STRINGSTRING
MRAP2 MRAP2 FMO2 FMO2 SIRT1 SIRT1 AMPD2 AMPD2 NR4A3 NR4A3 UBB UBB TSKU TSKU EIF4G1 EIF4G1 CD36 CD36 TRPV4 TRPV4 MEX3C MEX3C PRCP PRCP SQSTM1 SQSTM1 ALK ALK FOXO1 FOXO1 MFSD2A MFSD2A EDN2 EDN2 PRKAA2 PRKAA2 OMA1 OMA1 SGIP1 SGIP1 FMO4 FMO4 PM20D1 PM20D1 DLL1 DLL1 PASK PASK FMO1 FMO1 PRKAA1 PRKAA1 CRTC1 CRTC1 ACACB ACACB SUV39H1 SUV39H1 SLC35D3 SLC35D3 IRX3 IRX3 LEPR LEPR BMP8A BMP8A MLXIPL MLXIPL METRNL METRNL NR1D2 NR1D2 FLCN FLCN CRTC3 CRTC3 PPARGC1A PPARGC1A STAT3 STAT3 NMU NMU PIK3CA PIK3CA RRP8 RRP8
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splice isoforms or post-translational modifications are collapsed, i.e. each node represents all the proteins produced by a single, protein-coding gene locus.
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query proteins and first shell of interactors
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second shell of interactors
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proteins of unknown 3D structure
filled nodes:
a 3D structure is known or predicted
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Known Interactions
from curated databases
experimentally determined
Predicted Interactions
gene neighborhood
gene fusions
gene co-occurrence
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textmining
co-expression
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MRAP2Melanocortin-2 receptor accessory protein 2; Modulator of melanocortin receptor 4 (MC4R), a receptor involved in energy homeostasis. Plays a central role in the control of energy homeostasis and body weight regulation by increasing ligand- sensitivity of MC4R and MC4R-mediated generation of cAMP (By similarity). May also act as a negative regulator of MC2R: competes with MRAP for binding to MC2R and impairs the binding of corticotropin (ACTH) to MC2R. May also regulate activity of other melanocortin receptors (MC1R, MC3R and MC5R); however, additional evidence is required in vivo. (205 aa)
FMO2Dimethylaniline monooxygenase [N-oxide-forming] 2; Catalyzes the N-oxidation of certain primary alkylamines to their oximes via an N-hydroxylamine intermediate. Inactive toward certain tertiary amines, such as imipramine or chloropromazine. Can catalyze the S-oxidation of methimazole. (535 aa)
SIRT1NAD-dependent protein deacetylase sirtuin-1; NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expres [...] (747 aa)
AMPD2AMP deaminase 2; AMP deaminase plays a critical role in energy metabolism. Catalyzes the deamination of AMP to IMP and plays an important role in the purine nucleotide cycle. (879 aa)
NR4A3Nuclear receptor subfamily 4 group A member 3; Transcriptional activator that binds to regulatory elements in promoter regions in a cell- and response element (target)-specific manner. Induces gene expression by binding as monomers to the NR4A1 response element (NBRE) 5'-AAAAGGTCA-3' site and as homodimers to the Nur response element (NurRE) site in the promoter of their regulated target genes (By similarity). Plays a role in the regulation of proliferation, survival and differentiation of many different cell types and also in metabolism and inflammation. Mediates proliferation of vasc [...] (637 aa)
UBBPolyubiquitin-B; [Ubiquitin]: Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair [...] (229 aa)
TSKUTsukushin; Tsukushi, small leucine rich proteoglycan. (353 aa)
EIF4G1Eukaryotic translation initiation factor 4 gamma 1; Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome; Belongs to the eukaryotic initiation factor 4G family. (1606 aa)
CD36Platelet glycoprotein 4; Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor- ligand complexes. The depende [...] (472 aa)
TRPV4Transient receptor potential cation channel subfamily V member 4; Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by heat, low pH, citrate and phorbol esters. Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin- dependent mechanism with a negative feedback mechanism. Promotes cell-cell junction formation in skin keratinocytes and plays an important role in t [...] (871 aa)
MEX3CRNA-binding E3 ubiquitin-protein ligase MEX3C; E3 ubiquitin ligase responsible for the post-transcriptional regulation of common HLA-A allotypes. Binds to the 3' UTR of HLA-A2 mRNA, and regulates its levels by promoting mRNA decay. RNA binding is sufficient to prevent translation, but ubiquitin ligase activity is required for mRNA degradation. (659 aa)
PRCPLysosomal Pro-X carboxypeptidase; Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH. (517 aa)
SQSTM1Sequestosome-1; Autophagy receptor required for selective macroautophagy (aggrephagy). Functions as a bridge between polyubiquitinated cargo and autophagosomes. Interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family. Along with WDFY3, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with WDFY3, required to recruit ubiquitinated proteins to PML bodies in the nucleus. May regulate the activation of NFKB1 by TNF-alpha, nerve gro [...] (440 aa)
