INSI2_XENLA
ID INSI2_XENLA Reviewed; 218 AA.
AC Q66J27;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 55.
DE RecName: Full=Insulin-induced gene 2 protein {ECO:0000250|UniProtKB:Q9Y5U4};
DE Short=INSIG-2 {ECO:0000250|UniProtKB:Q9Y5U4};
GN Name=insig2 {ECO:0000250|UniProtKB:Q9Y5U4};
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=Kidney;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-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 22-hydroxycholesterol, 24-
CC hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol,
CC regulating interaction with scap and retention of the SCAP-SREBP
CC complex in the endoplasmic reticulum. In presence of oxysterol,
CC interacts with scap, retaining the SCAP-SREBP complex in the
CC endoplasmic reticulum, thereby preventing scap from escorting SREBPs to
CC the Golgi. Sterol deprivation reduce oxysterol-binding, disrupting the
CC interaction between insig2 and scap, thereby promoting Golgi transport
CC of the SCAP-SREBP complex, followed by processing and nuclear
CC translocation of SREBPs. Also regulates cholesterol synthesis by
CC regulating degradation of hmgcr. {ECO:0000250|UniProtKB:Q9Y5U4}.
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:Q9Y5U4}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9Y5U4}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9Y5U4}.
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 -!- DOMAIN: The KxHxx motif mediates association with the coatomer complex.
CC {ECO:0000250|UniProtKB:Q9Y5U4}.
CC -!- SIMILARITY: Belongs to the INSIG family. {ECO:0000305}.
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DR EMBL; BC081084; AAH81084.1; -; mRNA.
DR RefSeq; NP_001087688.1; NM_001094219.1.
DR RefSeq; XP_018089979.1; XM_018234490.1.
DR AlphaFoldDB; Q66J27; -.
DR SMR; Q66J27; -.
DR DNASU; 447512; -.
DR GeneID; 447512; -.
DR KEGG; xla:447512; -.
DR CTD; 447512; -.
DR Xenbase; XB-GENE-5777147; insig2.L.
DR OMA; KHLGEPH; -.
DR OrthoDB; 1342554at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10L.
DR Bgee; 447512; Expressed in oocyte 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:0006695; P:cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032933; P:SREBP signaling pathway; ISS:UniProtKB.
DR GO; GO:0036316; P:SREBP-SCAP complex retention in endoplasmic reticulum; ISS:UniProtKB.
DR InterPro; IPR025929; INSIG_fam.
DR PANTHER; PTHR15301; PTHR15301; 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..218
FT /note="Insulin-induced gene 2 protein"
FT /id="PRO_0000286803"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 22..44
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 45..63
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 64..81
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 82..96
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 97..119
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 120..122
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 123..141
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 142..146
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 147..168
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 169..182
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 183..200
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 201..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT MOTIF 212..218
FT /note="KxHxx"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5U4"
FT SITE 108
FT /note="Required for the recognition of 25-
FT hydroxycholesterol"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5U4"
SQ SEQUENCE 218 AA; 24359 MW; 2314F9647A138280 CRC64;
MGDRENVSYG SRPILAQKMN LLLRGFLLFL IGVFLALVLN LLQVQRNVTL FPPDVLSSLF
SSAWWVPLCC GTAAAAIGLL YPCIDRHLGE PHKFKREWSS VMRCVAVFVG INHASAKVDF
ANNMQLSLTL AALSIGLWWT FDRSRSGLGL GIGISFFATL VSQLLVYNGV YEYTAPDFLY
VRSWLPCIFF AGGITMGNIG RQLEMYERKA LVEKSHRD
