FANCM_HUMAN
ID FANCM_HUMAN Reviewed; 2048 AA.
AC Q8IYD8; B2RTQ9; Q3YFH9; Q8N9X6; Q9HCH6;
DT 25-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Fanconi anemia group M protein;
DE Short=Protein FACM;
DE EC=3.6.4.13 {ECO:0000269|PubMed:16116422, ECO:0000269|PubMed:17289582, ECO:0000269|PubMed:19423727, ECO:0000269|PubMed:20347429};
DE AltName: Full=ATP-dependent RNA helicase FANCM;
DE AltName: Full=Fanconi anemia-associated polypeptide of 250 kDa;
DE Short=FAAP250 {ECO:0000303|PubMed:16116422};
DE AltName: Full=Protein Hef ortholog {ECO:0000303|PubMed:16116422, ECO:0000303|PubMed:16116434};
GN Name=FANCM; Synonyms=KIAA1596;
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] (ISOFORM 1), IDENTIFICATION BY MASS
RP SPECTROMETRY, IDENTIFICATION IN THE FA CORE COMPLEX, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION, FUNCTION, MUTAGENESIS OF LYS-117, AND CATALYTIC ACTIVITY.
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Testis;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 794-2048 (ISOFORM 1), AND
RP VARIANTS LEU-878 AND ALA-1812.
RC TISSUE=Brain;
RX PubMed=10997877; DOI=10.1093/dnares/7.4.271;
RA Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVIII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:273-281(2000).
RN [6]
RP FUNCTION, DNA-BINDING, MUTAGENESIS OF GLY-116, AND IDENTIFICATION IN THE FA
RP CORE COMPLEX.
RX PubMed=16116434; DOI=10.1038/nsmb981;
RA Mosedale G., Niedzwiedz W., Alpi A., Perrina F., Pereira-Leal J.B.,
RA Johnson M., Langevin F., Pace P., Patel K.J.;
RT "The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-
RT suppressor pathway.";
RL Nat. Struct. Mol. Biol. 12:763-771(2005).
RN [7]
RP IDENTIFICATION IN THE FA CORE COMPLEX, INTERACTION WITH FAAP24, MUTAGENESIS
RP OF LYS-117, AND CATALYTIC ACTIVITY.
RX PubMed=17289582; DOI=10.1016/j.molcel.2007.01.003;
RA Ciccia A., Ling C., Coulthard R., Yan Z., Xue Y., Meetei A.R.,
RA Laghmani el H., Joenje H., McDonald N., de Winter J.P., Wang W., West S.C.;
RT "Identification of FAAP24, a Fanconi anemia core complex protein that
RT interacts with FANCM.";
RL Mol. Cell 25:331-343(2007).
RN [8]
RP FUNCTION, MUTAGENESIS OF LYS-117, AND CATALYTIC ACTIVITY.
RX PubMed=19423727; DOI=10.1182/blood-2009-02-207811;
RA Singh T.R., Bakker S.T., Agarwal S., Jansen M., Grassman E., Godthelp B.C.,
RA Ali A.M., Du C.H., Rooimans M.A., Fan Q., Wahengbam K., Steltenpool J.,
RA Andreassen P.R., Williams D.A., Joenje H., de Winter J.P., Meetei A.R.;
RT "Impaired FANCD2 monoubiquitination and hypersensitivity to camptothecin
RT uniquely characterize Fanconi anemia complementation group M.";
RL Blood 114:174-180(2009).
RN [9]
RP IDENTIFICATION IN THE FA CORE COMPLEX, IDENTIFICATION IN THE BRAFT COMPLEX,
RP INTERACTION WITH CENPS; CENPX AND FAAP24, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=20347428; DOI=10.1016/j.molcel.2010.01.039;
RA Yan Z., Delannoy M., Ling C., Daee D., Osman F., Muniandy P.A., Shen X.,
RA Oostra A.B., Du H., Steltenpool J., Lin T., Schuster B., Decaillet C.,
RA Stasiak A., Stasiak A.Z., Stone S., Hoatlin M.E., Schindler D.,
RA Woodcock C.L., Joenje H., Sen R., de Winter J.P., Li L., Seidman M.M.,
RA Whitby M.C., Myung K., Constantinousend A., Wang W.;
RT "A histone-fold complex and FANCM form a conserved DNA-remodeling complex
RT to maintain genome stability.";
RL Mol. Cell 37:865-878(2010).