ALKALK tyrosine kinase receptor; Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen- activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as o [...] (1620 aa)
FOXO1Forkhead box protein O1; Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalc [...] (655 aa)
MFSD2ASodium-dependent lysophosphatidylcholine symporter 1; Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (By similarity). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain (By similarity). Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain. Transports LPC carrying long-chain fa [...] (543 aa)
EDN2Endothelin-2; Endothelins are endothelium-derived vasoconstrictor peptides. (178 aa)
PRKAA25'-AMP-activated protein kinase catalytic subunit alpha-2; Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts a [...] (552 aa)
OMA1Metalloendopeptidase OMA1, mitochondrial; Metalloprotease that is part of the quality control system in the inner membrane of mitochondria. Following stress conditions that induce loss of mitochondrial membrane potential, mediates cleavage of OPA1 at S1 position, leading to OPA1 inactivation and negative regulation of mitochondrial fusion. May also cleave UQCC3 under these conditions. Its role in mitochondrial quality control is essential for regulating lipid metabolism as well as to maintain body temperature and energy expenditure under cold-stress conditions. Belongs to the peptidase [...] (524 aa)
SGIP1SH3-containing GRB2-like protein 3-interacting protein 1; May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis. (828 aa)
FMO4Dimethylaniline monooxygenase [N-oxide-forming] 4; This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. (558 aa)
PM20D1N-fatty-acyl-amino acid synthase/hydrolase PM20D1; Bidirectional N-fatty-acyl amino acid synthase/hydrolase that regulates the production of N-fatty-acyl amino acids. These metabolites are endogenous chemical uncouplers of mitochondrial respiration. In an UCP1-independent manner, maybe through interaction with mitochondrial transporters, they promote proton leakage into the mitochondrial matrix. Thereby, this secreted protein may indirectly regulate the bodily dissipation of chemical energy as heat through thermogenic respiration. (502 aa)
DLL1Delta-like protein 1; Transmembrane ligand protein of NOTCH1, NOTCH2 and NOTCH3 receptors that binds the extracellular domain (ECD) of Notch receptor in a cis and trans fashion manner. Following transinteraction, ligand cells produce mechanical force that depends of a clathrin-mediated endocytosis, requiring ligand ubiquitination, EPN1 interaction, and actin polymerisation; these events promote Notch receptor extracellular domain (NECD) transendocytosis and triggers Notch signaling through induction of cleavage, hyperphosphorylation, and nuclear accumulation of the intracellular domain [...] (723 aa)
PASKPAS domain-containing serine/threonine-protein kinase; Serine/threonine-protein kinase involved in energy homeostasis and protein translation. Phosphorylates EEF1A1, GYS1, PDX1 and RPS6. Probably plays a role under changing environmental conditions (oxygen, glucose, nutrition), rather than under standard conditions. Acts as a sensor involved in energy homeostasis: regulates glycogen synthase synthesis by mediating phosphorylation of GYS1, leading to GYS1 inactivation. May be involved in glucose-stimulated insulin production in pancreas and regulation of glucagon secretion by glucose in [...] (1330 aa)
FMO1Dimethylaniline monooxygenase [N-oxide-forming] 1; This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines. (532 aa)
PRKAA15'-AMP-activated protein kinase catalytic subunit alpha-1; Catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts a [...] (574 aa)
CRTC1CREB-regulated transcription coactivator 1; Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PGC1alpha and inducer of mitochondrial biogenesis in muscle cells. In the hippocampus, involved [...] (650 aa)
ACACBAcetyl-CoA carboxylase 2; Mitochondrial enzyme that catalyzes the carboxylation of acetyl-CoA to malonyl-CoA and plays a central role in fatty acid metabolism. Catalyzes a 2 steps reaction starting with the ATP-dependent carboxylation of the biotin carried by the biotin carboxyl carrier (BCC) domain followed by the transfer of the carboxyl group from carboxylated biotin to acetyl-CoA. Through the production of malonyl-CoA that allosterically inhibits carnitine palmitoyltransferase 1 at the mitochondria, negatively regulates fatty acid oxidation (By similarity). Together with its cytoso [...] (2458 aa)
SUV39H1Histone-lysine N-methyltransferase SUV39H1; Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also requir [...] (423 aa)
SLC35D3Solute carrier family 35 member D3; May play a role in hemostasis as a regulator of the biosynthesis of platelet-dense granules; Belongs to the TPT transporter family. SLC35D subfamily. (416 aa)
