Reviewed, UniProtKB/Swiss-Prot Q8IYD8 (FANCM_HUMAN)

Names and origin

Protein names

Recommended name:
    Fanconi anemia group M protein
      Short name=Protein FACM
    EC=3.6.1.-
Alternative name(s):
    ATP-dependent RNA helicase FANCM
    Fanconi anemia-associated polypeptide of 250 kDa
      Short name=FAAP250
    Protein Hef ortholog

Gene names

Name:	FANCM
Synonyms:	KIAA1596

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	2048 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	ATPase required for FANCD2 ubiquitination, a key reaction in DNA repair. Binds to ssDNA but not to dsDNA. Ref.1 Ref.5
Subunit structure	Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9, FANCM and FAAP24. The complex is not found in FA patients. Interacts with FAAP24. Interacts with EME1. Ref.6
Subcellular location	Nucleus. Ref.1
Post-translational modification	Phosphorylated; hyperphosphorylated in response to genotoxic stress. Ref.1
Involvement in disease	Defects in FANCM are a cause of Fanconi anemia (FA) [MIM:227650]. FA is a genetically heterogeneous, autosomal recessive disorder characterized by progressive pancytopenia, a diverse assortment of congenital malformations, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage), and defective DNA repair. Ref.1 Ref.5 Ref.6
Sequence similarities	Belongs to the DEAD box helicase family. DEAH subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.
Sequence caution	The sequence BAB13422.1 differs from that shown. Reason: Miscellaneous discrepancy. Intron retention.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Fanconi anemia
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA repair Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro DNA binding Inferred from electronic annotation. Source: UniProtKB-KW nuclease activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8IYD8-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8IYD8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     669-669: M → K
     670-2048: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2048	2048	Fanconi anemia group M protein		PRO_0000055176
Regions
	Domain	98 – 266	169	Helicase ATP-binding
	Domain	452 – 627	176	Helicase C-terminal
	Nucleotide binding	111 – 118	8	ATP Probable
	Region	1727 – 2048	322	Interaction with FAAP24 and EME1
	Motif	214 – 217	4	DEAH box
Natural variations
	Alternative sequence	669	1	M → K in isoform 2.		VSP_015989
	Alternative sequence	670 – 2048	1379	Missing in isoform 2.		VSP_015990
	Natural variant	175	1	S → F: dbSNP rs10138997.		VAR_023697
	Natural variant	878	1	V → L: dbSNP rs1367580. Ref.4		VAR_023698
	Natural variant	1812	1	P → A: dbSNP rs3736772. Ref.4		VAR_023699
Experimental info
	Mutagenesis	116	1	G → A: Reduces ATPase activity. Ref.5
	Mutagenesis	117	1	K → R: Abolishes ATPase activity. Ref.1
	Sequence conflict	68	1	L → F in BAC04159. Ref.2
