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Protein

Insulin-induced gene 2 protein

Gene

INSIG2

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. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR.2 Publications

Miscellaneous

Does not require nuclear SREBPs for its expression. When nuclear SREBP activity is low, is the only form of INSIG present in the cell.

GO - Molecular functioni

GO - Biological processi

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 2 protein
Short name:
INSIG-2
Gene namesi
Name:INSIG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000125629.14
HGNCiHGNC:20452 INSIG2
MIMi608660 gene
neXtProtiNX_Q9Y5U4

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
Transmembranei32 – 52HelicalSequence analysisAdd BLAST21
Transmembranei71 – 91HelicalSequence analysisAdd BLAST21
Transmembranei131 – 148HelicalSequence analysisAdd BLAST18
Transmembranei154 – 174HelicalSequence analysisAdd BLAST21
Transmembranei186 – 206HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi149D → A: Loss of ability to suppress the cleavage of SREBP2 and to accelerate the degradation of HMGCR. 1 Publication1

Organism-specific databases

DisGeNETi51141
OpenTargetsiENSG00000125629
PharmGKBiPA134890284

Polymorphism and mutation databases

BioMutaiINSIG2
DMDMi147646722

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002867971 – 225Insulin-induced gene 2 proteinAdd BLAST225

Proteomic databases

MaxQBiQ9Y5U4
PaxDbiQ9Y5U4
PeptideAtlasiQ9Y5U4
PRIDEiQ9Y5U4
ProteomicsDBi86507

PTM databases

iPTMnetiQ9Y5U4
PhosphoSitePlusiQ9Y5U4

Expressioni

Gene expression databases

BgeeiENSG00000125629 Expressed in 228 organ(s), highest expression level in right lobe of liver
CleanExiHS_INSIG2
ExpressionAtlasiQ9Y5U4 baseline and differential
GenevisibleiQ9Y5U4 HS

Organism-specific databases

HPAiCAB033861

Interactioni

Subunit structurei

Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with RNF145 (PubMed:29374057).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RNF5Q999425EBI-8503746,EBI-348482

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119325, 36 interactors
DIPiDIP-60913N
IntActiQ9Y5U4, 36 interactors
MINTiQ9Y5U4
STRINGi9606.ENSP00000245787

Structurei

3D structure databases

ProteinModelPortaliQ9Y5U4
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
InParanoidiQ9Y5U4
PhylomeDBiQ9Y5U4
TreeFamiTF331013

Family and domain databases

InterProiView protein in InterPro
IPR025929 INSIG_fam
PANTHERiPTHR15301 PTHR15301, 1 hit
PfamiView protein in Pfam
PF07281 INSIG, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q9Y5U4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAEGETESPG PKKCGPYISS VTSQSVNLMI RGVVLFFIGV FLALVLNLLQ
60 70 80 90 100
IQRNVTLFPP DVIASIFSSA WWVPPCCGTA SAVIGLLYPC IDRHLGEPHK
110 120 130 140 150
FKREWSSVMR CVAVFVGINH ASAKVDFDNN IQLSLTLAAL SIGLWWTFDR
160 170 180 190 200
SRSGFGLGVG IAFLATVVTQ LLVYNGVYQY TSPDFLYVRS WLPCIFFAGG
210 220
ITMGNIGRQL AMYECKVIAE KSHQE
Length:225
Mass (Da):24,778
Last modified:May 15, 2007 - v2
Checksum:i13E0392F1B30F08C
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DGZ4A0A0C4DGZ4_HUMAN
Insulin-induced gene protein
INSIG2
238Annotation score:
F8WCG8F8WCG8_HUMAN
Insulin-induced gene 2 protein
INSIG2
39Annotation score:

Sequence cautioni

The sequence AAD43048 differs from that shown. Reason: Frameshift at position 221.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527632 mRNA Translation: AAN28333.1
AF125392 mRNA Translation: AAD43048.1 Frameshift.
AK291433 mRNA Translation: BAF84122.1
AC009303 Genomic DNA Translation: AAX93280.1
CH471103 Genomic DNA Translation: EAW95199.1
BC022475 mRNA Translation: AAH22475.1
CCDSiCCDS2122.1
RefSeqiNP_001308258.1, NM_001321329.1
NP_001308259.1, NM_001321330.1
NP_001308260.1, NM_001321331.1
NP_001308261.1, NM_001321332.1
NP_001308262.1, NM_001321333.1
NP_057217.2, NM_016133.3
UniGeneiHs.7089

Genome annotation databases

EnsembliENST00000245787; ENSP00000245787; ENSG00000125629
GeneIDi51141
KEGGihsa:51141
UCSCiuc002tlk.4 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527632 mRNA Translation: AAN28333.1
AF125392 mRNA Translation: AAD43048.1 Frameshift.
AK291433 mRNA Translation: BAF84122.1
AC009303 Genomic DNA Translation: AAX93280.1
CH471103 Genomic DNA Translation: EAW95199.1
BC022475 mRNA Translation: AAH22475.1
CCDSiCCDS2122.1
RefSeqiNP_001308258.1, NM_001321329.1
NP_001308259.1, NM_001321330.1
NP_001308260.1, NM_001321331.1
NP_001308261.1, NM_001321332.1
NP_001308262.1, NM_001321333.1
NP_057217.2, NM_016133.3
UniGeneiHs.7089

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4J82X-ray1.46C/D221-225[»]
ProteinModelPortaliQ9Y5U4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119325, 36 interactors
DIPiDIP-60913N
IntActiQ9Y5U4, 36 interactors
MINTiQ9Y5U4
STRINGi9606.ENSP00000245787

PTM databases

iPTMnetiQ9Y5U4
PhosphoSitePlusiQ9Y5U4

Polymorphism and mutation databases

BioMutaiINSIG2
DMDMi147646722

Proteomic databases

MaxQBiQ9Y5U4
PaxDbiQ9Y5U4
PeptideAtlasiQ9Y5U4
PRIDEiQ9Y5U4
ProteomicsDBi86507

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000245787; ENSP00000245787; ENSG00000125629
GeneIDi51141
KEGGihsa:51141
UCSCiuc002tlk.4 human

Organism-specific databases

CTDi51141
DisGeNETi51141
EuPathDBiHostDB:ENSG00000125629.14
GeneCardsiINSIG2
HGNCiHGNC:20452 INSIG2
HPAiCAB033861
MIMi608660 gene
neXtProtiNX_Q9Y5U4
OpenTargetsiENSG00000125629
PharmGKBiPA134890284
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4363 Eukaryota
ENOG410XQ2M LUCA
GeneTreeiENSGT00580000081600
HOGENOMiHOG000253021
HOVERGENiHBG058958
InParanoidiQ9Y5U4
PhylomeDBiQ9Y5U4
TreeFamiTF331013

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiINSIG2 human
GeneWikiiINSIG2
GenomeRNAii51141
PROiPR:Q9Y5U4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125629 Expressed in 228 organ(s), highest expression level in right lobe of liver
CleanExiHS_INSIG2
ExpressionAtlasiQ9Y5U4 baseline and differential
GenevisibleiQ9Y5U4 HS

Family and domain databases

InterProiView protein in InterPro
IPR025929 INSIG_fam
PANTHERiPTHR15301 PTHR15301, 1 hit
PfamiView protein in Pfam
PF07281 INSIG, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiINSI2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5U4
Secondary accession number(s): A8K5W8, Q8TBI8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: September 12, 2018
This is version 113 of the entry and version 2 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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