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Q9BXW9 (FACD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fanconi anemia group D2 protein

Short name=Protein FACD2
Gene names
Name:FANCD2
Synonyms:FACD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1471 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by replicative stress. Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be involved in B-cell immunoglobulin isotype switching. Ref.1 Ref.6 Ref.7 Ref.8 Ref.12 Ref.16 Ref.17 Ref.18 Ref.21 Ref.22 Ref.23 Ref.26 Ref.39

Subunit structure

Interacts directly with FANCE and FANCI. Interacts with USP1 and MEN1. The ubiquitinated form specifically interacts with BRCA1 and BLM. Both the nonubiquitinated and the monoubiquitinated forms interact with BRCA2; this interaction is mediated by phosphorylated FANCG and the complex also includes XCCR3. The ubiquitinated form specifically interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to recruit MTMR15/FAN1 to sites of DNA damage. Interacts with DCLRE1B/Apollo. Ref.6 Ref.9 Ref.10 Ref.11 Ref.15 Ref.17 Ref.19 Ref.24 Ref.28 Ref.29 Ref.33 Ref.34 Ref.40 Ref.41 Ref.42

Subcellular location

Nucleus. 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. Ref.6 Ref.9 Ref.38 Ref.39

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. Ref.1 Ref.12 Ref.21

Developmental stage

Highly expressed in fetal oocytes, and in hematopoietic cells of the fetal liver and bone marrow (at protein level). Ref.12

Domain

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

Post-translational modification

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) Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is completed. 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. 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.

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. Ref.8 Ref.14 Ref.16

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence caution

The sequence BAB14132.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BXW9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Less abundant than isoform 2, may be not functional.
Isoform 2 (identifier: Q9BXW9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1428-1451: VSLQNPPESGTDGCILLIVLSWWS → DGEEDEVSAGEKEQDSDESYDDSD
     1452-1471: Missing.
Note: Contains a phosphoserine at position 1423. Contains a phosphothreonine at position 1426. Contains a phosphoserine at position 1435.
Isoform 3 (identifier: Q9BXW9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1229-1249: HTFVVFFRVMMAELEKTVKKI → FMKRNSSTGTWLFETSVSSST
     1250-1471: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q9BXW9-4)

The sequence of this isoform differs from the canonical sequence as follows:
     232-241: SDLLIENTSL → RWINPLSSSK
     242-1471: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14711471Fanconi anemia group D2 protein
PRO_0000087168

Regions

Region1 – 291291Interaction with FANCE
Region248 – 359112Interaction with BRCA2

Amino acid modifications

Modified residue81Phosphoserine Ref.43
Modified residue2221Phosphoserine; by ATM Ref.8
Modified residue5921Phosphoserine Ref.30
Modified residue5941Phosphoserine Ref.43
Modified residue7171Phosphoserine Ref.43
Modified residue14011Phosphoserine; by ATM Probable
Modified residue14041Phosphoserine; by ATM Ref.8
Modified residue14121Phosphoserine Ref.30 Ref.35 Ref.43
Cross-link561Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.6 Ref.32 Ref.40 Ref.41 Ref.42

