FAN1_AILME
ID FAN1_AILME Reviewed; 1025 AA.
AC D2HNY3;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 63.
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=PANDA_013441;
OS Ailuropoda melanoleuca (Giant panda).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Ursidae; Ailuropoda.
OX NCBI_TaxID=9646;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20010809; DOI=10.1038/nature08696;
RA Li R., Fan W., Tian G., Zhu H., He L., Cai J., Huang Q., Cai Q., Li B.,
RA Bai Y., Zhang Z., Zhang Y., Wang W., Li J., Wei F., Li H., Jian M., Li J.,
RA Zhang Z., Nielsen R., Li D., Gu W., Yang Z., Xuan Z., Ryder O.A.,
RA Leung F.C., Zhou Y., Cao J., Sun X., Fu Y., Fang X., Guo X., Wang B.,
RA Hou R., Shen F., Mu B., Ni P., Lin R., Qian W., Wang G., Yu C., Nie W.,
RA Wang J., Wu Z., Liang H., Min J., Wu Q., Cheng S., Ruan J., Wang M.,
RA Shi Z., Wen M., Liu B., Ren X., Zheng H., Dong D., Cook K., Shan G.,
RA Zhang H., Kosiol C., Xie X., Lu Z., Zheng H., Li Y., Steiner C.C.,
RA Lam T.T., Lin S., Zhang Q., Li G., Tian J., Gong T., Liu H., Zhang D.,
RA Fang L., Ye C., Zhang J., Hu W., Xu A., Ren Y., Zhang G., Bruford M.W.,
RA Li Q., Ma L., Guo Y., An N., Hu Y., Zheng Y., Shi Y., Li Z., Liu Q.,
RA Chen Y., Zhao J., Qu N., Zhao S., Tian F., Wang X., Wang H., Xu L., Liu X.,
RA Vinar T., Wang Y., Lam T.W., Yiu S.M., Liu S., Zhang H., Li D., Huang Y.,
RA Wang X., Yang G., Jiang Z., Wang J., Qin N., Li L., Li J., Bolund L.,
RA Kristiansen K., Wong G.K., Olson M., Zhang X., Li S., Yang H., Wang J.,
RA Wang J.;
RT "The sequence and de novo assembly of the giant panda genome.";
RL Nature 463:311-317(2010).
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. Not involved in
CC DNA double-strand breaks resection. 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. Acts at sites that have a 5'-terminal
CC phosphate anchor at a nick or a 1- or 2-nucleotide flap and is
CC augmented by a 3' flap. Also has endonuclease activity toward 5'-flaps.
CC {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). 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 -!- 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EFB17558.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; GL193105; EFB17558.1; ALT_INIT; Genomic_DNA.
DR RefSeq; XP_002924164.1; XM_002924118.3.
DR AlphaFoldDB; D2HNY3; -.
DR SMR; D2HNY3; -.
DR STRING; 9646.ENSAMEP00000016241; -.
DR PRIDE; D2HNY3; -.
DR GeneID; 100481860; -.
DR CTD; 22909; -.
DR eggNOG; KOG2143; Eukaryota.
DR HOGENOM; CLU_005116_3_0_1; -.
DR InParanoid; D2HNY3; -.
DR OMA; LEEHYMW; -.
DR OrthoDB; 1003565at2759; -.
DR TreeFam; TF312870; -.
DR Proteomes; UP000008912; Unassembled WGS sequence.
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; 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 3: Inferred from homology;
KW Coiled coil; DNA damage; DNA repair; Endonuclease; Exonuclease; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1025
FT /note="Fanconi-associated nuclease 1"
FT /id="PRO_0000398620"
FT DOMAIN 903..1015
FT /note="VRR-NUC"
FT ZN_FING 40..68
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 98..120
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 682..704
FT /evidence="ECO:0000255"
FT BINDING 43
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 46
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 58
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 842
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 968
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 968
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 983
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT BINDING 984
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9I2N0"
FT MOD_RES 182
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y2M0"
SQ SEQUENCE 1025 AA; 114770 MW; 9CC44B63953CB17E CRC64;
MSEGKSPAKK RARRSLSISK TKKNECNSII SFFNNVPPAK LACPICSKMV PRYDLNWHLD
EKCANNDNIT PVDLRHVGFT DSSGSTVNLT NTVLENVTPG KLSPSKASLT PDPSDSAKMG
IKQQTSPYFK NNKDLVFKNQ DKLRHHNVKV ITLGSLSSKL SRRYTEARRS ICKKNEEFAS
KSPQSPSSTV VRSPVDNCSE IEDKDQILEN SSQKENVFTC DSLNEQRTEH SVEDTKVLEA
ESQEATQECG RSPLTPAFSD NAFVLFSPDL TRGNPLRSTS EDSLEWETIT GIDGKDVEKC
EAGSCEEVKV TVASEAKTQL SDWEAKCHSS TPDDSKGCNI QDLLLEGDSD LKNEITCRIP
LEQGSSCDVP DKTVTVPPSH PYYLRSFLVV LKAVFENEED RMLFDEHEKE IVTKFYQLSA
SAQKLYVRLF QRKFSWLKMN KLEYEEIAPD LTPVIGELQQ AGFLQTESEL QELSEVLELL
SAPELKTLAK TFHLVNPNGQ KQQLVDTFLK LAKQPSVCTW GKNQPGIGAV ILKRAKGLAG
QALRVCKGPR AVFSRVLLLF SLTDSLEDEE AACGGQGQLS TVLLVNLGRM EFPRYTINRK
TQIFQDRDDL IRYAAAAHML SDISTAMANG NWKEANELSQ CAKSDWNKLK SHPSLRYHEN
LPLFLRCFTV GWIYTRILSR TVEILQRLHM YEEAVKELES LLSQRVYCPD SRGRWWDRLA
LNLHQHLKRL EPAIKCITEG LADPEVRTGH RLSLYQRALR LRESPSCQKY RHLFHQLPEV
TVGDVKHVTI TGRLCPQRGM GKSVFVMEAG GPTAPATVLC SVEEVALAYY RRSGFDQGIH
GEGSTFSTLY GLLLWDIIFM DGIPDVFRNA YQASPLDLCT DSFFASRGPA IEARLQRIHS
APAESLRAWV AAAWQAQEGR VASIVSWDRF ASLQQAQDLV SCLGGPVLSG VCRRLAADFR
HCRGGLPDLV VWNSQSRHFK LVEVKGPNDR LSHKQMLWLD ELQKLGADVE VCHVVAVGAK
SKSLT