RN [10]
RP IDENTIFICATION IN THE FA CORE COMPLEX, INTERACTION WITH CENPS, SUBCELLULAR
RP LOCATION, FUNCTION, MUTAGENESIS OF LYS-117, AND CATALYTIC ACTIVITY.
RX PubMed=20347429; DOI=10.1016/j.molcel.2010.01.036;
RA Singh T.R., Saro D., Ali A.M., Zheng X.-F., Du C., Killen M.W.,
RA Sachpatzidis A., Wahengbam K., Pierce A.J., Xiong Y., Sung P., Meetei A.R.;
RT "MHF1-MHF2, a histone-fold-containing protein complex, participates in the
RT Fanconi anemia pathway via FANCM.";
RL Mol. Cell 37:879-886(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34; SER-1673 AND SER-1674,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP INVOLVEMENT IN POF15, VARIANT POF15 1701-GLN--ILE-2048 DEL, AND
RP CHARACTERIZATION OF VARIANT POF15 1701-GLN--ILE-2048 DEL.
RX PubMed=29231814; DOI=10.7554/elife.30490;
RA Fouquet B., Pawlikowska P., Caburet S., Guigon C., Maekinen M., Tanner L.,
RA Hietala M., Urbanska K., Bellutti L., Legois B., Bessieres B., Gougeon A.,
RA Benachi A., Livera G., Rosselli F., Veitia R.A., Misrahi M.;
RT "A homozygous FANCM mutation underlies a familial case of non-syndromic
RT primary ovarian insufficiency.";
RL Elife 6:0-0(2017).
RN [13]
RP TISSUE SPECIFICITY, INVOLVEMENT IN SPGF28, AND VARIANTS SPGF28
RP 1701-GLN--ILE-2048 DEL AND 1931-ARG--ILE-2048 DEL.
RX PubMed=30075111; DOI=10.1016/j.ajhg.2018.07.005;
RG GEMINI Consortium;
RA Kasak L., Punab M., Nagirnaja L., Grigorova M., Minajeva A., Lopes A.M.,
RA Punab A.M., Aston K.I., Carvalho F., Laasik E., Smith L.B., Conrad D.F.,
RA Laan M.;
RT "Bi-allelic recessive loss-of-function variants in FANCM cause non-
RT obstructive azoospermia.";
RL Am. J. Hum. Genet. 103:200-212(2018).
RN [14]
RP INVOLVEMENT IN SPGF28.
RX PubMed=29895858; DOI=10.1038/s41436-018-0015-7;
RA Yin H., Ma H., Hussain S., Zhang H., Xie X., Jiang L., Jiang X., Iqbal F.,
RA Bukhari I., Jiang H., Ali A., Zhong L., Li T., Fan S., Zhang B., Gao J.,
RA Li Y., Nazish J., Khan T., Khan M., Zubair M., Hao Q., Fang H., Huang J.,
RA Huleihel M., Sha J., Pandita T.K., Zhang Y., Shi Q.;
RT "A homozygous FANCM frameshift pathogenic variant causes male
RT infertility.";
RL Genet. Med. 21:62-70(2019).
RN [15]
RP ERRATUM OF PUBMED:29895858.
RX PubMed=30158692; DOI=10.1038/s41436-018-0127-0;
RA Yin H., Ma H., Hussain S., Zhang H., Xie X., Jiang L., Jiang X., Iqbal F.,
RA Bukhari I., Jiang H., Ali A., Zhong L., Li T., Fan S., Zhang B., Gao J.,
RA Li Y., Nazish J., Khan T., Khan M., Zubair M., Hao Q., Fang H., Huang J.,
RA Huleihel M., Sha J., Pandita T.K., Zhang Y., Shi Q.;
RL Genet. Med. 21:266-266(2019).
