Q9HB96 (FANCE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fanconi anemia group E protein
Short name=Protein FACE

Gene names

Name:	FANCE
Synonyms:	FACE

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	536 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	As part of the Fanconi anemia (FA) complex functions in DNA cross-links repair. Required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Ref.7 Ref.12
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. Interacts with FANCC and FANCD2. Ref.8 Ref.9 Ref.10 Ref.11 Ref.16
Subcellular location	Nucleus Ref.7 Ref.12.
Post-translational modification	Phosphorylated. Phosphorylation by CHEK1 at Thr-346 and Ser-374 regulates its function in DNA cross-links repair. Ref.12 Ubiquitinated. Phosphorylation by CHEK1 induces polyubiquitination and degradation. Ref.12
Involvement in disease	Fanconi anemia complementation group E (FANCE) [MIM:600901]: 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.1

Ontologies

Keywords
Biological process	DNA damage DNA repair
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Fanconi anemia
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement. Source: Reactome
Cellular_component	Fanconi anaemia nuclear complex Inferred from direct assay PubMed 20347428Ref.16. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FANCC	Q00597	3	EBI-396803,EBI-81625
FANCD2	Q9BXW9	4	EBI-396803,EBI-359343

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 536

536

Fanconi anemia group E protein

PRO_0000087187

Regions

Region

150 – 371

222

Interaction with FANCC

Amino acid modifications

Modified residue

249

1

Phosphoserine Ref.13 Ref.14 Ref.15

Modified residue

346

1

Phosphothreonine; by CHEK1

Modified residue

374

1

Phosphoserine; by CHEK1

Natural variations

Natural variant

89

1

R → L. Ref.2
Corresponds to variant rs45600543 [ dbSNP | Ensembl ].

VAR_023372

Natural variant

184

1

P → Q in FA; uncertain pathological significance. Ref.17

VAR_038022

Natural variant

204

1

S → L. Ref.2
Corresponds to variant rs7761870 [ dbSNP | Ensembl ].

VAR_023373

Natural variant

340

1

G → R. Ref.2
Corresponds to variant rs45524646 [ dbSNP | Ensembl ].

VAR_023374

Natural variant

343

1

R → Q. Ref.2
Corresponds to variant rs45467798 [ dbSNP | Ensembl ].

VAR_023375

Natural variant

502

1

A → T. Ref.2
Corresponds to variant rs9462088 [ dbSNP | Ensembl ].

VAR_023376

Experimental info

Mutagenesis

346

1

T → A: Non-phosphorylatable by CHEK1, not polyubiquitinated and unable to complement the mitomycin C hypersensitivity of cells lacking FANCE; when associated with A-374. Ref.12

Mutagenesis

374

1

S → A: Non-phosphorylatable by CHEK1, not polyubiquitinated and unable to complement the mitomycin C hypersensitivity of cells lacking FANCE; when associated with A-346. Ref.12

Secondary structure

1

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536

Helix Strand Turn

Details...

