FGD4_RAT
ID FGD4_RAT Reviewed; 766 AA.
AC O88387;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 127.
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 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], PROTEIN SEQUENCE OF 41-65; 236-252; 276-291;
RP 365-396; 464-475; 478-493; 496-503; 510-551; 702-710 AND 716-428,
RP HOMOOLIGOMERIZATION, AND FUNCTION.
RC TISSUE=Brain;
RX PubMed=9668039; DOI=10.1074/jbc.273.30.18697;
RA Obaishi H., Nakanishi H., Mandai K., Satoh K., Satoh A., Takahashi K.,
RA Miyahara M., Nishioka H., Takaishi K., Takai Y.;
RT "Frabin, a novel FGD1-related actin filament-binding protein capable of
RT changing cell shape and activating c-Jun N-terminal kinase.";
RL J. Biol. Chem. 273:18697-18700(1998).
RN [2]
RP FUNCTION, ACTIN FIBER-BINDING DOMAIN, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10464238; DOI=10.1074/jbc.274.36.25197;
RA Umikawa M., Obaishi H., Nakanishi H., Satoh-Horikawa K., Takahashi K.,
RA Hotta I., Matsuura Y., Takai Y.;
RT "Association of frabin with the actin cytoskeleton is essential for
RT microspike formation through activation of Cdc42 small G protein.";
RL J. Biol. Chem. 274:25197-25200(1999).
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. Activates MAPK8.
CC {ECO:0000269|PubMed:10464238, ECO:0000269|PubMed:9668039}.
CC -!- SUBUNIT: Homooligomer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:10464238}. Cell projection, filopodium
CC {ECO:0000269|PubMed:10464238}. Note=Concentrated in filopodia and
CC poorly detected at lamellipodia. Binds along the sides of actin fibers.
CC -!- TISSUE SPECIFICITY: Detected in brain, lung, liver, skeletal muscle,
CC kidney, testis and cultured hippocampal neurons.
CC {ECO:0000269|PubMed:10464238}.
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.
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DR EMBL; AF038388; AAC27698.1; -; mRNA.
DR RefSeq; NP_640356.1; NM_139263.1.
DR AlphaFoldDB; O88387; -.
DR SMR; O88387; -.
DR STRING; 10116.ENSRNOP00000002491; -.
DR PaxDb; O88387; -.
DR Ensembl; ENSRNOT00000084177; ENSRNOP00000074767; ENSRNOG00000059491.
DR GeneID; 246174; -.
DR KEGG; rno:246174; -.
DR CTD; 121512; -.
DR RGD; 708357; Fgd4.
DR eggNOG; KOG4424; Eukaryota.
DR GeneTree; ENSGT00940000155765; -.
DR InParanoid; O88387; -.
DR OrthoDB; 652460at2759; -.
DR PhylomeDB; O88387; -.
DR Reactome; R-RNO-193648; NRAGE signals death through JNK.
DR Reactome; R-RNO-416482; G alpha (12/13) signalling events.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR PRO; PR:O88387; -.
DR Proteomes; UP000002494; Chromosome 11.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0030175; C:filopodium; ISO:RGD.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0003779; F:actin binding; IDA:MGI.
DR GO; GO:0051015; F:actin filament binding; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0030035; P:microspike assembly; ISO:RGD.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IMP:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:MGI.
DR GO; GO:0008360; P:regulation of cell shape; IMP:RGD.
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; Cell projection; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Guanine-nucleotide releasing factor;
KW Metal-binding; Phosphoprotein; Reference proteome; Repeat; Zinc;
KW Zinc-finger.
FT CHAIN 1..766
FT /note="FYVE, RhoGEF and PH domain-containing protein 4"
FT /id="PRO_0000080949"
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 REGION 43..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 745..766
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..69
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 111..162
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:0000250|UniProtKB:Q91ZT5"
SQ SEQUENCE 766 AA; 86454 MW; E34831DC0B0B334C CRC64;
MEESNPAPTS CASKGKHSKV SDLISHFEGG SVLSSYTDVQ KDSTMNLNIP QTPRQHGLTS
TTPQKLPSHK SPQKQEKDSD QNQGQHGCLA NGVAAAQSQM ECETEKEAAL SPETDTQTAA
ASPDAHVLNG VRNETTTDSA SSVTNSHDEN ACDSSCRTQG TDLGLPSKEG EPVIEAELQE
RENGLSTEGL NPLDQHHEVK ETNEQKLHKI ATELLLTERA YVSRLNLLDQ VFYCKLLEEA
NRGSFPAEMV NKIFSNISSI NAFHSKFLLP ELEKRMQEWE TTPRIGDILQ KLAPFLKMYG
EYVKGFDNAV ELVKNMTERV PQFKSVTEEI QKQKICGSLT LQHHMLEPIQ RIPRYEMLLK
DYLKKLSPDA PDWNDAKKSL EIISTAASHS NSAIRKMENL KKLLEIYEML GEEEDIVNPS
NELIKEGQIL KLAARNTSAQ ERYLFLFNNM LLYCVPRFSL VGSKFTVRTR VGIDGMKIVE
THNEEYPHTF QVSGKERTLE LQASSEQDKE EWIKALQESI DAFHQRHETF RNAIAKENDI
PLEVSTAELG KRAPRWIRDN EVTMCMKCKE SFNALTRRRH HCRACGHVVC WKCSDYKAQL
EYDGGRLNKV CKDCYQIMSG FAESEEKKRR GILEIESAEV SGNSEVCSFL QYMEKSKPWQ
KIWCVIPKQD PLVLYMYGAP QDVRAQATIP LLGYIVDDMP KSADLPHSFK LTQSKSVHSF
AADSEELKQK WLKIILLAVT GETPDGPSEH LDTLDNLPGP KEKSEC
