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Protein

Insulin-induced gene 1 protein

Gene

Insig1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

GO - Biological processi

  • cellular response to insulin stimulus Source: RGD
  • cholesterol metabolic process Source: UniProtKB-KW
  • response to estradiol Source: RGD
  • response to fatty acid Source: RGD
  • response to lipid Source: RGD
  • response to peptide hormone Source: RGD

Keywordsi

Biological processCholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-induced gene 1 protein
Short name:
INSIG-1
Alternative name(s):
Immediate-early protein CL-6
Insulin-induced growth response protein CL-6
Gene namesi
Name:Insig1
Synonyms:Cl-6
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 4

Organism-specific databases

RGDi708457 Insig1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001916771 – 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

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiQ08755
PRIDEiQ08755

Expressioni

Tissue specificityi

Highly expressed in liver and kidney.

Inductioni

By insulin and hepatectomy.

Gene expression databases

BgeeiENSRNOG00000006859
GenevisibleiQ08755 RN

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. Interacts with RNF145.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000009233

Family & Domainsi

Sequence similaritiesi

Belongs to the INSIG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4363 Eukaryota
ENOG410XQ2M LUCA
GeneTreeiENSGT00580000081600
HOGENOMiHOG000253021
HOVERGENiHBG058958
InParanoidiQ08755
OMAiEMMSIIT
OrthoDBiEOG091G0L61
PhylomeDBiQ08755
TreeFamiTF331013

Family and domain databases

InterProiView protein in InterPro
IPR009904 INSIG-1
IPR025929 INSIG_fam
PANTHERiPTHR15301 PTHR15301, 1 hit
PTHR15301:SF11 PTHR15301:SF11, 1 hit
PfamiView protein in Pfam
PF07281 INSIG, 1 hit

Sequencei

Sequence statusi: Complete.

Q08755-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRLHDHVWS YPSAGAARPY SLPRGMIAAA LCPQGPGAPE PEPAPRGQRE
60 70 80 90 100
GTAGFSARPG 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):28,232
Last modified:November 1, 1995 - v1
Checksum:i68DA7E609818F637
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L13619 mRNA Translation: AAA40938.1
BC078827 mRNA Translation: AAH78827.1
PIRiA47112
RefSeqiNP_071787.1, NM_022392.1
UniGeneiRn.772

Genome annotation databases

EnsembliENSRNOT00000009233; ENSRNOP00000009233; ENSRNOG00000006859
GeneIDi64194
KEGGirno:64194

Similar proteinsi

Entry informationi

Entry nameiINSI1_RAT
AccessioniPrimary (citable) accession number: Q08755
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: May 23, 2018
This is version 110 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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