FGD1_MOUSE
ID FGD1_MOUSE Reviewed; 960 AA.
AC P52734; Q921L2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=FYVE, RhoGEF and PH domain-containing protein 1;
DE AltName: Full=Faciogenital dysplasia 1 protein homolog;
DE AltName: Full=Rho/Rac guanine nucleotide exchange factor FGD1;
DE Short=Rho/Rac GEF;
DE AltName: Full=Zinc finger FYVE domain-containing protein 3;
GN Name=Fgd1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8535076; DOI=10.1007/bf00352375;
RA Pasteris N.G., de Gouyon B., Cadle A.B., Campbell K., Herman G.E.,
RA Gorski J.L.;
RT "Cloning and regional localization of the mouse faciogenital dysplasia
RT (Fgd1) gene.";
RL Mamm. Genome 6:658-661(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DBNL AND CTTN, AND
RP MUTAGENESIS OF PRO-159; PRO-162 AND LYS-164.
RX PubMed=12913069; DOI=10.1093/hmg/ddg209;
RA Hou P., Estrada L., Kinley A.W., Parsons J.T., Vojtek A.B., Gorski J.L.;
RT "Fgd1, the Cdc42 GEF responsible for faciogenital dysplasia, directly
RT interacts with cortactin and mAbp1 to modulate cell shape.";
RL Hum. Mol. Genet. 12:1981-1993(2003).
RN [5]
RP POSSIBLE INTERACTION WITH CCPG1.
RX PubMed=17000758; DOI=10.1128/mcb.00670-06;
RA Kostenko E.V., Olabisi O.O., Sahay S., Rodriguez P.L., Whitehead I.P.;
RT "Ccpg1, a novel scaffold protein that regulates the activity of the Rho
RT guanine nucleotide exchange factor Dbs.";
RL Mol. Cell. Biol. 26:8964-8975(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-710 AND SER-714, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Activates CDC42, a member of the Ras-like family of Rho- and
CC Rac proteins, by exchanging bound GDP for free GTP. Plays a role in
CC regulating the actin cytoskeleton and cell shape.
CC {ECO:0000269|PubMed:12913069}.
CC -!- SUBUNIT: Interacts with DBNL/ABP1 and CTTN. Binds CDC42 (By
CC similarity). May interact with CCPG1. {ECO:0000250,
CC ECO:0000269|PubMed:12913069}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12913069}. Cell
CC projection, lamellipodium {ECO:0000269|PubMed:12913069}. Cell
CC projection, ruffle {ECO:0000269|PubMed:12913069}. Cytoplasm,
CC cytoskeleton {ECO:0000269|PubMed:12913069}. Note=Associated with
CC membrane ruffles and lamellipodia.
CC -!- DOMAIN: The DH domain is involved in interaction with CCPG1.
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DR EMBL; U22325; AAA96001.1; -; mRNA.
DR EMBL; AL805937; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011462; AAH11462.1; -; mRNA.
DR CCDS; CCDS30467.1; -.
DR RefSeq; NP_032027.2; NM_008001.4.
DR AlphaFoldDB; P52734; -.
DR SMR; P52734; -.
DR BioGRID; 199637; 2.
DR IntAct; P52734; 2.
DR MINT; P52734; -.
DR STRING; 10090.ENSMUSP00000026296; -.
DR iPTMnet; P52734; -.
DR PhosphoSitePlus; P52734; -.
DR jPOST; P52734; -.
DR MaxQB; P52734; -.
DR PaxDb; P52734; -.
DR PRIDE; P52734; -.
DR ProteomicsDB; 271562; -.
DR Antibodypedia; 376; 61 antibodies from 20 providers.
DR DNASU; 14163; -.
DR Ensembl; ENSMUST00000026296; ENSMUSP00000026296; ENSMUSG00000025265.
DR GeneID; 14163; -.
DR KEGG; mmu:14163; -.
DR UCSC; uc009uow.2; mouse.
DR CTD; 2245; -.
DR MGI; MGI:104566; Fgd1.
DR VEuPathDB; HostDB:ENSMUSG00000025265; -.
DR eggNOG; KOG4424; Eukaryota.
DR GeneTree; ENSGT00940000159438; -.
DR InParanoid; P52734; -.
DR OMA; QQRWMAV; -.
DR OrthoDB; 652460at2759; -.
DR PhylomeDB; P52734; -.
DR TreeFam; TF316247; -.
DR Reactome; R-MMU-193648; NRAGE signals death through JNK.