Natural variations

Alternative sequence232 – 24110SDLLIENTSL → RWINPLSSSK in isoform 4.
VSP_013883
Alternative sequence242 – 14711230Missing in isoform 4.
VSP_013884
Alternative sequence1229 – 124921HTFVV…TVKKI → FMKRNSSTGTWLFETSVSSS T in isoform 3.
VSP_013885
Alternative sequence1250 – 1471222Missing in isoform 3.
VSP_013886
Alternative sequence1428 – 145124VSLQN…LSWWS → DGEEDEVSAGEKEQDSDESY DDSD in isoform 2.
VSP_013887
Alternative sequence1452 – 147120Missing in isoform 2.
VSP_013888
Natural variant331K → R. Ref.2
Corresponds to variant rs34691009 [ dbSNP | Ensembl ].
VAR_025827
Natural variant611T → M. Ref.2
Corresponds to variant rs35110529 [ dbSNP | Ensembl ].
VAR_025828
Natural variant651Q → H. Ref.2
Corresponds to variant rs36084488 [ dbSNP | Ensembl ].
VAR_025829
Natural variant1261S → G in FANCD2.
VAR_022559
Natural variant1721I → M. Ref.2
Corresponds to variant rs35173688 [ dbSNP | Ensembl ].
VAR_025830
Natural variant1931T → A. Ref.2
Corresponds to variant rs34936017 [ dbSNP | Ensembl ].
VAR_025831
Natural variant3021R → W in FANCD2. Ref.1
VAR_022560
Natural variant3281R → Q. Ref.2
Corresponds to variant rs35625434 [ dbSNP | Ensembl ].
VAR_025832
Natural variant4461L → V. Ref.2
Corresponds to variant rs34557223 [ dbSNP | Ensembl ].
VAR_025833
Natural variant4561L → R. Ref.2
Corresponds to variant rs35782247 [ dbSNP | Ensembl ].
VAR_025834
Natural variant6231Q → P. Ref.2
Corresponds to variant rs36070315 [ dbSNP | Ensembl ].
VAR_025835
Natural variant7141P → L Common polymorphism. Ref.1 Ref.2 Ref.43
Corresponds to variant rs3864017 [ dbSNP | Ensembl ].
VAR_022561
Natural variant8651K → R. Ref.2
Corresponds to variant rs35546777 [ dbSNP | Ensembl ].
VAR_025836
Natural variant9011G → V. Ref.2
Corresponds to variant rs35495399 [ dbSNP | Ensembl ].
VAR_025837
Natural variant12361R → H in FANCD2; no effect on ubiquitination. Ref.1
VAR_022562

Experimental info

Mutagenesis2221S → A: Reduces phosphorylation by ATM. No effect on ubiquitination, foci formation or DNA repair ability, but impairs S-phase checkpoint activation. Ref.8 Ref.26
Mutagenesis5611K → R: Abolishes ubiquitination; impairs chromatin binding, foci formation and DNA repair. Abolishes interaction with MTMR15/FAN1. No effect on S-222 phosphorylation by ATM. Ref.6 Ref.7 Ref.8 Ref.21 Ref.26 Ref.32 Ref.40 Ref.41 Ref.42
Mutagenesis12571S → A: No effect on phosphorylation by ATM. Ref.8
Mutagenesis14011S → A: Reduces phosphorylation by ATM; when associated with A-1404 and A-1418. Ref.8
Mutagenesis14041S → A: Reduces phosphorylation by ATM; when associated with A-1401 and A-1418. Ref.8
Mutagenesis14181S → A: Reduces phosphorylation by ATM; when associated with A-1401 and A-1404. Ref.8
Sequence conflict2571N → D in BAB14132. Ref.4
Sequence conflict5571L → S in BAB14132. Ref.4
Sequence conflict5891R → G in BAB14132. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 1, 2001. Version 1.
Checksum: 4F74873A1D45A9AE

FASTA1,471166,462
        10         20         30         40         50         60 
MVSKRRLSKS EDKESLTEDA SKTRKQPLSK KTKKSHIANE VEENDSIFVK LLKISGIILK 

        70         80         90        100        110        120 
TGESQNQLAV DQIAFQKKLF QTLRRHPSYP KIIEEFVSGL ESYIEDEDSF RNCLLSCERL 

       130        140        150        160        170        180 
QDEEASMGAS YSKSLIKLLL GIDILQPAII KTLFEKLPEY FFENKNSDEI NIPRLIVSQL 

       190        200        210        220        230        240 
KWLDRVVDGK DLTTKIMQLI SIAPENLQHD IITSLPEILG DSQHADVGKE LSDLLIENTS 

       250        260        270        280        290        300 
LTVPILDVLS SLRLDPNFLL KVRQLVMDKL SSIRLEDLPV IIKFILHSVT AMDTLEVISE 

       310        320        330        340        350        360 
LREKLDLQHC VLPSRLQASQ VKLKSKGRAS SSGNQESSGQ SCIILLFDVI KSAIRYEKTI 

       370        380        390        400        410        420 
SEAWIKAIEN TASVSEHKVF DLVMLFIIYS TNTQTKKYID RVLRNKIRSG CIQEQLLQST 

       430        440        450        460        470        480 
FSVHYLVLKD MCSSILSLAQ SLLHSLDQSI ISFGSLLYKY AFKFFDTYCQ QEVVGALVTH 

       490        500        510        520        530        540 
ICSGNEAEVD TALDVLLELV VLNPSAMMMN AVFVKGILDY LDNISPQQIR KLFYVLSTLA 

