O15287 (FANCG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fanconi anemia group G protein
Short name=Protein FACG

Alternative name(s):
DNA repair protein XRCC9

Gene names

Name:	FANCG
Synonyms:	XRCC9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	622 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Candidate tumor suppressor gene.
Subunit structure	Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is not found in FA patients. In complex with FANCF, FANCA and FANCL, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins. The complex with FANCC and FANCG may also include EIF2AK2 and HSP70. When phosphorylated at Ser-7, forms a complex with BRCA2, FANCD2 and XRCC3. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.17
Subcellular location	Nucleus. Cytoplasm. Note: The major form is nuclear. The minor form is cytoplasmic. Ref.17
Tissue specificity	Highly expressed in testis and thymus. Found in lymphoblasts.
Involvement in disease	Fanconi anemia complementation group G (FANCG) [MIM:614082]: A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.17
Sequence similarities	Contains 4 TPR repeats.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Fanconi anemia
Domain	Repeat TPR repeat
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement. Source: Reactome cell cycle checkpoint Traceable author statement Ref.1. Source: ProtInc mitochondrion organization Inferred from mutant phenotype PubMed 17060495. Source: UniProtKB ovarian follicle development Inferred from electronic annotation. Source: Compara response to radiation Inferred from electronic annotation. Source: Compara spermatid development Inferred from electronic annotation. Source: Compara
Cellular_component	Fanconi anaemia nuclear complex Inferred from direct assay PubMed 20347428Ref.14Ref.12Ref.13. Source: UniProtKB mitochondrion Inferred from direct assay PubMed 17060495. Source: UniProtKB
Molecular_function	damaged DNA binding Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FANCA	O15360	6	EBI-81610,EBI-81570
FANCF	Q9NPI8	4	EBI-81610,EBI-81589

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 622	622	Fanconi anemia group G protein		PRO_0000106292
Regions
	Repeat	246 – 279	34	TPR 1
	Repeat	344 – 377	34	TPR 2
	Repeat	453 – 486	34	TPR 3
	Repeat	514 – 547	34	TPR 4
Amino acid modifications
	Modified residue	7	1	Phosphoserine Ref.11
Natural variations
	Natural variant	71	1	L → P in FANCG; associated with a mild clinical phenotype; disruption of HES1-binding; no effect on FANCA-binding. Ref.15 Ref.17		VAR_017495
	Natural variant	294	1	G → E. Ref.3 Corresponds to variant rs17880082 [ dbSNP | Ensembl ].		VAR_021103
	Natural variant	297	1	T → I. Ref.3 Corresponds to variant rs2237857 [ dbSNP | Ensembl ].		VAR_020311
	Natural variant	330	1	P → S. Ref.3 Corresponds to variant rs4986940 [ dbSNP | Ensembl ].		VAR_021104
	Natural variant	378	1	S → L. Ref.3 Corresponds to variant rs4986939 [ dbSNP | Ensembl ].		VAR_021105
	Natural variant	430	1	K → E. Ref.3 Corresponds to variant rs17881054 [ dbSNP | Ensembl ].		VAR_021106
	Natural variant	513	1	R → Q. Ref.3 Corresponds to variant rs17885240 [ dbSNP | Ensembl ].		VAR_021107
	Natural variant	603	1	S → F. Ref.3 Corresponds to variant rs17878854 [ dbSNP | Ensembl ].		VAR_021108
	Natural variant	607	1	A → T in a colorectal cancer sample; somatic mutation. Ref.16		VAR_035864
Experimental info
	Mutagenesis	7	1	S → A: Loss of BRCA2-, FANCD2- and XRCC3-binding. No effect on complex formation with FANCA and FANCF. Ref.11
	Mutagenesis	383	1	S → A: No effect on BRCA2-, FANCA-, FANCF-, nor XRCC3-binding. Ref.11
	Mutagenesis	387	1	S → A: No effect on BRCA2-, FANCA-, FANCF-, nor XRCC3-binding. Ref.11
	Mutagenesis	546	1	G → R: No effect on HES1-, nor FANCA-binding. Ref.17

