0};
DE AltName: Full=FANCD2/FANCI-associated nuclease 1 {ECO:0000250|UniProtKB:Q9Y2M0};
DE AltName: Full=Myotubularin-related protein 15;
GN Name=fan1; Synonyms=mtmr15; ORFNames=si:ch211-163b1.2, si:ch211-201b11.2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP DISRUPTION PHENOTYPE.
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. 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. Probably keeps excising with 3'-
CC flap annealing until it reaches and unhooks the ICL. Acts at sites that
CC have a 5'-terminal phosphate anchor at a nick or a 1- or 2-nucleotide
CC flap and is augmented by a 3' flap. Also has endonuclease activity
CC toward 5'-flaps. {ECO:0000250|UniProtKB:Q9Y2M0}.
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:0000250|UniProtKB:Q9Y2M0};
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).
CC {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. {ECO:0000250|UniProtKB:Q9Y2M0}.
CC -!- DOMAIN: The UBZ4-type zinc finger specifically binds monoubiquitinated
CC fancd2. {ECO:0000250|UniProtKB:Q9Y2M0}.
CC -!- DISRUPTION PHENOTYPE: Increased DNA damage response, apoptosis and
CC development of abnormalities such as kidney cysts.
CC {ECO:0000269|PubMed:22772369}.
CC -!- SIMILARITY: Belongs to the FAN1 family. {ECO:0000305}.
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DR EMBL; BX548157; CAK04388.1; -; Genomic_DNA.
DR EMBL; CT025908; CAN88260.1; -; Genomic_DNA.
DR EMBL; BC151826; AAI51827.1; -; mRNA.
DR RefSeq; NP_001038546.2; NM_001045081.2.
DR AlphaFoldDB; Q1LWH4; -.
DR SMR; Q1LWH4; -.
DR STRING; 7955.ENSDARP00000084286; -.
DR PaxDb; Q1LWH4; -.
DR PRIDE; Q1LWH4; -.
DR GeneID; 565458; -.
DR KEGG; dre:565458; -.
DR CTD; 22909; -.
DR ZFIN; ZDB-GENE-030131-6225; fan1.
DR eggNOG; KOG2143; Eukaryota.
DR InParanoid; Q1LWH4; -.
DR OrthoDB; 1003565at2759; -.
DR PhylomeDB; Q1LWH4; -.
DR TreeFam; TF312870; -.
DR Reactome; R-DRE-6783310; Fanconi Anemia Pathway.
DR PRO; PR:Q1LWH4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008409; F:5'-3' exonuclease activity; ISS: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; 1.25.40.10; -; 1.
DR Gene3D; 3.40.1350.10; -; 1.
DR InterPro; IPR033315; Fan1-like.
DR InterPro; IPR006642; Rad18_UBZ4.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
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 2: Evidence at transcript level;
KW Coiled coil; DNA damage; DNA repair; Endonuclease; Exonuclease; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Nuclease; Nucleus; Reference proteome;
KW Zinc; Zinc-finger.
FT CHAIN 1..988
FT /note="Fanconi-associated nuclease 1"
FT /id="PRO_0000311226"
FT DOMAIN 866..978
FT /note="VRR-NUC"
FT ZN_FING 49..77
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 164..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 269..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 636..663
FT /evidence="ECO:0000255"
FT COMPBIAS 8..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 164..179
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..243
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..302
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 52
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 55
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 805
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 931
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 931
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 946
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 947
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT CONFLICT 4
FT /note="Q -> L (in Ref. 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 15
FT /note="M -> V (in Ref. 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="R -> H (in Ref. 1; CAN88260 and 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="K -> N (in Ref. 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 176
FT /note="D -> E (in Ref. 1; CAN88260 and 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="C -> Y (in Ref. 1; CAN88260 and 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="G -> E (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="I -> M (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 275
FT /note="D -> N (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="P -> H (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="C -> Y (in Ref. 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 467
FT /note="G -> D (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 591
FT /note="D -> A (in Ref. 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 613
FT /note="S -> N (in Ref. 1; CAK04388 and 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 632
FT /note="T -> N (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 775
FT /note="G -> E (in Ref. 1; CAN88260)"
FT /evidence="ECO:0000305"
FT CONFLICT 781
FT /note="L -> V (in Ref. 1; CAN88260 and 2; AAI51827)"
FT /evidence="ECO:0000305"
FT CONFLICT 868
FT /note="T -> I (in Ref. 2; AAI51827)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 988 AA; 110984 MW; 94BF5209054E10E8 CRC64;
MESQTGRKSA RRLSMTKKKS QSVCPIKERT SNGGAASITS FFRNTPPSKL ACPLCGKLVP
RYKINEHIDS QCQNFLVEDD GKQKEITKAP SNSALASNNE REKSPGDKDA DTSPFFKKNC
AVRRDSSETD SQAKPVKTVG LGSLSSKLSR RALRLSDESG VNLTRVSDNE KDHNADLNRS
QKENCMNSLT FGSERNGTDA DNILETEPEA SNQPQLKNVE KSASDSSISS DVHTSSSSVL
KRKSMEIPKN DTNTTETCIA HKKSRFFQSS IERGDESKVK SDQTEASSSA YDVPTSKSPI
KSKTTQEEIE KELNKTPANE HNMLDVEKVG EGSEQQPTRL PYYLRNFRTV LEAVLENEDD
RRLFNEDDFS TIQSFQQLSV PGQMLYVRLF QRKLKWLQVC KVEYTEISTD LRPVVQELVA
CGFLQTESEL HDLHEVLDLL PAPELRNLAK TFHLGRGGSQ KQQLVEGLLQ LGKQRSLFAG
QNNTAAVILK RAKQAAGSCV RLCRSSRVVF SRVLLLFTLT DTLEEEDLAS GGQGQLYTIL
LVNSGRLAFP EYTVHRSARL FKDRDDLIRY ETAMRALQEV IAAMQSGSWE DAYDLYTTAM
AAWQEIKDSC DLSHQEQLPV FLRCFTVGWT YTRILSRGVE ILQRLKRYED AVEQLRNLLS
QSVYCVDSRG RWWDRLALNL QQHLKQHEQA IGAIRDGLND PLARTGHKLS LYQRASRMKE
SASLKKYRLL LRDLPTVHVQ DVTHVTIRGQ LFPHEGGMGK SVFLRAASED EGSGGGQGTV
LMCSVEDLAL EHYRTLGFDQ GIHGEGSTFS TLFGLLMWDI IFMDGVPDVF LNPYQTCPLD
LHTDCFYGSR REAIEARAEM LREASVETLQ DLIADVWSTQ EGRVCALINW ERFSTPQQAQ
SLVACLGGHF LSGVFLRMAK DYRHCRGGLP DLVVWSTSSN KYKLVEVKGP NDRLSQKQQI
WLDELRKLGA DVEVCHVTAT GARGARRE
