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Protein

Insulin-induced gene 1 protein

Gene

INSIG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cholesterol metabolism, Lipid metabolism, Steroid metabolism, Sterol metabolism

Enzyme and pathway databases

BioCyciZFISH:G66-33004-MONOMER.
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:INSIG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:6083. INSIG1.

Subcellular locationi

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

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: Reactome
  • SREBP-SCAP-Insig complex Source: UniProtKB
Complete GO annotation...

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

HPAiCAB016358.

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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AMFRQ9UKV52EBI-6252425,EBI-1046367
CYP2C1P001802EBI-6252425,EBI-6251821From a different organism.
CYP2C2P001813EBI-6252425,EBI-4320576From a different organism.
HMGCRP003472EBI-6252425,EBI-11426687From a different organism.

Protein-protein interaction databases

BioGridi109850. 22 interactors.
DIPiDIP-61157N.
IntActiO15503. 9 interactors.
MINTiMINT-4723340.
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.
OMAiAMSGPEP.
OrthoDBiEOG091G0L61.
PhylomeDBiO15503.
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]

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 → T.1 PublicationCorresponds to variant rs1129825dbSNPEnsembl.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_005533.2. NM_005542.4. [O15503-1]
NP_938150.2. NM_198336.2.
NP_938151.1. NM_198337.2. [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

Cross-referencesi

Web resourcesi

Wikipedia

Insig1 entry

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_005533.2. NM_005542.4. [O15503-1]
NP_938150.2. NM_198336.2.
NP_938151.1. NM_198337.2. [O15503-2]
XP_016867666.1. XM_017012177.1. [O15503-1]
UniGeneiHs.520819.

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...

Protein-protein interaction databases

BioGridi109850. 22 interactors.
DIPiDIP-61157N.
IntActiO15503. 9 interactors.
MINTiMINT-4723340.
STRINGi9606.ENSP00000344741.

PTM databases

iPTMnetiO15503.
PhosphoSitePlusiO15503.

Polymorphism and mutation databases

BioMutaiINSIG1.

Proteomic databases

PaxDbiO15503.
PeptideAtlasiO15503.
PRIDEiO15503.

Protocols and materials databases

DNASUi3638.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3638.
DisGeNETi3638.
GeneCardsiINSIG1.
HGNCiHGNC:6083. INSIG1.
HPAiCAB016358.
MIMi602055. gene.
neXtProtiNX_O15503.
OpenTargetsiENSG00000186480.
PharmGKBiPA29890.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4363. Eukaryota.
ENOG410XQ2M. LUCA.
GeneTreeiENSGT00580000081600.
HOGENOMiHOG000253022.
HOVERGENiHBG058958.
InParanoidiO15503.
OMAiAMSGPEP.
OrthoDBiEOG091G0L61.
PhylomeDBiO15503.
TreeFamiTF331013.

Enzyme and pathway databases

BioCyciZFISH:G66-33004-MONOMER.
ReactomeiR-HSA-1655829. Regulation of cholesterol biosynthesis by SREBP (SREBF).

Miscellaneous databases

ChiTaRSiINSIG1. human.
GeneWikiiINSIG1.
GenomeRNAii3638.
PROiO15503.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000186480.
CleanExiHS_INSIG1.
ExpressionAtlasiO15503. baseline and differential.
GenevisibleiO15503. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O15503
Secondary accession number(s): A4D2N1
, A8K6L0, Q53XW8, Q9BUV5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: October 3, 2006
Last modified: November 2, 2016
This is version 140 of the entry and version 3 of the sequence. [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

Miscellaneous

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.