INSI1_CHICK
ID INSI1_CHICK Reviewed; 252 AA.
AC Q5ZMT9;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 83.
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};
GN ORFNames=RCJMB04_1d1 {ECO:0000303|PubMed:15642098};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ719295; CAG30954.1; -; mRNA.
DR RefSeq; NP_001026137.1; NM_001030966.1.
DR AlphaFoldDB; Q5ZMT9; -.
DR SMR; Q5ZMT9; -.
DR STRING; 9031.ENSGALP00000028029; -.
DR PaxDb; Q5ZMT9; -.
DR Ensembl; ENSGALT00000028082; ENSGALP00000028029; ENSGALG00000017394.
DR GeneID; 420442; -.
DR KEGG; gga:420442; -.
DR CTD; 3638; -.
DR VEuPathDB; HostDB:geneid_420442; -.
DR eggNOG; KOG4363; Eukaryota.
DR GeneTree; ENSGT00580000081600; -.
DR InParanoid; Q5ZMT9; -.
DR OMA; WSRHLVQ; -.
DR OrthoDB; 1342554at2759; -.
DR PhylomeDB; Q5ZMT9; -.
DR PRO; PR:Q5ZMT9; -.
DR Proteomes; UP000000539; Chromosome 2.
DR Bgee; ENSGALG00000017394; Expressed in liver and 12 other tissues.
DR ExpressionAtlas; Q5ZMT9; 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; 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..252
FT /note="Insulin-induced gene 1 protein"
FT /id="PRO_0000287388"
FT TOPO_DOM 1..59
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O15503"
FT TRANSMEM 60..82
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 83..101
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 102..119
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 120..134
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 135..157
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 158..160
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 161..179
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 180..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O15503"
FT TRANSMEM 185..206
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 207..220
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 221..238
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:A1T557"
FT TOPO_DOM 239..252
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O15503"
FT REGION 22..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 246..252
FT /note="KxHxx"
FT /evidence="ECO:0000250|UniProtKB:O15503"
FT SITE 146
FT /note="Required for the recognition of 25-
FT hydroxycholesterol"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5U4"
SQ SEQUENCE 252 AA; 27355 MW; B42032A882176B46 CRC64;
MPRLESGAWS CSCAARARHA ARPGEAAPKA DAMQSPSPSA GRAEREASGG SATTWRQHLV
QRSVVLFVVG AFMALVLNLL QIQRNVTLFP DEVIATLFSS AWWVPPCCGT AAAVVGLLYP
CIDSHLGEPH KFKREWASVM RCIAVFVGIN HASAKLDFAN NVQLSLTLAA LSLGLWWTFD
RSRSGLGLGI TIAFVATLIT QFLVYNGVYQ YTSPDFLYIR SWLPCIFFSG GVTVGNIGRQ
LAMGIPEKPH ND