       550        560        570        580        590        600 
FSKQNEASSH IQDDMHLVIR KQLSSTVFKY KLIGIIGAVT MAGIMAADRS ESPSLTQERA 

       610        620        630        640        650        660 
NLSDEQCTQV TSLLQLVHSC SEQSPQASAL YYDEFANLIQ HEKLDPKALE WVGHTICNDF 

       670        680        690        700        710        720 
QDAFVVDSCV VPEGDFPFPV KALYGLEEYD TQDGIAINLL PLLFSQDFAK DGGPVTSQES 

       730        740        750        760        770        780 
GQKLVSPLCL APYFRLLRLC VERQHNGNLE EIDGLLDCPI FLTDLEPGEK LESMSAKERS 

       790        800        810        820        830        840 
FMCSLIFLTL NWFREIVNAF CQETSPEMKG KVLTRLKHIV ELQIILEKYL AVTPDYVPPL 

       850        860        870        880        890        900 
GNFDVETLDI TPHTVTAISA KIRKKGKIER KQKTDGSKTS SSDTLSEEKN SECDPTPSHR 

       910        920        930        940        950        960 
GQLNKEFTGK EEKTSLLLHN SHAFFRELDI EVFSILHCGL VTKFILDTEM HTEATEVVQL 

       970        980        990       1000       1010       1020 
GPPELLFLLE DLSQKLESML TPPIARRVPF LKNKGSRNIG FSHLQQRSAQ EIVHCVFQLL 

      1030       1040       1050       1060       1070       1080 
TPMCNHLENI HNYFQCLAAE NHGVVDGPGV KVQEYHIMSS CYQRLLQIFH GLFAWSGFSQ 

      1090       1100       1110       1120       1130       1140 
PENQNLLYSA LHVLSSRLKQ GEHSQPLEEL LSQSVHYLQN FHQSIPSFQC ALYLIRLLMV 

      1150       1160       1170       1180       1190       1200 
ILEKSTASAQ NKEKIASLAR QFLCRVWPSG DKEKSNISND QLHALLCIYL EHTESILKAI 

      1210       1220       1230       1240       1250       1260 
EEIAGVGVPE LINSPKDASS STFPTLTRHT FVVFFRVMMA ELEKTVKKIE PGTAADSQQI 

      1270       1280       1290       1300       1310       1320 
HEEKLLYWNM AVRDFSILIN LIKVFDSHPV LHVCLKYGRL FVEAFLKQCM PLLDFSFRKH 

      1330       1340       1350       1360       1370       1380 
REDVLSLLET FQLDTRLLHH LCGHSKIHQD TRLTQHVPLL KKTLELLVCR VKAMLTLNNC 

      1390       1400       1410       1420       1430       1440 
REAFWLGNLK NRDLQGEEIK SQNSQESTAD ESEDDMSSQA SKSKATEVSL QNPPESGTDG 

      1450       1460       1470 
CILLIVLSWW SRTLPTYVYC QMLLCPFPFP P 

« Hide

Isoform 2 [UniParc].

Checksum: BF931980ADA67405
Show »

FASTA1,451164,128
Isoform 3 [UniParc].

Checksum: EAA0E12DE9F079D1
Show »

FASTA1,249140,737
Isoform 4 [UniParc].

Checksum: 4078C6A54D083DDE
Show »

