CYH3_MOUSE
ID CYH3_MOUSE Reviewed; 399 AA.
AC O08967; Q8CI93;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 168.
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;
DE Short=CLM3;
DE AltName: Full=SEC7 homolog C;
DE Short=mSec7-3;
GN Name=Cyth3; Synonyms=Grp1, Pscd3;
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 [GENOMIC DNA].
RX PubMed=9072969; DOI=10.1126/science.275.5308.1927;
RA Klarlund J.K., Guilherme A., Holik J.J., Virbasius J.V., Chawla A.,
RA Czech M.P.;
RT "Signaling by phosphoinositide-3,4,5-trisphosphate through proteins
RT containing pleckstrin and Sec7 homology domains.";
RL Science 275:1927-1930(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9744817; DOI=10.1016/s0014-5793(98)00937-5;
RA Kim H.-S., Chen Y., Lonai P.;
RT "Complex regulation of multiple cytohesin-like genes in murine tissues and
RT cells.";
RL FEBS Lett. 433:312-316(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=NIH Swiss;
RX PubMed=10605025; DOI=10.4049/jimmunol.164.1.308;
RA Korthauer U., Nagel W., Davis E.M., Le Beau M.M., Menon R.S.,
RA Mitchell E.O., Kozak C.A., Kolanus W., Bluestone J.A.;
RT "Anergic T lymphocytes selectively express an integrin regulatory protein
RT of the cytohesin family.";
RL J. Immunol. 164:308-318(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [5]
RP INTERACTION WITH TAMALIN.
RX PubMed=10828067; DOI=10.1074/jbc.275.22.16827;
RA Nevrivy D.J., Peterson V.J., Avram D., Ishmael J.E., Hansen S.G.,
RA Dowell P., Hruby D.E., Dawson M.I., Leid M.;
RT "Interaction of GRASP, a protein encoded by a novel retinoic acid-induced
RT gene, with members of the cytohesin family of guanine nucleotide exchange
RT factors.";
RL J. Biol. Chem. 275:16827-16836(2000).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 264-391 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE, LIPID-BINDING, AND DOMAIN.
RX PubMed=10983984; DOI=10.1016/s1097-2765(00)00037-x;
RA Ferguson K.M., Kavran J.M., Sankaran V.G., Fournier E., Isakoff S.J.,
RA Skolnik E.Y., Lemmon M.A.;
RT "Structural basis for discrimination of 3-phosphoinositides by pleckstrin
RT homology domains.";
RL Mol. Cell 6:373-384(2000).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 261-387 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 1,3,4,5-TETRAPHOSPHATE, DOMAIN, AND LIPID-BINDING.
RX PubMed=10983985; DOI=10.1016/s1097-2765(00)00038-1;
RA Lietzke S.E., Bose S., Cronin T., Klarlund J., Chawla A., Czech M.P.,
RA Lambright D.G.;
RT "Structural basis of 3-phosphoinositide recognition by pleckstrin homology
RT domains.";
RL Mol. Cell 6:385-394(2000).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 261-387 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE, LIPID-BINDING, DOMAIN, AND
RP MUTAGENESIS OF LYS-273; ARG-277; THR-280; LYS-282; ARG-284; TYR-295;
RP ARG-305; LYS-343; ASN-354 AND HIS-355.
RX PubMed=15359279; DOI=10.1038/sj.emboj.7600388;
RA Cronin T.C., DiNitto J.P., Czech M.P., Lambright D.G.;
RT "Structural determinants of phosphoinositide selectivity in splice variants
RT of Grp1 family PH domains.";
RL EMBO J. 23:3711-3720(2004).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 63-399 IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL 1,3,4,5-TETRAPHOSPHATE, FUNCTION, DOMAIN,
RP AUTOINHIBITORY REGION, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-388 AND
RP LYS-392, AND LIPID-BINDING.
RX PubMed=18042453; DOI=10.1016/j.molcel.2007.09.017;
RA DiNitto J.P., Delprato A., Gabe Lee M.T., Cronin T.C., Huang S.,
RA Guilherme A., Czech M.P., Lambright D.G.;
RT "Structural basis and mechanism of autoregulation in 3-phosphoinositide-
RT dependent Grp1 family Arf GTPase exchange factors.";
RL Mol. Cell 28:569-583(2007).
RN [11]
RP SUBCELLULAR LOCATION, INTERACTION WITH FRMD4A AND FRMD4B, AND MUTAGENESIS
RP OF GLU-161.
