CYH1_MOUSE
ID CYH1_MOUSE Reviewed; 398 AA.
AC Q9QX11; O88817; Q76MU4;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Cytohesin-1;
DE AltName: Full=PH, SEC7 and coiled-coil domain-containing protein 1;
DE Short=CLM1;
DE AltName: Full=SEC7 homolog A;
DE Short=mSec7-1;
GN Name=Cyth1; Synonyms=Pscd1;
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] (ISOFORM 2).
RC TISSUE=Brain;
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=B10D2/NSNJ; TISSUE=Lymph node;
RX PubMed=9745014; DOI=10.1007/s002510050444;
RA O'Rourke A.M., Escuro G., Feeney A.J.;
RT "Cloning and sequencing of cDNA encoding mouse cytohesin-1.";
RL Immunogenetics 48:354-355(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10978522; DOI=10.1016/s0167-4781(00)00160-3;
RA Goda N., Tanoue A., Kikuchi S., Tsujimoto G.;
RT "Cloning and characterization of the promoter of murine cytohesin-1 gene.";
RL Biochim. Biophys. Acta 1493:195-199(2000).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AUTOINHIBITION, AND MUTAGENESIS OF
RP LEU-385; LYS-389 AND SER-394.
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, and Spleen;
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 [6]
RP SUBCELLULAR LOCATION, INTERACTION WITH FRMD4A AND FRMD4B, SUBUNIT,
RP FUNCTION, AND MUTAGENESIS OF GLU-157.
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).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND UBIQUITINATION.
RX PubMed=29420262; DOI=10.1126/science.aan0814;
RA Mohanan V., Nakata T., Desch A.N., Levesque C., Boroughs A., Guzman G.,
RA Cao Z., Creasey E., Yao J., Boucher G., Charron G., Bhan A.K., Schenone M.,
RA Carr S.A., Reinecker H.C., Daly M.J., Rioux J.D., Lassen K.G., Xavier R.J.;
RT "C1orf106 is a colitis risk gene that regulates stability of epithelial
RT adherens junctions.";
RL Science 359:1161-1166(2018).
CC -!- FUNCTION: Promotes guanine-nucleotide exchange on ARF1, ARF5 and ARF6
CC (PubMed:18042453, PubMed:20080746). Promotes the activation of ARF
CC factors through replacement of GDP with GTP (PubMed:18042453). Plays an
CC important role in membrane trafficking, during junctional remodeling
CC and epithelial polarization, through regulation of ARF6 activity
CC (PubMed:20080746, PubMed:29420262). {ECO:0000269|PubMed:18042453,
CC ECO:0000269|PubMed:20080746, ECO:0000269|PubMed:29420262}.
CC -!- SUBUNIT: Interacts with TRIM23 and CYTIP (By similarity). Interacts
CC (via coiled-coil domain) with FRMD4A (via coiled-coil
CC domain)(PubMed:20080746). Interacts with FRMD4B (PubMed:20080746).
CC Found in a complex with PARD3, CYTH1 and FRMD4A (PubMed:20080746).
CC Interacts (via N-terminal domain) with INAVA (via N-terminal domain)
CC (By similarity). {ECO:0000250|UniProtKB:Q15438,
CC ECO:0000269|PubMed:20080746}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18042453,
CC ECO:0000269|PubMed:29420262}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18042453}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:18042453, ECO:0000269|PubMed:29420262}. Cell
CC junction, tight junction {ECO:0000269|PubMed:20080746}. Cell junction,
CC adherens junction {ECO:0000269|PubMed:20080746}. Note=Colocalized with
CC TJP1 during epithelial polarization (PubMed:20080746).
CC {ECO:0000269|PubMed:20080746}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9QX11-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9QX11-2; Sequence=VSP_006035;
CC -!- TISSUE SPECIFICITY: Expressed in colon and small intestine (at protein
CC level). {ECO:0000269|PubMed:29420262}.
CC -!- DOMAIN: Binds via its PH domain to the inositol head group of
CC phosphatidylinositol 3,4,5-trisphosphate. {ECO:0000250}.
CC -!- DOMAIN: Autoinhibited by its C-terminal basic region.
CC {ECO:0000269|PubMed:18042453}.
CC -!- PTM: Ubiquitinated by SCF(FBXW11) E3 ubiquitin-protein ligase complex.
CC Ubiquitination induces proteasomal degradation.
CC {ECO:0000269|PubMed:29420262}.
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DR EMBL; AB013464; BAA33428.1; -; mRNA.
DR EMBL; AF051337; AAC71694.1; -; mRNA.
DR EMBL; AB035538; BAB13509.1; -; mRNA.
DR CCDS; CCDS48997.1; -. [Q9QX11-2]
DR RefSeq; NP_001106169.1; NM_001112699.1. [Q9QX11-2]
DR RefSeq; NP_035310.2; NM_011180.3. [Q9QX11-1]
DR AlphaFoldDB; Q9QX11; -.
DR SMR; Q9QX11; -.
DR BioGRID; 202411; 6.
DR IntAct; Q9QX11; 4.
DR MINT; Q9QX11; -.
