Homo sapiens L. (human) [HSA]

FULL NAME: Fanconi anemia group D2 protein


DESCRIPTION:
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.

POST-TRANSLATIONAL MODIFICATION:
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.
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, BRCA2 and MTMR15/FAN1, DNA repair, and normal cell cycle progression, but not for phosphorylation on Ser-222 or interaction with MEN1.


RELATED PATHWAY(S):
Fanconi anemia (FA) pathway


RELATED DISEASE(S):
Fanconi anemia, complementation group D2 (FANCD2)


Amino acids sequence

        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  

Encoded by FANCD2 gene

FULL NAME: Fanconi anemia, complementation group D2


OTHER NAME(S):
DKFZp762A223
FA-D2
FA4
FACD
FAD
FAD2
FANCD
FLJ23826


DESCRIPTION:
The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group D2. This protein is monoubiquinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins (BRCA1 AND BRCA2) involved in homology-directed DNA repair. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]


Nucleic acid sequence

        10         20         30         40         50         60
atggtttcca aaagaagact gtcaaaatct gaggataaag agagcctgac agaagatgcc
        70         80         90        100        110        120
tccaaaacca ggaagcaacc actttccaaa aagacaaaga aatctcatat tgctaatgaa
       130        140        150        160        170        180
gttgaagaaa atgacagcat ctttgtaaag cttcttaaga tatcaggaat tattcttaaa
       190        200        210        220        230        240
acgggagaga gtcagaatca actagctgtg gatcaaatag ctttccaaaa gaagctcttt
       250        260        270        280        290        300
cagaccctga ggagacaccc ttcctatccc aaaataatag aagaatttgt tagtggcctg
       310        320        330        340        350        360
gagtcttaca ttgaggatga agacagtttc aggaactgcc ttttgtcttg tgagcgtctg
       370        380        390        400        410        420
caggatgagg aagccagtat gggtgcatct tattctaaga gtctcatcaa actgcttctg
       430        440        450        460        470        480
gggattgaca tactgcagcc tgccattatc aaaaccttat ttgagaagtt gccagaatat
       490        500        510        520        530        540
ttttttgaaa acaagaacag tgatgaaatc aacatacctc gactcattgt cagtcaacta
       550        560        570        580        590        600
aaatggcttg acagagttgt ggatggcaag gacctcacca ccaagatcat gcagctgatc
       610        620        630        640        650        660
agtattgctc cagagaacct gcagcatgac atcatcacca gcctacctga gatcctaggg
       670        680        690        700        710        720
gattcccagc acgctgatgt ggggaaagaa ctcagtgacc tactgataga gaatacttca
       730        740        750        760        770        780
ctcactgtcc caatcctgga tgtcctttca agcctccgac ttgacccaaa cttcctattg
       790        800        810        820        830        840
aaggttcgcc agttggtgat ggataagttg tcgtctatta gattggagga tttacctgtg
       850        860        870        880        890        900
ataataaagt tcattcttca ttccgtaaca gccatggata cacttgaggt aatttctgag
       910        920        930        940        950        960
cttcgggaga agttggatct gcagcattgt gttttgccat cacggttaca ggcttcccaa
       970        980        990       1000       1010       1020
gtaaagttga aaagtaaagg acgagcaagt tcctcaggaa atcaagaaag cagcggtcag
      1030       1040       1050       1060       1070       1080
agctgtatta ttctcctctt tgatgtaata aagtcagcta ttagatatga gaaaaccatt
      1090       1100       1110       1120       1130       1140
tcagaagcct ggattaaggc aattgaaaac actgcctcag tatctgaaca caaggtgttt
