ID   FANCF_HUMAN             Reviewed;         374 AA.
AC   Q9NPI8; Q52LM0;
DT   10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Fanconi anemia group F protein;
DE            Short=Protein FACF;
GN   Name=FANCF;
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], AND INVOLVEMENT IN FANCF.
RX   PubMed=10615118; DOI=10.1038/71626;
RA   de Winter J.P., Rooimans M.A., van der Weel L., van Berkel C.G.M.,
RA   de Groot J., Waisfisz Q., Pronk J.C., Arwert F., Mathew C.G., Scheper R.J.,
RA   Hoatlin M.E., Buchwald M., Joenje H.;
RT   "The Fanconi anaemia gene FANCF encodes a novel protein with homology to
RT   ROM.";
RL   Nat. Genet. 24:15-16(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [GENOMIC DNA], AND VARIANT LEU-320.
RG   NIEHS SNPs program;
RL   Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain, and Skin;
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   PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, X-RAY
RP   CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 156-357, MUTAGENESIS OF LEU-209;
RP   PHE-251; TYR-287; LEU-289; PHE-339; VAL-341 AND LEU-344, AND SUBUNIT.
RX   PubMed=17082180; DOI=10.1074/jbc.m608356200;
RA   Kowal P., Gurtan A.M., Stuckert P., D'Andrea A.D., Ellenberger T.;
RT   "Structural determinants of human FANCF protein that function in the
RT   assembly of a DNA damage signaling complex.";
RL   J. Biol. Chem. 282:2047-2055(2007).
RN   [6]
RP   SUBUNIT, AND SUBCELLULAR LOCATION.
RX   PubMed=11063725; DOI=10.1093/hmg/9.18.2665;
RA   de Winter J.P., van der Weel L., de Groot J., Stone S., Waisfisz Q.,
RA   Arwert F., Scheper R.J., Kruyt F.A.E., Hoatlin M.E., Joenje H.;
RT   "The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC
RT   and FANCG.";
RL   Hum. Mol. Genet. 9:2665-2674(2000).
RN   [7]
RP   IDENTIFICATION IN A COMPLEX WITH FANCA; FANCC; FANCE; FANCG AND FANCL.
RX   PubMed=12724401; DOI=10.1128/mcb.23.10.3417-3426.2003;
RA   Meetei A.R., Sechi S., Wallisch M., Yang D., Young M.K., Joenje H.,
RA   Hoatlin M.E., Wang W.;
RT   "A multiprotein nuclear complex connects Fanconi anemia and Bloom
RT   syndrome.";
RL   Mol. Cell. Biol. 23:3417-3426(2003).
RN   [8]
RP   IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCG AND
RP   FANCL.
RX   PubMed=15502827; DOI=10.1038/ng1458;
RA   Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C.,
RA   Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W.,
RA   Joenje H.;
RT   "X-linked inheritance of Fanconi anemia complementation group B.";
RL   Nat. Genet. 36:1219-1224(2004).
RN   [9]
RP   IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCG; FANCL
RP   AND FANCM.
RX   PubMed=16116422; DOI=10.1038/ng1626;
RA   Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P.,
RA   Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H.,
RA   de Winter J.P., Wang W.;
RT   "A human ortholog of archaeal DNA repair protein Hef is defective in
RT   Fanconi anemia complementation group M.";
RL   Nat. Genet. 37:958-963(2005).
RN   [10]
RP   INTERACTION WITH HES1, AND SUBCELLULAR LOCATION.
RX   PubMed=18550849; DOI=10.1182/blood-2008-04-152710;
RA   Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G.,
RA   Carreau M.;
RT   "HES1 is a novel interactor of the Fanconi anemia core complex.";
RL   Blood 112:2062-2070(2008).
CC   -!- FUNCTION: DNA repair protein that may operate in a postreplication
CC       repair or a cell cycle checkpoint function. May be implicated in
CC       interstrand DNA cross-link repair and in the maintenance of normal
CC       chromosome stability (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Belongs to the multisubunit FA complex composed of FANCA,
CC       FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is
CC       not found in FA patients. In complex with FANCA, FANCG and FANCL, but
CC       not with FANCC, nor FANCE, interacts with HES1; this interaction may be
CC       essential for the stability and nuclear localization of FA core complex
CC       proteins. {ECO:0000269|PubMed:11063725, ECO:0000269|PubMed:12724401,
CC       ECO:0000269|PubMed:15502827, ECO:0000269|PubMed:16116422,
CC       ECO:0000269|PubMed:17082180, ECO:0000269|PubMed:18550849}.
CC   -!- INTERACTION:
CC       Q9NPI8; O15360: FANCA; NbExp=5; IntAct=EBI-81589, EBI-81570;
CC       Q9NPI8; O15287: FANCG; NbExp=4; IntAct=EBI-81589, EBI-81610;
CC       Q9NPI8; P42858: HTT; NbExp=3; IntAct=EBI-81589, EBI-466029;
CC       Q9NPI8; Q8WWU5-7: TCP11; NbExp=3; IntAct=EBI-81589, EBI-17721485;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11063725,
CC       ECO:0000269|PubMed:18550849}.
