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FANCD2

Protein FULL name:

Fanconi anemia group D2 protein isoform a [Homo sapiens].


FANCD2 (Homo sapiens) is product of expression of FANCD2 gene.

Human diseases related to this protein:

FANCD2 is involved in:

HRR in Homo sapiens
     


Keywords:



FUNCTION: Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching.

SUBUNIT: Interacts directly with FANCE and FANCI. Interacts with USP1 and MEN1. The ubiquitinated form specifically interacts with BRCA1, BRCA2 and BLM.

INTERACTION: P51587:BRCA2; NbExp=9; IntAct=EBI-359343, EBI-79792; P51587:BRCA2; NbExp=2; IntAct=EBI-596878, EBI-79792; Q9HB96:FANCE; NbExp=2; IntAct=EBI-359343, EBI-396803; Q9NVI1:FANCI; NbExp=1; IntAct=EBI-359343, EBI-1013291; O00255:MEN1; NbExp=4; IntAct=EBI-359343, EBI-592789;

SUBCELLULAR LOCATION: Nucleus. Note=Concentrates in nuclear foci during S phase and upon genotoxic stress.

TISSUE SPECIFICITY: Highly expressed in germinal center cells of the spleen, tonsil, and reactive lymph nodes, and in the proliferating basal layer of squamous epithelium of tonsil, esophagus, oropharynx, larynx and cervix. Expressed in cytotrophoblastic cells of the placenta and exocrine cells of the pancreas (at protein level). Highly expressed in testis, where expression is restricted to maturing spermatocytes.

DEVELOPMENTAL STAGE: Highly expressed in fetal oocytes, and in hematopoietic cells of the fetal liver and bone marrow (at protein level).

DOMAIN: The C-terminal 24 residues of isoform 2 are required for its function.

PTM: Monoubiquitinated on Lys-561 during S phase and upon genotoxic stress (isoform 1 and isoform 2). Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. Monoubiquitination requires the FANCA-FANCB-FANCC-FANCE-FANCF- FANCG-FANCM complex, RPA1 and ATR, and is mediated by FANCL/PHF9. Ubiquitination is required for binding to chromatin, interaction with BRCA1 and BRCA2, DNA repair, and normal cell cycle progression, but not for phosphorylation on Ser-222 or interaction with MEN1.

PTM: Phosphorylated in response to various genotoxic stresses by ATM and/or ATR. Upon ionizing radiation, phosphorylated by ATM on Ser-222 and Ser-1404. Phosphorylation on Ser-222 is required for S-phase checkpoint activation, but not for ubiquitination, foci formation, or DNA repair. In contrast, phosphorylation by ATR on other sites may be required for ubiquitination and foci formation.

DISEASE: Defects in FANCD2 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.

SEQUENCE CAUTION: Sequence=BAB14132.1; Type=Erroneous initiation;

WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]

WEB RESOURCE: Name=Fanconi Anemia Mutation Database; [LINK]

WEB RESOURCE: Name=GeneReviews; [LINK]

WEB RESOURCE: Name=NIEHS-SNPs; [LINK]


NCBI GenPept GI number(s): 21361861
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot Q9BXW9 Q9BXW9
PFAM: - Q9BXW9 (Link - using uniprot id)
InterPro: - Q9BXW9 (Link - using uniprot id)
CATH: None  
SCOP: None  
PDB: - -


