Q00597 (FANCC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fanconi anemia group C protein
Short name=Protein FACC

Gene names

Name:	FANCC
Synonyms:	FAC, FACC

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	558 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. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1. Ref.12
Subunit structure	Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. This complex may also include HSP70. The complex is not found in FA patients. Interacts with ZBTB32. Upon IFNG induction, interacts with STAT1. Interacts with CDK1. Interacts with EIF2AK2; interaction between FA variants and EIF2AK2 may lead to augmented EIF2AK2 activation and cell death. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
Subcellular location	Nucleus. Cytoplasm. Note: The major form is nuclear. The minor form is cytoplasmic. Ref.8 Ref.9 Ref.10
Tissue specificity	Ubiquitous.
Developmental stage	Expression increases during S phase, is maximal at the G2/M transition, and declines during M phase (at protein level). Ref.10
Involvement in disease	Fanconi anemia complementation group C (FANCC) [MIM:227645]: 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.

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Fanconi anemia
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement. Source: Reactome germ cell development Inferred from electronic annotation. Source: Compara myeloid cell homeostasis Inferred from electronic annotation. Source: Compara nucleotide-excision repair Inferred from electronic annotation. Source: Compara protein complex assembly Traceable author statement PubMed 9398857. Source: ProtInc removal of superoxide radicals Inferred from electronic annotation. Source: Compara
Cellular_component	Fanconi anaemia nuclear complex Inferred from direct assay PubMed 20347428Ref.17. Source: UniProtKB cytosol Inferred from direct assay PubMed 9596688. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FANCE	Q9HB96	3	EBI-81625,EBI-396803

