INSI1_XENLA
ID INSI1_XENLA Reviewed; 251 AA.
AC Q6DF80;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 59.
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 laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Oocyte;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (JUL-2004) 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; BC076862; AAH76862.1; -; mRNA.
DR RefSeq; NP_001086601.1; NM_001093132.1.
DR AlphaFoldDB; Q6DF80; -.
DR SMR; Q6DF80; -.
DR DNASU; 446436; -.
DR GeneID; 446436; -.
DR KEGG; xla:446436; -.
DR CTD; 446436; -.
DR Xenbase; XB-GENE-6077599; insig1.L.
DR OMA; FWSCSCT; -.
DR OrthoDB; 1342554at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 446436; Expressed in kidney and 19 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0008142; F:oxysterol binding; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
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_0000287390"
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; 27569 MW; C4A3B397D33BAD88 CRC64;
MQTLEEHCWS CSCTRGRDKK GTKVSAWLAR RVGKAMSSLN SLLSLAYSTL ASSEGRSLIQ
RSLVLFTVGV FLALVLNLLQ IQRNVTLFPE EVIATIFSSA WWVPPCCGTA AAVVGLLYPC
IDSRIGEPHK FKREWASVMR CIAVFVGINH ASAKLDFANN VQLSLTLAAL SLGLWWTFDR
SRSGLGLGIT IAFLATLITQ FLVYNGVYQY TSPDFLYIRS WLPCIFFSGG VTVGNIGRQL
AMGSSEKTHG D