CC -!- FUNCTION: DNA-dependent ATPase component of the Fanconi anemia (FA)
CC core complex (PubMed:16116422). Required for the normal activation of
CC the FA pathway, leading to monoubiquitination of the FANCI-FANCD2
CC complex in response to DNA damage, cellular resistance to DNA cross-
CC linking drugs, and prevention of chromosomal breakage (PubMed:16116422,
CC PubMed:19423727, PubMed:20347428, PubMed:20347429, PubMed:29231814). In
CC complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-
CC structured DNA (fsDNA) and Holliday junction substrates
CC (PubMed:20347428, PubMed:20347429). Its ATP-dependent DNA branch
CC migration activity can process branched DNA structures such as a
CC movable replication fork. This activity is strongly stimulated in the
CC presence of CENPS and CENPX (PubMed:20347429). In complex with FAAP24,
CC efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and
CC 3'-flap substrates (PubMed:17289582). In vitro, on its own, strongly
CC binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA
CC (PubMed:16116434). {ECO:0000269|PubMed:16116422,
CC ECO:0000269|PubMed:16116434, ECO:0000269|PubMed:17289582,
CC ECO:0000269|PubMed:19423727, ECO:0000269|PubMed:20347428,
CC ECO:0000269|PubMed:20347429, ECO:0000269|PubMed:29231814}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000269|PubMed:16116422, ECO:0000269|PubMed:17289582,
CC ECO:0000269|PubMed:19423727, ECO:0000269|PubMed:20347429};
CC -!- SUBUNIT: Component of the Fanconi anemia (FA) core complex, which
CC consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG,
CC FANCL, FANCM, FAAP24 and FAAP100 (PubMed:16116422, PubMed:16116434,
CC PubMed:17289582). The FA core complex associates with Bloom syndrome
CC (BLM) complex, which consists of at least BLM, DNA topoisomerase 3-
CC alpha/TOP3A, RMI1/BLAP75, RPA1/RPA70 and RPA2/RPA32. This supercomplex
CC between FA and BLM complexes has been called BRAFT (PubMed:20347428).
CC Forms a discrete complex with CENPS and CENPX, called FANCM-MHF; this
CC interaction stimulates DNA binding and replication fork remodeling by
CC FANCM and stabilizes the binding partners (PubMed:20347428,
CC PubMed:20347429). Forms a heterodimer with FAAP24; this interaction
CC increases FANCM single-stranded DNA-binding activity (PubMed:17289582,
CC PubMed:20347428). {ECO:0000269|PubMed:16116422,
CC ECO:0000269|PubMed:16116434, ECO:0000269|PubMed:17289582,
CC ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429}.
CC -!- INTERACTION:
CC Q8IYD8; O95208-2: EPN2; NbExp=3; IntAct=EBI-3957237, EBI-12135243;
CC Q8IYD8; Q9BTP7: FAAP24; NbExp=10; IntAct=EBI-3957237, EBI-1045650;
CC Q8IYD8; P14373: TRIM27; NbExp=3; IntAct=EBI-3957237, EBI-719493;
CC Q8IYD8-1; Q9BTP7: FAAP24; NbExp=2; IntAct=EBI-16067666, EBI-1045650;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16116422,
CC ECO:0000269|PubMed:20347428, ECO:0000269|PubMed:20347429,
CC ECO:0000269|PubMed:29231814}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8IYD8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8IYD8-2; Sequence=VSP_015989, VSP_015990;
CC Name=3;
CC IsoId=Q8IYD8-3; Sequence=VSP_054504;
CC -!- TISSUE SPECIFICITY: Expressed in germ cells of fetal and adult ovaries.
CC In fetal ovaries, it is present in oogonia but expression is stronger
CC in pachytene stage oocytes. Expressed in oocytes arrested at the
CC diplotene stage of prophase I during the last trimester of pregnancy
CC and in adults (PubMed:29231814). Expressed in the testis
CC (PubMed:30075111). {ECO:0000269|PubMed:29231814,
CC ECO:0000269|PubMed:30075111}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout ovarian development (5-32
CC weeks post-fertilization (wpf)). Expression tends to be higher at 14
CC and 17 wpf. {ECO:0000269|PubMed:29231814}.
CC -!- PTM: Phosphorylated; hyperphosphorylated in response to genotoxic
CC stress. {ECO:0000269|PubMed:16116422}.
CC -!- DISEASE: Spermatogenic failure 28 (SPGF28) [MIM:618086]: An autosomal
CC recessive infertility disorder caused by spermatogenesis defects that
CC result in oligoasthenospermia or non-obstructive azoospermia.
CC {ECO:0000269|PubMed:29895858, ECO:0000269|PubMed:30075111}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Premature ovarian failure 15 (POF15) [MIM:618096]: An ovarian
CC disorder defined as the cessation of ovarian function under the age of
CC 40 years. It is characterized by oligomenorrhea or amenorrhea, in the
CC presence of elevated levels of serum gonadotropins and low estradiol.