Protein sequence:
MVSKRRLSKSEDKESLTEDASKTRKQPLSKKTKKSHIANEVEENDSIFVK
LLKISGIILKTGESQNQLAVDQIAFQKKLFQTLRRHPSYPKIIEEFVSGL
ESYIEDEDSFRNCLLSCERLQDEEASMGASYSKSLIKLLLGIDILQPAII
KTLFEKLPEYFFENKNSDEINIPRLIVSQLKWLDRVVDGKDLTTKIMQLI
SIAPENLQHDIITSLPEILGDSQHADVGKELSDLLIENTSLTVPILDVLS
SLRLDPNFLLKVRQLVMDKLSSIRLEDLPVIIKFILHSVTAMDTLEVISE
LREKLDLQHCVLPSRLQASQVKLKSKGRASSSGNQESSGQSCIILLFDVI
KSAIRYEKTISEAWIKAIENTASVSEHKVFDLVMLFIIYSTNTQTKKYID
RVLRNKIRSGCIQEQLLQSTFSVHYLVLKDMCSSILSLAQSLLHSLDQSI
ISFGSLLYKYAFKFFDTYCQQEVVGALVTHICSGNEAEVDTALDVLLELV
VLNPSAMMMNAVFVKGILDYLDNISPQQIRKLFYVLSTLAFSKQNEASSH
IQDDMHLVIRKQLSSTVFKYKLIGIIGAVTMAGIMAADRSESPSLTQERA
NLSDEQCTQVTSLLQLVHSCSEQSPQASALYYDEFANLIQHEKLDPKALE
WVGHTICNDFQDAFVVDSCVVPEGDFPFPVKALYGLEEYDTQDGIAINLL
PLLFSQDFAKDGGPVTSQESGQKLVSPLCLAPYFRLLRLCVERQHNGNLE
EIDGLLDCPIFLTDLEPGEKLESMSAKERSFMCSLIFLTLNWFREIVNAF
CQETSPEMKGKVLTRLKHIVELQIILEKYLAVTPDYVPPLGNFDVETLDI
TPHTVTAISAKIRKKGKIERKQKTDGSKTSSSDTLSEEKNSECDPTPSHR
GQLNKEFTGKEEKTSLLLHNSHAFFRELDIEVFSILHCGLVTKFILDTEM
HTEATEVVQLGPPELLFLLEDLSQKLESMLTPPIARRVPFLKNKGSRNIG
FSHLQQRSAQEIVHCVFQLLTPMCNHLENIHNYFQCLAAENHGVVDGPGV
KVQEYHIMSSCYQRLLQIFHGLFAWSGFSQPENQNLLYSALHVLSSRLKQ
GEHSQPLEELLSQSVHYLQNFHQSIPSFQCALYLIRLLMVILEKSTASAQ
NKEKIASLARQFLCRVWPSGDKEKSNISNDQLHALLCIYLEHTESILKAI
EEIAGVGVPELINSPKDASSSTFPTLTRHTFVVFFRVMMAELEKTVKKIE
PGTAADSQQIHEEKLLYWNMAVRDFSILINLIKVFDSHPVLHVCLKYGRL
FVEAFLKQCMPLLDFSFRKHREDVLSLLETFQLDTRLLHHLCGHSKIHQD
TRLTQHVPLLKKTLELLVCRVKAMLTLNNCREAFWLGNLKNRDLQGEEIK
SQNSQESTADESEDDMSSQASKSKATEVSLQNPPESGTDGCILLIVLSWW
SRTLPTYVYCQMLLCPFPFPP

FANCD2 (Homo sapiens) is able to recognize following damages:
FANCD2 (Homo sapiens) belongs to following protein families:
References:

