Gene/Proteome Database (LMPD)

LMPD ID
LMP006694
Gene ID
3638
Species
Homo sapiens (Human)
Gene Name
insulin induced gene 1
Gene Symbol
INSIG1
Synonyms
CL-6; CL6
Chromosome
7
Map Location
7q36
Summary
Oxysterols regulate cholesterol homeostasis through the liver X receptor (LXR)- and sterol regulatory element-binding protein (SREBP)-mediated signaling pathways. This gene is an insulin-induced gene. It encodes an endoplasmic reticulum (ER) membrane protein that plays a critical role in regulating cholesterol concentrations in cells. This protein binds to the sterol-sensing domains of SREBP cleavage-activating protein (SCAP) and HMG CoA reductase, and is essential for the sterol-mediated trafficking of the two proteins. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jun 2009]
Orthologs
View orthologs and multiple alignments for INSIG1

Proteins

insulin-induced gene 1 protein isoform 1
Refseq ID NP_005533
Protein GI 28882053
UniProt ID O15503
mRNA ID NM_005542
Length 277
RefSeq Status REVIEWED
MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSGPSLLAAHGAPDADPAPRGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVLNLLQIQRNVTLFPEEVIATIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKREWASVMRCIAVFVGINHASAKLDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIAFLATLITQFLVYNGVYQYTSPDFLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHSD
insulin-induced gene 1 protein isoform 2
Refseq ID NP_938150
Protein GI 28882053
UniProt ID O15503
mRNA ID NM_198336
Length 277
RefSeq Status REVIEWED
MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSGPSLLAAHGAPDADPAPRGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVLNLLQIQRNVTLFPEEVIATIFSSAWWVPPCCGTAAAVVGLLYPCIDSHLGEPHKFKREWASVMRCIAVFVGINHASAKLDFANNVQLSLTLAALSLGLWWTFDRSRSGLGLGITIAFLATLITQFLVYNGVYQYTSPDFLYIRSWLPCIFFSGGVTVGNIGRQLAMGVPEKPHSD
insulin-induced gene 1 protein isoform 3
Refseq ID NP_938151
Protein GI 38327531
UniProt ID O15503
mRNA ID NM_198337
Length 164
RefSeq Status REVIEWED
MPRLHDHFWSCSCAHSARRRGPPRASAAGLAAKVGEMINVSVSGPSLLAAHGAPDADPAPRGRSAAMSGPEPGSPYPNTWHHRLLQRSLVLFSVGVVLALVLNLLQIQRNVTLFPEEVIATIFSSAWWVPPCCGTAAGIHPQISSIFVLGSLVYFSQEASRWGT

Gene Information

Entrez Gene ID
3638
Gene Name
insulin induced gene 1
Gene Symbol
INSIG1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0032937 IDA:UniProtKB C SREBP-SCAP-Insig complex
GO:0005783 IDA:UniProtKB C endoplasmic reticulum
GO:0005789 TAS:Reactome C endoplasmic reticulum membrane
GO:0032933 IDA:UniProtKB P SREBP signaling pathway
GO:0008283 TAS:ProtInc P cell proliferation
GO:0006695 IEA:Ensembl P cholesterol biosynthetic process
GO:0060363 IEA:Ensembl P cranial suture morphogenesis
GO:0042472 IEA:Ensembl P inner ear morphogenesis
GO:0008152 TAS:ProtInc P metabolic process
GO:0042474 IEA:Ensembl P middle ear morphogenesis
GO:1901303 IMP:UniProtKB P negative regulation of cargo loading into COPII-coated vesicle
GO:0045599 IEA:Ensembl P negative regulation of fat cell differentiation
GO:0045717 IEA:Ensembl P negative regulation of fatty acid biosynthetic process
GO:0010894 IEA:Ensembl P negative regulation of steroid biosynthetic process
GO:0060021 IEA:Ensembl P palate development
GO:0044281 TAS:Reactome P small molecule metabolic process
GO:0006641 IEA:Ensembl P triglyceride metabolic process

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_111217 Metabolism
REACT_22258 Metabolism of lipids and lipoproteins
REACT_147797 Regulation of cholesterol biosynthesis by SREBP (SREBF)

Domain Information

InterPro Annotations

Accession Description
IPR009904 Insulin-induced gene 1 protein
IPR025929 Insulin-induced protein family

UniProt Annotations

Entry Information

Gene Name
insulin induced gene 1
Protein Entry
INSI1_HUMAN
UniProt ID
O15503
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O15503-1; Sequence=Displayed; Name=2; IsoId=O15503-2; Sequence=VSP_045084, VSP_045085; Note=No experimental confirmation available.;
Function 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. {ECO
Induction By insulin.
Interaction P00180:CYP2C1 (xeno); NbExp=2; IntAct=EBI-6252425, EBI-6251821; P00181:CYP2C2 (xeno); NbExp=3; IntAct=EBI-6252425, EBI-4320576;
Miscellaneous Expressed at high levels when nuclear SREBP levels are high as a result of sterol deprivation.
Ptm 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.
Similarity Belongs to the INSIG family.
Subcellular Location Endoplasmic reticulum membrane ; Multi-pass membrane protein .
Subunit 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. {ECO
Tissue Specificity Expressed in all tissues tested with highest expression in the liver.
Web Resource Name=Wikipedia; Note=Insig1 entry; URL="http://en.wikipedia.org/wiki/Insig1";