CC {ECO:0000269|PubMed:29231814}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DEAH subfamily.
CC FANCM sub-subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB13422.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Fanconi Anemia Mutation Database;
CC URL="https://www2.rockefeller.edu/fanconi/genes/jumpm";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DQ140356; AAZ53290.1; -; mRNA.
DR EMBL; AK093422; BAC04159.1; -; mRNA.
DR EMBL; AL121809; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC036056; AAH36056.1; -; mRNA.
DR EMBL; BC140776; AAI40777.1; -; mRNA.
DR EMBL; BC144511; AAI44512.1; -; mRNA.
DR EMBL; AB046816; BAB13422.1; ALT_SEQ; mRNA.
DR CCDS; CCDS32070.1; -. [Q8IYD8-1]
DR CCDS; CCDS76677.1; -. [Q8IYD8-3]
DR CCDS; CCDS81802.1; -. [Q8IYD8-2]
DR RefSeq; NP_001295062.1; NM_001308133.1. [Q8IYD8-3]
DR RefSeq; NP_001295063.1; NM_001308134.1. [Q8IYD8-2]
DR RefSeq; NP_065988.1; NM_020937.3. [Q8IYD8-1]
DR PDB; 4BXO; X-ray; 2.15 A; A=1798-2048.
DR PDB; 4DAY; X-ray; 3.30 A; C=1218-1251.
DR PDB; 4DRB; X-ray; 2.63 A; C/F/I=661-800.
DR PDB; 4E45; X-ray; 2.00 A; E/J/O=667-800.
DR PDB; 4M6W; X-ray; 2.90 A; A=1813-2031.
DR PDBsum; 4BXO; -.
DR PDBsum; 4DAY; -.
DR PDBsum; 4DRB; -.
DR PDBsum; 4E45; -.
DR PDBsum; 4M6W; -.
DR AlphaFoldDB; Q8IYD8; -.
DR SMR; Q8IYD8; -.
DR BioGRID; 121722; 64.
DR ComplexPortal; CPX-6266; Fanconi anemia FANCM-FAAP24-MHF anchoring complex.
DR CORUM; Q8IYD8; -.
DR DIP; DIP-43972N; -.
DR IntAct; Q8IYD8; 38.
DR MINT; Q8IYD8; -.
DR STRING; 9606.ENSP00000267430; -.
DR GlyGen; Q8IYD8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q8IYD8; -.
DR PhosphoSitePlus; Q8IYD8; -.
DR BioMuta; FANCM; -.
DR DMDM; 78099254; -.
DR EPD; Q8IYD8; -.
DR jPOST; Q8IYD8; -.
DR MassIVE; Q8IYD8; -.
DR MaxQB; Q8IYD8; -.
DR PaxDb; Q8IYD8; -.
DR PeptideAtlas; Q8IYD8; -.
DR PRIDE; Q8IYD8; -.
DR ProteomicsDB; 3447; -.
DR ProteomicsDB; 71158; -. [Q8IYD8-1]
DR ProteomicsDB; 71159; -. [Q8IYD8-2]
DR Antibodypedia; 23452; 223 antibodies from 30 providers.
DR DNASU; 57697; -.
DR Ensembl; ENST00000267430.10; ENSP00000267430.5; ENSG00000187790.11. [Q8IYD8-1]
DR Ensembl; ENST00000542564.6; ENSP00000442493.2; ENSG00000187790.11. [Q8IYD8-3]
DR Ensembl; ENST00000556036.5; ENSP00000450596.1; ENSG00000187790.11. [Q8IYD8-2]
DR GeneID; 57697; -.
DR KEGG; hsa:57697; -.
DR MANE-Select; ENST00000267430.10; ENSP00000267430.5; NM_020937.4; NP_065988.1.
DR UCSC; uc001wwc.3; human. [Q8IYD8-1]
DR CTD; 57697; -.
DR DisGeNET; 57697; -.
DR GeneCards; FANCM; -.
DR GeneReviews; FANCM; -.
DR HGNC; HGNC:23168; FANCM.
DR HPA; ENSG00000187790; Low tissue specificity.
DR MalaCards; FANCM; -.
DR MIM; 609644; gene.
DR MIM; 618086; phenotype.
