FGD3_HUMAN
ID FGD3_HUMAN Reviewed; 725 AA.
AC Q5JSP0; F8W7P2; Q4VX84; Q7Z7D9; Q8N5G1;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=FYVE, RhoGEF and PH domain-containing protein 3;
DE AltName: Full=Zinc finger FYVE domain-containing protein 5;
GN Name=FGD3; Synonyms=ZFYVE5;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Shan Y.X., Yu L.;
RT "Cloning and characterization of a human FGD3 gene: a novel faciogenital
RT dysplasia (FGD1; Aarskog syndrome) gene homolog.";
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-275.
RC TISSUE=Brain;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP STRUCTURE BY NMR OF 605-703.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the C-terminal PH domain of FYVE, RhoGEF and PH
RT domain containing protein 3 (FGD3) from human.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Promotes the formation of filopodia. May activate CDC42, a
CC member of the Ras-like family of Rho- and Rac proteins, by exchanging
CC bound GDP for free GTP. Plays a role in regulating the actin
CC cytoskeleton and cell shape (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}. Cytoplasm, cytoskeleton
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q5JSP0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5JSP0-2; Sequence=VSP_013074, VSP_013075;
CC Name=3;
CC IsoId=Q5JSP0-3; Sequence=VSP_055703;
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DR EMBL; AY211386; AAP20645.1; -; mRNA.
DR EMBL; AL389924; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL451065; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032429; AAH32429.1; -; mRNA.
DR EMBL; BC111054; AAI11055.1; -; mRNA.
DR CCDS; CCDS43849.1; -. [Q5JSP0-1]
DR CCDS; CCDS69619.1; -. [Q5JSP0-3]
DR RefSeq; NP_001077005.1; NM_001083536.1. [Q5JSP0-1]
DR RefSeq; NP_001273922.1; NM_001286993.1. [Q5JSP0-3]
DR RefSeq; NP_149077.2; NM_033086.2. [Q5JSP0-1]
DR RefSeq; XP_016870763.1; XM_017015274.1. [Q5JSP0-1]
DR PDB; 2COC; NMR; -; A=605-703.
DR PDBsum; 2COC; -.
DR AlphaFoldDB; Q5JSP0; -.
DR BMRB; Q5JSP0; -.
DR SMR; Q5JSP0; -.
DR BioGRID; 124618; 7.
DR IntAct; Q5JSP0; 5.
DR STRING; 9606.ENSP00000364631; -.
DR iPTMnet; Q5JSP0; -.
DR PhosphoSitePlus; Q5JSP0; -.
DR BioMuta; FGD3; -.
DR DMDM; 61213216; -.
DR EPD; Q5JSP0; -.
DR jPOST; Q5JSP0; -.
DR MassIVE; Q5JSP0; -.
DR MaxQB; Q5JSP0; -.
DR PaxDb; Q5JSP0; -.
DR PeptideAtlas; Q5JSP0; -.
DR PRIDE; Q5JSP0; -.
DR ProteomicsDB; 29981; -.
DR ProteomicsDB; 63166; -. [Q5JSP0-1]
DR ProteomicsDB; 63167; -. [Q5JSP0-2]
DR TopDownProteomics; Q5JSP0-1; -. [Q5JSP0-1]
DR Antibodypedia; 28323; 159 antibodies from 21 providers.
DR DNASU; 89846; -.
DR Ensembl; ENST00000337352.10; ENSP00000336914.6; ENSG00000127084.19. [Q5JSP0-1]
DR Ensembl; ENST00000375482.8; ENSP00000364631.3; ENSG00000127084.19. [Q5JSP0-1]
DR Ensembl; ENST00000416701.6; ENSP00000413833.2; ENSG00000127084.19. [Q5JSP0-3]
DR Ensembl; ENST00000467786.1; ENSP00000432310.1; ENSG00000127084.19. [Q5JSP0-2]
DR Ensembl; ENST00000468206.6; ENSP00000496819.1; ENSG00000127084.19. [Q5JSP0-1]
DR GeneID; 89846; -.
DR KEGG; hsa:89846; -.
DR MANE-Select; ENST00000375482.8; ENSP00000364631.3; NM_001083536.2; NP_001077005.1.
DR UCSC; uc004asw.3; human. [Q5JSP0-1]
DR CTD; 89846; -.
DR DisGeNET; 89846; -.
DR GeneCards; FGD3; -.
DR HGNC; HGNC:16027; FGD3.
DR HPA; ENSG00000127084; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 617554; gene.
DR neXtProt; NX_Q5JSP0; -.
DR OpenTargets; ENSG00000127084; -.
DR PharmGKB; PA28104; -.
DR VEuPathDB; HostDB:ENSG00000127084; -.
