FANCD2
entrez
2177
canonical
uniprot
Q9BXW9
canonical
ensembl
ENSG00000144554
resolver
ensp
ENSP00000287647
resolver
ensp
ENSP00000398754
resolver
ensp
ENSP00000501999
resolver
ensp
ENSP00000502379
resolver
ensp
ENSP00000729305
resolver
enst
ENST00000676013
resolver
genesymbol
FANCD2
resolver
genesymbol_syn
FACD
resolver
hgnc
HGNC:3585
resolver
uniprot
A0A6Q8PFY3
resolver
uniprot
Q2LA86
resolver
uniprot
Q69YP9
resolver
uniprot
Q6PJN7
resolver
uniprot
Q9BQ06
resolver
uniprot
Q9H9T9
resolver
uniprot_entry
A0A6Q8PFY3_HUMAN
resolver
uniprot_entry
FACD2_HUMAN
resolver
uniprot_sec
Q2LA86
resolver
uniprot_sec
Q69YP9
resolver
uniprot_sec
Q6PJN7
resolver
uniprot_sec
Q9BQ06
resolver
uniprot_sec
Q9H9T9
resolver
amino_acid_sequence
MVSKRRLSKSEDKESLTEDASKTRKQPLSKKTKKSHIANEVEENDSIFVKLLKISGIILKTGESQNQLAVDQIAFQKKLFQTLRRHPSYPKIIEEFVSGLESYIEDEDSFRNCLLSCERLQDEEASMGASYSKSLIKLLLGIDILQPAIIKTLFEKLPEYFFENKNSDEINIPRLIVSQLKWLDRVVDGKDLTTKIMQLISIAPENLQHDIITSLPEILGDSQHADVGKELSDLLIENTSLTVPILDVLSSLRLDPNFLLKVRQLVMDKLSSIRLEDLPVIIKFILHSVTAMDTLEVISELREKLDLQHCVLPSRLQASQVKLKSKGRASSSGNQESSGQSCIILLFDVIKSAIRYEKTISEAWIKAIENTASVSEHKVFDLVMLFIIYSTNTQTKKYIDRVLRNKIRSGCIQEQLLQSTFSVHYLVLKDMCSSILSLAQSLLHSLDQSIISFGSLLYKYAFKFFDTYCQQEVVGALVTHICSGNEAEVDTALDVLLELVVLNPSAMMMNAVFVKGILDYLDNISPQQIRKLFYVLSTLAFSKQNEASSHIQDDMHLVIRKQLSSTVFKYKLIGIIGAVTMAGIMAADRSESPSLTQERANLSDEQCTQVTSLLQLVHSCSEQSPQASALYYDEFANLIQHEKLDPKALEWVGHTICNDFQDAFVVDSCVVPEGDFPFPVKALYGLEEYDTQDGIAINLLPLLFSQDFAKDGGPVTSQESGQKLVSPLCLAPYFRLLRLCVERQHNGNLEEIDGLLDCPIFLTDLEPGEKLESMSAKERSFMCSLIFLTLNWFREIVNAFCQETSPEMKGKVLTRLKHIVELQIILEKYLAVTPDYVPPLGNFDVETLDITPHTVTAISAKIRKKGKIERKQKTDGSKTSSSDTLSEEKNSECDPTPSHRGQLNKEFTGKEEKTSLLLHNSHAFFRELDIEVFSILHCGLVTKFILDTEMHTEATEVVQLGPPELLFLLEDLSQKLESMLTPPIARRVPFLKNKGSRNIGFSHLQQRSAQEIVHCVFQLLTPMCNHLENIHNYFQCLAAENHGVVDGPGVKVQEYHIMSSCYQRLLQIFHGLFAWSGFSQPENQNLLYSALHVLSSRLKQGEHSQPLEELLSQSVHYLQNFHQSIPSFQCALYLIRLLMVILEKSTASAQNKEKIASLARQFLCRVWPSGDKEKSNISNDQLHALLCIYLEHTESILKAIEEIAGVGVPELINSPKDASSSTFPTLTRHTFVVFFRVMMAELEKTVKKIEPGTAADSQQIHEEKLLYWNMAVRDFSILINLIKVFDSHPVLHVCLKYGRLFVEAFLKQCMPLLDFSFRKHREDVLSLLETFQLDTRLLHHLCGHSKIHQDTRLTQHVPLLKKTLELLVCRVKAMLTLNNCREAFWLGNLKNRDLQGEEIKSQNSQESTADESEDDMSSQASKSKATEDGEEDEVSAGEKEQDSDESYDDSD
uniprot
proteins
disease_involvement
DISEASE: Fanconi anemia complementation group D2 (FANCD2) [MIM:227646]: 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. {ECO:0000269|PubMed:11239453}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Required for maintenance of chromosomal stability (PubMed:11239453, PubMed:14517836). Promotes accurate and efficient pairing of homologs during meiosis (PubMed:14517836). Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing (PubMed:15671039, PubMed:15650050, PubMed:30335751, PubMed:36385258). The FANCI-FANCD2 complex binds and scans double-stranded DNA (dsDNA) for DNA damage; this complex stalls at DNA junctions between double-stranded DNA and single-stranded DNA (By similarity). May participate in S phase and G2 phase checkpoint activation upon DNA damage (PubMed:15377654). Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress (PubMed:15454491, PubMed:15661754). Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress (PubMed:15661754, PubMed:19465921). Promotes BRCA2/FANCD1 loading onto damaged chromatin (PubMed:11239454, PubMed:12239151, PubMed:12086603, PubMed:15115758, PubMed:15199141, PubMed:15671039, PubMed:18212739). May also be involved in B-cell immunoglobulin isotype switching. {ECO:0000250|UniProtKB:Q68Y81, ECO:0000269|PubMed:11239453, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:14517836, ECO:0000269|PubMed:15115758, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15377654, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:15661754, ECO:0000269|PubMed:15671039, ECO:0000269|PubMed:19465921, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:36385258}.
uniprot
proteins
mass_dalton
164128
uniprot
proteins
mutagenesis
MUTAGEN 222; /note="S->A: Reduces phosphorylation by ATM. No effect on ubiquitination, foci formation or DNA repair ability, but impairs S-phase checkpoint activation."; /evidence="ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:15650050"; MUTAGEN 561; /note="K->R: Abolishes ubiquitination; impairs chromatin binding, foci formation and DNA repair. Abolishes interaction with MTMR15/FAN1. No effect on S-222 phosphorylation by ATM."; /evidence="ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12239151, ECO:0000269|PubMed:15454491, ECO:0000269|PubMed:15650050, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073"; MUTAGEN 1257; /note="S->A: No effect on phosphorylation by ATM."; /evidence="ECO:0000269|PubMed:12086603"; MUTAGEN 1401; /note="S->A: Reduces phosphorylation by ATM; when associated with A-1404 and A-1418."; /evidence="ECO:0000269|PubMed:12086603"; MUTAGEN 1404; /note="S->A: Reduces phosphorylation by ATM; when associated with A-1401 and A-1418."; /evidence="ECO:0000269|PubMed:12086603"; MUTAGEN 1418; /note="S->A: Reduces phosphorylation by ATM; when associated with A-1401 and A-1404."; /evidence="ECO:0000269|PubMed:12086603
uniprot
proteins
post_translational_modification
PTM: Monoubiquitinated on Lys-561 during S phase and upon genotoxic stress by FANCL in complex with E2 ligases UBE2T or UBE2W (isoform 1 and isoform 2) (PubMed:11239454, PubMed:12973351, PubMed:19111657, PubMed:20603015, PubMed:20603016, PubMed:20603073, PubMed:36385258). Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed (PubMed:15694335, PubMed:36385258). Monoubiquitination requires the joint intervention of the FANC core complex, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, and FANCM, and proteins involved in cell cycle checkpoints and DNA repair, including RPA1, ATR, CHEK1 and BRCA1, and is mediated by FANCL/PHF9 (PubMed:12973351). Monoubiquitination prevents DNA release from the FANCI-FANCD2 complex (By similarity). FANCD2 is only ubiquitinated in the FANCI-FANCD2 complex and the monoubiquitination of FANCD2 is promoted by phosphorylation of FANCI (By similarity). Ubiquitination is required for binding to chromatin, interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression, but not for phosphorylation on Ser-222 or interaction with MEN1 (PubMed:12086603, PubMed:15650050). {ECO:0000250|UniProtKB:Q68Y81, ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:12973351, ECO:0000269|PubMed:15694335, ECO:0000269|PubMed:19111657, ECO:0000269|PubMed:20603015, ECO:0000269|PubMed:20603016, ECO:0000269|PubMed:20603073, ECO:0000269|PubMed:30335751, ECO:0000269|PubMed:36385258}.; PTM: Phosphorylated in response to various genotoxic stresses by ATM and/or ATR (PubMed:14988723, PubMed:15314022). Upon ionizing radiation, phosphorylated by ATM on Ser-222 and Ser-1404 (PubMed:12086603). Phosphorylation on Ser-222 is required for S-phase checkpoint activation, but not for ubiquitination, foci formation, or DNA repair (PubMed:12086603, PubMed:15650050). In contrast, phosphorylation by ATR on other sites may be required for ubiquitination and foci formation. {ECO:0000269|PubMed:12086603, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15650050}.
uniprot
proteins
protein_family
Fanconi anemia protein FANCD2 family
uniprot
proteins
pubmed
11239453
uniprot
proteins
pubmed
11239454
uniprot
proteins
pubmed
12086603
uniprot
proteins
pubmed
12093742
uniprot
proteins
pubmed
12239151
uniprot
proteins
pubmed
12649160
uniprot
proteins
pubmed
12874027
uniprot
proteins
pubmed
12973351
uniprot
proteins
pubmed
14517836
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14988723
uniprot
proteins
pubmed
15115758
uniprot
proteins
pubmed
15199141
uniprot
proteins
pubmed
15257300
uniprot
proteins
pubmed
15314022
uniprot
proteins
pubmed
15377654
uniprot
proteins
pubmed
15454491
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15502827
uniprot
proteins
pubmed
15650050
uniprot
proteins
pubmed
15661754
uniprot
proteins
pubmed
15671039
uniprot
proteins
pubmed
15694335
uniprot
proteins
pubmed
16116422
uniprot
proteins
pubmed
16916645
uniprot
proteins
pubmed
17412408
uniprot
proteins
pubmed
17460694
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18212739
uniprot
proteins
pubmed
18469862
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19111657
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19465921
uniprot
proteins
pubmed
19465922
uniprot
proteins
pubmed
19995904
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20603015
uniprot
proteins
pubmed
20603016
uniprot
proteins
pubmed
20603073
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
30335751
uniprot
proteins
pubmed
36385258
uniprot
proteins
sequence_length
1451
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:12093742, ECO:0000269|PubMed:19465921, ECO:0000269|PubMed:19465922, ECO:0000269|PubMed:30335751}. Note=Concentrates in nuclear foci during S phase and upon genotoxic stress. At the onset of mitosis, excluded from chromosomes and diffuses into the cytoplasm, returning to the nucleus at the end of cell division. Observed in a few spots localized in pairs on the sister chromatids of mitotic chromosome arms and not centromeres, one on each chromatids. These foci coincide with common fragile sites and could be sites of replication fork stalling. The foci are frequently interlinked through BLM-associated ultra-fine DNA bridges. Following aphidicolin treatment, targets chromatid gaps and breaks.
uniprot
proteins