FGD4_MOUSE
ID FGD4_MOUSE Reviewed; 766 AA.
AC Q91ZT5; A1L355; Q3UEB6; Q8BW60; Q8BZI7; Q91ZT3; Q91ZT4;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=FYVE, RhoGEF and PH domain-containing protein 4;
DE AltName: Full=Actin filament-binding protein frabin;
DE AltName: Full=FGD1-related F-actin-binding protein;
GN Name=Fgd4;
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] (ISOFORMS 1; 2 AND 3), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=11527409; DOI=10.1006/bbrc.2001.5481;
RA Ikeda W., Nakanishi H., Takekuni K., Itoh S., Takai Y.;
RT "Identification of splicing variants of Frabin with partly different
RT functions and tissue distribution.";
RL Biochem. Biophys. Res. Commun. 286:1066-1072(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-754 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, Diencephalon, and Oviduct;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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.
RX PubMed=10871857; DOI=10.1038/sj.onc.1203631;
RA Ono Y., Nakanishi H., Nishimura M., Kakizaki M., Takahashi K., Miyahara M.,
RA Satoh-Horikawa K., Mandai K., Takai Y.;
RT "Two actions of frabin: direct activation of Cdc42 and indirect activation
RT of Rac.";
RL Oncogene 19:3050-3058(2000).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=11952837; DOI=10.1046/j.1365-2443.2002.00524.x;
RA Kim Y., Ikeda W., Nakanishi H., Tanaka Y., Takekuni K., Itoh S., Monden M.,
RA Takai Y.;
RT "Association of frabin with specific actin and membrane structures.";
RL Genes Cells 7:413-420(2002).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=17564959; DOI=10.1086/518428;
RA Delague V., Jacquier A., Hamadouche T., Poitelon Y., Baudot C.,
RA Boccaccio I., Chouery E., Chaouch M., Kassouri N., Jabbour R., Grid D.,
RA Megarbane A., Haase G., Levy N.;
RT "Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause
RT autosomal recessive Charcot-Marie-Tooth type 4H.";
RL Am. J. Hum. Genet. 81:1-16(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-716, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
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 MAPK8 (By
CC similarity). Plays a role in regulating the actin cytoskeleton and cell
CC shape. Promotes the formation of lamellipodia. {ECO:0000250,
CC ECO:0000269|PubMed:10871857, ECO:0000269|PubMed:11527409}.
CC -!- SUBUNIT: Homooligomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000250}. Cell
CC projection, filopodium {ECO:0000250}. Note=Concentrated in filopodia
CC and poorly detected at lamellipodia. Binds along the sides of actin
CC fibers (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Frabin alpha;
CC IsoId=Q91ZT5-1; Sequence=Displayed;
CC Name=2; Synonyms=Frabin beta;
CC IsoId=Q91ZT5-2; Sequence=VSP_013086, VSP_013087;
CC Name=3; Synonyms=Frabin gamma;
CC IsoId=Q91ZT5-3; Sequence=VSP_013084, VSP_013085;
CC Name=4;
CC IsoId=Q91ZT5-4; Sequence=VSP_013083, VSP_013084, VSP_013085;
CC -!- TISSUE SPECIFICITY: Detected in thymus, lung, heart, skeletal muscle,
CC small intestine, liver, kidney, spleen and testis. Expressed in all
CC parts of the brain and in the spinal cord at embryonic, postnatal, and
CC adult stages. Levels of expression are lower in postnatal and adult
CC tissues than in embryonic tissues. {ECO:0000269|PubMed:11527409,
CC ECO:0000269|PubMed:17564959}.
CC -!- DOMAIN: The part of the protein spanning the actin filament-binding
CC domain together with the DH domain and the first PH domain is necessary
CC and sufficient for microspike formation. Activation of MAPK8 requires
CC the presence of all domains with the exception of the actin filament-
CC binding domain (By similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF402611; AAL05631.1; -; mRNA.
DR EMBL; AF402612; AAL05632.1; -; mRNA.
DR EMBL; AF402613; AAL05633.1; -; mRNA.
DR EMBL; AK034504; BAC28733.1; -; mRNA.
DR EMBL; AK054242; BAC35703.2; -; mRNA.
DR EMBL; AK149626; BAE28995.1; -; mRNA.
DR EMBL; BC129902; AAI29903.1; -; mRNA.
DR EMBL; BC129903; AAI29904.1; -; mRNA.
DR CCDS; CCDS27986.1; -. [Q91ZT5-1]
DR RefSeq; NP_001288747.1; NM_001301818.1. [Q91ZT5-1]
DR RefSeq; NP_631978.1; NM_139232.3. [Q91ZT5-1]
DR RefSeq; XP_006522090.1; XM_006522027.3. [Q91ZT5-1]
DR RefSeq; XP_006522092.1; XM_006522029.2. [Q91ZT5-1]
DR AlphaFoldDB; Q91ZT5; -.
DR SMR; Q91ZT5; -.
DR BioGRID; 230224; 40.
DR STRING; 10090.ENSMUSP00000125174; -.
DR iPTMnet; Q91ZT5; -.
DR PhosphoSitePlus; Q91ZT5; -.
DR MaxQB; Q91ZT5; -.
DR PaxDb; Q91ZT5; -.
DR PeptideAtlas; Q91ZT5; -.
DR PRIDE; Q91ZT5; -.
DR ProteomicsDB; 267460; -. [Q91ZT5-1]
DR ProteomicsDB; 267461; -. [Q91ZT5-2]
DR ProteomicsDB; 267462; -. [Q91ZT5-3]
DR ProteomicsDB; 267463; -. [Q91ZT5-4]
DR Antibodypedia; 48934; 104 antibodies from 20 providers.