DR MIM; 618096; phenotype.
DR neXtProt; NX_Q8IYD8; -.
DR OpenTargets; ENSG00000187790; -.
DR Orphanet; 84; Fanconi anemia.
DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation.
DR PharmGKB; PA134943156; -.
DR VEuPathDB; HostDB:ENSG00000187790; -.
DR eggNOG; KOG0354; Eukaryota.
DR eggNOG; KOG0442; Eukaryota.
DR GeneTree; ENSGT00940000156480; -.
DR HOGENOM; CLU_002513_3_2_1; -.
DR InParanoid; Q8IYD8; -.
DR OMA; EQPWDRE; -.
DR OrthoDB; 989616at2759; -.
DR PhylomeDB; Q8IYD8; -.
DR TreeFam; TF324610; -.
DR PathwayCommons; Q8IYD8; -.
DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway.
DR SignaLink; Q8IYD8; -.
DR SIGNOR; Q8IYD8; -.
DR BioGRID-ORCS; 57697; 142 hits in 1092 CRISPR screens.
DR ChiTaRS; FANCM; human.
DR GenomeRNAi; 57697; -.
DR Pharos; Q8IYD8; Tbio.
DR PRO; PR:Q8IYD8; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q8IYD8; protein.
DR Bgee; ENSG00000187790; Expressed in sperm and 134 other tissues.
DR ExpressionAtlas; Q8IYD8; baseline and differential.
DR Genevisible; Q8IYD8; HS.
DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal.
DR GO; GO:0071821; C:FANCM-MHF complex; IDA:UniProtKB.
DR GO; GO:0043240; C:Fanconi anaemia nuclear complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0043138; F:3'-5' DNA helicase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0000400; F:four-way junction DNA binding; IBA:GO_Central.
DR GO; GO:0009378; F:four-way junction helicase activity; IBA:GO_Central.
DR GO; GO:0004518; F:nuclease activity; IEA:InterPro.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0045003; P:double-strand break repair via synthesis-dependent strand annealing; IBA:GO_Central.
DR GO; GO:0036297; P:interstrand cross-link repair; IDA:ComplexPortal.
DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; IMP:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; IMP:UniProtKB.
DR GO; GO:0071932; P:replication fork reversal; IBA:GO_Central.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IMP:UniProtKB.
DR CDD; cd18033; DEXDc_FANCM; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR IDEAL; IID00484; -.
DR InterPro; IPR006166; ERCC4_domain.
DR InterPro; IPR031879; FANCM-MHF-bd.
DR InterPro; IPR039686; FANCM/Mph1-like.
DR InterPro; IPR044749; FANCM_DEXDc.
DR InterPro; IPR006935; Helicase/UvrB_N.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011335; Restrct_endonuc-II-like.
DR InterPro; IPR010994; RuvA_2-like.
DR PANTHER; PTHR14025:SF20; PTHR14025:SF20; 1.
DR Pfam; PF02732; ERCC4; 1.
DR Pfam; PF16783; FANCM-MHF_bd; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF04851; ResIII; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00891; ERCC4; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF47781; SSF47781; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF52980; SSF52980; 1.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Disease variant;
KW DNA damage; DNA repair; DNA-binding; Helicase; Hydrolase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Premature ovarian failure;
KW Reference proteome.
FT CHAIN 1..2048
FT /note="Fanconi anemia group M protein"
FT /id="PRO_0000055176"
FT DOMAIN 98..266
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 452..627
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 661..800
FT /note="Interaction with CENPS/CENPSX"
FT /evidence="ECO:0000269|PubMed:20347428"
FT REGION 1433..1476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1518..1540
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1668..1809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1727..2048
FT /note="Interaction with FAAP24"
FT /evidence="ECO:0000269|PubMed:17289582"
FT MOTIF 214..217
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT COMPBIAS 1..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1444..1463
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1518..1539
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1668..1683
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1684..1767
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1783..1803
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 111..118
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1673
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1674
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 228..253
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054504"
FT VAR_SEQ 669
FT /note="M -> K (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015989"
FT VAR_SEQ 670..2048
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_015990"
FT VARIANT 175
FT /note="S -> F (in dbSNP:rs10138997)"
FT /id="VAR_023697"
FT VARIANT 208
FT /note="I -> M (in dbSNP:rs45547534)"
FT /id="VAR_061827"
FT VARIANT 878
FT /note="V -> L (in dbSNP:rs1367580)"
FT /evidence="ECO:0000269|PubMed:10997877"
FT /id="VAR_023698"
FT VARIANT 1701..2048
FT /note="Missing (in POF15 and SPGF28; loss-of-function
FT mutation resulting in impaired FANCD2 monoubiquitination in
FT response to DNA damage)"
FT /evidence="ECO:0000269|PubMed:29231814,
FT ECO:0000269|PubMed:30075111"
FT /id="VAR_081138"
FT VARIANT 1812
FT /note="P -> A (in dbSNP:rs3736772)"
FT /evidence="ECO:0000269|PubMed:10997877"
FT /id="VAR_023699"
FT VARIANT 1931..2048
FT /note="Missing (in SPGF28; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30075111"
FT /id="VAR_081139"
FT MUTAGEN 116
FT /note="G->A: Reduces ATPase activity."
