STRINGSTRING
HMGCR HMGCR AUP1 AUP1 PLPP2 PLPP2 CALR CALR USH2A USH2A RNF139 RNF139 HMGB2 HMGB2 ALB ALB AMFR AMFR SCAP SCAP GAPDH GAPDH FAF2 FAF2 PXDN PXDN CANX CANX INSIG2 INSIG2 GLCCI1 GLCCI1 TECR TECR INS INS GALNT11 GALNT11 RNF145 RNF145 LDLR LDLR MYC MYC EHD1 EHD1 PHGDH PHGDH ACTB ACTB B2M B2M SYVN1 SYVN1 ABCA1 ABCA1 XPR1 XPR1 ABCG1 ABCG1 SREBF2 SREBF2 MYLIP MYLIP PXDNL PXDNL INSIG1 INSIG1 UBE2G2 UBE2G2
Nodes:
Network nodes represent proteins
splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
Node Color
colored nodes:
query proteins and first shell of interactors
white nodes:
second shell of interactors
Node Content
empty nodes:
proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
Edges:
Edges represent protein-protein associations
associations are meant to be specific and meaningful, i.e. proteins jointly contribute to a shared function; this does not necessarily mean they are physically binding to each other.
Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
Others
textmining
co-expression
protein homology
Your Input:
HMGCR3-hydroxy-3-methylglutaryl-coenzyme A 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)
AUP1Ancient ubiquitous protein 1; 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; Belongs to the AUP1 family. (410 aa)
PLPP2Phospholipid phosphatase 2; Magnesium-independent phospholipid phosphatase that catalyzes the dephosphorylation of a variety of glycerolipid and sphingolipid phosphate esters including phosphatidate/PA, lysophosphatidate/LPA, sphingosine 1-phosphate/S1P and ceramide 1-phosphate/C1P. Has no apparent extracellular phosphatase activity and therefore most probably acts intracellularly. Also acts on N-oleoyl ethanolamine phosphate/N-(9Z-octadecenoyl)-ethanolamine phosphate, a potential physiological compound. Through dephosphorylation of these bioactive lipid mediators produces new bioactiv [...] (309 aa)
CALRCalreticulin; Calcium-binding chaperone that promotes folding, oligomeric assembly and quality control in the endoplasmic reticulum (ER) via the calreticulin/calnexin cycle. This lectin interacts transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER. Interacts with the DNA-binding domain of NR3C1 and mediates its nuclear export. Involved in maternal gene expression regulation. May participate in oocyte maturation via the regulation of calcium homeostasis (By similarity); Belongs to the calreticulin family. (417 aa)
USH2AUsherin; Involved in hearing and vision as member of the USH2 complex. In the inner ear, required for the maintenance of the hair bundle ankle formation, which connects growing stereocilia in developing cochlear hair cells. In retina photoreceptors, the USH2 complex is required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport. (5202 aa)
RNF139E3 ubiquitin-protein ligase RNF139; 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)
HMGB2High mobility group protein B2; Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. In the nucleus is an abundant chromatin-associated non-histone protein involved in transcription, chromatin remodeling and V(D)J recombination and probably other processes. Binds DNA with a preference to non- canonical DNA structures such as single-stranded DNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bring [...] (209 aa)
ALBSerum albumin; Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc. Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific man [...] (609 aa)
AMFRE3 ubiquitin-protein ligase AMFR; 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 from the ER by the complex into t [...] (643 aa)
SCAPSterol regulatory element-binding protein cleavage-activating protein; 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, prot [...] (1279 aa)
GAPDHGlyceraldehyde-3-phosphate dehydrogenase; Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC. Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations throu [...] (335 aa)
FAF2FAS-associated factor 2; Plays an important role in endoplasmic reticulum-associated degradation (ERAD) that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway. Involved in inhibition of lipid droplet degradation by binding to phospholipase PNPL2 and inhibiting its activity by promoting dissociation of PNPL2 from its endogenous activator, ABHD5 which inhibits the rate of triacylglycerol hydrolysis. (445 aa)
PXDNPeroxidasin homolog; Displays low peroxidase activity and is likely to participate in H(2)O(2) metabolism and peroxidative reactions in the cardiovascular system. Plays a role in extracellular matrix formation. (1479 aa)
CANXCalnexin; Calcium-binding protein that interacts with newly synthesized glycoproteins in the endoplasmic reticulum. It may act in assisting protein assembly and/or in the retention within the ER of unassembled protein subunits. It seems to play a major role in the quality control apparatus of the ER by the retention of incorrectly folded proteins. Associated with partial T-cell antigen receptor complexes that escape the ER of immature thymocytes, it may function as a signaling complex regulating thymocyte maturation. Additionally it may play a role in receptor-mediated endocytosis at t [...] (592 aa)
INSIG2Insulin-induced gene 2 protein; 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. (225 aa)
GLCCI1Glucocorticoid-induced transcript 1 protein; Glucocorticoid induced 1. (547 aa)
TECRVery-long-chain enoyl-CoA reductase; Involved in both the production of very long-chain fatty acids for sphingolipid synthesis and the degradation of the sphingosine moiety in sphingolipids through the sphingosine 1-phosphate metabolic pathway. Catalyzes the last of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme reduces the trans-2,3-enoyl- CoA fatty acid intermediate to an acyl-CoA that can be furth [...] (308 aa)
