CYH3_HUMAN
ID CYH3_HUMAN Reviewed; 400 AA.
AC O43739; A4D2N8;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 21-FEB-2001, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Cytohesin-3;
DE AltName: Full=ARF nucleotide-binding site opener 3;
DE Short=Protein ARNO3;
DE AltName: Full=General receptor of phosphoinositides 1;
DE Short=Grp1;
DE AltName: Full=PH, SEC7 and coiled-coil domain-containing protein 3;
GN Name=CYTH3 {ECO:0000312|HGNC:HGNC:9504}; Synonyms=ARNO3, GRP1, PSCD3;
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), LIPID-BINDING, DOMAIN, AND
RP SUBCELLULAR LOCATION.
RX PubMed=9742223; DOI=10.1042/bj3350139;
RA Venkateswarlu K., Gunn-Moore F., Oatey P.B., Tavare J.M., Cullen P.J.;
RT "Nerve growth factor- and epidermal growth factor-stimulated translocation
RT of the ADP-ribosylation factor-exchange factor GRP1 to the plasma membrane
RT of PC12 cells requires activation of phosphatidylinositol 3-kinase and the
RT GRP1 pleckstrin homology domain.";
RL Biochem. J. 335:139-146(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND FUNCTION.
RC TISSUE=Placenta;
RX PubMed=9707577; DOI=10.1073/pnas.95.17.9926;
RA Franco M., Boretto J., Robineau S., Monier S., Goud B., Chardin P.,
RA Chavrier P.;
RT "ARNO3, a Sec7-domain guanine nucleotide exchange factor for ADP
RT ribosylation factor 1, is involved in the control of Golgi structure and
RT function.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:9926-9931(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [6]
RP ALTERNATIVE SPLICING.
RX PubMed=10652308; DOI=10.1074/jbc.275.5.3221;
RA Ogasawara M., Kim S.C., Adamik R., Togawa A., Ferrans V.J., Takeda K.,
RA Kirby M., Moss J., Vaughan M.;
RT "Similarities in function and gene structure of cytohesin-4 and cytohesin-
RT 1, guanine nucleotide-exchange proteins for ADP-ribosylation factors.";
RL J. Biol. Chem. 275:3221-3230(2000).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=17398095; DOI=10.1016/j.cub.2007.03.007;
RA Hofmann I., Thompson A., Sanderson C.M., Munro S.;
RT "The Arl4 family of small G proteins can recruit the cytohesin Arf6
RT exchange factors to the plasma membrane.";
RL Curr. Biol. 17:711-716(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 247-400 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE AND ARF6, FUNCTION, DOMAIN,
RP LIPID-BINDING, MUTAGENESIS OF 398-ASN--LYS-400, AUTOINHIBITORY REGION, AND
RP INTERACTION WITH ARF6.
RX PubMed=23940353; DOI=10.1073/pnas.1301883110;
RA Malaby A.W., van den Berg B., Lambright D.G.;
RT "Structural basis for membrane recruitment and allosteric activation of
RT cytohesin family Arf GTPase exchange factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:14213-14218(2013).
CC -!- FUNCTION: Promotes guanine-nucleotide exchange on ARF1 and ARF6.
CC Promotes the activation of ARF factors through replacement of GDP with
CC GTP. Plays a role in the epithelial polarization (By similarity).
CC {ECO:0000250|UniProtKB:O08967, ECO:0000269|PubMed:23940353,
CC ECO:0000269|PubMed:9707577}.
CC -!- SUBUNIT: Interacts with TAMALIN (By similarity). Interacts with ARF6
CC (PubMed:23940353). Interacts with FRMD4A (By similarity). Interacts
CC with FRMD4B (By similarity). {ECO:0000250|UniProtKB:O08967,
CC ECO:0000269|PubMed:23940353}.
