FGD2_MOUSE
ID FGD2_MOUSE Reviewed; 655 AA.
AC Q8BY35; O88841; Q2L9D2; Q3U195; Q7TSE3; Q8VDH4;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=FYVE, RhoGEF and PH domain-containing protein 2;
GN Name=Fgd2;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Spleen;
RX PubMed=10458911; DOI=10.1006/geno.1999.5903;
RA Pasteris N.G., Gorski J.L.;
RT "Isolation, characterization, and mapping of the mouse and human Fgd2
RT genes, faciogenital dysplasia (FGD1; Aarskog syndrome) gene homologues.";
RL Genomics 60:57-66(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, MUTAGENESIS OF SER-287; ASN-288; GLN-454 AND TRP-455, AND
RP DOMAIN DH; PH AND FYVE-TYPE ZINC-FINGER.
RC STRAIN=C57BL/10 X DBA/2; TISSUE=Spleen;
RX DOI=10.1074/jbc.M803957200;
RA Huber C., Martensson A., Bokoch G.M., Nemazee D., Gavin A.L.;
RT "FGD2, a CDC42-specific exchange factor expressed by antigen-presenting
RT cells, localizes to early endosomes and active membrane ruffles.";
RL J. Biol. Chem. 283:34002-34012(2008).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Spleen, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RA Brathwaite M.E., Waeltz P., Qian Y., Dudekula D., Schlessinger D.,
RA Nagaraja R.;
RT "Genomic sequence analysis in the mouse T-complex region.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 195-655.
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-39; SER-47; THR-644
RP AND SER-654, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Spleen;
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. Activates JNK1 via
CC CDC42 but not RAC1. Binds to phosphatidylinositol 4,5-bisphosphate,
CC phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 5-
CC monophosphate, phosphatidylinositol 4-monophosphate and
CC phosphatidylinositol 3-monophosphate. {ECO:0000269|Ref.2}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|Ref.2}. Nucleus
CC {ECO:0000269|Ref.2}. Early endosome {ECO:0000269|Ref.2}. Early endosome
CC membrane {ECO:0000269|Ref.2}. Cell projection, ruffle membrane
CC {ECO:0000269|Ref.2}. Cytoplasm, cytoskeleton {ECO:0000305|Ref.2}.
CC Note=Recruitment to the endosome and ruffle membrane requires the
CC presence of phosphoinositides.
CC -!- TISSUE SPECIFICITY: Lymph node, spleen, B-lymphocytes and macrophages
CC (at protein level). Expressed at high levels in lymph node, spleen, B-
CC lymphocytes and bone marrow macrophages. Expressed at lower levels in
CC mature bone marrow dendritic cells. In both immature and mature B-
CC cells, expression is down-regulated by prior B-cell receptor signaling.
CC Expression remains high in resting B and memory cells but declines upon
CC differentiation into plasma cells. {ECO:0000269|PubMed:10458911,
CC ECO:0000269|Ref.2}.
CC -!- DOMAIN: The FYVE-type zinc-finger is necessary for early endosome
CC localization. Recruitment to endosomal membranes via this domain
CC requires the presence of phosphatidylinositol 3-phosphate or other
CC phosphatidylinositides. {ECO:0000269|Ref.2}.
CC -!- DOMAIN: The PH domain is necessary for localization to the ruffle
CC membrane. Recruitment to ruffle membrane occurs through binding of
CC phosphoinositides by the PH domain. This domain also contributes to the
CC lipid-binding properties of the protein. {ECO:0000269|Ref.2}.
CC -!- DOMAIN: The DH domain is necessary for its ability to activate JNK1 via
CC CDC42. {ECO:0000269|Ref.2}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC35430.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH21845.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
CC Sequence=AAP45200.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF017368; AAC35430.1; ALT_FRAME; mRNA.
DR EMBL; DQ344523; ABC70180.1; -; mRNA.
DR EMBL; AK042260; BAC31206.1; -; mRNA.
DR EMBL; AK156151; BAE33605.1; -; mRNA.
DR EMBL; AY301264; AAP45199.1; -; Genomic_DNA.
DR EMBL; AY301264; AAP45200.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC021845; AAH21845.1; ALT_SEQ; mRNA.
DR CCDS; CCDS37537.1; -.
DR RefSeq; NP_001153010.1; NM_001159538.1.
DR RefSeq; NP_038738.2; NM_013710.4.
DR RefSeq; XP_006524363.1; XM_006524300.3.
DR RefSeq; XP_011244775.1; XM_011246473.2.
DR AlphaFoldDB; Q8BY35; -.
DR SMR; Q8BY35; -.
DR BioGRID; 204940; 1.
DR STRING; 10090.ENSMUSP00000024810; -.
DR iPTMnet; Q8BY35; -.
DR PhosphoSitePlus; Q8BY35; -.
DR EPD; Q8BY35; -.
DR MaxQB; Q8BY35; -.