      1150       1160       1170       1180       1190       1200
gacctggtga tgcttttcat catctatagc accaatactc agacaaagaa gtacattgac
      1210       1220       1230       1240       1250       1260
agggtgctaa gaaataagat tcgatcaggc tgcattcaag aacagctgct ccagagtaca
      1270       1280       1290       1300       1310       1320
ttctctgttc attacttagt tcttaaggat atgtgttcat ccattctgtc gctggctcag
      1330       1340       1350       1360       1370       1380
agtttgcttc actctctaga ccagagtata atttcatttg gcagtctcct atacaaatat
      1390       1400       1410       1420       1430       1440
gcatttaagt tttttgacac gtactgccag caggaagtgg ttggtgcctt agtgacccat
      1450       1460       1470       1480       1490       1500
atctgcagtg ggaatgaagc tgaagttgat actgccttag atgtccttct agagttggta
      1510       1520       1530       1540       1550       1560
gtgttaaacc catctgctat gatgatgaat gctgtctttg taaagggcat tttagattat
      1570       1580       1590       1600       1610       1620
ctggataaca tatcccctca gcaaatacga aaactcttct atgttctcag cacactggca
      1630       1640       1650       1660       1670       1680
tttagcaaac agaatgaagc cagcagccac atccaggatg acatgcactt ggtgataaga
      1690       1700       1710       1720       1730       1740
aagcagctct ctagcaccgt attcaagtac aagctcattg ggattattgg tgctgtgacc
      1750       1760       1770       1780       1790       1800
atggctggca tcatggcggc agacagaagt gaatcaccta gtttgaccca agagagagcc
      1810       1820       1830       1840       1850       1860
aacctgagcg atgagcagtg cacacaggtg acctccttgt tgcagttggt tcattcctgc
      1870       1880       1890       1900       1910       1920
agtgagcagt ctcctcaggc ctctgcactt tactatgatg aatttgccaa cctgatccaa
      1930       1940       1950       1960       1970       1980
catgaaaagc tggatccaaa agccctggaa tgggttgggc ataccatctg taatgatttc
      1990       2000       2010       2020       2030       2040
caggatgcct tcgtagtgga ctcctgtgtt gttccggaag gtgactttcc atttcctgtg
      2050       2060       2070       2080       2090       2100
aaagcactgt acggactgga agaatacgac actcaggatg ggattgccat aaacctcctg
      2110       2120       2130       2140       2150       2160
ccgctgctgt tttctcagga ctttgcaaaa gatgggggtc cggtgacctc acaggaatca
      2170       2180       2190       2200       2210       2220
ggccaaaaat tggtgtctcc gctgtgcctg gctccgtatt tccggttact gagactttgt
      2230       2240       2250       2260       2270       2280
gtggagagac agcataacgg aaacttggag gagattgatg gtctactaga ttgtcctata
      2290       2300       2310       2320       2330       2340
ttcctaactg acctggagcc tggagagaag ttggagtcca tgtctgctaa agagcgttca
      2350       2360       2370       2380       2390       2400
ttcatgtgtt ctctcatatt tcttactctc aactggttcc gagagattgt aaatgccttc
      2410       2420       2430       2440       2450       2460
tgccaggaaa catcacctga gatgaagggg aaggtgctca ctcggttaaa gcacattgta
      2470       2480       2490       2500       2510       2520
gaattgcaaa taatcctgga aaagtacttg gcagtcaccc cagactatgt ccctcctctt
      2530       2540       2550       2560       2570       2580
ggaaactttg atgtggaaac tttagatata acacctcata ctgttactgc tatttcagca
      2590       2600       2610       2620       2630       2640
aaaatcagaa agaaaggaaa aatagaaagg aaacaaaaaa cagatggcag caagacatcc
      2650       2660       2670       2680       2690       2700
tcctctgaca cactttcaga agagaaaaat tcagaatgtg accctacgcc atctcataga
      2710       2720       2730       2740       2750       2760
ggccagctaa acaaggagtt cacagggaag gaagaaaaga catcattgtt actacataat