	Sequence conflict	1460	1	I → V in BAB13422. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 25, 2005. Version 2. Checksum: BDE0D6640B73C255	FASTA	2,048	232,191
	10 20 30 40 50 60 MSGRQRTLFQ TWGSSISRSS GTPGCSSGTE RPQSPGSSKA PLPAAAEAQL ESDDDVLLVA 70 80 90 100 110 120 AYEAERQLCL ENGGFCTSAG ALWIYPTNCP VRDYQLHISR AALFCNTLVC LPTGLGKTFI 130 140 150 160 170 180 AAVVMYNFYR WFPSGKVVFM APTKPLVTQQ IEACYQVMGI PQSHMAEMTG STQASTRKEI 190 200 210 220 230 240 WCSKRVLFLT PQVMVNDLSR GACPAAEIKC LVIDEAHKAL GNYAYCQVVR ELVKYTNHFR 250 260 270 280 290 300 ILALSATPGS DIKAVQQVIT NLLIGQIELR SEDSPDILTY SHERKVEKLI VPLGEELAAI 310 320 330 340 350 360 QKTYIQILES FARSLIQRNV LMRRDIPNLT KYQIILARDQ FRKNPSPNIV GIQQGIIEGE 370 380 390 400 410 420 FAICISLYHG YELLQQMGMR SLYFFLCGIM DGTKGMTRSK NELGRNEDFM KLYNHLECMF 430 440 450 460 470 480 ARTRSTSANG ISAIQQGDKN KKFVYSHPKL KKLEEVVIEH FKSWNAENTT EKKRDETRVM 490 500 510 520 530 540 IFSSFRDSVQ EIAEMLSQHQ PIIRVMTFVG HASGKSTKGF TQKEQLEVVK QFRDGGYNTL 550 560 570 580 590 600 VSTCVGEEGL DIGEVDLIIC FDSQKSPIRL VQRMGRTGRK RQGRIVIILS EGREERIYNQ 610 620 630 640 650 660 SQSNKRSIYK AISSNRQVLH FYQRSPRMVP DGINPKLHKM FITHGVYEPE KPSRNLQRKS 670 680 690 700 710 720 SIFSYRDGMR QSSLKKDWFL SEEEFKLWNR LYRLRDSDEI KEITLPQVQF SSLQNEENKP 730 740 750 760 770 780 AQESTTGIHQ LSLSEWRLWQ DHPLPTHQVD HSDRCRHFIG LMQMIEGMRH EEGECSYELE 790 800 810 820 830 840 VESYLQMEDV TSTFIAPRNE SNNLASDTFI THKKSSFIKN INQGSSSSVI ESDEECAEIV 850 860 870 880 890 900 KQTHIKPTKI VSLKKKVSKE IKKDQLKKEN NHGIIDSVDN DRNSTVENIF QEDLPNDKRT 910 920 930 940 950 960 SDTDEIAATC TINENVIKEP CVLLTECQFT NKSTSSLAGN VLDSGYNSFN DEKSVSSNLF 970 980 990 1000 1010 1020 LPFEEELYIV RTDDQFYNCH SLTKEVLANV ERFLSYSPPP LSGLSDLEYE IAKGTALENL 1030 1040 1050 1060 1070 1080 LFLPCAEHLR SDKCTCLLSH SAVNSQQNLE LNSLKCINYP SEKSCLYDIP NDNISDEPSL 1090 1100 1110 1120 1130 1140 CDCDVHKHNQ NENLVPNNRV QIHRSPAQNL VGENNHDVDN SDLPVLSTDQ DESLLLFEDV 1150 1160 1170 1180 1190 1200 NTEFDDVSLS PLNSKSESLP VSDKTAISET PLVSQFLISD ELLLDNNSEL QDQITRDANS 1210 1220 1230 1240 1250 1260 FKSRDQRGVQ EEKVKNHEDI FDCSRDLFSV TFDLGFCSPD SDDEILEHTS DSNRPLDDLY 1270 1280 1290 1300 1310 1320 GRYLEIKEIS DANYVSNQAL IPRDHSKNFT SGTVIIPSNE DMQNPNYVHL PLSAAKNEEL 1330 1340 1350 1360 1370 1380 LSPGYSQFSL PVQKKVMSTP LSKSNTLNSF SKIRKEILKT PDSSKEKVNL QRFKEALNST 1390 1400 1410 1420 1430 1440 FDYSEFSLEK SKSSGPMYLH KSCHSVEDGQ LLTSNESEDD EIFRRKVKRA KGNVLNSPED 1450 1460 1470 1480 1490 1500 QKNSEVDSPL HAVKKRRFPI NRSELSSSDE SENFPKPCSQ LEDFKVCNGN ARRGIKVPKR 1510 1520 1530 1540 1550 1560 QSHLKHVARK FLDDEAELSE EDAEYVSSDE NDESENEQDS SLLDFLNDET QLSQAINDSE 1570 1580 1590 1600 1610 1620 MRAIYMKSLR SPMMNNKYKM IHKTHKNINI FSQIPEQDET YLEDSFCVDE EESCKGQSSE 1630 1640 1650 1660 1670 1680 EEVCVDFNLI TDDCFANSKK YKTRRAVMLK EMMEQNCAHS KKKLSRIILP DDSSEEENNV 1690 1700 1710 1720 1730 1740 NDKRESNIAV NPSTVKKNKQ QDHCLNSVPS GSSAQSKVRS TPRVNPLAKQ SKQTSLNLKD 1750 1760 1770 1780 1790 1800 TISEVSDFKP QNHNEVQSTT PPFTTVDSQK DCRKFPVPQK DGSALEDSST SGASCSKSRP 1810 1820 1830 1840 1850 1860 HLAGTHTSLR LPQEGKGTCI LVGGHEITSG LEVISSLRAI HGLQVEVCPL NGCDYIVSNR 1870 1880 1890 1900 1910 1920 MVVERRSQSE MLNSVNKNKF IEQIQHLQSM FERICVIVEK DREKTGDTSR MFRRTKSYDS 1930 1940 1950 1960 1970 1980 LLTTLIGAGI RILFSSCQEE TADLLKELSL VEQRKNVGIH VPTVVNSNKS EALQFYLSIP 1990 2000 2010 2020 2030 2040 NISYITALNM CHQFSSVKRM ANSSLQEISM YAQVTHQKAE EIYRYIHYVF DIQMLPNDLN QDRLKSDI