CC -!- INTERACTION:
CC O43739; Q96HB5-4: CCDC120; NbExp=3; IntAct=EBI-741648, EBI-10185348;
CC O43739; Q969H4: CNKSR1; NbExp=4; IntAct=EBI-741648, EBI-741671;
CC O43739; Q8N0S2: SYCE1; NbExp=3; IntAct=EBI-741648, EBI-6872807;
CC O43739-2; P53365: ARFIP2; NbExp=3; IntAct=EBI-11974015, EBI-638194;
CC O43739-2; Q96HB5: CCDC120; NbExp=4; IntAct=EBI-11974015, EBI-744556;
CC O43739-2; Q969H4: CNKSR1; NbExp=4; IntAct=EBI-11974015, EBI-741671;
CC O43739-2; P80217-2: IFI35; NbExp=3; IntAct=EBI-11974015, EBI-12823003;
CC O43739-2; Q8WWN9: IPCEF1; NbExp=3; IntAct=EBI-11974015, EBI-4401965;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cell membrane
CC {ECO:0000250|UniProtKB:O08967}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O08967}. Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:O08967}. Cell junction, tight junction
CC {ECO:0000250|UniProtKB:O08967}. Note=Translocates from the cytosol to
CC membranes enriched in phosphatidylinositol 3,4,5-trisphosphate.
CC {ECO:0000250|UniProtKB:O08967}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43739-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43739-2; Sequence=VSP_006039;
CC -!- TISSUE SPECIFICITY: Almost absent from liver, thymus and peripheral
CC blood lymphocytes.
CC -!- DOMAIN: Binds via its PH domain to the inositol head group of
CC phosphatidylinositol 3,4,5-trisphosphate.
CC -!- DOMAIN: Autoinhibited by its C-terminal basic region.
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DR EMBL; AJ005197; CAA06434.1; -; mRNA.
DR EMBL; AJ223957; CAA11686.1; -; mRNA.
DR EMBL; CH236963; EAL23717.1; -; Genomic_DNA.
DR EMBL; CH878731; EAW55046.1; -; Genomic_DNA.
DR EMBL; BC028717; AAH28717.1; -; mRNA.
DR CCDS; CCDS5346.1; -. [O43739-2]
DR RefSeq; NP_004218.1; NM_004227.3. [O43739-2]
DR PDB; 4KAX; X-ray; 1.85 A; B=247-400.
DR PDB; 6U3E; EM; 53.00 A; A/B=13-400.
DR PDB; 6U3G; EM; 53.00 A; A/B=13-400.
DR PDBsum; 4KAX; -.
DR PDBsum; 6U3E; -.
DR PDBsum; 6U3G; -.
DR AlphaFoldDB; O43739; -.
DR BMRB; O43739; -.
DR SMR; O43739; -.
DR BioGRID; 114686; 46.
DR CORUM; O43739; -.
DR DIP; DIP-60444N; -.
DR IntAct; O43739; 14.
DR STRING; 9606.ENSP00000297044; -.
DR BindingDB; O43739; -.
DR ChEMBL; CHEMBL3259466; -.
DR DrugBank; DB01863; Inositol 1,3,4,5-Tetrakisphosphate.
DR DrugBank; DB03344; Inositol-(1,3,4,5,6)-Pentakisphosphate.
DR iPTMnet; O43739; -.
DR PhosphoSitePlus; O43739; -.
DR BioMuta; CYTH3; -.
DR EPD; O43739; -.
DR jPOST; O43739; -.
DR MassIVE; O43739; -.
DR MaxQB; O43739; -.
DR PaxDb; O43739; -.
DR PeptideAtlas; O43739; -.
DR PRIDE; O43739; -.
DR ProteomicsDB; 49142; -. [O43739-1]
DR ProteomicsDB; 49143; -. [O43739-2]
DR Antibodypedia; 2818; 202 antibodies from 33 providers.
DR DNASU; 9265; -.
DR Ensembl; ENST00000350796.8; ENSP00000297044.7; ENSG00000008256.16. [O43739-2]
DR Ensembl; ENST00000396741.3; ENSP00000379967.3; ENSG00000008256.16. [O43739-1]
DR GeneID; 9265; -.
DR KEGG; hsa:9265; -.
DR MANE-Select; ENST00000350796.8; ENSP00000297044.7; NM_004227.4; NP_004218.1. [O43739-2]
DR UCSC; uc003spt.4; human. [O43739-1]
DR CTD; 9265; -.
DR DisGeNET; 9265; -.
DR GeneCards; CYTH3; -.
DR HGNC; HGNC:9504; CYTH3.
DR HPA; ENSG00000008256; Low tissue specificity.
DR MIM; 605081; gene.
DR neXtProt; NX_O43739; -.
DR OpenTargets; ENSG00000008256; -.
DR PharmGKB; PA164718590; -.
