FACD2_RAT
ID FACD2_RAT Reviewed; 1451 AA.
AC Q6IV68;
DT 07-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 2.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Fanconi anemia group D2 protein homolog;
DE Short=Protein FACD2;
GN Name=Fancd2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar Kyoto; TISSUE=Liver;
RA Rosemann M.F., Ivashkevich A., Lichtmannegger J.;
RT "Strain specific allelic variations in the rat FanCD2 coding sequence.";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Required for maintenance of chromosomal stability. Promotes
CC accurate and efficient pairing of homologs during meiosis. Involved in
CC the repair of DNA double-strand breaks, both by homologous
CC recombination and single-strand annealing. May participate in S phase
CC and G2 phase checkpoint activation upon DNA damage. Plays a role in
CC preventing breakage and loss of missegregating chromatin at the end of
CC cell division, particularly after replication stress (By similarity).
CC Promotes BRCA2/FANCD1 loading onto damaged chromatin. May also be
CC involved in B-cell immunoglobulin isotype switching (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Interacts directly with FANCE and FANCI. Interacts with USP1
CC and MEN1. The ubiquitinated form specifically interacts with BRCA1 and
CC BLM. Both the nonubiquitinated and the monoubiquitinated forms interact
CC with BRCA2; this interaction is mediated by phosphorylated FANCG and
CC the complex also includes XCCR3. The ubiquitinated form specifically
CC interacts with MTMR15/FAN1 (via UBZ-type zinc finger), leading to
CC recruit MTMR15/FAN1 to sites of DNA damage. Interacts with
CC DCLRE1B/Apollo. Interacts with POLN. Interacts with UHRF1 and UHRF2;
CC these interactions promote FANCD2 activation.
CC {ECO:0000250|UniProtKB:Q9BXW9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Concentrates in
CC nuclear foci during S phase and upon genotoxic stress. {ECO:0000250}.
CC -!- PTM: Monoubiquitinated on Lys-561 during S phase and upon genotoxic
CC stress by FANCL in complex with E2 ligases UBE2T or UBE2W.
CC Deubiquitinated by USP1 as cells enter G2/M, or once DNA repair is
CC completed. Monoubiquitination requires the joint intervention of the
CC FANC core complex, including FANCA, FANCB, FANCC, FANCE, FANCF, FANCG,
CC and FANCM, and proteins involved in cell cycle checkpoints and DNA
CC repair, including RPA1, ATR, CHEK1 and BRCA1, and is mediated by
CC FANCL/PHF9. Ubiquitination is required for binding to chromatin,
CC interaction with BRCA1, BRCA2 and MTMR15/FAN1, DNA repair, and normal
CC cell cycle progression (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on several sites including Ser-222 and Ser-1401 in
CC response to genotoxic stress. {ECO:0000250}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAT40425.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY621075; AAT40425.1; ALT_INIT; mRNA.
DR RefSeq; NP_001001719.1; NM_001001719.1.
DR AlphaFoldDB; Q6IV68; -.
DR SMR; Q6IV68; -.
DR STRING; 10116.ENSRNOP00000033638; -.
DR PhosphoSitePlus; Q6IV68; -.
DR PaxDb; Q6IV68; -.
DR PRIDE; Q6IV68; -.
DR GeneID; 312641; -.
DR KEGG; rno:312641; -.
DR UCSC; RGD:1303172; rat.
DR CTD; 2177; -.
DR RGD; 1303172; Fancd2.
DR eggNOG; KOG4712; Eukaryota.
DR InParanoid; Q6IV68; -.
DR OrthoDB; 979208at2759; -.
DR PhylomeDB; Q6IV68; -.
DR TreeFam; TF101106; -.
DR Reactome; R-RNO-6783310; Fanconi Anemia Pathway.
DR PRO; PR:Q6IV68; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000793; C:condensed chromosome; ISO:RGD.
DR GO; GO:1990391; C:DNA repair complex; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0070182; F:DNA polymerase binding; ISO:RGD.
DR GO; GO:0048854; P:brain morphogenesis; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:RGD.
DR GO; GO:1990918; P:double-strand break repair involved in meiotic recombination; IBA:GO_Central.
DR GO; GO:0007276; P:gamete generation; ISO:RGD.
DR GO; GO:0007129; P:homologous chromosome pairing at meiosis; ISO:RGD.
DR GO; GO:0036297; P:interstrand cross-link repair; IBA:GO_Central.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISO:RGD.
DR GO; GO:2000348; P:regulation of CD40 signaling pathway; ISO:RGD.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
DR GO; GO:0045589; P:regulation of regulatory T cell differentiation; ISO:RGD.
