Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Insulin-induced gene 1 protein

Gene

INSIG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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.5 Publications

Miscellaneous

Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation.

GO - Biological processi

  • cell proliferation Source: ProtInc
  • cellular response to sterol Source: UniProtKB
  • cholesterol biosynthetic process Source: Ensembl
  • cholesterol homeostasis Source: UniProtKB
  • cranial suture morphogenesis Source: Ensembl
  • inner ear morphogenesis Source: Ensembl
  • middle ear morphogenesis Source: Ensembl
  • negative regulation of cargo loading into COPII-coated vesicle Source: UniProtKB
  • negative regulation of fat cell differentiation Source: Ensembl
  • negative regulation of fatty acid biosynthetic process Source: Ensembl
  • negative regulation of protein exit from endoplasmic reticulum Source: UniProtKB
  • negative regulation of steroid biosynthetic process Source: Ensembl
  • palate development Source: Ensembl
  • SREBP-SCAP complex retention in endoplasmic reticulum Source: UniProtKB
  • SREBP signaling pathway Source: UniProtKB
  • triglyceride metabolic process Source: Ensembl

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-1655829 Regulation of cholesterol biosynthesis by SREBP (SREBF)

Names & Taxonomyi

Protein namesi
Recommended name:
Insulin-induced gene 1 protein
Short name:
INSIG-1
Gene namesi
Name:INSIG1Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000186480.12
HGNCiHGNC:6083 INSIG1
MIMi602055 gene
neXtProtiNX_O15503

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 – 87Cytoplasmic1 PublicationAdd BLAST87
Transmembranei88 – 108HelicalSequence analysisAdd BLAST21
Topological domaini109 – 126LumenalSequence analysisAdd BLAST18
Transmembranei127 – 147HelicalSequence analysisAdd BLAST21
Topological domaini148 – 160Cytoplasmic1 PublicationAdd BLAST13
Transmembranei161 – 177HelicalSequence analysisAdd BLAST17
Topological domaini178 – 182LumenalSequence analysis5
Transmembranei183 – 203HelicalSequence analysisAdd BLAST21
Topological domaini204 – 209Cytoplasmic1 Publication6
Transmembranei210 – 230HelicalSequence analysisAdd BLAST21
Topological domaini231 – 241LumenalSequence analysisAdd BLAST11
Transmembranei242 – 262HelicalSequence analysisAdd BLAST21
Topological domaini263 – 277Cytoplasmic1 PublicationAdd BLAST15

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi156K → R: Loss of ubiquitination and degradation. 1 Publication1
Mutagenesisi158K → R: Loss of ubiquitination and degradation. 1 Publication1
Mutagenesisi205D → A: Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR. 1 Publication1

Organism-specific databases

DisGeNETi3638
OpenTargetsiENSG00000186480
PharmGKBiPA29890

Polymorphism and mutation databases

BioMutaiINSIG1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001916751 – 277Insulin-induced gene 1 proteinAdd BLAST277

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki156Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki158Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

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 RNF139.2 Publications

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Proteomic databases

PaxDbiO15503
PeptideAtlasiO15503
PRIDEiO15503

PTM databases

iPTMnetiO15503
PhosphoSitePlusiO15503

Expressioni

Tissue specificityi

Expressed in all tissues tested with highest expression in the liver.1 Publication

Inductioni

By insulin.

Gene expression databases

BgeeiENSG00000186480
CleanExiHS_INSIG1
ExpressionAtlasiO15503 baseline and differential
GenevisibleiO15503 HS

Organism-specific databases

HPAiHPA071524

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 (PubMed:29374057).6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109850, 22 interactors
DIPiDIP-61157N
IntActiO15503, 12 interactors
MINTiO15503
STRINGi9606.ENSP00000344741