DR VEuPathDB; HostDB:ENSG00000008256; -.
DR eggNOG; KOG0930; Eukaryota.
DR GeneTree; ENSGT00940000155825; -.
DR HOGENOM; CLU_032820_3_0_1; -.
DR InParanoid; O43739; -.
DR OMA; INTRKAD; -.
DR OrthoDB; 657055at2759; -.
DR PhylomeDB; O43739; -.
DR TreeFam; TF352091; -.
DR PathwayCommons; O43739; -.
DR Reactome; R-HSA-6811438; Intra-Golgi traffic.
DR SignaLink; O43739; -.
DR BioGRID-ORCS; 9265; 15 hits in 1080 CRISPR screens.
DR ChiTaRS; CYTH3; human.
DR GeneWiki; CYTH3; -.
DR GenomeRNAi; 9265; -.
DR Pharos; O43739; Tbio.
DR PRO; PR:O43739; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; O43739; protein.
DR Bgee; ENSG00000008256; Expressed in endothelial cell and 182 other tissues.
DR Genevisible; O43739; HS.
DR GO; GO:0005912; C:adherens junction; ISS:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:Ensembl.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:UniProtKB.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; ISS:UniProtKB.
DR GO; GO:0048193; P:Golgi vesicle transport; IMP:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IEA:Ensembl.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR CDD; cd00171; Sec7; 1.
DR Gene3D; 1.10.1000.11; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR023394; Sec7_C_sf.
DR InterPro; IPR000904; Sec7_dom.
DR InterPro; IPR035999; Sec7_dom_sf.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF01369; Sec7; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00222; Sec7; 1.
DR SUPFAM; SSF48425; SSF48425; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50190; SEC7; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Coiled coil; Cytoplasm; Guanine-nucleotide releasing factor; Lipid-binding;
KW Membrane; Reference proteome; Tight junction.
FT CHAIN 1..400
FT /note="Cytohesin-3"
FT /id="PRO_0000120200"
FT DOMAIN 77..206
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 264..381
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 392..400
FT /note="C-terminal autoinhibitory region"
FT /evidence="ECO:0000269|PubMed:23940353"
FT COILED 14..61
FT /evidence="ECO:0000255"
FT BINDING 273..281
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT BINDING 285
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000269|PubMed:23940353"
FT BINDING 296
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000269|PubMed:23940353"
FT BINDING 306
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000269|PubMed:23940353"
FT BINDING 355
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol-3,4,5-trisphosphate)"
FT /ligand_id="ChEBI:CHEBI:57836"
FT /evidence="ECO:0000269|PubMed:23940353"
FT VAR_SEQ 277
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:9707577, ECO:0000303|PubMed:9742223"
FT /id="VSP_006039"
FT MUTAGEN 398..400
FT /note="NKK->AAA: Abolishes autoinhibition and increases
FT guanine-nucleotide exchange activity."
FT /evidence="ECO:0000269|PubMed:23940353"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 266..274
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 282..290
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 293..299
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 306..310
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 315..319
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 322..331
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:4KAX"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:4KAX"
FT HELIX 366..379
FT /evidence="ECO:0007829|PDB:4KAX"
FT HELIX 384..396
FT /evidence="ECO:0007829|PDB:4KAX"
SQ SEQUENCE 400 AA; 46349 MW; 87FB917899EE957D CRC64;
MDEDGGGEGG GVPEDLSLEE REELLDIRRR KKELIDDIER LKYEIAEVMT EIDNLTSVEE
SKTTQRNKQI AMGRKKFNMD PKKGIQFLIE NDLLQSSPED VAQFLYKGEG LNKTVIGDYL
GERDEFNIKV LQAFVELHEF ADLNLVQALR QFLWSFRLPG EAQKIDRMME AFASRYCLCN
PGVFQSTDTC YVLSFAIIML NTSLHNHNVR DKPTAERFIA MNRGINEGGD LPEELLRNLY
ESIKNEPFKI PEDDGNDLTH TFFNPDREGW LLKLGGGRVK TWKRRWFILT DNCLYYFEYT
TDKEPRGIIP LENLSIREVE DPRKPNCFEL YNPSHKGQVI KACKTEADGR VVEGNHVVYR
ISAPSPEEKE EWMKSIKASI SRDPFYDMLA TRKRRIANKK
