ID   INSI1_DANRE             Reviewed;         251 AA.
AC   Q8AV61;
DT   15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=Insulin-induced gene 1 protein {ECO:0000303|PubMed:12242332};
DE            Short=INSIG-1 {ECO:0000303|PubMed:12242332};
GN   Name=insig1 {ECO:0000303|PubMed:12242332};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=12242332; DOI=10.1073/pnas.162488899;
RA   Yabe D., Brown M.S., Goldstein J.L.;
RT   "Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks
RT   export of sterol regulatory element-binding proteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:12753-12758(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=AB; TISSUE=Embryo;
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Oxysterol-binding protein that mediates feedback control of
CC       cholesterol synthesis by controlling both endoplasmic reticulum to
CC       Golgi transport of scap and degradation of hmgcr. Acts as a negative
CC       regulator of cholesterol biosynthesis by mediating the retention of the
CC       SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the
CC       processing of sterol regulatory element-binding proteins (SREBPs).
CC       Binds oxysterol, including 25-hydroxycholesterol, regulating
CC       interaction with scap and retention of the SCAP-SREBP complex in the
CC       endoplasmic reticulum. In presence of oxysterol, interacts with scap,
CC       retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby
CC       preventing scap from escorting SREBPs to the Golgi. Sterol deprivation
CC       reduces oxysterol-binding, disrupting the interaction between insig1
CC       and scap, thereby promoting Golgi transport of the SCAP-SREBP complex,
CC       followed by processing and nuclear translocation of SREBPs. Also
CC       regulates cholesterol synthesis by regulating degradation of hmgcr.
CC       {ECO:0000250|UniProtKB:O15503}.
CC   -!- SUBUNIT: Interacts with scap; interaction is direct and only takes
CC       place in the presence of sterols; it prevents interaction between scap
CC       and the coat protein complex II (COPII). Associates with the SCAP-SREBP
CC       complex; association is mediated via its interaction with scap and only
CC       takes place in the presence of sterols. {ECO:0000250|UniProtKB:O15503}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:O15503}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:O15503}.
CC   -!- DOMAIN: The KxHxx motif mediates association with the coatomer complex.
CC       {ECO:0000250|UniProtKB:O15503}.
CC   -!- DOMAIN: Binds oxysterols in a pocket within their transmembrane domains
CC       and interacts with SCAP via transmembrane domains 3 and 4.
CC       {ECO:0000250|UniProtKB:Q9Y5U4}.
CC   -!- SIMILARITY: Belongs to the INSIG family. {ECO:0000305}.
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DR   EMBL; AF527626; AAN28327.1; -; mRNA.
DR   EMBL; BC045341; AAH45341.1; -; mRNA.
DR   RefSeq; NP_956163.1; NM_199869.1.
DR   AlphaFoldDB; Q8AV61; -.
DR   SMR; Q8AV61; -.
DR   STRING; 7955.ENSDARP00000104993; -.
DR   PaxDb; Q8AV61; -.
DR   Ensembl; ENSDART00000013785; ENSDARP00000018378; ENSDARG00000010658.
DR   Ensembl; ENSDART00000185074; ENSDARP00000147776; ENSDARG00000113413.
DR   GeneID; 334189; -.
DR   KEGG; dre:334189; -.
DR   CTD; 3638; -.
DR   ZFIN; ZDB-GENE-030131-6121; insig1.
DR   eggNOG; KOG4363; Eukaryota.
DR   GeneTree; ENSGT00580000081600; -.
DR   HOGENOM; CLU_092922_0_0_1; -.
DR   InParanoid; Q8AV61; -.
DR   OMA; FWSCSCT; -.
DR   OrthoDB; 1342554at2759; -.
DR   PhylomeDB; Q8AV61; -.
DR   TreeFam; TF331013; -.
DR   PRO; PR:Q8AV61; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Chromosome 7.
DR   Bgee; ENSDARG00000010658; Expressed in intestine and 27 other tissues.
DR   ExpressionAtlas; Q8AV61; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0032937; C:SREBP-SCAP-Insig complex; IBA:GO_Central.
DR   GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IBA:GO_Central.
DR   GO; GO:0032933; P:SREBP signaling pathway; IBA:GO_Central.
DR   GO; GO:0036316; P:SREBP-SCAP complex retention in endoplasmic reticulum; IBA:GO_Central.
DR   GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR   InterPro; IPR009904; INSIG-1.
DR   InterPro; IPR025929; INSIG_fam.
DR   PANTHER; PTHR15301; PTHR15301; 2.
DR   PANTHER; PTHR15301:SF11; PTHR15301:SF11; 2.
DR   Pfam; PF07281; INSIG; 1.
PE   2: Evidence at transcript level;
KW   Cholesterol metabolism; Endoplasmic reticulum; Lipid metabolism;
KW   Lipid-binding; Membrane; Reference proteome; Steroid metabolism;
KW   Sterol metabolism; Transmembrane; Transmembrane helix.
FT   CHAIN           1..251
FT                   /note="Insulin-induced gene 1 protein"
FT                   /id="PRO_0000287389"
FT   TOPO_DOM        1..58
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:O15503"
FT   TRANSMEM        59..81
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000250|UniProtKB:A1T557"
FT   TOPO_DOM        82..100
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        101..118
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000250|UniProtKB:A1T557"
FT   TOPO_DOM        119..133
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        134..156
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000250|UniProtKB:A1T557"
FT   TOPO_DOM        157..159
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        160..178
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000250|UniProtKB:A1T557"
FT   TOPO_DOM        179..183
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:O15503"
FT   TRANSMEM        184..205
FT                   /note="Helical; Name=5"
FT                   /evidence="ECO:0000250|UniProtKB:A1T557"
FT   TOPO_DOM        206..219
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        220..237
FT                   /note="Helical; Name=6"
FT                   /evidence="ECO:0000250|UniProtKB:A1T557"
FT   TOPO_DOM        238..251
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:O15503, ECO:0000305"
FT   MOTIF           245..251
FT                   /note="KxHxx"
FT                   /evidence="ECO:0000250|UniProtKB:O15503"
FT   SITE            145
FT                   /note="Required for the recognition of 25-
FT                   hydroxycholesterol"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y5U4"
SQ   SEQUENCE   251 AA;  27596 MW;  11BEAEAFA6DC0B3A CRC64;
     MPRLEEHCWS CSCSTSVKTK DLSSAGWIVC KTGEMMSIIT SVLSHAYGSL HSLQSANLIR
     RGLVLFIVGV VLALVLNLLQ IQRNVTLFPE EVLDTLFSSA WWIPLCCGTA AAVVGLLYPC
     LDHHLGEPHK FKREWASVMR CIAVFVGINH ASAKLDFANN VQLSLTLAAL SLGLWWTFDR
     SRSGFGLGLT TALLATLIAQ LLVYNGIYQY TSPDFLYVRS WLPCIFFSGG VTVGNIGRQL
     AMGSTEKIHN D