FT /evidence="ECO:0000269|PubMed:16116434"
FT MUTAGEN 117
FT /note="K->R: Abolishes ATPase activity. Loss of DNA branch
FT migration activity, even in the presence of CENPS/CENPX.
FT Loss of cross-linker resistance. No effect on FAAP24-
FT binding, nor on FANCD2 and FANCI monoubiquitination."
FT /evidence="ECO:0000269|PubMed:16116422,
FT ECO:0000269|PubMed:17289582, ECO:0000269|PubMed:19423727,
FT ECO:0000269|PubMed:20347429"
FT CONFLICT 68
FT /note="L -> F (in Ref. 2; BAC04159)"
FT /evidence="ECO:0000305"
FT CONFLICT 1460
FT /note="I -> V (in Ref. 5; BAB13422)"
FT /evidence="ECO:0000305"
FT HELIX 682..691
FT /evidence="ECO:0007829|PDB:4E45"
FT STRAND 698..700
FT /evidence="ECO:0007829|PDB:4DRB"
FT STRAND 702..704
FT /evidence="ECO:0007829|PDB:4E45"
FT TURN 711..713
FT /evidence="ECO:0007829|PDB:4DRB"
FT STRAND 728..730
FT /evidence="ECO:0007829|PDB:4E45"
FT HELIX 737..739
FT /evidence="ECO:0007829|PDB:4E45"
FT STRAND 747..749
FT /evidence="ECO:0007829|PDB:4E45"
FT HELIX 753..768
FT /evidence="ECO:0007829|PDB:4E45"
FT HELIX 776..781
FT /evidence="ECO:0007829|PDB:4E45"
FT HELIX 782..784
FT /evidence="ECO:0007829|PDB:4E45"
FT HELIX 787..789
FT /evidence="ECO:0007829|PDB:4E45"
FT STRAND 1819..1823
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1826..1829
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1831..1838
FT /evidence="ECO:0007829|PDB:4BXO"
FT STRAND 1844..1848
FT /evidence="ECO:0007829|PDB:4BXO"
FT STRAND 1854..1856
FT /evidence="ECO:0007829|PDB:4M6W"
FT STRAND 1858..1867
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1868..1872
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1877..1888
FT /evidence="ECO:0007829|PDB:4BXO"
FT STRAND 1892..1899
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1916..1927
FT /evidence="ECO:0007829|PDB:4BXO"
FT STRAND 1931..1937
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1938..1954
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1970..1977
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1984..1993
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 1997..2001
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 2005..2012
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 2016..2027
FT /evidence="ECO:0007829|PDB:4BXO"
FT HELIX 2032..2034
FT /evidence="ECO:0007829|PDB:4BXO"
