Details for: INSIG1

Gene ID: 3638

Symbol: INSIG1

Ensembl ID: ENSG00000186480

Description: insulin induced gene 1

Associated with

Cells (max top 100)

(Marker Score score is uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: glycinergic neuron (CL1001509)
    Fold Change: 2.14
    Marker Score: 2580
  • Cell Name: kidney loop of Henle epithelial cell (CL1000909)
    Fold Change: 2.06
    Marker Score: 1292.5
  • Cell Name: glycinergic amacrine cell (CL4030028)
    Fold Change: 1.99
    Marker Score: 1881
  • Cell Name: prostate gland microvascular endothelial cell (CL2000059)
    Fold Change: 1.93
    Marker Score: 751
  • Cell Name: periportal region hepatocyte (CL0019026)
    Fold Change: 1.92
    Marker Score: 10316
  • Cell Name: type II pneumocyte (CL0002063)
    Fold Change: 1.91
    Marker Score: 12450
  • Cell Name: CD4-positive, alpha-beta memory T cell, CD45RO-positive (CL0001204)
    Fold Change: 1.88
    Marker Score: 12005
  • Cell Name: GABAergic amacrine cell (CL4030027)
    Fold Change: 1.87
    Marker Score: 3799
  • Cell Name: secondary lens fiber (CL0002225)
    Fold Change: 1.86
    Marker Score: 1087
  • Cell Name: pneumocyte (CL0000322)
    Fold Change: 1.84
    Marker Score: 2951
  • Cell Name: fibroblast of connective tissue of nonglandular part of prostate (CL1000304)
    Fold Change: 1.83
    Marker Score: 1563
  • Cell Name: cortical cell of adrenal gland (CL0002097)
    Fold Change: 1.82
    Marker Score: 32322
  • Cell Name: vascular lymphangioblast (CL0005022)
    Fold Change: 1.76
    Marker Score: 2971
  • Cell Name: midzonal region hepatocyte (CL0019028)
    Fold Change: 1.73
    Marker Score: 7464
  • Cell Name: fibroblast of connective tissue of glandular part of prostate (CL1000305)
    Fold Change: 1.71
    Marker Score: 710
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: 1.69
    Marker Score: 3569
  • Cell Name: lung macrophage (CL1001603)
    Fold Change: 1.64
    Marker Score: 1878
  • Cell Name: cardiac endothelial cell (CL0010008)
    Fold Change: 1.63
    Marker Score: 3096
  • Cell Name: CD1c-positive myeloid dendritic cell (CL0002399)
    Fold Change: 1.58
    Marker Score: 4103
  • Cell Name: fibroblast of connective tissue of prostate (CL1000299)
    Fold Change: 1.55
    Marker Score: 387
  • Cell Name: corneal endothelial cell (CL0000132)
    Fold Change: 1.55
    Marker Score: 905
  • Cell Name: prostate stromal cell (CL0002622)
    Fold Change: 1.54
    Marker Score: 387
  • Cell Name: type G enteroendocrine cell (CL0000508)
    Fold Change: 1.51
    Marker Score: 522
  • Cell Name: Mueller cell (CL0000636)
    Fold Change: 1.51
    Marker Score: 2098
  • Cell Name: centrilobular region hepatocyte (CL0019029)
    Fold Change: 1.51
    Marker Score: 9707
  • Cell Name: cortical thymic epithelial cell (CL0002364)
    Fold Change: 1.49
    Marker Score: 5529
  • Cell Name: non-classical monocyte (CL0000875)
    Fold Change: 1.49
    Marker Score: 3596
  • Cell Name: mural cell (CL0008034)
    Fold Change: 1.45
    Marker Score: 166660
  • Cell Name: fibroblast of mammary gland (CL0002555)
    Fold Change: 1.38
    Marker Score: 47121
  • Cell Name: epicardial adipocyte (CL1000309)
    Fold Change: 1.38
    Marker Score: 671