RX PubMed=20080746; DOI=10.1073/pnas.0908423107;
RA Ikenouchi J., Umeda M.;
RT "FRMD4A regulates epithelial polarity by connecting Arf6 activation with
RT the PAR complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:748-753(2010).
CC -!- FUNCTION: Promotes guanine-nucleotide exchange on ARF1. Promotes the
CC activation of ARF factors through replacement of GDP with GTP
CC (PubMed:18042453). Plays a role in the epithelial polarization
CC (PubMed:20080746). {ECO:0000269|PubMed:18042453,
CC ECO:0000269|PubMed:20080746}.
CC -!- SUBUNIT: Interacts with TAMALIN. Interacts with FRMD4A
CC (PubMed:20080746). Interacts with FRMD4B (PubMed:20080746).
CC {ECO:0000269|PubMed:10828067, ECO:0000269|PubMed:10983984,
CC ECO:0000269|PubMed:10983985, ECO:0000269|PubMed:15359279,
CC ECO:0000269|PubMed:18042453, ECO:0000269|PubMed:20080746}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cell membrane
CC {ECO:0000269|PubMed:18042453}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18042453}. Cell junction, adherens junction
CC {ECO:0000269|PubMed:20080746}. Cell junction, tight junction
CC {ECO:0000269|PubMed:20080746}. Note=Translocates from the cytosol to
CC membranes enriched in phosphatidylinositol 3,4,5-trisphosphate.
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; AF001871; AAB60876.1; -; Genomic_DNA.
DR EMBL; AB013470; BAA33433.1; -; mRNA.
DR EMBL; AF084221; AAF23858.1; -; mRNA.
DR EMBL; BC035296; AAH35296.2; -; mRNA.
DR CCDS; CCDS19845.1; -.
DR RefSeq; NP_035312.3; NM_011182.4.
DR PDB; 1FGY; X-ray; 1.50 A; A=261-387.
DR PDB; 1FGZ; X-ray; 2.05 A; A=261-387.
DR PDB; 1FHW; X-ray; 1.90 A; A/B=264-391.
DR PDB; 1FHX; X-ray; 2.50 A; A/B=264-391.
DR PDB; 1U2B; X-ray; 1.80 A; A=261-387.
DR PDB; 2R09; X-ray; 1.90 A; A/B=63-399.
DR PDB; 2R0D; X-ray; 2.04 A; A/B=63-399.
DR PDB; 6BBP; EM; 35.00 A; A=63-399.
DR PDB; 6BBQ; EM; 35.00 A; A=63-399.
DR PDBsum; 1FGY; -.
DR PDBsum; 1FGZ; -.
DR PDBsum; 1FHW; -.
DR PDBsum; 1FHX; -.
DR PDBsum; 1U2B; -.
DR PDBsum; 2R09; -.
DR PDBsum; 2R0D; -.
DR PDBsum; 6BBP; -.
DR PDBsum; 6BBQ; -.
DR AlphaFoldDB; O08967; -.
DR BMRB; O08967; -.
DR SASBDB; O08967; -.
DR SMR; O08967; -.
DR BioGRID; 202413; 5.
DR IntAct; O08967; 4.
DR MINT; O08967; -.
DR STRING; 10090.ENSMUSP00000112157; -.
DR ChEMBL; CHEMBL3763004; -.
DR iPTMnet; O08967; -.
DR PhosphoSitePlus; O08967; -.
DR PaxDb; O08967; -.
DR PRIDE; O08967; -.
DR ProteomicsDB; 285443; -.
DR Antibodypedia; 2818; 202 antibodies from 33 providers.
DR DNASU; 19159; -.
DR Ensembl; ENSMUST00000116456; ENSMUSP00000112157; ENSMUSG00000018001.
DR GeneID; 19159; -.
DR KEGG; mmu:19159; -.
DR UCSC; uc009ako.2; mouse.
DR CTD; 9265; -.
DR MGI; MGI:1335107; Cyth3.
DR VEuPathDB; HostDB:ENSMUSG00000018001; -.
DR eggNOG; KOG0930; Eukaryota.
DR GeneTree; ENSGT00940000155825; -.
DR InParanoid; O08967; -.
DR OMA; INTRKAD; -.
DR OrthoDB; 657055at2759; -.
DR PhylomeDB; O08967; -.
DR TreeFam; TF352091; -.
DR Reactome; R-MMU-6811438; Intra-Golgi traffic.
DR BioGRID-ORCS; 19159; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Cyth3; mouse.