	Isoform 2. Checksum: A10DBC94FFA28C0B	FASTA	669	75,579
	10 20 30 40 50 60 MSGRQRTLFQ TWGSSISRSS GTPGCSSGTE RPQSPGSSKA PLPAAAEAQL ESDDDVLLVA 70 80 90 100 110 120 AYEAERQLCL ENGGFCTSAG ALWIYPTNCP VRDYQLHISR AALFCNTLVC LPTGLGKTFI 130 140 150 160 170 180 AAVVMYNFYR WFPSGKVVFM APTKPLVTQQ IEACYQVMGI PQSHMAEMTG STQASTRKEI 190 200 210 220 230 240 WCSKRVLFLT PQVMVNDLSR GACPAAEIKC LVIDEAHKAL GNYAYCQVVR ELVKYTNHFR 250 260 270 280 290 300 ILALSATPGS DIKAVQQVIT NLLIGQIELR SEDSPDILTY SHERKVEKLI VPLGEELAAI 310 320 330 340 350 360 QKTYIQILES FARSLIQRNV LMRRDIPNLT KYQIILARDQ FRKNPSPNIV GIQQGIIEGE 370 380 390 400 410 420 FAICISLYHG YELLQQMGMR SLYFFLCGIM DGTKGMTRSK NELGRNEDFM KLYNHLECMF 430 440 450 460 470 480 ARTRSTSANG ISAIQQGDKN KKFVYSHPKL KKLEEVVIEH FKSWNAENTT EKKRDETRVM 490 500 510 520 530 540 IFSSFRDSVQ EIAEMLSQHQ PIIRVMTFVG HASGKSTKGF TQKEQLEVVK QFRDGGYNTL 550 560 570 580 590 600 VSTCVGEEGL DIGEVDLIIC FDSQKSPIRL VQRMGRTGRK RQGRIVIILS EGREERIYNQ 610 620 630 640 650 660 SQSNKRSIYK AISSNRQVLH FYQRSPRMVP DGINPKLHKM FITHGVYEPE KPSRNLQRKS SIFSYRDGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M." Meetei A.R., Medhurst A.L., Ling C., Xue Y., Singh T.R., Bier P., Steltenpool J., Stone S., Dokal I., Mathew C.G., Hoatlin M., Joenje H., de Winter J.P., Wang W. Nat. Genet. 37:958-963(2005) [PubMed: 16116422] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCG AND FANCL, SUBCELLULAR LOCATION, DISEASE, PHOSPHORYLATION, FUNCTION, MUTAGENESIS OF LYS-117.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Testis.
[4]	"Prediction of the coding sequences of unidentified human genes. XVIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Kikuno R., Nakayama M., Hirosawa M., Ohara O. DNA Res. 7:273-281(2000) [PubMed: 10997877] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 794-2048 (ISOFORM 1), VARIANTS LEU-878 AND ALA-1812. Tissue: Brain.
[5]	"The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway." Mosedale G., Niedzwiedz W., Alpi A., Perrina F., Pereira-Leal J.B., Johnson M., Langevin F., Pace P., Patel K.J. Nat. Struct. Mol. Biol. 12:763-771(2005) [PubMed: 16116434] [Abstract] Cited for: DNA-BINDING, MUTAGENESIS OF GLY-116, IDENTIFICATION AS PART OF THE FA COMPLEX, FUNCTION.
[6]	"Identification of FAAP24, a Fanconi anemia core complex protein that interacts with FANCM." Ciccia A., Ling C., Coulthard R., Yan Z., Xue Y., Meetei A.R., Laghmani el H., Joenje H., McDonald N., de Winter J.P., Wang W., West S.C. Mol. Cell 25:331-343(2007) [PubMed: 17289582] [Abstract] Cited for: INTERACTION WITH EME1 AND FAAP24.
+	Additional computationally mapped references.

