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SREBF1 SREBF1 SREBF2 SREBF2 SCAP SCAP ERLIN2 ERLIN2 INSIG1 INSIG1 UBC UBC VCP VCP RNF139 RNF139 HMGCR HMGCR AMFR AMFR FAF2 FAF2
"INSIG1" - insulin induced gene 1 in Homo sapiens
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INSIG1insulin induced gene 1; 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 regul [...] (277 aa)    
Predicted Functional Partners:
SCAP
SREBF chaperone; Escort protein required for cholesterol as well as lipid homeostasis. Regulates export of the SCAP/SREBF complex from the ER upon low cholesterol. Formation of a ternary complex with INSIG at high sterol concentrations leads to masking of an ER-export signal in SCAP and retention of the complex in the ER. Low sterol concentrations trigger release of INSIG, a conformational change in the SSC domain of SCAP, unmasking of the ER export signal, recruitment into COPII-coated vesicles, transport to the Golgi complex, proteolytic cleavage of SREBF in the Golgi, release of the [...] (1279 aa)
        score_image score_image score_image   0.999
HMGCR
3-hydroxy-3-methylglutaryl-CoA reductase; Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins (888 aa)
      score_image score_image   score_image   0.998
SREBF2
sterol regulatory element binding transcription factor 2; Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5’-ATCACCCCAC-3’) found in the flanking region of the LDRL and HMG-CoA synthase genes (1141 aa)
        score_image score_image score_image   0.997
AMFR
autocrine motility factor receptor, E3 ubiquitin protein ligase; E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97- AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97- AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released f [...] (643 aa)
        score_image   score_image   0.991
VCP
valosin containing protein; Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. The ternary complex containing UFD1L, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the e [...] (806 aa)
        score_image   score_image   0.988
UBC
ubiquitin C (685 aa)
        score_image   score_image   0.986
FAF2
Fas associated factor family member 2; May play a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome (445 aa)
        score_image   score_image   0.984
ERLIN2
ER lipid raft associated 2; Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Also involved in ITPR1 degradation by the ERAD pathway (339 aa)
        score_image   score_image   0.977
RNF139
ring finger protein 139; E3-ubiquitin ligase; acts as a negative regulator of the cell proliferation through mechanisms involving G2/M arrest and cell death. Required for MHC class I ubiquitination in cells expressing the cytomegalovirus protein US2 before dislocation from the endoplasmic reticulum (ER). Affects SREBP processing by hindering the SREBP/SCAP complex translocation from the ER to the Golgi, thereby reducing SREBF2 target gene expression. Required for INSIG1 ubiquitination. May be required for EIF3 complex ubiquitination. May function as a signaling receptor (664 aa)
        score_image   score_image   0.972
SREBF1
sterol regulatory element binding transcription factor 1; Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5’-ATCACCCCAC-3’). Has dual sequence specificity binding to both an E-box motif (5’-ATCACGTGA-3’) and to SRE-1 (5’-ATCACCCCAC-3’) (1177 aa)
        score_image   score_image   0.968
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, Homo, Homo sapiens, human, man
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