DR STRING; 10090.ENSMUSP00000017276; -.
DR iPTMnet; Q9QX11; -.
DR PhosphoSitePlus; Q9QX11; -.
DR EPD; Q9QX11; -.
DR MaxQB; Q9QX11; -.
DR PaxDb; Q9QX11; -.
DR PRIDE; Q9QX11; -.
DR ProteomicsDB; 283997; -. [Q9QX11-1]
DR ProteomicsDB; 283998; -. [Q9QX11-2]
DR Antibodypedia; 19745; 259 antibodies from 33 providers.
DR DNASU; 19157; -.
DR Ensembl; ENSMUST00000017276; ENSMUSP00000017276; ENSMUSG00000017132. [Q9QX11-2]
DR Ensembl; ENSMUST00000106305; ENSMUSP00000101912; ENSMUSG00000017132. [Q9QX11-1]
DR GeneID; 19157; -.
DR KEGG; mmu:19157; -.
DR UCSC; uc011yil.1; mouse. [Q9QX11-1]
DR CTD; 9267; -.
DR MGI; MGI:1334257; Cyth1.
DR VEuPathDB; HostDB:ENSMUSG00000017132; -.
DR eggNOG; KOG0930; Eukaryota.
DR GeneTree; ENSGT00940000157519; -.
DR HOGENOM; CLU_032820_3_0_1; -.
DR InParanoid; Q9QX11; -.
DR TreeFam; TF352091; -.
DR Reactome; R-MMU-6811438; Intra-Golgi traffic.
DR BioGRID-ORCS; 19157; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Cyth1; mouse.
DR PRO; PR:Q9QX11; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q9QX11; protein.
DR Bgee; ENSMUSG00000017132; Expressed in vestibular membrane of cochlear duct and 230 other tissues.
DR ExpressionAtlas; Q9QX11; baseline and differential.
DR Genevisible; Q9QX11; MM.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005923; C:bicellular tight junction; IDA:MGI.
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:0098888; C:extrinsic component of presynaptic membrane; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0090162; P:establishment of epithelial cell polarity; IMP:MGI.
DR GO; GO:0032012; P:regulation of ARF protein signal transduction; IEA:InterPro.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:MGI.
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 Acetylation; Alternative splicing; Cell junction; Cell membrane;
KW Coiled coil; Cytoplasm; Guanine-nucleotide releasing factor; Lipid-binding;
KW Membrane; Reference proteome; Tight junction; Ubl conjugation.
FT CHAIN 1..398
FT /note="Cytohesin-1"
FT /id="PRO_0000120195"
FT DOMAIN 73..202
FT /note="SEC7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00189"
FT DOMAIN 260..377
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT REGION 1..60
FT /note="Necessary for localization at adherens junction"
FT /evidence="ECO:0000269|PubMed:20080746"
FT REGION 388..396
FT /note="C-terminal autoinhibitory region"
FT /evidence="ECO:0000250"
FT COILED 10..67
FT /evidence="ECO:0000255"
FT BINDING 269..277
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:0000250"
FT BINDING 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 /evidence="ECO:0000250"
FT BINDING 292
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:0000250"
FT BINDING 302
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:0000250"
FT BINDING 351
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:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q15438"
FT VAR_SEQ 273
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9744817"
FT /id="VSP_006035"
FT MUTAGEN 157
FT /note="E->K: Impairs epithelium polarity."
FT /evidence="ECO:0000269|PubMed:20080746"
FT MUTAGEN 385
FT /note="L->A: Impairs autoinhibition; when associated with
FT A-389. Impairs translocation to the cell membrane."
FT /evidence="ECO:0000269|PubMed:18042453"
FT MUTAGEN 389
FT /note="K->A: Impairs autoinhibition; when associated with
FT A-385. Impairs translocation to the cell membrane."
FT /evidence="ECO:0000269|PubMed:18042453"
FT MUTAGEN 394
FT /note="S->E: Increases guanine exchange factor activity."
FT /evidence="ECO:0000269|PubMed:18042453"
FT CONFLICT 3
FT /note="D -> E (in Ref. 2; AAC71694)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 398 AA; 46274 MW; 79E06E2364282E85 CRC64;
MEDDDSYVPS DLTAEERQEL ENIRRRKQEL LADIQRLKEE IAEVANEIES LGSTEERKNM
QRNKQVAMGR KKFNMDPKKG IQFLIENGLL KNTCEDIAQF LYKGEGLNKT AIGDYLGERD
EFSIQVLHAF VELHEFTDLN LVQALRQFLW SFRLPGEAQK IDRMMEAFAQ RYCQCNTGVF
QSTDTCYVLS FAIIMLNTSL HNPNVKDKPT VERFIAMNRG INDGGDLPEE LLRNLYESIK
NEPFKIPEDD GNDLTHTFFN PDREGWLLKL GGGRVKTWKR RWFILTDNCL YYFEYTTDKE
PRGIIPLENL SIREVEDSKK PNCFELYIPD NKDQVIKACK TEADGRVVEG NHTVYRISAP
TPEEKEDWIK CIKAAISRDP FYEMLAARKK KVSSTKRH