Web resources

Fanconi Anemia Mutation Database

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	DQ140356 mRNA. Translation: AAZ53290.1. AK093422 mRNA. Translation: BAC04159.1. BC036056 mRNA. Translation: AAH36056.1. AB046816 mRNA. Translation: BAB13422.1. Sequence problems.
IPI	IPI00176581. IPI00217755.
RefSeq	NP_065988.1.
UniGene	Hs.509229
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q8IYD8.
Proteomic databases
PRIDE	Q8IYD8.
Genome annotation databases
Ensembl	ENSG00000187790. Homo sapiens. [Contig view]
GeneID	57697.
KEGG	hsa:57697.
Organism-specific databases
GeneCards	GC14P044675.
H-InvDB	HIX0011623.
HGNC	HGNC:23168. FANCM.
MIM	227650. phenotype. 609644. gene+phenotype.
Orphanet	84. Fanconi anemia.
PharmGKB	PA134943156.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8IYD8.
HOVERGEN	Q8IYD8.
OMA	Q8IYD8. GIMDGTK.
Gene expression databases
ArrayExpress	Q8IYD8.
Bgee	Q8IYD8.
CleanEx	HS_FANCM.
GermOnline	ENSG00000187790. Homo sapiens.
Family and domain databases
InterPro	IPR014001. DEAD-like_N. IPR001650. DNA/RNA_helicase_C. IPR011545. DNA/RNA_helicase_DEAD/DEAH_N. IPR002464. DNA/RNA_helicase_DEAH_CS. IPR006166. DNA_repair_nuc_XPF/helicase. IPR014021. Helicase_SF1/SF2_ATP-bd. [Graphical view]
Gene3D	G3DSA:3.40.50.10130. DNA_repair_nuc_XPF/helicase. 1 hit.
Pfam	PF00270. DEAD. 1 hit. PF02732. ERCC4. 1 hit. PF00271. Helicase_C. 1 hit. [Graphical view]
SMART	SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view]
PROSITE	PS00690. DEAH_ATP_HELICASE. False negative. PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	64551.
SOURCE	Search...

Entry information

Entry name

FANCM_HUMAN

Accession

Primary (citable) accession number: Q8IYD8
Secondary accession number(s): Q3YFH9, Q8N9X6, Q9HCH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	October 25, 2005
Last modified:	June 16, 2009
This is version 63 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)