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 27-MAR-2024, entry version 182. 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; P49736: MCM2; NbExp=5; IntAct=EBI-3957237, EBI-374819; 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; 65. DR ComplexPortal; CPX-6266; Fanconi anemia FANCM-FAAP24-MHF anchoring complex. DR CORUM; Q8IYD8; -. DR DIP; DIP-43972N; -. DR IntAct; Q8IYD8; 46. DR MINT; Q8IYD8; -. DR STRING; 9606.ENSP00000267430; -. DR GlyCosmos; Q8IYD8; 1 site, 1 glycan. DR GlyGen; Q8IYD8; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000267430; -. DR PeptideAtlas; Q8IYD8; -. DR ProteomicsDB; 3447; -. DR ProteomicsDB; 71158; -. [Q8IYD8-1] DR ProteomicsDB; 71159; -. [Q8IYD8-2] DR Antibodypedia; 23452; 236 antibodies from 30 providers. DR DNASU; 57697; -. DR Ensembl; ENST00000267430.10; ENSP00000267430.5; ENSG00000187790.12. [Q8IYD8-1] DR Ensembl; ENST00000542564.6; ENSP00000442493.2; ENSG00000187790.12. [Q8IYD8-3] DR Ensembl; ENST00000556036.6; ENSP00000450596.1; ENSG00000187790.12. [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 AGR; HGNC:23168; -. DR CTD; 57697; -. DR DisGeNET; 57697; -. DR GeneCards; FANCM; -. DR GeneReviews; FANCM; -. DR HGNC; HGNC:23168; FANCM. DR HPA; ENSG00000187790; Tissue enhanced (testis). 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; MQMLPND; -. DR OrthoDB; 12149at2759; -. DR PhylomeDB; Q8IYD8; -. DR TreeFam; TF324610; -. DR PathwayCommons; Q8IYD8; -. DR Reactome; R-HSA-6783310; Fanconi Anemia Pathway. DR Reactome; R-HSA-9833482; PKR-mediated signaling. DR SignaLink; Q8IYD8; -. DR SIGNOR; Q8IYD8; -. DR BioGRID-ORCS; 57697; 160 hits in 1170 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 136 other cell types or tissues. DR ExpressionAtlas; Q8IYD8; baseline and differential. DR GO; GO:0000785; C:chromatin; IDA:ComplexPortal. DR GO; GO:0005829; C:cytosol; TAS:Reactome. 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:0000712; P:resolution of meiotic recombination intermediates; IMP:UniProtKB. DR CDD; cd18033; DEXDc_FANCM; 1. DR CDD; cd12091; FANCM_ID; 1. DR CDD; cd18801; SF2_C_FANCM_Hef; 1. DR CDD; cd20077; XPF_nuclease_FANCM; 1. DR Gene3D; 3.40.50.10130; -; 1. DR Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1. DR Gene3D; 1.20.1320.20; hef helicase domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR IDEAL; IID00484; -. DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom. DR InterPro; IPR006166; ERCC4_domain. DR InterPro; IPR031879; FANCM-MHF-bd. DR InterPro; IPR039686; FANCM/Mph1-like_ID. DR InterPro; IPR044749; FANCM_DEXDc. 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 InterPro; IPR047418; XPF_nuclease_FANCM. DR PANTHER; PTHR14025; FANCONI ANEMIA GROUP M FANCM FAMILY MEMBER; 1. DR PANTHER; PTHR14025:SF20; FANCONI ANEMIA GROUP M PROTEIN; 1. DR Pfam; PF00270; DEAD; 1. DR Pfam; PF02732; ERCC4; 1. DR Pfam; PF16783; FANCM-MHF_bd; 1. DR Pfam; PF00271; Helicase_C; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00891; ERCC4; 1. DR SMART; SM00490; HELICc; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF52980; Restriction endonuclease-like; 1. DR SUPFAM; SSF47781; RuvA domain 2-like; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR Genevisible; Q8IYD8; HS. 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; uncertain 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 FT FAAP24-binding, nor on FANCD2 and FANCI FT 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 //