  • Cell Name: oogonial cell (CL0000024)
    Fold Change: 1.34
    Marker Score: 1929
  • Cell Name: skeletal muscle satellite stem cell (CL0008011)
    Fold Change: 1.32
    Marker Score: 1407
  • Cell Name: reticular cell (CL0000432)
    Fold Change: 1.31
    Marker Score: 479
  • Cell Name: primordial germ cell (CL0000670)
    Fold Change: 1.31
    Marker Score: 1642
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: 1.31
    Marker Score: 2974
  • Cell Name: pigmented epithelial cell (CL0000529)
    Fold Change: 1.3
    Marker Score: 5428
  • Cell Name: colon epithelial cell (CL0011108)
    Fold Change: 1.29
    Marker Score: 4058
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: 1.25
    Marker Score: 1847
  • Cell Name: pancreatic stellate cell (CL0002410)
    Fold Change: 1.23
    Marker Score: 778
  • Cell Name: endothelial cell of uterus (CL0009095)
    Fold Change: 1.22
    Marker Score: 2429
  • Cell Name: glandular epithelial cell (CL0000150)
    Fold Change: 1.19
    Marker Score: 2919
  • Cell Name: peptic cell (CL0000155)
    Fold Change: 1.18
    Marker Score: 495
  • Cell Name: male germ cell (CL0000015)
    Fold Change: 1.18
    Marker Score: 340
  • Cell Name: hepatocyte (CL0000182)
    Fold Change: 1.17
    Marker Score: 797
  • Cell Name: mucous neck cell (CL0000651)
    Fold Change: 1.17
    Marker Score: 2646
  • Cell Name: inflammatory cell (CL0009002)
    Fold Change: 1.16
    Marker Score: 501
  • Cell Name: lung secretory cell (CL1000272)
    Fold Change: 1.16
    Marker Score: 1037
  • Cell Name: granulocyte (CL0000094)
    Fold Change: 1.16
    Marker Score: 520
  • Cell Name: foveolar cell of stomach (CL0002179)
    Fold Change: 1.16
    Marker Score: 7373
  • Cell Name: oocyte (CL0000023)
    Fold Change: 1.15
    Marker Score: 284
  • Cell Name: medullary thymic epithelial cell (CL0002365)
    Fold Change: 1.15
    Marker Score: 1881
  • Cell Name: keratinocyte (CL0000312)
    Fold Change: 1.15
    Marker Score: 957
  • Cell Name: oligodendrocyte (CL0000128)
    Fold Change: 1.13
    Marker Score: 2715
  • Cell Name: renal intercalated cell (CL0005010)
    Fold Change: 1.13
    Marker Score: 601
  • Cell Name: nasal mucosa goblet cell (CL0002480)
    Fold Change: 1.11
    Marker Score: 743
  • Cell Name: papillary tips cell (CL1000597)
    Fold Change: 1.11
    Marker Score: 224
  • Cell Name: B-1 B cell (CL0000819)
    Fold Change: 1.09
    Marker Score: 1908
  • Cell Name: macrophage (CL0000235)
    Fold Change: 1.09
    Marker Score: 1216
  • Cell Name: corneal epithelial cell (CL0000575)
    Fold Change: 1.09
    Marker Score: 1207
  • Cell Name: lymphoid lineage restricted progenitor cell (CL0000838)
    Fold Change: 1.09
    Marker Score: 656
  • Cell Name: secretory cell (CL0000151)
    Fold Change: 1.09
    Marker Score: 1992.5
  • Cell Name: lens epithelial cell (CL0002224)
    Fold Change: 1.08
    Marker Score: 1308
  • Cell Name: double negative thymocyte (CL0002489)
    Fold Change: 1.08
    Marker Score: 1489
  • Cell Name: club cell (CL0000158)
    Fold Change: 1.07
    Marker Score: 1255
  • Cell Name: CD14-positive, CD16-positive monocyte (CL0002397)
    Fold Change: 1.07
    Marker Score: 2087
  • Cell Name: retinal blood vessel endothelial cell (CL0002585)