DR DNASU; 224014; -.
DR Ensembl; ENSMUST00000161188; ENSMUSP00000123763; ENSMUSG00000022788. [Q91ZT5-2]
DR Ensembl; ENSMUST00000161861; ENSMUSP00000125174; ENSMUSG00000022788. [Q91ZT5-1]
DR Ensembl; ENSMUST00000162671; ENSMUSP00000125736; ENSMUSG00000022788. [Q91ZT5-1]
DR GeneID; 224014; -.
DR KEGG; mmu:224014; -.
DR UCSC; uc007yip.2; mouse. [Q91ZT5-1]
DR UCSC; uc007yis.1; mouse. [Q91ZT5-2]
DR UCSC; uc007yit.3; mouse. [Q91ZT5-3]
DR UCSC; uc007yiu.3; mouse. [Q91ZT5-4]
DR CTD; 121512; -.
DR MGI; MGI:2183747; Fgd4.
DR VEuPathDB; HostDB:ENSMUSG00000022788; -.
DR eggNOG; KOG4424; Eukaryota.
DR GeneTree; ENSGT00940000155765; -.
DR InParanoid; Q91ZT5; -.
DR OMA; EREHSFY; -.
DR OrthoDB; 652460at2759; -.
DR PhylomeDB; Q91ZT5; -.
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; 224014; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Fgd4; mouse.
DR PRO; PR:Q91ZT5; -.
DR Proteomes; UP000000589; Chromosome 16.
DR RNAct; Q91ZT5; protein.
DR Bgee; ENSMUSG00000022788; Expressed in epithelium of small intestine and 243 other tissues.
DR ExpressionAtlas; Q91ZT5; baseline and differential.
DR Genevisible; Q91ZT5; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030175; C:filopodium; IDA:MGI.
DR GO; GO:0030027; C:lamellipodium; IDA:MGI.
DR GO; GO:0003779; F:actin binding; ISO:MGI.
DR GO; GO:0051015; F:actin filament binding; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0046847; P:filopodium assembly; IBA:GO_Central.
DR GO; GO:0030032; P:lamellipodium assembly; IDA:MGI.
DR GO; GO:0030035; P:microspike assembly; IDA:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0008360; P:regulation of cell shape; ISO:MGI.
DR CDD; cd15791; PH1_FDG4; 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; IPR037742; FDG4_N_PH.
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; 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 Actin-binding; Alternative splicing; Cell projection; Cytoplasm;
KW Cytoskeleton; Guanine-nucleotide releasing factor; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..766
FT /note="FYVE, RhoGEF and PH domain-containing protein 4"
FT /id="PRO_0000080948"
FT DOMAIN 206..393
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 422..521
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 643..740
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT ZN_FING 559..619
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 1..150
FT /note="Actin filament-binding"
FT /evidence="ECO:0000250"
FT REGION 47..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..173
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 746..766
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 565
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 568
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 582
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 585
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 590
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 593
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 611
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 614
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT MOD_RES 702
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96M96"
FT MOD_RES 716
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 1..44
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_013083"
FT VAR_SEQ 504
FT /note="S -> R (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11527409,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_013084"
FT VAR_SEQ 505..766
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:11527409,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_013085"
FT VAR_SEQ 589..603
FT /note="VCWKCSDYKAQLEYD -> SEASSLSQLLEMVYR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11527409"
FT /id="VSP_013086"
FT VAR_SEQ 604..766
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11527409"
FT /id="VSP_013087"
FT CONFLICT 36
FT /note="Y -> C (in Ref. 2; BAC35703)"
FT /evidence="ECO:0000305"
FT CONFLICT 49
FT /note="I -> V (in Ref. 2; BAC35703)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="E -> K (in Ref. 2; BAE28995)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 766 AA; 86541 MW; 06BC1C01C6FCA274 CRC64;
MEESNPAPTS CTSKGKHSKV SDLISHFEGG SVLSSYIDLQ KDSTMNLNIP QTLGQPGLTS
SPPRKFLPQH SPQKQENDPD QTQGQHGCLA NGVVAAQNQM ECEDEKETTL SPEMAIQTAA
ASPDTHVLNG ERNETITDSA SSIANSHDEN ASDSSCRTPG TDLGLPSKEG EPGMDAELQE
RENGVNTMGL DTLDQHHEVK ETNEQKLHKI ATELLLTERA YVSRLDLLDQ VFYCKLLEEA
NRGSFPAEMV NKIFSNISSI NAFHSKFLLP ELEKRMQEWE TTPRIGDILQ KLAPFLKMYG
EYVKGFDNAV ELVKTMTERV PQFKSVTEEI QKQKICGSLT LQHHMLEPIQ RIPRYEMLLK
DYLKKLSPDS PDWNDAKKSL EIISTAASHS NSAIRKMENL KKLLEIYEML GEEEDIVNPS
NELIKEGQIL KLAARNTSAQ ERYLFLFNNM LLYCVPRFSL VGSKFTVRTR VGIDGMKIVE
THNEEYPHTF QISGKERTLE LQASSEQDKE EWIKALQESI DAFHQRHETF RNAIAKENDI
PLEVSTAELG KRAPRWIRDN EVTMCMKCKE SFNALTRRRH HCRACGHVVC WKCSDYKAQL
EYDGGRLNKV CKDCYQIISG FTDSEEKKRR GILEIESAEV SGNSEVCSFL QYMEKSKPWQ
KIWCVIPKQD PLVLYMYGAP QDVRAQATIP LLGYVVDDMP KSADLPHSFK LTQSKSVHSF
AADNEELKQK WLKIILLAVT GETPDGPSEH LATLNNLPGP KKKSEC