DR Reactome; R-MMU-416482; G alpha (12/13) signalling events.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
DR BioGRID-ORCS; 14163; 6 hits in 70 CRISPR screens.
DR ChiTaRS; Fgd1; mouse.
DR PRO; PR:P52734; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P52734; protein.
DR Bgee; ENSMUSG00000025265; Expressed in rostral migratory stream and 237 other tissues.
DR ExpressionAtlas; P52734; baseline and differential.
DR Genevisible; P52734; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0001726; C:ruffle; IDA:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:MGI.
DR GO; GO:0046847; P:filopodium assembly; ISO:MGI.
DR GO; GO:0008360; P:regulation of cell shape; IDA:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISO:MGI.
DR CDD; cd01219; PH1_FGD1; 1.
DR CDD; cd13236; PH2_FGD1-4; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR035941; FGD1-4_PH2.
DR InterPro; IPR035939; FGD1_PH1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000306; Znf_FYVE.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF00169; PH; 2.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; SSF48065; 1.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 2.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Cytoskeleton;
KW Guanine-nucleotide releasing factor; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..960
FT /note="FYVE, RhoGEF and PH domain-containing protein 1"
FT /id="PRO_0000080941"
FT DOMAIN 372..560
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 589..688
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 820..920
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 729..789
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 226..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 701..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 922..960
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 171..187
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 132..190
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..254
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..299
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..351
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 735
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 738
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 752
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 755
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 760
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 763
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 781
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 784
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P98174"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P98174"
FT MOD_RES 710
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 159
FT /note="P->A: Abolishes binding to DBNL."
FT /evidence="ECO:0000269|PubMed:12913069"
FT MUTAGEN 162
FT /note="P->A: Abolishes binding to DBNL."
FT /evidence="ECO:0000269|PubMed:12913069"
FT MUTAGEN 164
FT /note="K->E: No effect on binding to DBNL."
FT /evidence="ECO:0000269|PubMed:12913069"
FT CONFLICT 504
FT /note="G -> R (in Ref. 1; AAA96001)"
FT /evidence="ECO:0000305"
FT CONFLICT 633
FT /note="S -> T (in Ref. 1; AAA96001)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 960 AA; 106365 MW; E3E489BA2F3AE056 CRC64;
MHGHRVPGGP GPSDPERSAA NTPGAAPLAC ADSDPGALEP GLPVSRGSGT ALGGPLDPQF
VGPSDASLGA PPSSRVLPCG PSPQHHRALR FSYHLEGSQP RPGLHQGNRI LVKSLSLDPG
QSLEPHPEGP QRLRSDPGPP TEIPGPRPSP LKRAPGPKPQ VPPKPSYLQM PRVLPPPEPI
PPPPSRPLPA DPRVAKGLVP RAEASTSSAA VSSLIEKFER EPVIVASDRP APGPCPVPPE
PAMLPQPPPQ PTGSQLPEGE ASRCLFLLAP GPRDGEKVPN RDSGIDSISS PSNSEETCFV
SDDGPPIHSL CPGPPALASM PVALADPHRP GSQEVDSDLE EEEEEEEEEK EREIPVPPME
RQESVELTVQ QKVFHIANEL LQTEKAYVSR LHLLDQVFCA RLLEEARNRS SFPADVVHGI
FSNICSIYCF HQQFLLPELE KRMEEWDRYP RIGDILQKLA PFLKMYGEYV KNFDRAVELV
NTWTERSTQF KVIIHEVQKE EACGNLTLQH HMLEPVQRIP RYELLLKDYL LKLPHGSPDS
KDAQKSLELI ATAAEHSNAA IRKMERMHKL LKVYELLGGE EDIVSPTKEL IKEGHILKLS
AKNGTTQDRY LILFNDRLLY CVPRLRLLGQ KFSVRARIDV DGMELKESSN LNMPRTFLVS
GKQRSLELQA RTEEEKKDWV QAINSTLLKH EQTLETFKLL NSTNRDDEDT PPNSPNVDLG
KRAPTPIREK EVTMCMRCQE PFNSITKRRH HCKACGHVVC GKCSEFRARL IYDNNRSNRV
CTDCYVALHG APGSSPACSQ HTPQRRRSIL EKQASVAAEN SVICSFLHYM EKGGKGWHKA
WFVVPENEPL VLYIYGAPQD VKAQRSLPLI GFEVGPPEAG ERPDRRHVFK ITQSHLSWYF
SPETEELQRR WMAVLGRAGR GDTFCPGPTL SEDKEMEETP VAASGATAEP PEASQTRDKT