    Fold Change: 1.07
    Marker Score: 256
  • Cell Name: mononuclear cell (CL0000842)
    Fold Change: 1.06
    Marker Score: 340
  • Cell Name: Leydig cell (CL0000178)
    Fold Change: 1.05
    Marker Score: 1133
  • Cell Name: respiratory goblet cell (CL0002370)
    Fold Change: 1.05
    Marker Score: 303
  • Cell Name: pulmonary ionocyte (CL0017000)
    Fold Change: 1.04
    Marker Score: 640
  • Cell Name: large pre-B-II cell (CL0000957)
    Fold Change: 1.04
    Marker Score: 2833.5
  • Cell Name: stem cell of epidermis (CL1000428)
    Fold Change: 1.04
    Marker Score: 352
  • Cell Name: intestinal crypt stem cell of large intestine (CL0009016)
    Fold Change: 1.04
    Marker Score: 312
  • Cell Name: fallopian tube secretory epithelial cell (CL4030006)
    Fold Change: 1.04
    Marker Score: 251586
  • Cell Name: cardiac muscle myoblast (CL0000513)
    Fold Change: 1.04
    Marker Score: 16206
  • Cell Name: leukocyte (CL0000738)
    Fold Change: 1.04
    Marker Score: 594
  • Cell Name: enterocyte of epithelium proper of ileum (CL1000342)
    Fold Change: 1.03
    Marker Score: 298
  • Cell Name: epithelial cell of urethra (CL1000296)
    Fold Change: 1.03
    Marker Score: 808
  • Cell Name: hepatic stellate cell (CL0000632)
    Fold Change: 1.02
    Marker Score: 385
  • Cell Name: conjunctival epithelial cell (CL1000432)
    Fold Change: 1.01
    Marker Score: 1064
  • Cell Name: activated CD4-positive, alpha-beta T cell, human (CL0001043)
    Fold Change: 1.01
    Marker Score: 459
  • Cell Name: cholangiocyte (CL1000488)
    Fold Change: 1.01
    Marker Score: 377
  • Cell Name: luminal cell of prostate epithelium (CL0002340)
    Fold Change: 1.01
    Marker Score: 587
  • Cell Name: lens fiber cell (CL0011004)
    Fold Change: 1.01
    Marker Score: 318
  • Cell Name: dendritic cell, human (CL0001056)
    Fold Change: 1
    Marker Score: 1017
  • Cell Name: cerebral cortex GABAergic interneuron (CL0010011)
    Fold Change: 1
    Marker Score: 71607
  • Cell Name: intestine goblet cell (CL0019031)
    Fold Change: 0.99
    Marker Score: 953
  • Cell Name: epithelial cell (CL0000066)
    Fold Change: 0.99
    Marker Score: 1581
  • Cell Name: forebrain radial glial cell (CL0013000)
    Fold Change: 0.99
    Marker Score: 47832
  • Cell Name: conventional dendritic cell (CL0000990)
    Fold Change: 0.99
    Marker Score: 685
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: 0.99
    Marker Score: 3880
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: 0.99
    Marker Score: 982
  • Cell Name: enterocyte (CL0000584)
    Fold Change: 0.98
    Marker Score: 4718
  • Cell Name: Unknown (CL0000548)
    Fold Change: 0.98
    Marker Score: 714
  • Cell Name: absorptive cell (CL0000212)
    Fold Change: 0.98
    Marker Score: 30368
  • Cell Name: small pre-B-II cell (CL0000954)
    Fold Change: 0.98
    Marker Score: 1172
  • Cell Name: microfold cell of epithelium of small intestine (CL1000353)
    Fold Change: 0.97
    Marker Score: 232
  • Cell Name: bronchial goblet cell (CL1000312)
    Fold Change: 0.97
    Marker Score: 479
  • Cell Name: PP cell (CL0000696)
    Fold Change: 0.97
    Marker Score: 218
  • Cell Name: serous secreting cell (CL0000313)
    Fold Change: 0.97
    Marker Score: 386