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J81X-ray1.74C/D273-277[»]
ProteinModelPortaliO15503
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the INSIG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4363 Eukaryota
ENOG410XQ2M LUCA
GeneTreeiENSGT00580000081600
HOGENOMiHOG000253022
HOVERGENiHBG058958
InParanoidiO15503
OMAiEMMSIIT
OrthoDBiEOG091G0L61
PhylomeDBiO15503
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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15503-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPRLHDHFWS CSCAHSARRR GPPRASAAGL AAKVGEMINV SVSGPSLLAA
60 70 80 90 100
HGAPDADPAP RGRSAAMSGP EPGSPYPNTW HHRLLQRSLV LFSVGVVLAL
110 120 130 140 150
VLNLLQIQRN VTLFPEEVIA TIFSSAWWVP PCCGTAAAVV GLLYPCIDSH
160 170 180 190 200
LGEPHKFKRE WASVMRCIAV FVGINHASAK LDFANNVQLS LTLAALSLGL
210 220 230 240 250
WWTFDRSRSG LGLGITIAFL ATLITQFLVY NGVYQYTSPD FLYIRSWLPC
260 270
IFFSGGVTVG NIGRQLAMGV PEKPHSD
Length:277
Mass (Da):29,987
Last modified:October 3, 2006 - v3
Checksum:i198068D53C658A58
GO
Isoform 2 (identifier: O15503-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     138-164: AVVGLLYPCIDSHLGEPHKFKREWASV → GIHPQISSIFVLGSLVYFSQEASRWGT
     165-277: Missing.

Note: No experimental confirmation available.
Show »
Length:164
Mass (Da):17,530
Checksum:i06076ED6ACE57C04
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti31 – 32AA → PP in AAB69121 (PubMed:9268630).Curated2
Sequence conflicti99A → T in AAB69121 (PubMed:9268630).Curated1
Sequence conflicti170 – 172VFV → GFG in AAB69121 (PubMed:9268630).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02768327A → T1 PublicationCorresponds to variant dbSNP:rs1129825Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045084138 – 164AVVGL…EWASV → GIHPQISSIFVLGSLVYFSQ EASRWGT in isoform 2. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_045085165 – 277Missing in isoform 2. 1 PublicationAdd BLAST113

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U96876 Genomic DNA Translation: AAB69121.1
AY112745 mRNA Translation: AAM44086.1
BT007227 mRNA Translation: AAP35891.1
AK291675 mRNA Translation: BAF84364.1
DN996424 mRNA No translation available.
AC144652 Genomic DNA No translation available.
AC231970 Genomic DNA No translation available.
CH236962 Genomic DNA Translation: EAL23729.1
CH236962 Genomic DNA Translation: EAL23730.1
CH471149 Genomic DNA Translation: EAX04529.1
CH471149 Genomic DNA Translation: EAX04530.1
BC001880 mRNA Translation: AAH01880.1
CCDSiCCDS5938.1 [O15503-1]
CCDS5939.1 [O15503-2]
RefSeqiNP_001333519.1, NM_001346590.1
NP_001333520.1, NM_001346591.1
NP_001333521.1, NM_001346592.1 [O15503-1]
NP_001333522.1, NM_001346593.1 [O15503-2]
NP_001333523.1, NM_001346594.1
NP_005533.2, NM_005542.5 [O15503-1]
NP_938150.2, NM_198336.3
NP_938151.1, NM_198337.3 [O15503-2]
XP_016867666.1, XM_017012177.1 [O15503-1]
UniGeneiHs.520819

Genome annotation databases

EnsembliENST00000340368; ENSP00000344741; ENSG00000186480 [O15503-1]
ENST00000342407; ENSP00000344035; ENSG00000186480 [O15503-2]
GeneIDi3638
KEGGihsa:3638
UCSCiuc003wly.3 human [O15503-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiINSI1_HUMAN
AccessioniPrimary (citable) accession number: O15503
Secondary accession number(s): A4D2N1
, A8K6L0, Q53XW8, Q9BUV5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 3, 2006
Last modified: April 25, 2018
This is version 150 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health