DR eggNOG; KOG4424; Eukaryota.
DR GeneTree; ENSGT00940000159597; -.
DR HOGENOM; CLU_011755_1_1_1; -.
DR InParanoid; Q5JSP0; -.
DR OMA; WNTNPRL; -.
DR PhylomeDB; Q5JSP0; -.
DR TreeFam; TF316247; -.
DR PathwayCommons; Q5JSP0; -.
DR Reactome; R-HSA-193648; NRAGE signals death through JNK.
DR Reactome; R-HSA-416482; G alpha (12/13) signalling events.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR SignaLink; Q5JSP0; -.
DR SIGNOR; Q5JSP0; -.
DR BioGRID-ORCS; 89846; 9 hits in 1064 CRISPR screens.
DR ChiTaRS; FGD3; human.
DR EvolutionaryTrace; Q5JSP0; -.
DR GeneWiki; FGD3; -.
DR GenomeRNAi; 89846; -.
DR Pharos; Q5JSP0; Tbio.
DR PRO; PR:Q5JSP0; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q5JSP0; protein.
DR Bgee; ENSG00000127084; Expressed in granulocyte and 149 other tissues.
DR ExpressionAtlas; Q5JSP0; baseline and differential.
DR Genevisible; Q5JSP0; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0001726; C:ruffle; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0046847; P:filopodium assembly; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
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; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000306; Znf_FYVE.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF00169; PH; 1.
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 SUPFAM; SSF57903; SSF57903; 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 3D-structure; Alternative splicing; Cytoplasm; Cytoskeleton;
KW Guanine-nucleotide releasing factor; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..725
FT /note="FYVE, RhoGEF and PH domain-containing protein 3"
FT /id="PRO_0000080944"
FT DOMAIN 157..341
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 370..469
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 604..703
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 532..588
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 487..532
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 703..725
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..87
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..510
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 538
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 541
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 555
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 558
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 563
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 566
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 580
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 583
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 596..634
FT /note="KTPTADPQPSLLCGPLRLSESGETWSEVWAAIPMSDPQV -> VGAPSSCSP
FT PGGAAEPPDTCSCAPAAPAASAFGVSLGPG (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_013074"
FT VAR_SEQ 596
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_055703"
FT VAR_SEQ 635..725
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_013075"
FT VARIANT 275
FT /note="V -> I (in dbSNP:rs3802384)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_021492"
FT STRAND 605..618
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 620..626
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 635..638
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 644..646
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 648..650
FT /evidence="ECO:0007829|PDB:2COC"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 656..658
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 662..664
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 667..676
FT /evidence="ECO:0007829|PDB:2COC"
FT STRAND 679..687
FT /evidence="ECO:0007829|PDB:2COC"
FT HELIX 688..702
FT /evidence="ECO:0007829|PDB:2COC"
SQ SEQUENCE 725 AA; 79401 MW; 665A7FF5BE16B44B CRC64;
MESGRGSSTP PGPIAALGMP DTGPGSSSLG KLQALPVGPR AHCGDPVSLA AAGDGSPDIG
PTGELSGSLK IPNRDSGIDS PSSSVAGENF PCEEGLEAGP SPTVLGAHAE MALDSQVPKV
TPQEEADSDV GEEPDSENTP QKADKDAGLA QHSGPQKLLH IAQELLHTEE TYVKRLHLLD
QVFCTRLTDA GIPPEVIMGI FSNISSIHRF HGQFLLPELK TRITEEWDTN PRLGDILQKL
APFLKMYGEY VKNFDRAVGL VSTWTQRSPL FKDVVHSIQK QEVCGNLTLQ HHMLEPVQRV
PRYELLLKDY LKRLPQDAPD RKDAERSLEL ISTAANHSNA AIRKVEKMHK LLEVYEQLGG
EEDIVNPANE LIKEGQIQKL SAKNGTPQDR HLFLFNSMIL YCVPKLRLMG QKFSVREKMD
ISGLQVQDIV KPNTAHTFII TGRKRSLELQ TRTEEEKKEW IQIIQATIEK HKQNSETFKA
FGGAFSQDED PSLSPDMPIT STSPVEPVVT TEGSSGAAGL EPRKLSSKTR RDKEKQSCKS
CGETFNSITK RRHHCKLCGA VICGKCSEFK AENSRQSRVC RDCFLTQPVA PESTEKTPTA
DPQPSLLCGP LRLSESGETW SEVWAAIPMS DPQVLHLQGG SQDGRLPRTI PLPSCKLSVP
DPEERLDSGH VWKLQWAKQS WYLSASSAEL QQQWLETLST AAHGDTAQDS PGALQLQVPM
GAAAP