CC   -!- DISEASE: Fanconi anemia complementation group F (FANCF) [MIM:603467]: A
CC       disorder affecting all bone marrow elements and resulting in anemia,
CC       leukopenia and thrombopenia. It is associated with cardiac, renal and
CC       limb malformations, dermal pigmentary changes, and a predisposition to
CC       the development of malignancies. At the cellular level it is associated
CC       with hypersensitivity to DNA-damaging agents, chromosomal instability
CC       (increased chromosome breakage) and defective DNA repair.
CC       {ECO:0000269|PubMed:10615118}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/294/FANCF";
CC   -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database;
CC       URL="https://www2.rockefeller.edu/fanconi/genes/jumpf";
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="https://egp.gs.washington.edu/data/fancf/";
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DR   EMBL; AF181995; AAF26298.1; -; mRNA.
DR   EMBL; AF181994; AAF26297.1; -; mRNA.
DR   EMBL; AK023153; BAB14433.1; -; mRNA.
DR   EMBL; AY928335; AAX09677.1; -; Genomic_DNA.
DR   EMBL; BC047028; AAH47028.1; -; mRNA.
DR   EMBL; BC093867; AAH93867.1; -; mRNA.
DR   EMBL; BC101807; AAI01808.1; -; mRNA.
DR   CCDS; CCDS7857.1; -.
DR   RefSeq; NP_073562.1; NM_022725.3.
DR   PDB; 2IQC; X-ray; 2.40 A; A=156-357.
DR   PDB; 7KZP; EM; 3.10 A; F=1-374.
DR   PDB; 7KZQ; EM; 4.20 A; F=1-374.
DR   PDB; 7KZR; EM; 4.20 A; F=1-374.
DR   PDB; 7KZS; EM; 4.20 A; F=1-374.
DR   PDB; 7KZT; EM; 4.20 A; F=1-374.
DR   PDB; 7KZV; EM; 4.20 A; F=1-374.
DR   PDBsum; 2IQC; -.
DR   PDBsum; 7KZP; -.
DR   PDBsum; 7KZQ; -.
DR   PDBsum; 7KZR; -.
DR   PDBsum; 7KZS; -.
DR   PDBsum; 7KZT; -.
DR   PDBsum; 7KZV; -.
DR   AlphaFoldDB; Q9NPI8; -.
DR   EMDB; EMD-23085; -.
DR   EMDB; EMD-23086; -.
DR   EMDB; EMD-23087; -.
DR   EMDB; EMD-23088; -.
DR   EMDB; EMD-23089; -.
DR   EMDB; EMD-23090; -.
DR   SMR; Q9NPI8; -.
DR   BioGRID; 108483; 26.
DR   ComplexPortal; CPX-6263; Fanconi anemia ubiquitin ligase complex.
DR   CORUM; Q9NPI8; -.
DR   IntAct; Q9NPI8; 12.
DR   MINT; Q9NPI8; -.
DR   STRING; 9606.ENSP00000330875; -.
DR   BindingDB; Q9NPI8; -.
DR   ChEMBL; CHEMBL2157856; -.
DR   MoonDB; Q9NPI8; Predicted.
DR   iPTMnet; Q9NPI8; -.
DR   PhosphoSitePlus; Q9NPI8; -.
DR   BioMuta; FANCF; -.
DR   DMDM; 23821547; -.
DR   EPD; Q9NPI8; -.
DR   jPOST; Q9NPI8; -.
DR   MassIVE; Q9NPI8; -.
DR   MaxQB; Q9NPI8; -.
DR   PaxDb; 9606-ENSP00000330875; -.
DR   PeptideAtlas; Q9NPI8; -.
DR   ProteomicsDB; 82022; -.
DR   Pumba; Q9NPI8; -.
DR   Antibodypedia; 25340; 229 antibodies from 27 providers.
DR   DNASU; 2188; -.
DR   Ensembl; ENST00000327470.6; ENSP00000330875.3; ENSG00000183161.6.
DR   GeneID; 2188; -.
DR   KEGG; hsa:2188; -.
DR   MANE-Select; ENST00000327470.6; ENSP00000330875.3; NM_022725.4; NP_073562.1.
DR   UCSC; uc001mql.2; human.
DR   AGR; HGNC:3587; -.
DR   CTD; 2188; -.
DR   DisGeNET; 2188; -.
DR   GeneCards; FANCF; -.
DR   GeneReviews; FANCF; -.
DR   HGNC; HGNC:3587; FANCF.
DR   HPA; ENSG00000183161; Low tissue specificity.
DR   MalaCards; FANCF; -.
DR   MIM; 603467; phenotype.
DR   MIM; 613897; gene.
DR   neXtProt; NX_Q9NPI8; -.
DR   OpenTargets; ENSG00000183161; -.
DR   Orphanet; 84; Fanconi anemia.
DR   PharmGKB; PA28001; -.
DR   VEuPathDB; HostDB:ENSG00000183161; -.
DR   eggNOG; ENOG502S2Z3; Eukaryota.
DR   GeneTree; ENSGT00390000005623; -.