Identical and Related Proteins

Unique RefSeq proteins for LMP006694 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
28882053 RefSeq NP_005533 277 insulin-induced gene 1 protein isoform 1
28882053 RefSeq NP_938150 277 insulin-induced gene 1 protein isoform 2
38327531 RefSeq NP_938151 164 insulin-induced gene 1 protein isoform 3

Identical Sequences to LMP006694 proteins

Reference Database Accession Length Protein Name
GI:28882053 DBBJ BAF84364.1 277 unnamed protein product [Homo sapiens]
GI:28882053 DBBJ BAF84364.1 277 unnamed protein product [Homo sapiens]
GI:38327531 GenBank EAL23730.1 164 insulin induced gene 1 [Homo sapiens]
GI:28882053 GenBank AAX32373.1 277 insulin induced gene 1 [synthetic construct]
GI:28882053 GenBank AAX32373.1 277 insulin induced gene 1 [synthetic construct]
GI:28882053 GenBank EAX04529.1 277 insulin induced gene 1, isoform CRA_a [Homo sapiens]
GI:28882053 GenBank EAX04529.1 277 insulin induced gene 1, isoform CRA_a [Homo sapiens]
GI:38327531 GenBank EAX04530.1 164 insulin induced gene 1, isoform CRA_b [Homo sapiens]
GI:28882053 GenBank EAX04532.1 277 insulin induced gene 1, isoform CRA_a [Homo sapiens]
GI:28882053 GenBank EAX04532.1 277 insulin induced gene 1, isoform CRA_a [Homo sapiens]
GI:38327531 GenBank AED39026.1 164 Sequence 861 from patent US 7883858
GI:28882053 GenBank AIC49069.1 277 INSIG1, partial [synthetic construct]
GI:28882053 GenBank AIC49069.1 277 INSIG1, partial [synthetic construct]
GI:28882053 SwissProt O15503.3 277 RecName: Full=Insulin-induced gene 1 protein; Short=INSIG-1 [Homo sapiens]
GI:28882053 SwissProt O15503.3 277 RecName: Full=Insulin-induced gene 1 protein; Short=INSIG-1 [Homo sapiens]

Related Sequences to LMP006694 proteins

Reference Database Accession Length Protein Name
GI:28882053 GenBank AAP36909.1 278 Homo sapiens insulin induced gene 1, partial [synthetic construct]
GI:28882053 GenBank AAP36909.1 278 Homo sapiens insulin induced gene 1, partial [synthetic construct]
GI:28882053 GenBank AAX43961.1 278 insulin induced gene 1, partial [synthetic construct]
GI:28882053 GenBank AAX43961.1 278 insulin induced gene 1, partial [synthetic construct]
GI:28882053 GenBank AAX43962.1 278 insulin induced gene 1, partial [synthetic construct]
GI:28882053 GenBank AAX43962.1 278 insulin induced gene 1, partial [synthetic construct]
GI:28882053 GenBank ACM82662.1 278 Sequence 8160 from patent US 6812339
GI:28882053 GenBank ACM82662.1 278 Sequence 8160 from patent US 6812339
GI:38327531 GenBank JAA05650.1 164 insulin induced gene 1 [Pan troglodytes]
GI:38327531 GenBank JAA21596.1 164 insulin induced gene 1 [Pan troglodytes]
GI:38327531 GenBank JAA33454.1 164 insulin induced gene 1 [Pan troglodytes]
GI:28882053 RefSeq XP_001145726.1 277 PREDICTED: insulin-induced gene 1 protein isoform X2 [Pan troglodytes]
GI:28882053 RefSeq XP_001145726.1 277 PREDICTED: insulin-induced gene 1 protein isoform X2 [Pan troglodytes]
GI:38327531 RefSeq XP_519478.2 164 PREDICTED: insulin-induced gene 1 protein isoform X3 [Pan troglodytes]
GI:28882053 RefSeq XP_004046588.1 277 PREDICTED: insulin-induced gene 1 protein isoform 1 [Gorilla gorilla gorilla]
GI:28882053 RefSeq XP_004046588.1 277 PREDICTED: insulin-induced gene 1 protein isoform 1 [Gorilla gorilla gorilla]
GI:38327531 RefSeq XP_004046589.1 164 PREDICTED: insulin-induced gene 1 protein isoform 2 [Gorilla gorilla gorilla]
GI:38327531 RefSeq XP_005551313.1 164 PREDICTED: insulin-induced gene 1 protein isoform X2 [Macaca fascicularis]