Title Authors Journal
Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Garcia-Higuera I, Taniguchi T, Ganesan S, Meyn MS, Timmers C, Hejna J, Grompe M, D'Andrea AD Mol Cell Jan. 1, 2001
Positional cloning of a novel Fanconi anemia gene, FANCD2. Timmers C, Taniguchi T, Hejna J, Reifsteck C, Lucas L, Bruun D, Thayer M, Cox B, Olson S, D'Andrea AD, Moses R, Grompe M Mol Cell Jan. 1, 2001
Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways. Taniguchi T, Garcia-Higuera I, Xu B, Andreassen PR, Gregory RC, Kim ST, Lane WS, Kastan MB, D'Andrea AD Cell May 17, 2002
FANCE: the link between Fanconi anaemia complex assembly and activity. Pace P, Johnson M, Tan WM, Mosedale G, Sng C, Hoatlin M, de Winter J, Joenje H, Gergely F, Patel KJ EMBO J July 1, 2002
S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D'Andrea AD Blood Oct. 1, 2002
Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems. Gordon SM, Buchwald M Blood July 1, 2003
Menin associates with FANCD2, a protein involved in repair of DNA damage. Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, Hua X Cancer Res July 15, 2003
FANCD2 protein is expressed in proliferating cells of human tissues that are cancer-prone in Fanconi anaemia. Holzel M, van Diest PJ, Bier P, Wallisch M, Hoatlin ME, Joenje H, de Winter JP J Pathol Oct. 1, 2003
A novel ubiquitin ligase is deficient in Fanconi anemia. Meetei AR, de Winter JP, Medhurst AL, Wallisch M, Waisfisz Q, van de Vrugt HJ, Oostra AB, Yan Z, Ling C, Bishop CE, Hoatlin ME, Joenje H, Wang W Nat Genet Oct. 1, 2003
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 TO, 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 Feb. 1, 2004
The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. Pichierri P, Rosselli F EMBO J March 10, 2004
Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. Hussain S, Wilson JB, Medhurst AL, Hejna J, Witt E, Ananth S, Davies A, Masson JY, Moses R, West SC, de Winter JP, Ashworth A, Jones NJ, Mathew CG Hum Mol Genet June 15, 2004
Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Wang X, Andreassen PR, D'Andrea AD Mol Cell Biol July 1, 2004
BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks. Pichierri P, Franchitto A, Rosselli F EMBO J Aug. 4, 2004
ATR couples FANCD2 monoubiquitination to the DNA-damage response. Andreassen PR, D'Andrea AD, Taniguchi T Genes Dev Aug. 15, 2004
Large-scale characterization of HeLa cell nuclear phosphoproteins. Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villen J, Li J, Cohn MA, Cantley LC, Gygi SP Proc Natl Acad Sci U S A Aug. 17, 2004
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J Genome Res Oct. 1, 2004
X-linked inheritance of Fanconi anemia complementation group B. Meetei AR, Levitus M, Xue Y, Medhurst AL, Zwaan M, Ling C, Rooimans MA, Bier P, Hoatlin M, Pals G, de Winter JP, Wang W, Joenje H Nat Genet Nov. 1, 2004
A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint. Freie BW, Ciccone SL, Li X, Plett PA, Orschell CM, Srour EF, Hanenberg H, Schindler D, Lee SH, Clapp DW J Biol Chem Dec. 3, 2004
Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Montes de Oca R, Andreassen PR, Margossian SP, Gregory RC, Taniguchi T, Wang X, Houghtaling S, Grompe M, D'Andrea AD Blood Jan. 1, 2005
The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Nijman SM, Huang TT, Dirac AM, Brummelkamp TR, Kerkhoven RM, D'Andrea AD, Bernards R Mol Cell Jan. 4, 2005
Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Nakanishi K, Yang YG, Pierce AJ, Taniguchi T, Digweed M, D'Andrea AD, Wang ZQ, Jasin M Proc Natl Acad Sci U S A Feb. 25, 2005
The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability. Howlett NG, Taniguchi T, Durkin SG, D'Andrea AD, Glover TW Hum Mol Genet March 1, 2005
Fanconi anemia complementation group D2 (FANCD2) functions independently of BRCA2- and RAD51-associated homologous recombination in response to DNA damage. Ohashi A, Zdzienicka MZ, Chen J, Couch FJ J Biol Chem April 15, 2005
A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Meetei AR, Medhurst AL, Ling C, Xue Y, Singh TR, Bier P, Steltenpool J, Stone S, Dokal I, Mathew CG, Hoatlin M, Joenje H, de Winter JP, Wang W Nat Genet Sept. 1, 2005
Tyrosine phosphorylated Par3 regulates epithelial tight junction assembly promoted by EGFR signaling. Wang Y, Du D, Fang L, Yang G, Zhang C, Zeng R, Ullrich A, Lottspeich F, Chen Z EMBO J Nov. 1, 2006
The full-ORF clone resource of the German cDNA Consortium. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I BMC Genomics Jan. 1, 2007
Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair. Smogorzewska A, Matsuoka S, Vinciguerra P, McDonald ER 3rd, Hurov KE, Luo J, Ballif BA, Gygi SP, Hofmann K, D'Andrea AD, Elledge SJ Cell April 20, 2007
ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Matsuoka S, Ballif BA, Smogorzewska A, McDonald ER 3rd, Hurov KE, Luo J, Bakalarski CE, Zhao Z, Solimini N, Lerenthal Y, Shiloh Y, Gygi SP, Elledge SJ Science May 25, 2007
FANCI is a second monoubiquitinated member of the Fanconi anemia pathway. Sims AE, Spiteri E, Sims RJ 3rd, Arita AG, Lach FP, Landers T, Wurm M, Freund M, Neveling K, Hanenberg H, Auerbach AD, Huang TT Nat Struct Mol Biol June 1, 2007
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A Aug. 5, 2008
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M Mol Cell Aug. 8, 2008
Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Wang B, Malik R, Nigg EA, Korner R Anal Chem Dec. 15, 2008
Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK Sci Signal Jan. 1, 2009
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem June 1, 2009
Large-scale proteomics analysis of the human kinome. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H Mol Cell Proteomics July 1, 2009


Last modification of this entry: Oct. 12, 2010.

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