FANCF_HUMAN
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 03-AUG-2022, entry version 171.
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="http://atlasgeneticsoncology.org/Genes/FANCFID294.html";
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 SMR; Q9NPI8; -.
DR BioGRID; 108483; 22.
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; Q9NPI8; -.
DR PeptideAtlas; Q9NPI8; -.
DR PRIDE; Q9NPI8; -.
DR ProteomicsDB; 82022; -.
DR Antibodypedia; 25340; 195 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 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; 1404593at2759; -.
DR PhylomeDB; Q9NPI8; -.
DR TreeFam; TF332957; -.
DR PathwayCommons; Q9NPI8; -.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; Q9NPI8; -.
DR SIGNOR; Q9NPI8; -.
DR BioGRID-ORCS; 2188; 133 hits in 1080 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 155 other tissues.
DR ExpressionAtlas; Q9NPI8; baseline and differential.
DR Genevisible; Q9NPI8; HS.
DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal.
DR GO; GO:0043240; C:Fanconi anaemia nuclear complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IBA:GO_Central.
DR GO; GO:0036297; P:interstrand cross-link repair; IC:ComplexPortal.
DR GO; GO:0006513; P:protein monoubiquitination; IDA:ComplexPortal.
DR DisProt; DP02782; -.
DR Gene3D; 1.25.40.490; -; 1.
DR InterPro; IPR035428; FANCF.
DR InterPro; IPR038505; FANCF_C_sf.
DR PANTHER; PTHR14449; PTHR14449; 1.
DR Pfam; PF11107; FANCF; 1.
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