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 558	558	Fanconi anemia group C protein		PRO_0000087184
Natural variations
	Natural variant	26	1	S → F. Ref.20 Corresponds to variant rs1800361 [ dbSNP | Ensembl ].		VAR_005225
	Natural variant	80	1	I → T. Ref.4 Corresponds to variant rs4647419 [ dbSNP | Ensembl ].		VAR_016339
	Natural variant	139	1	G → E. Ref.4 Ref.19 Ref.20 Corresponds to variant rs1800362 [ dbSNP | Ensembl ].		VAR_005226
	Natural variant	190	1	L → F. Ref.21 Corresponds to variant rs1800364 [ dbSNP | Ensembl ].		VAR_005227
	Natural variant	195	1	D → V in FA. Ref.20 Corresponds to variant rs1800365 [ dbSNP | Ensembl ].		VAR_005228
	Natural variant	312	1	I → V. Ref.21 Corresponds to variant rs1800366 [ dbSNP | Ensembl ].		VAR_005229
	Natural variant	449	1	V → M. Ref.4 Ref.21 Corresponds to variant rs1800367 [ dbSNP | Ensembl ].		VAR_005230
	Natural variant	465	1	Q → R. Ref.21 Corresponds to variant rs1800368 [ dbSNP | Ensembl ].		VAR_005231
	Natural variant	496	1	L → R in FA. Ref.21		VAR_005232
	Natural variant	554	1	L → P in FA; loss of activity; loss of CDK1-binding and IFNG-induced STAT1-binding; abnormal EIF2AK2 activation and augmented cell death. Ref.1 Ref.10 Ref.12 Ref.14 Ref.18 Ref.20		VAR_005233
Experimental info
	Mutagenesis	64	1	F → A: No loss of protection from cross-linking agent-induced toxicity. No effect on IFNG-induced STAT1-binding. Ref.12
	Mutagenesis	66	1	T → A: No effect on protective function from mitomycin C-genotoxicity. Ref.12
	Mutagenesis	249	1	S → A: No effect on protective function from mitomycin C-genotoxicity. Loss of IFNG-induced STAT1-binding. Ref.12
	Mutagenesis	251	1	E → A: No effect on protective function from mitomycin C-genotoxicity. Loss of IFNG-induced STAT1-binding. Ref.12
	Mutagenesis	529	1	T → A: No effect on protective function from mitomycin C-genotoxicity. Ref.12
	Mutagenesis	531	1	Y → A: No effect on protective function from mitomycin C-genotoxicity. No effect on IFNG-induced STAT1-binding. Ref.12
	Sequence conflict	294	1	Missing in AAA53104. Ref.3
	Sequence conflict	438	1	Missing in CAA47348. Ref.1
	Sequence conflict	438	1	Missing in CAA47347. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q00597 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: C9DDFFAC725D050C	FASTA	558	63,429
	10 20 30 40 50 60 MAQDSVDLSC DYQFWMQKLS VWDQASTLET QQDTCLHVAQ FQEFLRKMYE ALKEMDSNTV 70 80 90 100 110 120 IERFPTIGQL LAKACWNPFI LAYDESQKIL IWCLCCLINK EPQNSGQSKL NSWIQGVLSH 130 140 150 160 170 180 ILSALRFDKE VALFTQGLGY APIDYYPGLL KNMVLSLASE LRENHLNGFN TQRRMAPERV 190 200 210 220 230 240 ASLSRVCVPL ITLTDVDPLV EALLICHGRE PQEILQPEFF EAVNEAILLK KISLPMSAVV 250 260 270 280 290 300 CLWLRHLPSL EKAMLHLFEK LISSERNCLR RIECFIKDSS LPQAACHPAI FRVVDEMFRC 310 320 330 340 350 360 ALLETDGALE IIATIQVFTQ CFVEALEKAS KQLRFALKTY FPYTSPSLAM VLLQDPQDIP 370 380 390 400 410 420 RGHWLQTLKH ISELLREAVE DQTHGSCGGP FESWFLFIHF GGWAEMVAEQ LLMSAAEPPT 430 440 450 460 470 480 ALLWLLAFYY GPRDGRQQRA QTMVQVKAVL GHLLAMSRSS SLSAQDLQTV AGQGTDTDLR 490 500 510 520 530 540 APAQQLIRHL LLNFLLWAPG GHTIAWDVIT LMAHTAEITH EIIGFLDQTL YRWNRLGIES 550 PRSEKLAREL LKELRTQV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of cDNAs for Fanconi's anaemia by functional complementation." Strathdee C.A., Gavish H., Shannon W.R., Buchwald M. Nature 356:763-767(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT FA PRO-554. Tissue: Lymphoid tissue.
[2]	Erratum Strathdee C.A., Gavish H., Shannon W.R., Buchwald M. Nature 358:434-434(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION TO 179-192.
[3]	"Characterisation of the exon structure of the Fanconi anaemia group C gene by vectorette PCR." Gibson R.A., Buchwald M., Roberts R.G., Mathew C.G. Hum. Mol. Genet. 2:35-38(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-80; GLU-139 AND MET-449.
[5]	"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].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Colon.
[8]	"The Fanconi anemia polypeptide FACC is localized to the cytoplasm." Yamashita T., Barber D.L., Zhu Y., Wu N., D'Andrea A.D. Proc. Natl. Acad. Sci. U.S.A. 91:6712-6716(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells." Youssoufian H. Proc. Natl. Acad. Sci. U.S.A. 91:7975-7979(1994) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[10]	"The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2." Kupfer G.M., Yamashita T., Naf D., Suliman A., Asano S., D'Andrea A.D. Blood 90:1047-1054(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDK1, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, CHARACTERIZATION OF VARIANT FA PRO-554.
[11]	"A novel BTB/POZ transcriptional repressor protein interacts with the Fanconi anemia group C protein and PLZF." Hoatlin M.E., Zhi Y., Ball H., Silvey K., Melnick A., Stone S., Arai S., Hawe N., Owen G., Zelent A., Licht J.D. Blood 94:3737-3747(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZBTB32.
[12]	"The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality." Pang Q., Christianson T.A., Keeble W., Diaz J., Faulkner G.R., Reifsteck C., Olson S., Bagby G.C. Blood 98:1392-1401(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STAT1, CHARACTERIZATION OF VARIANT FA PRO-554, MUTAGENESIS OF PHE-64; THR-66; SER-249; GLU-251; THR-529 AND TYR-531.
[13]	"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; FANCE; FANCF; FANCG AND FANCL.
[14]	"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; FANCG AND HSP70, CHARACTERIZATION OF VARIANT FA PRO-554.
[15]	"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; FANCE; FANCF; FANCG AND FANCL.
[16]	"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; FANCE; FANCF; FANCG; FANCL AND FANCM.
[17]	"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.
[18]	"A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein." Gavish H., Dos Santos C.C., Buchwald M. Hum. Mol. Genet. 2:123-126(1993) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANT FA PRO-554.
[19]	"A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews." Whitney M.A., Saito H., Jakops P.M., Gibson R.A., Moses R.E., Grompe M. Nat. Genet. 4:202-205(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLU-139.
[20]	"Mutation analysis of the Fanconi anemia gene FACC." Verlander P.C., Lin J.D., Udono M.U., Zhang Q., Gibson R.A., Mathew C.G., Auerbach A.D. Am. J. Hum. Genet. 54:595-601(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS FA VAL-195 AND PRO-554, VARIANTS PHE-26 AND GLU-139.
[21]	"Novel mutations and polymorphisms in the Fanconi anemia group C gene." Gibson R.A., Morgan N.V., Goldstein L.H., Pearson I.C., Kesterton I.P., Foot N.J., Jansen S., Havenga C., Pearson T., de Ravel T.J., Cohn R.J., Marques I.M., Dokal I., Roberts I., Marsh J., Ball S., Milner R.D., Llerena J.C. Jr. , Samochatova E., Mohan S.P., Vasudevan P., Birjandi F., Hajianpour A., Murer-Orlando M., Mathew C.G. Hum. Mutat. 8:140-148(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PHE-190; VAL-312; MET-449 AND ARG-465, VARIANT FA ARG-496.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Fanconi Anemia Mutation Database

