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 24-JAN-2024, entry version 132. 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. 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; AF038388; AAC27698.1; -; mRNA. DR RefSeq; NP_640356.1; NM_139263.1. DR AlphaFoldDB; O88387; -. DR SMR; O88387; -. DR STRING; 10116.ENSRNOP00000074767; -. DR PhosphoSitePlus; O88387; -. DR PaxDb; 10116-ENSRNOP00000002491; -. DR Ensembl; ENSRNOT00000084177.2; ENSRNOP00000074767.2; ENSRNOG00000059491.2. DR Ensembl; ENSRNOT00055004930; ENSRNOP00055003653; ENSRNOG00055003163. DR Ensembl; ENSRNOT00060004232; ENSRNOP00060002972; ENSRNOG00060002642. DR Ensembl; ENSRNOT00065013507; ENSRNOP00065010011; ENSRNOG00065008509. DR KEGG; rno:246174; -. DR AGR; RGD:708357; -. DR CTD; 121512; -. DR RGD; 708357; Fgd4. DR eggNOG; KOG4424; Eukaryota. DR GeneTree; ENSGT00940000155765; -. DR InParanoid; O88387; -. DR OrthoDB; 5385125at2759; -. 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; cd15741; FYVE_FGD1_2_4; 1. DR CDD; cd15791; PH1_FDG4; 1. DR CDD; cd13236; PH2_FGD1-4; 1. DR CDD; cd00160; RhoGEF; 1. DR Gene3D; 1.20.900.10; Dbl homology (DH) domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR12673; FACIOGENITAL DYSPLASIA PROTEIN; 1. DR PANTHER; PTHR12673:SF98; FYVE, RHOGEF AND PH DOMAIN-CONTAINING PROTEIN 4; 1. 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; DBL homology domain (DH-domain); 1. DR SUPFAM; SSF50729; PH domain-like; 2. 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 //