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Protein

Insulin-induced gene 1 protein

Gene

Insig1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth (By similarity).By similarity

GO - Biological processi

  • cholesterol biosynthetic process Source: MGI
  • cholesterol metabolic process Source: MGI
  • cranial suture morphogenesis Source: MGI
  • inner ear morphogenesis Source: MGI
  • middle ear morphogenesis Source: MGI
  • negative regulation of cargo loading into COPII-coated vesicle Source: MGI
  • negative regulation of fat cell differentiation Source: MGI
  • negative regulation of fatty acid biosynthetic process Source: MGI
  • negative regulation of steroid biosynthetic process Source: MGI
  • palate development Source: MGI
  • response to sterol depletion Source: MGI
  • SREBP signaling pathway Source: MGI
  • sterol biosynthetic process Source: MGI
  • triglyceride metabolic process Source: MGI
Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-induced gene 1 protein
Short name:
INSIG-1
Gene namesi
Name:Insig1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1916289. Insig1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 69CytoplasmicBy similarityAdd BLAST69
Transmembranei70 – 90HelicalSequence analysisAdd BLAST21
Topological domaini91 – 108LumenalSequence analysisAdd BLAST18
Transmembranei109 – 129HelicalSequence analysisAdd BLAST21
Topological domaini130 – 142CytoplasmicBy similarityAdd BLAST13
Transmembranei143 – 159HelicalSequence analysisAdd BLAST17
Topological domaini160 – 164LumenalSequence analysis5
Transmembranei165 – 185HelicalSequence analysisAdd BLAST21
Topological domaini186 – 191CytoplasmicBy similarity6
Transmembranei192 – 212HelicalSequence analysisAdd BLAST21
Topological domaini213 – 223LumenalSequence analysisAdd BLAST11
Transmembranei224 – 244HelicalSequence analysisAdd BLAST21
Topological domaini245 – 259CytoplasmicBy similarityAdd BLAST15

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001916761 – 259Insulin-induced gene 1 proteinAdd BLAST259

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki138Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki140Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Ubiquitinated. Subsequent to sterol deprivation, the SCAP-SREBF2 complex becomes dissociated from INSIG1, is then ubiquitinated and degraded in proteasomes. Although ubiquitination is required for rapid INSIG1 degradation, it is not required for release of the SCAP-SREBP complex. Ubiquitinated by RNF139 (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ8BGI3.
PRIDEiQ8BGI3.

PTM databases

PhosphoSitePlusiQ8BGI3.

Expressioni

Gene expression databases

BgeeiENSMUSG00000045294.
CleanExiMM_INSIG1.
GenevisibleiQ8BGI3. MM.

Interactioni

Subunit structurei

Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with HMGCR (via its SSD); the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with AMFR/gp78 (via its membrane domain); the interaction recruits HMCR at the ER membrane for its ubiquitination and degradation by the sterol-mediated ERAD pathway (By similarity).By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061877.

Structurei

3D structure databases

ProteinModelPortaliQ8BGI3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the INSIG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4363. Eukaryota.
ENOG410XQ2M. LUCA.
GeneTreeiENSGT00580000081600.
HOGENOMiHOG000253021.
HOVERGENiHBG058958.
InParanoidiQ8BGI3.
OMAiEMMSIIT.
OrthoDBiEOG091G0L61.
PhylomeDBiQ8BGI3.
TreeFamiTF331013.

Family and domain databases

InterProiIPR009904. INSIG-1.
IPR025929. INSIG_fam.
[Graphical view]
PANTHERiPTHR15301:SF11. PTHR15301:SF11. 1 hit.
PfamiPF07281. INSIG. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8BGI3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRLHDHVWN YPSAGAARPY SLPRGMIAAA ACPQGPGVPE PEHAPRGQRA
60 70 80 90 100
GTTGCSARPG SWHHDLVQRS LVLFSFGVVL ALVLNLLQIQ RNVTLFPDEV
110 120 130 140 150
IATIFSSAWW VPPCCGTAAA VVGLLYPCID SHLGEPHKFK REWASVMRCI
160 170 180 190 200
AVFVGINHAS AKLDFANNVQ LSLTLAALSL GLWWTFDRSR SGLGLGITIA
210 220 230 240 250
FLATLITQFL VYNGVYQYTS PDFLYIRSWL PCIFFSGGVT VGNIGRQLAM

GVPEKPHSD
Length:259
Mass (Da):28,213
Last modified:March 1, 2003 - v1
Checksum:i964AD1FAA8EE610D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28A → G in BAE22733 (PubMed:16141072).Curated1
Sequence conflicti63H → Y in BAE22733 (PubMed:16141072).Curated1
Sequence conflicti199I → N in BAE22733 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527630 mRNA. Translation: AAN28331.1.
AK088380 mRNA. Translation: BAC40316.1.
AK135941 mRNA. Translation: BAE22733.1.
AK139913 mRNA. Translation: BAE24179.1.
AK151186 mRNA. Translation: BAE30185.1.
BC132167 mRNA. Translation: AAI32168.1.
BC132499 mRNA. Translation: AAI32500.1.
CCDSiCCDS19142.1.
RefSeqiNP_705746.1. NM_153526.5.
UniGeneiMm.30221.

Genome annotation databases

EnsembliENSMUST00000059155; ENSMUSP00000061877; ENSMUSG00000045294.
GeneIDi231070.
KEGGimmu:231070.
UCSCiuc012dtq.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527630 mRNA. Translation: AAN28331.1.
AK088380 mRNA. Translation: BAC40316.1.
AK135941 mRNA. Translation: BAE22733.1.
AK139913 mRNA. Translation: BAE24179.1.
AK151186 mRNA. Translation: BAE30185.1.
BC132167 mRNA. Translation: AAI32168.1.
BC132499 mRNA. Translation: AAI32500.1.
CCDSiCCDS19142.1.
RefSeqiNP_705746.1. NM_153526.5.
UniGeneiMm.30221.

3D structure databases

ProteinModelPortaliQ8BGI3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000061877.

PTM databases

PhosphoSitePlusiQ8BGI3.

Proteomic databases

PaxDbiQ8BGI3.
PRIDEiQ8BGI3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000059155; ENSMUSP00000061877; ENSMUSG00000045294.
GeneIDi231070.
KEGGimmu:231070.
UCSCiuc012dtq.1. mouse.

Organism-specific databases

CTDi3638.
MGIiMGI:1916289. Insig1.

Phylogenomic databases

eggNOGiKOG4363. Eukaryota.
ENOG410XQ2M. LUCA.
GeneTreeiENSGT00580000081600.
HOGENOMiHOG000253021.
HOVERGENiHBG058958.
InParanoidiQ8BGI3.
OMAiEMMSIIT.
OrthoDBiEOG091G0L61.
PhylomeDBiQ8BGI3.
TreeFamiTF331013.

Miscellaneous databases

PROiQ8BGI3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000045294.
CleanExiMM_INSIG1.
GenevisibleiQ8BGI3. MM.

Family and domain databases

InterProiIPR009904. INSIG-1.
IPR025929. INSIG_fam.
[Graphical view]
PANTHERiPTHR15301:SF11. PTHR15301:SF11. 1 hit.
PfamiPF07281. INSIG. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiINSI1_MOUSE
AccessioniPrimary (citable) accession number: Q8BGI3
Secondary accession number(s): A2RSM6, Q3UAX9, Q3UX30
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: March 1, 2003
Last modified: November 2, 2016
This is version 98 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.