DR EvolutionaryTrace; O08967; -.
DR PRO; PR:O08967; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O08967; protein.
DR Bgee; ENSMUSG00000018001; Expressed in superior cervical ganglion and 254 other tissues.
DR ExpressionAtlas; O08967; baseline and differential.
DR Genevisible; O08967; MM.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0005923; C:bicellular tight junction; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0001726; C:ruffle; IPI:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0005547; F:phosphatidylinositol-3,4,5-trisphosphate binding; IDA:MGI.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; IMP:MGI.
DR GO; GO:0048193; P:Golgi vesicle transport; ISS:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:MGI.
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; Cell junction; Cell membrane; Coiled coil; Cytoplasm;
KW Guanine-nucleotide releasing factor; Lipid-binding; Membrane;
KW Reference proteome; Tight junction.
FT CHAIN 1..399
FT /note="Cytohesin-3"
FT /id="PRO_0000120201"
FT DOMAIN 77..206
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 264..380
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 391..399
FT /note="C-terminal autoinhibitory region"
FT COILED 14..61
FT /evidence="ECO:0000255"
FT BINDING 273..280
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 284
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:10983984,
FT ECO:0000269|PubMed:15359279"
FT BINDING 295
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:10983984,
FT ECO:0000269|PubMed:15359279"
FT BINDING 305
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:10983984,
FT ECO:0000269|PubMed:15359279"
FT BINDING 354
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:10983984,
FT ECO:0000269|PubMed:15359279"
FT MUTAGEN 161
FT /note="E->K: Impairs epithelium polarization."
FT /evidence="ECO:0000269|PubMed:20080746"
FT MUTAGEN 273
FT /note="K->A: Abolishes phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 277
FT /note="R->A,G: Reduces phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 280
FT /note="T->A,G: Reduces phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 282
FT /note="K->A: Reduces phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 284
FT /note="R->A: Abolishes phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 295
FT /note="Y->F: Reduces phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 305
FT /note="R->A: Abolishes phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 343
FT /note="K->A: Abolishes phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 354
FT /note="N->A: Slightly reduces phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 355
FT /note="H->A: Abolishes phosphatidylinositol 3,4,5-
FT trisphosphate binding."
FT /evidence="ECO:0000269|PubMed:15359279"
FT MUTAGEN 388
FT /note="L->A: Impairs autoinhibition; when associated with
FT A-392."
FT /evidence="ECO:0000269|PubMed:18042453"
FT MUTAGEN 392
FT /note="K->A: Impairs autoinhibition; when associated with
FT A-388."
FT /evidence="ECO:0000269|PubMed:18042453"
FT HELIX 64..79
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 98..107
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 113..121
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 125..136
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 145..152
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 162..179
FT /evidence="ECO:0007829|PDB:2R09"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 187..205
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 215..221
FT /evidence="ECO:0007829|PDB:2R09"
FT TURN 222..225
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 233..245
FT /evidence="ECO:0007829|PDB:2R09"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:2R09"
FT STRAND 266..274
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 276..278
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 281..289
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 292..298
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 305..309
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 314..318
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 324..330
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 342..344
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:1FGY"
FT STRAND 356..361
FT /evidence="ECO:0007829|PDB:1FGY"
FT HELIX 365..381
FT /evidence="ECO:0007829|PDB:1FGY"
FT TURN 383..386
FT /evidence="ECO:0007829|PDB:1FGY"
SQ SEQUENCE 399 AA; 46280 MW; 00F7FEB9C3849157 CRC64;
MDEGGGGEGG SVPEDLSLEE REELLDIRRR KKELIDDIER LKYEIAEVMT EIDNLTSVEE
SKTTQRNKQI AMGRKKFNMD PKKGIQFLIE NDLLQSSPED VAQFLYKGEG LNKTVIGDYL
GERDDFNIKV LQAFVELHEF ADLNLVQALR QFLWSFRLPG EAQKIDRMME AFASRYCLCN
PGVFQSTDTC YVLSFAIIML NTSLHNHNVR DKPTAERFIT MNRGINEGGD LPEELLRNLY
ESIKNEPFKI PEDDGNDLTH TFFNPDREGW LLKLGGRVKT WKRRWFILTD NCLYYFEYTT
DKEPRGIIPL ENLSIREVED PRKPNCFELY NPSHKGQVIK ACKTEADGRV VEGNHVVYRI
SAPSPEEKEE WMKSIKASIS RDPFYDMLAT RKRRIANKK