INSInsulin A chain; Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. (110 aa)
GALNT11Polypeptide N-acetylgalactosaminyltransferase 11; Polypeptide N-acetylgalactosaminyltransferase that catalyzes the initiation of protein O-linked glycosylation and is involved in left/right asymmetry by mediating O-glycosylation of NOTCH1. O- glycosylation of NOTCH1 promotes activation of NOTCH1, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). Polypeptide N-acetylgalactosaminyltransferases catalyze the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Displays the same enzyme a [...] (608 aa)
RNF145RING finger protein 145; E3 ubiquitin ligase that catalyzes the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. In response to bacterial infection, negatively regulates the phagocyte oxidative burst by controlling the turnover of the NADPH oxidase complex subunits. Promotes monoubiquitination of CYBA and 'Lys-48'- linked polyubiquitination and degradation of CYBB NADPH oxidase catalytic subunits, both essential for the generation of antimicrobial reactive oxygen species. Involved in the maintenance of cholesterol homeostasis. In response to hi [...] (693 aa)
LDLRLow-density lipoprotein receptor; Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. (Microbial infection) Acts as a receptor for Vesicular stomatitis virus; Belongs to the LDLR family. (860 aa)
MYCMyc proto-oncogene protein; Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes. Binds to the VEGFA promoter, promoting VEGFA production and subsequent sprouting angiogenesis. Regulator of somatic reprogramming, controls self-renewal of embryonic stem cells. Functions with TAF6L to activate target gene expression through RNA polymerase II pause release (By similarity). (454 aa)
EHD1EH domain-containing protein 1; ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes vesiculation of endocytic membranes. Acts in early endocytic membrane fusion and membrane trafficking of recycling endosomes. Recruited to endosomal membranes upon nerve growth factor stimulation, indirectly regulates neurite outgrowth (By similarity). Plays a role in myoblast fusion (By similarity). Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating [...] (548 aa)
PHGDHD-3-phosphoglycerate dehydrogenase; Catalyzes the reversible oxidation of 3-phospho-D-glycerate to 3-phosphonooxypyruvate, the first step of the phosphorylated L- serine biosynthesis pathway. Also catalyzes the reversible oxidation of 2-hydroxyglutarate to 2-oxoglutarate and the reversible oxidation of (S)-malate to oxaloacetate; Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family. (533 aa)
ACTBActin, cytoplasmic 1, N-terminally processed; Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction. In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA. (375 aa)
B2MBeta-2-microglobulin form pI 5.3; Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. Exogenously applied M.tuberculosis EsxA or EsxA-EsxB (or EsxA expressed in host) binds B2M and decreases its export to the cell surface (total protein levels do not change), probably leading to defects in class I antigen presentation. Belongs to the beta-2-microglobulin family. (119 aa)
SYVN1E3 ubiquitin-protein ligase synoviolin; Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation. Component of the endoplasmic reticulum quality control (ERQC) system also called ER- associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from [...] (617 aa)
ABCA1Phospholipid-transporting ATPase ABCA1; Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. Thereby, participates to phospholipids transfer to apoliproteins to form nascent high density lipoproteins/HDLs. Transports preferentially phosphatidylcholine over phosphatidylserine. May play a similar role in the efflux of intracellular cholesterol to apoliproteins and the formation of nascent high density lipoproteins/HDLs ; Belongs to the ABC transporter superfamily. ABCA family. (2261 aa)
XPR1Xenotropic and polytropic retrovirus receptor 1; Plays a role in phosphate homeostasis. Mediates phosphate export from the cell. Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7); these are important intracellular signaling molecules. (696 aa)
ABCG1ATP-binding cassette sub-family G member 1; Catalyzes the efflux of phospholipids such as sphingomyelin, cholesterol and its oxygenated derivatives like 7beta- hydroxycholesterol and this transport is coupled to hydrlysis of ATP. The lipid efflux is ALB-dependent. Is an active component of the macrophage lipid export complex. Could also be involved in intracellular lipid transport processes. The role in cellular lipid homeostasis may not be limited to macrophages. Prevents cell death by transporting cytotoxic 7beta- hydroxycholesterol ; Belongs to the ABC transporter superfamily. ABCG [...] (678 aa)
SREBF2Processed sterol regulatory element-binding protein 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)
MYLIPE3 ubiquitin-protein ligase MYLIP; E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR. (445 aa)
PXDNLPeroxidasin-like protein; [Isoform PMR1]: Endonuclease selectively degrading some target mRNAs while they are engaged by translating ribosomes, among which albumin and beta-globin mRNAs. (1463 aa)
INSIG1Insulin-induced gene 1 protein; 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 pla [...] (277 aa)
UBE2G2Ubiquitin-conjugating enzyme E2 G2; Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'- linked polyubiquitination. Involved in endoplasmic reticulum-associated degradation (ERAD). (165 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (20%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.