FASTA24127,501

References

« Hide 'large scale' references
[1]"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 A.D., Moses R., Grompe M.
Mol. Cell 7:241-248(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE SPECIFICITY, VARIANTS FANCD2 TRP-302 AND HIS-1236, VARIANT LEU-714.
Tissue: Lymphoblast.
[2]NIEHS SNPs program
Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-33; MET-61; HIS-65; MET-172; ALA-193; GLN-328; VAL-446; ARG-456; PRO-623; LEU-714; ARG-865 AND VAL-901.
[3]"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] (ISOFORM 4).
Tissue: Lung.
[4]"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. expand/collapse author list , 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] OF 161-860 (ISOFORM 1).
Tissue: Teratocarcinoma.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 502-1471 (ISOFORM 3).
Tissue: Melanoma.
[6]"Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway."
Garcia-Higuera I., Taniguchi T., Ganesan S., Meyn M.S., Timmers C., Hejna J., Grompe M., D'Andrea A.D.
Mol. Cell 7:249-262(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, UBIQUITINATION AT LYS-561, MUTAGENESIS OF LYS-561, INTERACTION WITH BRCA1, IDENTIFICATION BY MASS SPECTROMETRY.
[7]"S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51."
Taniguchi T., Garcia-Higuera I., Andreassen P.R., Gregory R.C., Grompe M., D'Andrea A.D.
Blood 100:2414-2420(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, UBIQUITINATION, MUTAGENESIS OF LYS-561.
[8]"Convergence of the Fanconi anemia and ataxia telangiectasia signaling pathways."
Taniguchi T., Garcia-Higuera I., Xu B., Andreassen P.R., Gregory R.C., Kim S.-T., Lane W.S., Kastan M.B., D'Andrea A.D.
Cell 109:459-472(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-222 AND SER-1404, MUTAGENESIS OF SER-222; LYS-561; SER-1257; SER-1401; SER-1404 AND SER-1418, IDENTIFICATION BY MASS SPECTROMETRY.
[9]"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: SUBCELLULAR LOCATION, INTERACTION WITH FANCE.
[10]"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 FANCE.
[11]"Menin associates with FANCD2, a protein involved in repair of DNA damage."
Jin S., Mao H., Schnepp R.W., Sykes S.M., Silva A.C., D'Andrea A.D., Hua X.
Cancer Res. 63:4204-4210(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEN1, IDENTIFICATION BY MASS SPECTROMETRY.
[12]"FANCD2 protein is expressed in proliferating cells of human tissues that are cancer-prone in Fanconi anaemia."
Hoelzel M., van Diest P.J., Bier P., Wallisch M., Hoatlin M.E., Joenje H., de Winter J.P.
J. Pathol. 201:198-203(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, FUNCTION.
[13]"A novel ubiquitin ligase is deficient in Fanconi anemia."
Meetei A.R., de Winter J.P., Medhurst A.L., Wallisch M., Waisfisz Q., van de Vrugt H.J., Oostra A.B., Yan Z., Ling C., Bishop C.E., Hoatlin M.E., Joenje H., Wang W.
Nat. Genet. 35:165-170(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY FANCL.
[14]"The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways."
Pichierri P., Rosselli F.
EMBO J. 23:1178-1187(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY ATR.
[15]"BLM and the FANC proteins collaborate in a common pathway in response to stalled replication forks."
Pichierri P., Franchitto A., Rosselli F.
EMBO J. 23:3154-3163(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BLM.
[16]"ATR couples FANCD2 monoubiquitination to the DNA-damage response."
Andreassen P.R., D'Andrea A.D., Taniguchi T.
Genes Dev. 18:1958-1963(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION BY ATR, UBIQUITINATION.
[17]"Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways."
Hussain S., Wilson J.B., Medhurst A.L., Hejna J., Witt E., Ananth S., Davies A., Masson J.-Y., Moses R., West S.C., de Winter J.P., Ashworth A., Jones N.J., Mathew C.G.
Hum. Mol. Genet. 13:1241-1248(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BRCA2.
[18]"A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint."
Freie B.W., Ciccone S.L.M., Li X., Plett P.A., Orschell C.M., Srour E.F., Hanenberg H., Schindler D., Lee S.-H., Clapp D.W.
J. Biol. Chem. 279:50986-50993(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin."
Wang X.Z., Andreassen P.R., D'Andrea A.D.
Mol. Cell. Biol. 24:5850-5862(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION, INTERACTION WITH BRCA2.
[20]"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: UBIQUITINATION.
[21]"Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin."
Montes de Oca R., Andreassen P.R., Margossian S.P., Gregory R.C., Taniguchi T., Wang X.Z., Houghtaling S., Grompe M., D'Andrea A.D.
Blood 105:1003-1009(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-561, CHARACTERIZATION (ISOFORM 2).
[22]"The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability."
Howlett N.G., Taniguchi T., Durkin S.G., D'Andrea A.D., Glover T.W.
Hum. Mol. Genet. 14:693-701(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[23]"FANCD2 functions independently of BRCA2 and RAD51 associated homologous recombination in response to DNA damage."
Ohashi A., Zdzienicka M.Z., Chen J., Couch F.J.
J. Biol. Chem. 280:14877-14883(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[24]"The deubiquitinating enzyme USP1 regulates the Fanconi Anemia pathway."
Nijman S.M.B., Huang T.T., Dirac A.M.G., Brummelkamp T.R., Kerkhoven R.M., D'Andrea A.D., Bernards R.
Mol. Cell 17:331-339(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH USP1, DEUBIQUITINATION.