DR   HOGENOM; CLU_770617_0_0_1; -.
DR   InParanoid; Q9NPI8; -.
DR   OMA; LQWARYL; -.
DR   OrthoDB; 2901228at2759; -.
DR   PhylomeDB; Q9NPI8; -.
DR   TreeFam; TF332957; -.
DR   PathwayCommons; Q9NPI8; -.
DR   Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR   Reactome; R-HSA-9833482; PKR-mediated signaling.
DR   SignaLink; Q9NPI8; -.
DR   SIGNOR; Q9NPI8; -.
DR   BioGRID-ORCS; 2188; 153 hits in 1164 CRISPR screens.
DR   ChiTaRS; FANCF; human.
DR   EvolutionaryTrace; Q9NPI8; -.
DR   GeneWiki; FANCF; -.
DR   GenomeRNAi; 2188; -.
DR   Pharos; Q9NPI8; Tchem.
DR   PRO; PR:Q9NPI8; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q9NPI8; Protein.
DR   Bgee; ENSG00000183161; Expressed in secondary oocyte and 157 other cell types or tissues.
DR   ExpressionAtlas; Q9NPI8; baseline and differential.
DR   GO; GO:0000785; C:chromatin; IDA:ComplexPortal.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0043240; C:Fanconi anaemia nuclear complex; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0006974; P:DNA damage response; IBA:GO_Central.
DR   GO; GO:0036297; P:interstrand cross-link repair; NAS:ComplexPortal.
DR   DisProt; DP02782; -.
DR   Gene3D; 1.25.40.490; -; 1.
DR   InterPro; IPR035428; FANCF.
DR   InterPro; IPR038505; FANCF_C_sf.
DR   PANTHER; PTHR14449:SF2; FANCONI ANEMIA GROUP F PROTEIN; 1.
DR   PANTHER; PTHR14449; FANCONI ANEMIA GROUP F PROTEIN FANCF; 1.
DR   Pfam; PF11107; FANCF; 1.
DR   Genevisible; Q9NPI8; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; DNA damage; DNA repair;
KW   Fanconi anemia; Nucleus; Reference proteome.
FT   CHAIN           1..374
FT                   /note="Fanconi anemia group F protein"
FT                   /id="PRO_0000087188"
FT   VARIANT         295
FT                   /note="V -> I (in dbSNP:rs7103293)"
FT                   /id="VAR_050988"
FT   VARIANT         320
FT                   /note="P -> L (in dbSNP:rs45451294)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_022270"
FT   MUTAGEN         209
FT                   /note="L->R: Reduced monoubiquitination of FANCD2."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   MUTAGEN         251
FT                   /note="F->R: Reduced monoubiquitination of FANCD2."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   MUTAGEN         287
FT                   /note="Y->A: Strongly reduced monoubiquitination of FANCD2;
FT                   when associated with A-289; A-339; A-341 and A-344."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   MUTAGEN         289
FT                   /note="L->A: Strongly reduced monoubiquitination of FANCD2;
FT                   when associated with A-287; A-339; A-341 and A-344."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   MUTAGEN         339
FT                   /note="F->A: Strongly reduced monoubiquitination of FANCD2;
FT                   when associated with A-287; A-289; A-341 and A-344."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   MUTAGEN         341
FT                   /note="V->A: Strongly reduced monoubiquitination of FANCD2;
FT                   when associated with A-287; A-289; A-339 and A-344."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   MUTAGEN         344
FT                   /note="L->A: Strongly reduced monoubiquitination of FANCD2;
FT                   when associated with A-287; A-289; A-339 and A-341."
FT                   /evidence="ECO:0000269|PubMed:17082180"
FT   HELIX           160..174
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           186..195
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           198..209
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           235..243
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           245..254
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           257..266
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           268..270
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           271..283
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   STRAND          286..288
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   TURN            289..292
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   STRAND          293..295
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           304..315
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           319..335
FT                   /evidence="ECO:0007829|PDB:2IQC"
FT   HELIX           346..354
FT                   /evidence="ECO:0007829|PDB:2IQC"
SQ   SEQUENCE   374 AA;  42254 MW;  1F295CD1FBE6ED7D CRC64;
     MESLLQHLDR FSELLAVSST TYVSTWDPAT VRRALQWARY LRHIHRRFGR HGPIRTALER
     RLHNQWRQEG GFGRGPVPGL ANFQALGHCD VLLSLRLLEN RALGDAARYH LVQQLFPGPG
     VRDADEETLQ ESLARLARRR SAVHMLRFNG YRENPNLQED SLMKTQAELL LERLQEVGKA
     EAERPARFLS SLWERLPQNN FLKVIAVALL QPPLSRRPQE ELEPGIHKSP GEGSQVLVHW
     LLGNSEVFAA FCRALPAGLL TLVTSRHPAL SPVYLGLLTD WGQRLHYDLQ KGIWVGTESQ
     DVPWEELHNR FQSLCQAPPP LKDKVLTALE TCKAQDGDFE VPGLSIWTDL LLALRSGAFR
     KRQVLGLSAG LSSV
//