IRX3Iroquois-class homeodomain protein IRX-3; Transcription factor involved in SHH-dependent neural patterning. Together with NKX2-2 and NKX6-1 acts to restrict the generation of motor neurons to the appropriate region of the neural tube. Belongs to the class I proteins of neuronal progenitor factors, which are repressed by SHH signals. Involved in the transcriptional repression of MNX1 in non-motor neuron cells. Acts as a regulator of energy metabolism. (501 aa)
LEPRLeptin receptor; Receptor for hormone LEP/leptin (Probable). On ligand binding, mediates LEP central and peripheral effects through the activation of different signaling pathways such as JAK2/STAT3 and MAPK cascade/FOS. In the hypothalamus, LEP acts as an appetite- regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones (By similarity). In the periphery, increases basal metabolism, influences [...] (1165 aa)
BMP8ABone morphogenetic protein 8A; Induces cartilage and bone formation. May be the osteoinductive factor responsible for the phenomenon of epithelial osteogenesis. Plays a role in calcium regulation and bone homeostasis (By similarity). Signaling protein involved in regulation of thermogenesis and energy balance. Proposed to increase the peripheral response of brown adipose tissue (BAT) to adrenergic stimulation while acting centrally in the hypothalamus to increase sympathetic output to BAT. (402 aa)
MLXIPLCarbohydrate-responsive element-binding protein; Transcriptional repressor. Binds to the canonical and non- canonical E box sequences 5'-CACGTG-3' (By similarity). (852 aa)
METRNLMeteorin-like protein; Hormone induced following exercise or cold exposure that promotes energy expenditure. Induced either in the skeletal muscle after exercise or in adipose tissue following cold exposure and is present in the circulation. Able to stimulate energy expenditure associated with the browning of the white fat depots and improves glucose tolerance. Does not promote an increase in a thermogenic gene program via direct action on adipocytes, but acts by stimulating several immune cell subtypes to enter the adipose tissue and activate their prothermogenic actions. Stimulates a [...] (311 aa)
NR1D2Nuclear receptor subfamily 1 group D member 2; Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components ARNTL/BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 co [...] (579 aa)
FLCNFolliculin; May be a tumor suppressor. May be involved in energy and/or nutrient sensing through the AMPK and mTOR signaling pathways. May regulate phosphorylation of RPS6KB1. (579 aa)
CRTC3CREB-regulated transcription coactivator 3; Transcriptional coactivator for CREB1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of CREB1 'Ser-133' phosphorylation. Enhances the interaction of CREB1 with TAF4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of PPARGC1A and inducer of mitochondrial biogenesis in muscle cells. Also coactivator for TAX acti [...] (619 aa)
PPARGC1APeroxisome proliferator-activated receptor gamma coactivator 1-alpha; Transcriptional coactivator for steroid receptors and nuclear receptors. Greatly increases the transcriptional activity of PPARG and thyroid hormone receptor on the uncoupling protein promoter. Can regulate key mitochondrial genes that contribute to the program of adaptive thermogenesis. Plays an essential role in metabolic reprogramming in response to dietary availability through coordination of the expression of a wide array of genes involved in glucose and fatty acid metabolism. Induces the expression of PERM1 in [...] (798 aa)
STAT3Signal transducer and activator of transcription 3; Signal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Acts as a regulator of inflammatory response by regulating differenti [...] (770 aa)
NMUNeuromedin precursor-related peptide 33; [Neuromedin-U-25]: Ligand for receptors NMUR1 and NMUR2 (By similarity). Stimulates muscle contractions of specific regions of the gastrointestinal tract. In humans, NmU stimulates contractions of the ileum and urinary bladder. [Neuromedin precursor-related peptide 36]: Does not function as a ligand for either NMUR1 or NMUR2. Indirectly induces prolactin release from lactotroph cells in the pituitary gland, probably via the hypothalamic dopaminergic system. (174 aa)
PIK3CAPhosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform; Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Participates in cellular signaling in response to v [...] (1068 aa)
RRP8Ribosomal RNA-processing protein 8; Essential component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone- modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the complex, RRP8 binds to H3K9me2 and pr [...] (456 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
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