[25]"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: UBIQUITINATION.
[26]"Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair."
Nakanishi K., Yang Y.-G., Pierce A.J., Taniguchi T., Digweed M., D'Andrea A.D., Wang Z.-Q., Jasin M.
Proc. Natl. Acad. Sci. U.S.A. 102:1110-1115(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF SER-222 AND LYS-561.
[27]"UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation."
Machida Y.J., Machida Y., Chen Y., Gurtan A.M., Kupfer G.M., D'Andrea A.D., Dutta A.
Mol. Cell 23:589-596(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[28]"Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA repair."
Smogorzewska A., Matsuoka S., Vinciguerra P., McDonald E.R. III, Hurov K.E., Luo J., Ballif B.A., Gygi S.P., Hofmann K., D'Andrea A.D., Elledge S.J.
Cell 129:289-301(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FANCI.
[29]"FANCI is a second monoubiquitinated member of the Fanconi anemia pathway."
Sims A.E., Spiteri E., Sims R.J. III, Arita A.G., Lach F.P., Landers T., Wurm M., Freund M., Neveling K., Hanenberg H., Auerbach A.D., Huang T.T.
Nat. Struct. Mol. Biol. 14:564-567(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FANCI.
[30]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-592 AND SER-1412, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[31]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[32]"Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI."
Alpi A.F., Pace P.E., Babu M.M., Patel K.J.
Mol. Cell 32:767-777(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-561, MUTAGENESIS OF LYS-561.
[33]"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; FANCG AND XRCC3.
[34]"Snm1B/Apollo mediates replication fork collapse and S Phase checkpoint activation in response to DNA interstrand cross-links."
Bae J.B., Mukhopadhyay S.S., Liu L., Zhang N., Tan J., Akhter S., Liu X., Shen X., Li L., Legerski R.J.
Oncogene 27:5045-5056(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DCLRE1B.
[35]"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-1412, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[36]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[37]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[38]"Replication stress induces sister-chromatid bridging at fragile site loci in mitosis."
Chan K.L., Palmai-Pallag T., Ying S., Hickson I.D.
Nat. Cell Biol. 11:753-760(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[39]"The FANC pathway and BLM collaborate during mitosis to prevent micro-nucleation and chromosome abnormalities."
Naim V., Rosselli F.
Nat. Cell Biol. 11:761-768(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[40]"Identification of KIAA1018/FAN1, a DNA repair nuclease recruited to DNA damage by monoubiquitinated FANCD2."
MacKay C., Declais A.C., Lundin C., Agostinho A., Deans A.J., MacArtney T.J., Hofmann K., Gartner A., West S.C., Helleday T., Lilley D.M., Rouse J.
Cell 142:65-76(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, MUTAGENESIS OF LYS-561.
[41]"Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents."
Kratz K., Schopf B., Kaden S., Sendoel A., Eberhard R., Lademann C., Cannavo E., Sartori A.A., Hengartner M.O., Jiricny J.
Cell 142:77-88(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, MUTAGENESIS OF LYS-561.
[42]"A genetic screen identifies FAN1, a Fanconi anemia-associated nuclease necessary for DNA interstrand crosslink repair."
Smogorzewska A., Desetty R., Saito T.T., Schlabach M., Lach F.P., Sowa M.E., Clark A.B., Kunkel T.A., Harper J.W., Colaiacovo M.P., Elledge S.J.
Mol. Cell 39:36-47(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-561, INTERACTION WITH MTMR15, MUTAGENESIS OF LYS-561.
[43]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-594; SER-717 AND SER-1412, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1423; THR-1426 AND SER-1435 (ISOFORM 2), VARIANT [LARGE SCALE ANALYSIS] LEU-714, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[44]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[45]"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-1435 (ISOFORM 2), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF230336 mRNA. Translation: AAL05980.1.
AF273251 expand/collapse EMBL AC list , AF273222, AF273223, AF273227, AF273231, AF273235, AF273243, AF273241, AF273239, AF273245, AF273246, AF273247, AF273248, AF273249, AF273250, AF273236, AF273237, AF273238, AF273224, AF273226, AF273228, AF273230, AF273232, AF273234, AF273240, AF273242, AF273244, AF273233, AF273229, AF273225 Genomic DNA. Translation: AAK18772.1.
AF273251 expand/collapse EMBL AC list , AF273222, AF273223, AF273224, AF273225, AF273226, AF273227, AF273228, AF273229, AF273230, AF273231, AF273232, AF273233, AF273234, AF273235, AF273236, AF273237, AF273238, AF273239, AF273240, AF273241, AF273242, AF273243, AF273244, AF273245, AF273246, AF273247, AF273248, AF273249, AF273250 Genomic DNA. Translation: AAK18773.1.
AF340183 mRNA. Translation: AAK15369.1.
DQ341263 Genomic DNA. Translation: ABC67466.1.
BC013582 mRNA. Translation: AAH13582.1.
AK022613 mRNA. Translation: BAB14132.1. Different initiation.
AL832427 mRNA. Translation: CAH10647.1.
CCDSCCDS2595.1. [Q9BXW9-1]
CCDS33696.1. [Q9BXW9-2]
RefSeqNP_001018125.1. NM_001018115.1. [Q9BXW9-2]
NP_149075.2. NM_033084.3. [Q9BXW9-1]
XP_005265003.1. XM_005264946.1. [Q9BXW9-2]
XP_006713084.1. XM_006713021.1. [Q9BXW9-1]
XP_006713085.1. XM_006713022.1. [Q9BXW9-1]
UniGeneHs.208388.