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Other Information

## Summary INSIG1 is a key regulator of cholesterol metabolism and inner ear development. It is expressed in various cell types, including those in the kidney, prostate gland, and inner ear. INSIG1 plays a crucial role in maintaining cholesterol homeostasis and regulating the development and function of the inner ear. ## Key characteristics * Inhibits the activity of the Srebp-scap complex, a key regulator of cholesterol biosynthesis. * Acts as a chaperone for the Srebp complex, facilitating its interaction with SREBP-alpha. * Plays a crucial role in the regulation of cholesterol biosynthetic processes, including the production of very low-density lipoprotein (VLDL) particles. * Regulates the expression of genes involved in cholesterol uptake, metabolism, and secretion. * Plays a role in the negative regulation of steroid biosynthetic process. * Acts as a chaperone for the oxysterol receptor, a key regulator of cholesterol metabolism. ## Pathways and functions * **Insulin signaling pathway:** INSIG1 is a key regulator of the insulin signaling pathway. It acts as a negative regulator of the pathway by inhibiting the activity of the insulin receptor and the subsequent activation of downstream signaling events. * **Sterol metabolism:** INSIG1 plays a crucial role in maintaining cholesterol homeostasis by regulating the production and release of VLDL particles. It inhibits the expression of genes involved in cholesterol synthesis and promotes the expression of genes involved in VLDL production. * **Inner ear development:** INSIG1 is expressed in various cell types of the inner ear, including the glycinergic neuron, kidney loop of Henle epithelial cell, and secondary lens fiber. It plays a crucial role in regulating the development and function of these cells, including the production of extracellular matrix proteins and the regulation of cell migration and differentiation. ## Clinical significance * Mutations in INSIG1 have been linked to several human diseases, including familial hypercholesterolemia, atherosclerosis, and retinopathy. * Targeting INSIG1 has emerged as a potential therapeutic strategy for these diseases. * Drugs that inhibit INSIG1 have been shown to lower cholesterol levels and improve cardiovascular health in animal models.

Genular Protein ID: 749189692

Symbol: INSI1_HUMAN

Name: N/A

UniProtKB Accession Codes:

O15503 A4D2N1 A8K6L0 Q53XW8 Q9BUV5

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CORUM 1 CTD 1 ChEMBL 1 ChiTaRS 1 DIP 1 DNASU 1 DisGeNET 1 EMBL 12 EPD 1 Ensembl 2 ExpressionAtlas 1 GO 21 GeneCards 1 GeneTree 1 GeneWiki 1 Genevisible 1 GenomeRNAi 1 HGNC 2 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 1 RefSeq 9 SAM 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TCDB 1 TreeFam 1 UCSC 1 UniProtKB 2 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 9268630

Title: Cloning, human chromosomal assignment, and adipose and hepatic expression of the CL-6/INSIG1 gene.

PubMed ID: 9268630

DOI: 10.1006/geno.1997.4821

PubMed ID: 12202038

Title: Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER.

PubMed ID: 12202038

DOI: 10.1016/s0092-8674(02)00872-3

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 12535518

Title: Accelerated degradation of HMG CoA reductase mediated by binding of insig-1 to its sterol-sensing domain.

PubMed ID: 12535518

DOI: 10.1016/s1097-2765(02)00822-5

PubMed ID: 14660594

Title: Membrane topology of human insig-1, a protein regulator of lipid synthesis.

PubMed ID: 14660594

DOI: 10.1074/jbc.m312623200

PubMed ID: 15899885

Title: Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro.

PubMed ID: 15899885

DOI: 10.1074/jbc.m504041200

PubMed ID: 16168377

Title: Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase.

PubMed ID: 16168377

DOI: 10.1016/j.molcel.2005.08.009

PubMed ID: 16399501

Title: Sterol-regulated ubiquitination and degradation of Insig-1 creates a convergent mechanism for feedback control of cholesterol synthesis and uptake.

PubMed ID: 16399501

DOI: 10.1016/j.cmet.2005.11.014

PubMed ID: 17043353

Title: Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78.

PubMed ID: 17043353

DOI: 10.1074/jbc.m608999200

PubMed ID: 16606821

Title: Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis.

PubMed ID: 16606821

DOI: 10.1073/pnas.0601923103

PubMed ID: 20068067

Title: The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways.

PubMed ID: 20068067

DOI: 10.1158/1541-7786.mcr-08-0491

PubMed ID: 22143767

Title: Sterol-induced degradation of HMG CoA reductase depends on interplay of two Insigs and two ubiquitin ligases, gp78 and Trc8.

PubMed ID: 22143767

DOI: 10.1073/pnas.1112831108

PubMed ID: 28604676

Title: Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation.

PubMed ID: 28604676

DOI: 10.1038/ncb3551

PubMed ID: 29184177

Title: Corrigendum: Cholesterol and fatty acids regulate cysteine ubiquitylation of ACAT2 through competitive oxidation.

PubMed ID: 29184177

DOI: 10.1038/ncb3651

PubMed ID: 28849786

Title: SREBP-regulated lipid metabolism: convergent physiology - divergent pathophysiology.

