Details of the Target

General Information of Target

Target ID LDTP14161
Target Name Insulin-induced gene 2 protein (INSIG2)
Gene Name INSIG2
Gene ID 51141
Synonyms
Insulin-induced gene 2 protein; INSIG-2
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAEAGTGEPSPSVEGEHGTEYDTLPSDTVSLSDSDSDLSLPGGAEVEALSPMGLPGEEDS
GPDEPPSPPSGLLPATVQPFHLRGMSSTFSQRSRDIFDCLEGAARRAPSSVAHTSMSDNG
GFKRPLAPSGRSPVEGLGRAHRSPASPRVPPVPDYVAHPERWTKYSLEDVTEVSEQSNQA
TALAFLGSQSLAAPTDCVSSFNQDPSSCGEGRVIFTKPVRGVEARHERKRVLGKVGEPGR
GGLGNPATDRGEGPVELAHLAGPGSPEAEEWGSHHGGLQEVEALSGSVHSGSVPGLPPVE
TVGFHGSRKRSRDHFRNKSSSPEDPGAEV
Target Bioclass
Transporter and channel
Family
INSIG family
Subcellular location
Endoplasmic reticulum membrane
Function
Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2. Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBF1/SREBP1 and SREBF2/SREBP2 to the Golgi. Sterol deprivation or phosphorylation by PCK1 reduce oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBF1/SREBP1 and SREBF2/SREBP2. Also regulates cholesterol synthesis by regulating degradation of HMGCR: initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase RNF139.
Uniprot ID
Q9Y5U4
Ensemble ID
ENST00000245787.9
HGNC ID
HGNC:20452