Sequences

	Sequence		Length	Mass (Da)
	O15287 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 4BC7475472AC3C84	FASTA	622	68,554
	10 20 30 40 50 60 MSRQTTSVGS SCLDLWREKN DRLVRQAKVA QNSGLTLRRQ QLAQDALEGL RGLLHSLQGL 70 80 90 100 110 120 PAAVPVLPLE LTVTCNFIIL RASLAQGFTE DQAQDIQRSL ERVLETQEQQ GPRLEQGLRE 130 140 150 160 170 180 LWDSVLRASC LLPELLSALH RLVGLQAALW LSADRLGDLA LLLETLNGSQ SGASKDLLLL 190 200 210 220 230 240 LKTWSPPAEE LDAPLTLQDA QGLKDVLLTA FAYRQGLQEL ITGNPDKALS SLHEAASGLC 250 260 270 280 290 300 PRPVLVQVYT ALGSCHRKMG NPQRALLYLV AALKEGSAWG PPLLEASRLY QQLGDTTAEL 310 320 330 340 350 360 ESLELLVEAL NVPCSSKAPQ FLIEVELLLP PPDLASPLHC GTQSQTKHIL ASRCLQTGRA 370 380 390 400 410 420 GDAAEHYLDL LALLLDSSEP RFSPPPSPPG PCMPEVFLEA AVALIQAGRA QDALTLCEEL 430 440 450 460 470 480 LSRTSSLLPK MSRLWEDARK GTKELPYCPL WVSATHLLQG QAWVQLGAQK VAISEFSRCL 490 500 510 520 530 540 ELLFRATPEE KEQGAAFNCE QGCKSDAALQ QLRAAALISR GLEWVASGQD TKALQDFLLS 550 560 570 580 590 600 VQMCPGNRDT YFHLLQTLKR LDRRDEATAL WWRLEAQTKG SHEDALWSLP LYLESYLSWI 610 620 RPSDRDAFLE EFRTSLPKSC DL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human XRCC9 gene corrects chromosomal instability and mutagen sensitivities in CHO UV40 cells." Liu N., Lamerdin J.E., Tucker J.D., Zhou Z.-Q., Walter C.A., Albala J.S., Busch D.B., Thompson L.H. Proc. Natl. Acad. Sci. U.S.A. 94:9232-9237(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The Fanconi anaemia group G gene FANCG is identical with XRCC9." De Winter J.P., Waisfisz Q., Rooimans M.A., Van Berkel C.G.M., Bosnoyan-Collins L., Alon N., Carreau M., Bender O., Demuth I., Schindler D., Pronk J.C., Arwert F., Hoehn H., Digweed M., Buchwald M., Joenje H. Nat. Genet. 20:281-283(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[3]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLU-294; ILE-297; SER-330; LEU-378; GLU-430; GLN-513 AND PHE-603.
[4]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney and Uterus.
[6]	"Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex." Garcia-Higuera I., Kuang Y., Naf D., Wasik J., D'Andrea A.D. Mol. Cell. Biol. 19:4866-4873(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome." Meetei A.R., Sechi S., Wallisch M., Yang D., Young M.K., Joenje H., Hoatlin M.E., Wang W. Mol. Cell. Biol. 23:3417-3426(2003) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCC; FANCE; FANCF AND FANCL.
[8]	"The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR)." Zhang X., Li J., Sejas D.P., Rathbun K.R., Bagby G.C., Pang Q. J. Biol. Chem. 279:43910-43919(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH EIF2AK2; FANCA; FANCC AND HSP70.
[9]	"X-linked inheritance of Fanconi anemia complementation group B." Meetei A.R., Levitus M., Xue Y., Medhurst A.L., Zwaan M., Ling C., Rooimans M.A., Bier P., Hoatlin M., Pals G., de Winter J.P., Wang W., Joenje H. Nat. Genet. 36:1219-1224(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF AND FANCL.
[10]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH FANCA; FANCB; FANCC; FANCE; FANCF; FANCL AND FANCM.
[11]	"FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3." Wilson J.B., Yamamoto K., Marriott A.S., Hussain S., Sung P., Hoatlin M.E., Mathew C.G., Takata M., Thompson L.H., Kupfer G.M., Jones N.J. Oncogene 27:3641-3652(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BRCA2; FANCD2 AND XRCC3, PHOSPHORYLATION AT SER-7, MUTAGENESIS OF SER-7; SER-383 AND SER-387.
[12]	"FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway." Ali A.M., Pradhan A., Singh T.R., Du C., Li J., Wahengbam K., Grassman E., Auerbach A.D., Pang Q., Meetei A.R. Blood 119:3285-3294(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE FA COMPLEX.
[13]	"A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubiquitination to the Fanconi anemia DNA repair network." Yan Z., Guo R., Paramasivam M., Shen W., Ling C., Fox D. III, Wang Y., Oostra A.B., Kuehl J., Lee D.Y., Takata M., Hoatlin M.E., Schindler D., Joenje H., de Winter J.P., Li L., Seidman M.M., Wang W. Mol. Cell 47:61-75(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE FA COMPLEX.
[14]	"Regulation of Rev1 by the Fanconi anemia core complex." Kim H., Yang K., Dejsuphong D., D'Andrea A.D. Nat. Struct. Mol. Biol. 19:164-170(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE FA COMPLEX.
[15]	"Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9." Demuth I., Wlodarski M., Tipping A.J., Morgan N.V., de Winter J.P., Thiel M., Grasl S., Schindler D., D'Andrea A.D., Altay C., Kayserili H., Zatterale A., Kunze J., Ebell W., Mathew C.G., Joenje H., Sperling K., Digweed M. Eur. J. Hum. Genet. 8:861-868(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FANCG PRO-71.
[16]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-607.
[17]	"HES1 is a novel interactor of the Fanconi anemia core complex." Tremblay C.S., Huang F.F., Habi O., Huard C.C., Godin C., Levesque G., Carreau M. Blood 112:2062-2070(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FANCG PRO-71, INTERACTION WITH HES1, SUBCELLULAR LOCATION, MUTAGENESIS OF GLY-546.
+	Additional computationally mapped references.

Web resources

Fanconi Anemia Mutation Database

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	U70310 mRNA. Translation: AAB80802.1. AJ007669 mRNA. Translation: CAA07602.1. AY795970 Genomic DNA. Translation: AAV40841.1. AC004472 Genomic DNA. Translation: AAC07981.1. AL353795 Genomic DNA. Translation: CAH70994.1. BC000032 mRNA. Translation: AAH00032.1. BC011623 mRNA. Translation: AAH11623.1.
IPI	IPI00005769.
PIR	T02244.
RefSeq	NP_004620.1. NM_004629.1.
UniGene	Hs.591084.
3D structure databases
ProteinModelPortal	O15287.
ModBase	Search...
Protein-protein interaction databases
IntAct	O15287. 11 interactions.
MINT	MINT-96443.
STRING	9606.ENSP00000367910.
PTM databases
PhosphoSite	O15287.
Proteomic databases
PaxDb	O15287.
PRIDE	O15287.
Protocols and materials databases
DNASU	2189.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378643; ENSP00000367910; ENSG00000221829.
GeneID	2189.
KEGG	hsa:2189.
UCSC	uc003zwb.1. human.
Organism-specific databases
CTD	2189.
GeneCards	GC09M035073.
HGNC	HGNC:3588. FANCG.
HPA	CAB008105.
MIM	602956. gene. 614082. phenotype.
neXtProt	NX_O15287.
Orphanet	84. Fanconi anemia.
PharmGKB	PA28002.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG40254.
HOGENOM	HOG000231403.
HOVERGEN	HBG051551.
InParanoid	O15287.
KO	K10894.
OMA	SLAQGFT.
OrthoDB	EOG40CHGW.
PhylomeDB	O15287.
Enzyme and pathway databases
Pathway_Interaction_DB	bard1pathway. BARD1 signaling events.
Reactome	REACT_216. DNA Repair.
Gene expression databases
ArrayExpress	O15287.
Bgee	O15287.
CleanEx	HS_FANCG.
Genevestigator	O15287.
GermOnline	ENSG00000165281. Homo sapiens.
Family and domain databases
Gene3D	1.25.40.10. 1 hit.
InterPro	IPR001440. TPR-1. IPR011990. TPR-like_helical. IPR019734. TPR_repeat. [Graphical view]
Pfam	PF00515. TPR_1. 1 hit. [Graphical view]
SMART	SM00028. TPR. 3 hits. [Graphical view]
PROSITE	PS50005. TPR. False negative. PS50293. TPR_REGION. False negative. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	2189.
NextBio	8847.
SOURCE	Search...

Entry information

Entry name

FANCG_HUMAN

Accession

Primary (citable) accession number: O15287

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 132 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.