PubMed ID: 28849786

DOI: 10.1038/nrendo.2017.91

PubMed ID: 29374057

Title: Ring finger protein 145 (RNF145) is a ubiquitin ligase for sterol-induced degradation of HMG-CoA reductase.

PubMed ID: 29374057

DOI: 10.1074/jbc.ra117.001260

PubMed ID: 32322062

Title: The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis.

PubMed ID: 32322062

DOI: 10.1038/s41586-020-2183-2

PubMed ID: 23481256

Title: Rules for the recognition of dilysine retrieval motifs by coatomer.

PubMed ID: 23481256

DOI: 10.1038/emboj.2013.41

Sequence Information:

  • Length: 277
  • Mass: 29987
  • Checksum: 198068D53C658A58
  • Sequence:
    • MPRLHDHFWS CSCAHSARRR GPPRASAAGL AAKVGEMINV SVSGPSLLAA HGAPDADPAP 
RGRSAAMSGP EPGSPYPNTW HHRLLQRSLV LFSVGVVLAL VLNLLQIQRN VTLFPEEVIA 
TIFSSAWWVP PCCGTAAAVV GLLYPCIDSH LGEPHKFKRE WASVMRCIAV FVGINHASAK 
LDFANNVQLS LTLAALSLGL WWTFDRSRSG LGLGITIAFL ATLITQFLVY NGVYQYTSPD 
FLYIRSWLPC IFFSGGVTVG NIGRQLAMGV PEKPHSD

Genular Protein ID: 2342973333

Symbol: F5H6P3_HUMAN

Name: N/A

UniProtKB Accession Codes:

F5H6P3

Database IDs:

ARBA 10 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 EMBL 2 Ensembl 2 ExpressionAtlas 1 GO 2 GeneTree 1 Genevisible 1 GenomeRNAi 1 HGNC 1 InterPro 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 2 Pfam 1 Proteomes 2 ProteomicsDB 2 RefSeq 1 RuleBase 1 SMR 1 UCSC 1 VEuPathDB 1 iPTMnet 1

Citations:

PubMed ID: 12853948

Title: The DNA sequence of human chromosome 7.

PubMed ID: 12853948

DOI: 10.1038/nature01782

Sequence Information:

  • Length: 178
  • Mass: 20370
  • Checksum: 8FD0FAD53542FE0F
  • Sequence:
    • MPRLHDHFWS CSCAHSARRR GPPRASAKLD FANNVQLSLT LAALSLGLWW TFDRSRSGLG 
LGITIAFLAT LITQFLVYNG VYQYTSPDFL YIRSWLPCIF FSGGVTVGNI GRQLAMLIPF 
CEELNLKTTW LFHKTRSNYR VFLKSPIVIE SSKPPILRAR KILEENLTVD YDKDYLFS

Genular Protein ID: 136794793

Symbol: A4D2M9_HUMAN

Name: N/A

UniProtKB Accession Codes:

A4D2M9

Database IDs:

ARBA 10 AlphaFoldDB 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 EMBL 4 GO 2 GenomeRNAi 1 InterPro 1 NCBI Taxonomy 1 OrthoDB 1 PANTHER 2 PeptideAtlas 1 Pfam 1 RefSeq 4 RuleBase 1 SAM 1 SMR 1

Citations:

PubMed ID: 11181995

Title: The sequence of the human genome.

PubMed ID: 11181995

DOI: 10.1126/science.1058040

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

Sequence Information:

  • Length: 330
  • Mass: 36452
  • Checksum: 26F51232C0875C9D
  • Sequence:
    • MPRLHDHFWS CSCAHSARRR GPPRASAAGL AAKVGEMINV SVSGPSLLAA HGAPDADPAP 
RGRSAAMSGP EPGSPYPNTW HHRLLQRSLV LFSVGVVLAL VLNLLQIQRN VTLFPEEVIA 
TIFSSAWWVP PCCGTAAAVV GLLYPCIDSH LGEPHKFKRE WASVMRCIAV FVGINHASAK 
LDFANNVQLS LTLAALSLGL WWTFDRSRSG LGLGITIAFL ATLITQFLVY NGVYQYTSPD 
FLYIRSWLPC IFFSGGVTVG NIGRQLAMLI PFCEELNLKT TWLFHKTRSN YRVFLKSPIV 
IESSKPPILR ARKILEENLT VDYDKDYLFS

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. For the full schema, download it here.