ID   INSI1_XENTR             Reviewed;         251 AA.
AC   Q0V9G6;
DT   15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 1.
DT   03-AUG-2022, entry version 82.
DE   RecName: Full=Insulin-induced gene 1 protein {ECO:0000250|UniProtKB:O15503};
DE            Short=INSIG-1 {ECO:0000250|UniProtKB:O15503};
GN   Name=insig1 {ECO:0000250|UniProtKB:O15503};
OS   Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX   NCBI_TaxID=8364;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=N6; TISSUE=Liver;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (AUG-2006) 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; BC121578; AAI21579.1; -; mRNA.
DR   RefSeq; NP_001072938.1; NM_001079470.1.
DR   RefSeq; XP_012820421.1; XM_012964967.2.
DR   AlphaFoldDB; Q0V9G6; -.
DR   SMR; Q0V9G6; -.
DR   STRING; 8364.ENSXETP00000029557; -.
DR   PaxDb; Q0V9G6; -.
DR   PRIDE; Q0V9G6; -.
DR   DNASU; 780766; -.
DR   Ensembl; ENSXETT00000029557; ENSXETP00000029557; ENSXETG00000013492.
DR   GeneID; 780766; -.
DR   KEGG; xtr:780766; -.
DR   CTD; 3638; -.
DR   Xenbase; XB-GENE-487039; insig1.
DR   eggNOG; KOG4363; Eukaryota.
DR   HOGENOM; CLU_092922_0_0_1; -.
DR   InParanoid; Q0V9G6; -.
DR   OMA; FWSCSCT; -.
DR   OrthoDB; 1342554at2759; -.
DR   PhylomeDB; Q0V9G6; -.
DR   TreeFam; TF331013; -.
DR   Proteomes; UP000008143; Chromosome 6.
DR   Proteomes; UP000790000; Unplaced.
DR   Bgee; ENSXETG00000013492; Expressed in liver and 13 other tissues.
DR   ExpressionAtlas; Q0V9G6; 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; 1.
DR   PANTHER; PTHR15301:SF11; PTHR15301:SF11; 1.
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_0000287391"
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"
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;  27658 MW;  8556DF21F909E1EA CRC64;
     MQTLEEHCWS CSCTRGRDKK GTRLSTWLAQ RAAKAMSSLN SLLSLAYHTL ASSEGRSLIR
     RSLVLFAVGV FLALVLNLLQ IQRNVTLFPE EVIATIFSSA WWVPPCCGTA AAVVGLLYPC
     IDSHLGEPHK FKREWASVMR CIAVFVGINH ASAKLDFANN VQLSLTLAAL SLGLWWTFDR
     SRSGLGLGIT IAFLATLITQ FLVYNGVYQY TSPDFLYIRS WLPCIFFSGG VTVGNIGRQL
     AMGSSEKTHS D