Helix

282 – 299

18

Helix

311 – 314

4

Helix

315 – 318

4

Helix

321 – 331

11

Helix

333 – 335

3

Helix

338 – 350

13

Helix

357 – 374

18

Helix

381 – 393

13

Helix

395 – 408

14

Helix

414 – 425

12

Helix

431 – 443

13

Helix

448 – 458

11

Helix

466 – 477

12

Helix

487 – 499

13

Helix

501 – 503

3

Helix

506 – 516

11

Beta strand

518 – 523

6

Helix

524 – 534

11

Sequences

	Sequence		Length	Mass (Da)
	Q9HB96 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 0E94D8C469C791A5	FASTA	536	58,711
	10 20 30 40 50 60 MATPDAGLPG AEGVEPAPWA QLEAPARLLL QALQAGPEGA RRGLGVLRAL GSRGWEPFDW 70 80 90 100 110 120 GRLLEALCRE EPVVQGPDGR LELKPLLLRL PRICQRNLMS LLMAVRPSLP ESGLLSVLQI 130 140 150 160 170 180 AQQDLAPDPD AWLRALGELL RRDLGVGTSM EGASPLSERC QRQLQSLCRG LGLGGRRLKS 190 200 210 220 230 240 PQAPDPEEEE NRDSQQPGKR RKDSEEEAAS PEGKRVPKRL RCWEEEEDHE KERPEHKSLE 250 260 270 280 290 300 SLADGGSASP IKDQPVMAVK TGEDGSNLDD AKGLAESLEL PKAIQDQLPR LQQLLKTLEE 310 320 330 340 350 360 GLEGLEDAPP VELQLLHECS PSQMDLLCAQ LQLPQLSDLG LLRLCTWLLA LSPDLSLSNA 370 380 390 400 410 420 TVLTRSLFLG RILSLTSSAS RLLTTALTSF CAKYTYPVCS ALLDPVLQAP GTGPAQTELL 430 440 450 460 470 480 CCLVKMESLE PDAQVLMLGQ ILELPWKEET FLVLQSLLER QVEMTPEKFS VLMEKLCKKG 490 500 510 520 530 LAATTSMAYA KLMLTVMTKY QANITETQRL GLAMALEPNT TFLRKSLKAA LKHLGP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of a cDNA representing the Fanconi anemia complementation group E gene." de Winter J.P., Leveille F., van Berkel C.G.M., Rooimans M.A., van der Weel L., Steltenpool J., Demuth I., Morgan N.V., Alon N., Bosnoyan-Collins L., Lightfoot J., Leegwater P.A., Waisfisz Q., Komatsu K., Arwert F., Pronk J.C., Mathew C.G., Digweed M., Buchwald M., Joenje H. Am. J. Hum. Genet. 67:1306-1308(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], DISEASE.
[2]	NIEHS SNPs program Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-89; LEU-204; ARG-340; GLN-343 AND THR-502.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Testis.
[4]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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: Eye.
[7]	"FANCE: the link between Fanconi anaemia complex assembly and activity." Pace P., Johnson M., Tan W.M., Mosedale G., Sng C., Hoatlin M.E., de Winter J.P., Joenje H., Gergely F., Patel K.J. EMBO J. 21:3414-3423(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[8]	"Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems." Gordon S.M., Buchwald M. Blood 102:136-141(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FANCC AND FANCD2.
[9]	"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; FANCF; FANCG AND FANCL.
[10]	"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; FANCF; FANCG AND FANCL.
[11]	"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; FANCF; FANCG; FANCL AND FANCM.
[12]	"Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway." Wang X., Kennedy R.D., Ray K., Stuckert P., Ellenberger T., D'Andrea A.D. Mol. Cell. Biol. 27:3098-3108(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN DNA REPAIR, SUBCELLULAR LOCATION, PHOSPHORYLATION BY CHEK1 AT THR-346 AND SER-374, MUTAGENESIS OF THR-346 AND SER-374, UBIQUITINATION.
[13]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-249, MASS SPECTROMETRY.
[16]	"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.
[17]	"Genetic subtyping of Fanconi anemia by comprehensive mutation screening." Ameziane N., Errami A., Leveille F., Fontaine C., de Vries Y., van Spaendonk R.M., de Winter J.P., Pals G., Joenje H. Hum. Mutat. 29:159-166(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT FA GLN-184.
+	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

AF265210 mRNA. Translation: AAG16743.1.
DQ020173 Genomic DNA. Translation: AAY26395.1.
AK292522 mRNA. Translation: BAF85211.1.
AL022721 Genomic DNA. Translation: CAD92504.1.
CH471081 Genomic DNA. Translation: EAX03830.1.
BC046359 mRNA. Translation: AAH46359.1.

IPI

IPI00030252.

RefSeq

NP_068741.1. NM_021922.2.

UniGene

Hs.302003.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ILR	X-ray	2.00	A	273-536	[»]

ProteinModelPortal

Q9HB96.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32845N.

IntAct

Q9HB96. 7 interactions.

MINT

MINT-157013.

STRING

9606.ENSP00000229769.

PTM databases

PhosphoSite

Q9HB96.

Polymorphism databases

DMDM

45476978.

Proteomic databases

PaxDb

Q9HB96.

PRIDE

Q9HB96.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000229769; ENSP00000229769; ENSG00000112039.

GeneID

2178.

KEGG

hsa:2178.

UCSC

uc003oko.1. human.

Organism-specific databases

CTD

2178.

GeneCards

GC06P035563.

HGNC

HGNC:3586. FANCE.

HPA

CAB014893.

MIM

600901. phenotype.
613976. gene.

neXtProt

NX_Q9HB96.

Orphanet

84. Fanconi anemia.

PharmGKB

PA28000.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42377.

HOGENOM

HOG000013179.

InParanoid

Q9HB96.

KO

K10892.

OMA

PQLCQRN.

OrthoDB

EOG4FR0RS.

PhylomeDB

Q9HB96.

Enzyme and pathway databases

Pathway_Interaction_DB

bard1pathway. BARD1 signaling events.

Reactome

REACT_216. DNA Repair.

Gene expression databases

Bgee

Q9HB96.

CleanEx

HS_FANCE.

Genevestigator

Q9HB96.

GermOnline

ENSG00000112039. Homo sapiens.

Family and domain databases

InterPro

IPR021025. Fanconi_anaemia_gr_E_prot_C.
[Graphical view]

Pfam

PF11510. FA_FANCE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9HB96.

GenomeRNAi

2178.

NextBio

8797.

SOURCE

Search...

Entry information

Entry name

FANCE_HUMAN

Accession

Primary (citable) accession number: Q9HB96
Secondary accession number(s): A8K907, Q4ZGH2

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2004
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 105 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.