DR GO; GO:0010332; P:response to gamma radiation; ISO:RGD.
DR CDD; cd11721; FANCD2; 1.
DR InterPro; IPR029448; FANCD2.
DR PANTHER; PTHR32086; PTHR32086; 1.
DR Pfam; PF14631; FancD2; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; DNA damage; DNA repair; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1451
FT /note="Fanconi anemia group D2 protein homolog"
FT /id="PRO_0000087170"
FT REGION 1..291
FT /note="Interaction with FANCE"
FT /evidence="ECO:0000250"
FT REGION 248..359
FT /note="Interaction with BRCA2"
FT /evidence="ECO:0000250"
FT REGION 858..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1399..1451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1399..1421
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1433..1451
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 222
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXW9"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXW9"
FT MOD_RES 1257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXW9"
FT MOD_RES 1406
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXW9"
FT MOD_RES 1414
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BXW9"
FT CROSSLNK 561
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9BXW9"
SQ SEQUENCE 1451 AA; 163621 MW; 5FE7FC72DA46834D CRC64;
MVSKRSRLDF EDKETLAEDA SKIMKQPLSK LAKKSCGSHE VEENGSVFVR LLKASGLTLK
TGDNQNQLGV DQIIFQRKLF QALRKHPSYP KVIEEFVNGL ESYTEDIDSL RNCLLSCERL
QDEEASMGTF YSKSLIKLLL GIDILQPAII KMLFEKVPQF LFESESRDGI SMPRLIISQL
KWLDRIVDSK DLTTQMMQLI SVAPVNLQHD FITSLPEILG DSQHANVGKE LSELLVQNTS
LTVPILDVFS SLRLDPNFLS EIRQLVMGKL SSVRLEDLPV IVKFILHSVT DSTSLEVIAE
LREKLNVQHF TLPSRIQASQ SKLKSKGLAS SSGNQENSDK DCIVLLFDVI KSAIRYEKTI
SEAWIKAIER IQSAAEHKAL DVAMLLIIYG TSTQTKKGVE RLLRNKIQSD CIQEQLLDST
FSTHCLVLKD ICPSILLLAQ TLFHSQDQRI ILFGSLLCKY AFKFFDTYCQ QEVVGALVTH
VCSGNEAEVD AALDVLLELI VLNASAMRLN AAFIKGILDY LENMSPQQIR KIFCILSTLA
FSQQPGTSNH IQDDMHLVIR KQLSSTVFKY KLIGIIGAVT MAGIMAEDRT MPSNSTQRSA
SVSSEQHTQV TSLLQLVHSC TEHSPWASSL YYDEFANLIQ ERKLAPKTLE WVAQTIFNDF
QDAFVVDFCA VPEGDFPFPV KALYGLEECN TQDGIVINLL PLFFQEFAKD VSQVTSQESS
QKSMSPLCLA SHFRLLRLCV ARQHNGNLDE IDALLDCPLF LPDLEPGEKL ESMSAKDRSL
MCSLTFLTFN WFREVVNAFC QQTSPEMKGK VLSRLKDLVE LQEILEKYLA VIPDYVPPFT
SVDLDTLDVI PRSNSAVAAK SRHKGKTGGK KQKADSSTAS CTDTLLTEDT SECDVAPSGK
SQVDKESTGK EGKTFVSLQN YRAFFRELDI EVFSILHSGL VTKFILDTEM HTEATEVVQL
GPAELLFLLE DLSQKLENRL TPSFTKRVCF FKNKGSRNIG FSHLHQRSVQ DIVHCVVQLL
TPMCNHLENI HNFFQCLGAE NLSVNDKARV TAQEHYTMSS CYQKLLQVFH ALLAWKGFTH
QSNHRLLRSA LEVLASRLKQ TEEGQPLEEL LSQSFSYLQN LQHSIPSFQC GLYLLRLLMA
LLEKSAVPTQ KKEKLASLAK QLLCRAWPHG DKEKNPTFND HLHDLLCIYL EHTDNVLKAI
EEITGVGVPE LVNAPKDASS STFPTLTRHT FVIFFRVMMA ELEKTVKGLQ AGTATDSQQV
HEEKLLYWNM AVRDFSILIN LMKVFDSYPV LHVCLKYGRR FVEAFLKQCM PLLDFSFRKH
RDDVLSLLQT LQLNTRLLHH LCGHSKIHQD TRLTKHVPLL KKSLELLVCR VKAMLVLNNC
REAFWLGTLK NRDLQGEEII SQHPSSPENT SEDSEDGMTS YVSRNRAIED GEDEANDGQD
RDSDESDDSS S