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info  		C215(3.52)  LDD3325  [1]
IA-alkyne
 Probe Info  		C215(6.48)  LDD1705  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0226  AC11 HEK-293T C215(1.05)  LDD1509  [3]
 LDCM0278  AC19 HEK-293T C215(1.22)  LDD1517  [3]
 LDCM0287  AC27 HEK-293T C215(1.06)  LDD1526  [3]
 LDCM0290  AC3 HEK-293T C215(1.12)  LDD1529  [3]
 LDCM0296  AC35 HEK-293T C215(1.06)  LDD1535  [3]
 LDCM0305  AC43 HEK-293T C215(1.08)  LDD1544  [3]
 LDCM0314  AC51 HEK-293T C215(0.97)  LDD1553  [3]
 LDCM0322  AC59 HEK-293T C215(1.00)  LDD1561  [3]
 LDCM0369  CL100 HEK-293T C194(1.14)  LDD1573  [3]
 LDCM0373  CL104 HEK-293T C194(1.01)  LDD1577  [3]
 LDCM0377  CL108 HEK-293T C194(0.97)  LDD1581  [3]
 LDCM0382  CL112 HEK-293T C194(1.01)  LDD1586  [3]
 LDCM0386  CL116 HEK-293T C194(0.96)  LDD1590  [3]
 LDCM0391  CL120 HEK-293T C194(1.03)  LDD1595  [3]
 LDCM0395  CL124 HEK-293T C194(1.01)  LDD1599  [3]
 LDCM0399  CL128 HEK-293T C194(1.00)  LDD1603  [3]
 LDCM0403  CL16 HEK-293T C194(1.15)  LDD1607  [3]
 LDCM0406  CL19 HEK-293T C215(1.26)  LDD1610  [3]
 LDCM0416  CL28 HEK-293T C194(1.11)  LDD1620  [3]
 LDCM0420  CL31 HEK-293T C215(1.16)  LDD1624  [3]
 LDCM0429  CL4 HEK-293T C194(1.02)  LDD1633  [3]
 LDCM0430  CL40 HEK-293T C194(1.18)  LDD1634  [3]
 LDCM0433  CL43 HEK-293T C215(1.08)  LDD1637  [3]
 LDCM0443  CL52 HEK-293T C194(1.08)  LDD1646  [3]
 LDCM0446  CL55 HEK-293T C215(1.22)  LDD1649  [3]
 LDCM0456  CL64 HEK-293T C194(0.98)  LDD1659  [3]
 LDCM0459  CL67 HEK-293T C215(1.25)  LDD1662  [3]
 LDCM0462  CL7 HEK-293T C215(1.26)  LDD1665  [3]
 LDCM0469  CL76 HEK-293T C194(1.06)  LDD1672  [3]
 LDCM0472  CL79 HEK-293T C215(1.17)  LDD1675  [3]
 LDCM0482  CL88 HEK-293T C194(1.08)  LDD1685  [3]
 LDCM0486  CL91 HEK-293T C215(1.34)  LDD1689  [3]
 LDCM0022  KB02 AU565 C215(3.00)  LDD2265  [1]
 LDCM0023  KB03 AU565 C215(5.01)  LDD2682  [1]
 LDCM0024  KB05 UACC257 C215(3.52)  LDD3325  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 6 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase (EBP) EBP family Q15125
Probable glutathione peroxidase 8 (GPX8) Glutathione peroxidase family Q8TED1
(Lyso)-N-acylphosphatidylethanolamine lipase (ABHD4) Peptidase S33 family Q8TB40
E3 ubiquitin-protein ligase RNF5 (RNF5) RNF5 family Q99942
17-beta-hydroxysteroid dehydrogenase 13 (HSD17B13) Short-chain dehydrogenases/reductases (SDR) family Q7Z5P4
V-type proton ATPase 21 kDa proteolipid subunit c'' (ATP6V0B) V-ATPase proteolipid subunit family Q99437
Transporter and channel
Click To Hide/Show 11 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Gap junction alpha-8 protein (GJA8) Connexin family P48165
Lysosomal-associated transmembrane protein 5 (LAPTM5) LAPTM4/LAPTM5 transporter family Q13571
LHFPL tetraspan subfamily member 5 protein (LHFPL5) LHFP family Q8TAF8
Monocarboxylate transporter 10 (SLC16A10) Monocarboxylate porter (TC 2.A.1.13) family Q8TF71
ER membrane protein complex subunit 5 (MMGT1) Membrane magnesium transporter (TC 1.A.67) family Q8N4V1
Aquaporin-2 (AQP2) MIP/aquaporin (TC 1.A.8) family P41181
Aquaporin-6 (AQP6) MIP/aquaporin (TC 1.A.8) family Q13520
Sodium channel regulatory subunit beta-3 (SCN3B) Sodium channel auxiliary subunit SCN3B family Q9NY72
Transmembrane protein 14B (TMEM14B) TMEM14 family Q9NUH8
Stromal interaction molecule 1 (STIM1) . Q13586
Thioredoxin-related transmembrane protein 2 (TMX2) . Q9Y320
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cyclic AMP-responsive element-binding protein 3-like protein 1 (CREB3L1) BZIP family Q96BA8
GPCR
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
G-protein coupled receptor 37-like 1 (GPR37L1) G-protein coupled receptor 1 family O60883
Probable G-protein coupled receptor 152 (GPR152) G-protein coupled receptor 1 family Q8TDT2
Immunoglobulin
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Killer cell immunoglobulin-like receptor 2DL3 (KIR2DL3) Immunoglobulin superfamily P43628
Poliovirus receptor (PVR) Nectin family P15151
B-cell antigen receptor complex-associated protein alpha chain (CD79A) . P11912
Cytokine and receptor
Click To Hide/Show 3 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Prolactin receptor (PRLR) Type I cytokine receptor family P16471
Interferon gamma receptor 2 (IFNGR2) Type II cytokine receptor family P38484
Tumor necrosis factor receptor superfamily member 5 (CD40) . P25942
Other
Click To Hide/Show 8 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Complexin-4 (CPLX4) Complexin/synaphin family Q7Z7G2
Cytochrome b-245 chaperone 1 (CYBC1) CYBC1 family Q9BQA9
Protein FAM209A (FAM209A) FAM209 family Q5JX71
Golgi membrane protein 1 (GOLM1) GOLM family Q8NBJ4
Transmembrane protein 45B (TMEM45B) TMEM45 family Q96B21
Vacuolar ATPase assembly integral membrane protein VMA21 (VMA21) VMA21 family Q3ZAQ7
Bcl-2-interacting killer (BIK) . Q13323
Transmembrane protein 52B (TMEM52B) . Q4KMG9

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 An Activity-Guided Map of Electrophile-Cysteine Interactions in Primary Human T Cells. Cell. 2020 Aug 20;182(4):1009-1026.e29. doi: 10.1016/j.cell.2020.07.001. Epub 2020 Jul 29.
3 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402