DR PaxDb; Q8BY35; -.
DR PeptideAtlas; Q8BY35; -.
DR PRIDE; Q8BY35; -.
DR ProteomicsDB; 271563; -.
DR Antibodypedia; 29766; 66 antibodies from 17 providers.
DR DNASU; 26382; -.
DR Ensembl; ENSMUST00000024810; ENSMUSP00000024810; ENSMUSG00000024013.
DR GeneID; 26382; -.
DR KEGG; mmu:26382; -.
DR UCSC; uc008bsx.2; mouse.
DR CTD; 221472; -.
DR MGI; MGI:1347084; Fgd2.
DR VEuPathDB; HostDB:ENSMUSG00000024013; -.
DR eggNOG; KOG4424; Eukaryota.
DR GeneTree; ENSGT00940000161251; -.
DR HOGENOM; CLU_011755_2_1_1; -.
DR InParanoid; Q8BY35; -.
DR OMA; IMNSERS; -.
DR OrthoDB; 652460at2759; -.
DR PhylomeDB; Q8BY35; -.
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; 26382; 4 hits in 71 CRISPR screens.
DR PRO; PR:Q8BY35; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q8BY35; protein.
DR Bgee; ENSMUSG00000024013; Expressed in ear vesicle and 136 other tissues.
DR ExpressionAtlas; Q8BY35; baseline and differential.
DR Genevisible; Q8BY35; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001726; C:ruffle; IDA:MGI.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1901981; F:phosphatidylinositol phosphate binding; IDA:MGI.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0046847; P:filopodium assembly; IBA:GO_Central.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IGI:MGI.
DR CDD; cd13386; PH1_FGD2; 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; IPR037797; FGD2_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; IPR011011; Znf_FYVE_PHD.
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 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 Cell membrane; Cell projection; Cytoplasm; Cytoskeleton; Endosome;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..655
FT /note="FYVE, RhoGEF and PH domain-containing protein 2"
FT /id="PRO_0000080943"
FT DOMAIN 102..290
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 319..418
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 544..641
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 458..518
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 21..52
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 84..103
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 464
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 467
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 481
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 484
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 489
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 492
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 510
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 513
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 10
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 644
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 654
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 287
FT /note="S->A: No effect on early endosome localization and
FT reduced JNK1 activation; when associated with A-288."
FT /evidence="ECO:0000269|Ref.2"
FT MUTAGEN 288
FT /note="N->A: No effect on early endosome localization and
FT reduced JNK1 activation; when associated with A-287."
FT /evidence="ECO:0000269|Ref.2"
FT MUTAGEN 454
FT /note="Q->K: Loss of early endosome localization; when
FT associated with T-455."
FT /evidence="ECO:0000269|Ref.2"
FT MUTAGEN 455
FT /note="W->T: Loss of early endosome localization; when
FT associated with K-454."
FT /evidence="ECO:0000269|Ref.2"
FT CONFLICT 39
FT /note="S -> I (in Ref. 1; ABC70180 and 2; AAC35430)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="E -> D (in Ref. 1; ABC70180)"
FT /evidence="ECO:0000305"
FT CONFLICT 560..561
FT /note="RS -> ST (in Ref. 3; BAE33605)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 655 AA; 74634 MW; F5272F107A29BDBE CRC64;
MERACEKQDS VCNLVAVFEN NRTPGEAPGS HSLEDQPHSP EHQLSLSPEP WEAPPVKEAL
KSEFRPVSRT YLSSLKNKLS SGAWRRSCQP GVSPGPETQE PEEKRVVREL LETEQAYVAR
LHLLDQVFFQ ELLREAGRSK AFPEDVVKLI FSNISSIYRF HAQFFLPELQ RRVDDWAATP
RIGDVIQKLA PFLKMYSEYV KNFERAAELL ATWMDKSQPF QEVVTRIQCS EASSSLTLQH
HMLEPVQRIP RYELLLKEYV QKLPAQAPDL EDAQRALDMI FSAAQHSNAA IAEMERLQGL
WDVYQRLGLE DDIVDPSNTL LREGPVLKIS FRRSDPMERY LVLFNNMLLY CVPRVLQVGA
QFQVRTRIDV AGMKVRELTD AEFPHSFLVS GKQRTLELQA RSRDEMVSWM QACQAAIDQV
EKRSETFKAA VQGPQGDTQE PKPQVEELGL RAPQWVRDKM VTMCMRCQEP FNALTRRRHH
CRACGYVVCA KCSDYRAELK YDSNRPNRVC LTCYTFLTGN VLPQGKEDKR RGILEKEASA
APEQSLVCSF LQLIGDKCSR SLPRSWCVIP RDDPLVLYVY AAPQDTKAHT SIPLLGYQVI
SGPQGDPRVF QLQQSGQQYT FKAESVELQG RWVTAIKRAA SGRTPEGPDE EDVSD