SQ SEQUENCE 2048 AA; 232191 MW; BDE0D6640B73C255 CRC64;
MSGRQRTLFQ TWGSSISRSS GTPGCSSGTE RPQSPGSSKA PLPAAAEAQL ESDDDVLLVA
AYEAERQLCL ENGGFCTSAG ALWIYPTNCP VRDYQLHISR AALFCNTLVC LPTGLGKTFI
AAVVMYNFYR WFPSGKVVFM APTKPLVTQQ IEACYQVMGI PQSHMAEMTG STQASTRKEI
WCSKRVLFLT PQVMVNDLSR GACPAAEIKC LVIDEAHKAL GNYAYCQVVR ELVKYTNHFR
ILALSATPGS DIKAVQQVIT NLLIGQIELR SEDSPDILTY SHERKVEKLI VPLGEELAAI
QKTYIQILES FARSLIQRNV LMRRDIPNLT KYQIILARDQ FRKNPSPNIV GIQQGIIEGE
FAICISLYHG YELLQQMGMR SLYFFLCGIM DGTKGMTRSK NELGRNEDFM KLYNHLECMF
ARTRSTSANG ISAIQQGDKN KKFVYSHPKL KKLEEVVIEH FKSWNAENTT EKKRDETRVM
IFSSFRDSVQ EIAEMLSQHQ PIIRVMTFVG HASGKSTKGF TQKEQLEVVK QFRDGGYNTL
VSTCVGEEGL DIGEVDLIIC FDSQKSPIRL VQRMGRTGRK RQGRIVIILS EGREERIYNQ
SQSNKRSIYK AISSNRQVLH FYQRSPRMVP DGINPKLHKM FITHGVYEPE KPSRNLQRKS
SIFSYRDGMR QSSLKKDWFL SEEEFKLWNR LYRLRDSDEI KEITLPQVQF SSLQNEENKP
AQESTTGIHQ LSLSEWRLWQ DHPLPTHQVD HSDRCRHFIG LMQMIEGMRH EEGECSYELE
VESYLQMEDV TSTFIAPRNE SNNLASDTFI THKKSSFIKN INQGSSSSVI ESDEECAEIV
KQTHIKPTKI VSLKKKVSKE IKKDQLKKEN NHGIIDSVDN DRNSTVENIF QEDLPNDKRT
SDTDEIAATC TINENVIKEP CVLLTECQFT NKSTSSLAGN VLDSGYNSFN DEKSVSSNLF
LPFEEELYIV RTDDQFYNCH SLTKEVLANV ERFLSYSPPP LSGLSDLEYE IAKGTALENL
LFLPCAEHLR SDKCTCLLSH SAVNSQQNLE LNSLKCINYP SEKSCLYDIP NDNISDEPSL
CDCDVHKHNQ NENLVPNNRV QIHRSPAQNL VGENNHDVDN SDLPVLSTDQ DESLLLFEDV
NTEFDDVSLS PLNSKSESLP VSDKTAISET PLVSQFLISD ELLLDNNSEL QDQITRDANS
FKSRDQRGVQ EEKVKNHEDI FDCSRDLFSV TFDLGFCSPD SDDEILEHTS DSNRPLDDLY
GRYLEIKEIS DANYVSNQAL IPRDHSKNFT SGTVIIPSNE DMQNPNYVHL PLSAAKNEEL
LSPGYSQFSL PVQKKVMSTP LSKSNTLNSF SKIRKEILKT PDSSKEKVNL QRFKEALNST
FDYSEFSLEK SKSSGPMYLH KSCHSVEDGQ LLTSNESEDD EIFRRKVKRA KGNVLNSPED
QKNSEVDSPL HAVKKRRFPI NRSELSSSDE SENFPKPCSQ LEDFKVCNGN ARRGIKVPKR
QSHLKHVARK FLDDEAELSE EDAEYVSSDE NDESENEQDS SLLDFLNDET QLSQAINDSE
MRAIYMKSLR SPMMNNKYKM IHKTHKNINI FSQIPEQDET YLEDSFCVDE EESCKGQSSE
EEVCVDFNLI TDDCFANSKK YKTRRAVMLK EMMEQNCAHS KKKLSRIILP DDSSEEENNV
NDKRESNIAV NPSTVKKNKQ QDHCLNSVPS GSSAQSKVRS TPRVNPLAKQ SKQTSLNLKD
TISEVSDFKP QNHNEVQSTT PPFTTVDSQK DCRKFPVPQK DGSALEDSST SGASCSKSRP
HLAGTHTSLR LPQEGKGTCI LVGGHEITSG LEVISSLRAI HGLQVEVCPL NGCDYIVSNR
MVVERRSQSE MLNSVNKNKF IEQIQHLQSM FERICVIVEK DREKTGDTSR MFRRTKSYDS
LLTTLIGAGI RILFSSCQEE TADLLKELSL VEQRKNVGIH VPTVVNSNKS EALQFYLSIP
NISYITALNM CHQFSSVKRM ANSSLQEISM YAQVTHQKAE EIYRYIHYVF DIQMLPNDLN
QDRLKSDI