      2770       2780       2790       2800       2810       2820
tcccatgctt ttttccgaga gctggacatt gaggtcttct ctattctaca ttgtggactt
      2830       2840       2850       2860       2870       2880
gtgacgaagt tcatcttaga tactgaaatg cacactgaag ctacagaagt tgtgcaactt
      2890       2900       2910       2920       2930       2940
gggccccctg agctgctttt cttgctggaa gatctctccc agaagctgga gagtatgctg
      2950       2960       2970       2980       2990       3000
acacctccta ttgccaggag agtccccttt ctcaagaaca aaggaagccg gaatattgga
      3010       3020       3030       3040       3050       3060
ttctcacatc tccaacagag atctgcccaa gaaattgttc attgtgtttt tcaactgctg
      3070       3080       3090       3100       3110       3120
accccaatgt gtaaccacct ggagaacatt cacaactatt ttcagtgttt agctgctgag
      3130       3140       3150       3160       3170       3180
aatcacggtg tagttgatgg accaggagtg aaagttcagg agtaccacat aatgtcttcc
      3190       3200       3210       3220       3230       3240
tgctatcaga ggctgctgca gatttttcat gggctttttg cttggagtgg attttctcaa
      3250       3260       3270       3280       3290       3300
cctgaaaatc agaatttact gtattcagcc ctccatgtcc ttagtagccg actgaaacag
      3310       3320       3330       3340       3350       3360
ggagaacaca gccagccttt ggaggaacta ctcagccaga gcgtccatta cttgcagaat
      3370       3380       3390       3400       3410       3420
ttccatcaaa gcattcccag tttccagtgt gctctttatc tcatcagact tttgatggtt
      3430       3440       3450       3460       3470       3480
attttggaga aatcaacagc ttctgctcag aacaaagaaa aaattgcttc ccttgccaga
      3490       3500       3510       3520       3530       3540
caattcctct gtcgggtgtg gccaagtggg gataaagaga agagcaacat ctctaatgac
      3550       3560       3570       3580       3590       3600
cagctccatg ctctgctctg tatctacctg gagcacacag agagcattct gaaggccata
      3610       3620       3630       3640       3650       3660
gaggagattg ctggtgttgg tgtcccagaa ctgatcaact ctcctaaaga tgcatcttcc
      3670       3680       3690       3700       3710       3720
tccacattcc ctacactgac caggcatact tttgttgttt tcttccgtgt gatgatggct
      3730       3740       3750       3760       3770       3780
gaactagaga agacggtgaa aaaaattgag cctggcacag cagcagactc gcagcagatt
      3790       3800       3810       3820       3830       3840
catgaagaga aactcctcta ctggaacatg gctgttcgag acttcagtat cctcatcaac
      3850       3860       3870       3880       3890       3900
ttgataaagg tatttgatag tcatcctgtt ctgcatgtat gtttgaagta tgggcgtctc
      3910       3920       3930       3940       3950       3960
tttgtggaag catttctgaa gcaatgtatg ccgctcctag acttcagttt tagaaaacac
      3970       3980       3990       4000       4010       4020
cgggaagatg ttctgagctt actggaaacc ttccagttgg acacaaggct gcttcatcac
      4030       4040       4050       4060       4070       4080
ctgtgtgggc attccaagat tcaccaggac acgagactca cccaacatgt gcctctgctc
      4090       4100       4110       4120       4130       4140
aaaaagaccc tggaactttt agtttgcaga gtcaaagcta tgctcactct caacaattgt
      4150       4160       4170       4180       4190       4200
agagaggctt tctggctggg caatctaaaa aaccgggact tgcagggtga agagattaag
      4210       4220       4230       4240       4250       4260
tcccaaaatt cccaggagag cacagcagat gagagtgagg atgacatgtc atcccaggcc
      4270       4280       4290       4300       4310       4320
tccaagagca aagccactga ggatggtgaa gaagacgaag taagtgctgg agaaaaggag
      4330       4340       4350
caagatagtg atgagagtta tgatgactct gattag  

Last modification date: Oct. 2, 2011