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	X66894 mRNA. Translation: CAA47348.1. X66893 mRNA. Translation: CAA47347.1. L02664 , L02651, L02652, L02653, L02654, L02655, L02656, L02657, L02658, L02659, L02660, L02661, L02662, L02663 Genomic DNA. Translation: AAA53104.1. AY220878 Genomic DNA. Translation: AAO26042.1. AL157384, AL354893 Genomic DNA. Translation: CAH70886.1. AL354893, AL157384 Genomic DNA. Translation: CAI41329.1. CH471174 Genomic DNA. Translation: EAW92626.1. BC015748 mRNA. Translation: AAH15748.1.
IPI	IPI00023608.
PIR	S21733.
RefSeq	NP_000127.2. NM_000136.2. NP_001230672.1. NM_001243743.1.
UniGene	Hs.494529.
3D structure databases
ProteinModelPortal	Q00597.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32846N.
IntAct	Q00597. 3 interactions.
MINT	MINT-110041.
STRING	9606.ENSP00000289081.
PTM databases
PhosphoSite	Q00597.
Polymorphism databases
DMDM	1706762.
Proteomic databases
PaxDb	Q00597.
PRIDE	Q00597.
Protocols and materials databases
DNASU	2176.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000289081; ENSP00000289081; ENSG00000158169. ENST00000375305; ENSP00000364454; ENSG00000158169.
GeneID	2176.
KEGG	hsa:2176.
UCSC	uc004avh.3. human.
Organism-specific databases
CTD	2176.
GeneCards	GC09M097861.
HGNC	HGNC:3584. FANCC.
HPA	CAB017793.
MIM	227645. phenotype. 613899. gene.
neXtProt	NX_Q00597.
Orphanet	84. Fanconi anemia.
PharmGKB	PA27997.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG44530.
HOGENOM	HOG000043097.
HOVERGEN	HBG051548.
InParanoid	Q00597.
KO	K10890.
OMA	LKTYFPY.
OrthoDB	EOG4K6G49.
PhylomeDB	Q00597.
Enzyme and pathway databases
Pathway_Interaction_DB	bard1pathway. BARD1 signaling events.
Reactome	REACT_216. DNA Repair.
Gene expression databases
ArrayExpress	Q00597.
Bgee	Q00597.
CleanEx	HS_FANCC.
Genevestigator	Q00597.
GermOnline	ENSG00000158169. Homo sapiens.
Family and domain databases
InterPro	IPR000686. Fanconi. [Graphical view]
PANTHER	PTHR16798. PTHR16798. 1 hit.
Pfam	PF02106. Fanconi_C. 1 hit. [Graphical view]
PIRSF	PIRSF018417. FACC_protein. 1 hit.
PRINTS	PR00494. FANCONICGENE.
ProtoNet	Search...
Other
GenomeRNAi	2176.
NextBio	8787.
SOURCE	Search...

Entry information

Entry name

FANCC_HUMAN

Accession

Primary (citable) accession number: Q00597
Secondary accession number(s): B1ALR8

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 122 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.