3D structure databases

ProteinModelPortalQ9BXW9.
SMRQ9BXW9. Positions 46-848.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108474. 40 interactions.
DIPDIP-27606N.
DIP-29382N.
IntActQ9BXW9. 19 interactions.
MINTMINT-190855.
STRING9606.ENSP00000287647.

Chemistry

ChEMBLCHEMBL2157857.

PTM databases

PhosphoSiteQ9BXW9.

Polymorphism databases

DMDM67461071.

Proteomic databases

MaxQBQ9BXW9.
PaxDbQ9BXW9.
PRIDEQ9BXW9.

Protocols and materials databases

DNASU2177.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287647; ENSP00000287647; ENSG00000144554. [Q9BXW9-1]
ENST00000383806; ENSP00000373317; ENSG00000144554. [Q9BXW9-3]
ENST00000383807; ENSP00000373318; ENSG00000144554. [Q9BXW9-2]
ENST00000419585; ENSP00000398754; ENSG00000144554. [Q9BXW9-2]
ENST00000431693; ENSP00000399354; ENSG00000144554. [Q9BXW9-4]
GeneID2177.
KEGGhsa:2177.
UCSCuc003buv.3. human. [Q9BXW9-4]
uc003buw.3. human. [Q9BXW9-1]
uc003bux.1. human. [Q9BXW9-2]

Organism-specific databases

CTD2177.
GeneCardsGC03P010068.
GeneReviewsFANCD2.
H-InvDBHIX0003045.
HGNCHGNC:3585. FANCD2.
HPACAB016117.
HPA054101.
MIM227646. phenotype.
613984. gene.
neXtProtNX_Q9BXW9.
Orphanet84. Fanconi anemia.
PharmGKBPA27999.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG305332.
HOGENOMHOG000060189.
HOVERGENHBG060904.
InParanoidQ9BXW9.
KOK10891.
OMASHIQDDM.
OrthoDBEOG7QZGB3.
PhylomeDBQ9BXW9.
TreeFamTF101106.

Enzyme and pathway databases

ReactomeREACT_216. DNA Repair.

Gene expression databases

ArrayExpressQ9BXW9.
BgeeQ9BXW9.
CleanExHS_FANCD2.
GenevestigatorQ9BXW9.

Family and domain databases

InterProIPR029448. FANCD2.
[Graphical view]
PfamPF14631. FancD2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFANCD2. human.
GeneWikiFANCD2.
GenomeRNAi2177.
NextBio8791.
PROQ9BXW9.
SOURCESearch...

Entry information

Entry nameFACD2_HUMAN
AccessionPrimary (citable) accession number: Q9BXW9
Secondary accession number(s): Q2LA86 expand/collapse secondary AC list , Q69YP9, Q6PJN7, Q9BQ06, Q9H9T9
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM