STRINGSTRING
SERPINA5 SERPINA5 H3C13 H3C13 DNAH8 DNAH8 TCFL5 TCFL5 PNPLA2 PNPLA2 ATAD1 ATAD1 ACSL4 ACSL4 H3-5 H3-5 INSIG1 INSIG1 SREBF1 SREBF1 VCP VCP H3C12 H3C12 SREBF2 SREBF2 TOMM20 TOMM20 H3-4 H3-4 SCD SCD ITPR3 ITPR3 PCNA PCNA VDAC1 VDAC1 GAPDH GAPDH REEP1 REEP1 MFN2 MFN2 MFN1 MFN1 STIM1 STIM1 VPS13D VPS13D MYC MYC ACTB ACTB ABHD5 ABHD5 MAP1LC3B MAP1LC3B H3-2 H3-2 RMDN3 RMDN3 FAF2 FAF2 UFD1 UFD1 SQLE SQLE TARDBP TARDBP UBXN4 UBXN4 CANX CANX H3-3B H3-3B SIGMAR1 SIGMAR1 MYCN MYCN TOMM70 TOMM70 HMGCR HMGCR AMFR AMFR UBXN1 UBXN1 ALB ALB UBXN7 UBXN7 HSPA9 HSPA9 ITPR1 ITPR1 NPLOC4 NPLOC4
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:
SERPINA5Plasma serine protease inhibitor; Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coa [...] (406 aa)
H3C13Histone H3.2; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (136 aa)
DNAH8Dynein heavy chain 8, axonemal; Force generating protein of respiratory cilia. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Involved in sperm motility; implicated in sperm flagellar assembly (By similarity). (4707 aa)
TCFL5Transcription factor-like 5 protein; Putative transcription factor. Isoform 3 may play a role in early spermatogenesis. (500 aa)
PNPLA2Patatin-like phospholipase domain-containing protein 2; Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets. Also has acylglycerol transacylase activity. May act coordinately with LIPE/HLS within the lipolytic cascade. Regulates adiposome size and may be involved in the degradation of adiposomes. May play an important role in energy homeostasis. May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion. (504 aa)
ATAD1ATPase family AAA domain-containing protein 1; ATPase that plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory. Required for NMDA-stimulated AMPAR internalization and inhibition of GRIA1 and GRIA2 recycling back to the plasma membrane; these activities are ATPase-dependent (By similarity). (361 aa)
ACSL4Long-chain-fatty-acid--CoA ligase 4; Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoA for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially activates arachidonate and eicosapentaenoate as substrates. Preferentially activates 8,9-EET > 14,15-EET > 5,6-EET > 11,12-EET. Modulates glucose- stimulated insulin secretion by regulating the levels of unesterified EETs (By similarity). Modulates prostaglandin E2 secretion. Belongs to the ATP-dependent AMP-binding enzyme family. (711 aa)
H3-5Histone H3.3C; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Hominid-specific H3.5/H3F3C preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes. (135 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)
SREBF1Processed sterol regulatory element-binding protein 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)
VCPTransitional endoplasmic reticulum ATPase; 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 UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is neces [...] (806 aa)
H3C12Histone H3.1; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (136 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)
TOMM20Mitochondrial import receptor subunit TOM20 homolog; Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with TOM22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the TOM40 translocation pore (By similarity). Required for the translocation across the mitochondrial outer membrane of cytochrome P450 monooxygenases. Belongs to the Tom20 family. (145 aa)
H3-4Histone H3.1t; Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. (136 aa)
SCDAcyl-CoA desaturase; Stearyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates. Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA. Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids. Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation (By simi [...] (359 aa)
ITPR3Inositol 1,4,5-trisphosphate receptor type 3; Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. (2671 aa)
PCNAProliferating cell nuclear antigen; Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'- phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA rep [...] (261 aa)
VDAC1Voltage-dependent anion-selective channel protein 1; Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. May participate in the formation of the permeability transition p [...] (283 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)
REEP1Receptor expression-enhancing protein 1; Required for endoplasmic reticulum (ER) network formation, shaping and remodeling; it links ER tubules to the cytoskeleton. May also enhance the cell surface expression of odorant receptors. May play a role in long-term axonal maintenance. (208 aa)
MFN2Mitofusin-2; Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks. Membrane clustering requires GTPase activity and may involve a major rearrangement of the coiled coil domains (Probable). Plays a central role in mitochondrial metabolism and may be associated with obesity and/or apoptosis processes (By similarity). Plays an important role in the [...] (757 aa)
MFN1Mitofusin-1; Mitochondrial outer membrane GTPase that mediates mitochondrial clustering and fusion. Membrane clustering requires GTPase activity. It may involve a major rearrangement of the coiled coil domains. Mitochondria are highly dynamic organelles, and their morphology is determined by the equilibrium between mitochondrial fusion and fission events. Overexpression induces the formation of mitochondrial networks (in vitro). Has low GTPase activity. (741 aa)
STIM1Stromal interaction molecule 1; Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores. Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release- activated Ca(2+) (CRAC) channel subunit ORAI1. Involved in enamel formation. Activated following interaction with STIMATE, leading to promote STIM1 conformational switch. (791 aa)
VPS13DVacuolar protein sorting-associated protein 13D; Functions in promoting mitochondrial clearance by mitochondrial autophagy (mitophagy), also possibly by positively regulating mitochondrial fission. Mitophagy plays an important role in regulating cell health and mitochondrial size and homeostasis. (4388 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)
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)
ABHD51-acylglycerol-3-phosphate O-acyltransferase ABHD5; Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfert of an acyl group on a lysophosphatidic acid. Functions preferentially with 1-oleoyl- lysophosphatidic acid followed by 1-palmitoyl-lysophosphatidic acid, 1- stearoyl-lysophosphatidic acid and 1-arachidonoyl-lysophosphatidic acid as lipid acceptor. Functions preferentially with arachidonoyl-CoA followed by oleoyl-CoA as acyl group donors (By similarity). Functions in phosphatidic acid biosynthesis. May regulate the cellular storage of triacylglycero [...] (349 aa)
MAP1LC3BMicrotubule-associated proteins 1A/1B light chain 3B; Ubiquitin-like modifier involved in formation of autophagosomal vacuoles (autophagosomes). Plays a role in mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Whereas LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Promotes primary ciliogenesis by removing OFD1 from centriolar satellit [...] (125 aa)
H3-2H3.2 histone. (136 aa)
RMDN3Regulator of microtubule dynamics protein 3; Involved in cellular calcium homeostasis regulation. May participate in differentiation and apoptosis of keratinocytes. Overexpression induces apoptosis; Belongs to the RMDN family. (470 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)
UFD1Ubiquitin recognition factor in ER-associated degradation protein 1; Essential component of the ubiquitin-dependent proteolytic pathway which degrades ubiquitin fusion proteins. The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1- VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope. It may be involved in the development of some ectoderm-deriv [...] (307 aa)
SQLESqualene monooxygenase; Catalyzes the stereospecific oxidation of squalene to (S)- 2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis. (574 aa)
TARDBPTAR DNA-binding protein 43; RNA-binding protein that is involved in various steps of RNA biogenesis and processing. Preferentially binds, via its two RNA recognition motifs RRM1 and RRM2, to GU-repeats on RNA molecules predominantly localized within long introns and in the 3'UTR of mRNAs. In turn, regulates the splicing of many non-coding and protein-coding RNAs including proteins involved in neuronal survival, as well as mRNAs that encode proteins relevant for neurodegenerative diseases. Plays a role in maintaining mitochondrial homeostasis by regulating the processing of mitochondria [...] (414 aa)
UBXN4UBX domain-containing protein 4; Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD. (508 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)
H3-3BHistone H3.3; Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in [...] (136 aa)
SIGMAR1Sigma non-opioid intracellular receptor 1; Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. [...] (223 aa)
MYCNN-myc proto-oncogene protein; Positively regulates the transcription of MYCNOS in neuroblastoma cells. (464 aa)
TOMM70Mitochondrial import receptor subunit TOM70; Receptor that accelerates the import of all mitochondrial precursor proteins. (608 aa)
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)
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)
UBXN1UBX domain-containing protein 1; Ubiquitin-binding protein that plays a role in the modulation of innate immune response. Blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, UBXN1 is induced and recruited to the RLR component MAVS. In turn, interferes with MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. This function probably serves as a brake to prevent excessive RLR signaling. Interferes with the TNFalpha-triggered NF-kappa-B pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs) and thereby inhibi [...] (312 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)
UBXN7UBX domain-containing protein 7; Ubiquitin-binding adapter that links a subset of NEDD8- associated cullin ring ligases (CRLs) to the segregase VCP/p97, to regulate turnover of their ubiquitination substrates. (489 aa)
HSPA9Stress-70 protein, mitochondrial; Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU. Regulates erythropoiesis via stabilization of ISC assembly. May play a role in the control of cell proliferation and cellular aging (By similarity). Belongs to the heat shock protein 70 family. (679 aa)
ITPR1Inositol 1,4,5-trisphosphate receptor type 1; Intracellular channel that mediates calcium release from the endoplasmic reticulum following stimulation by inositol 1,4,5- trisphosphate. Involved in the regulation of epithelial secretion of electrolytes and fluid through the interaction with AHCYL1 (By similarity). Plays a role in ER stress-induced apoptosis. Cytoplasmic calcium released from the ER triggers apoptosis by the activation of CaM kinase II, eventually leading to the activation of downstream apoptosis pathways (By similarity). (2743 aa)
NPLOC4Nuclear protein localization protein 4 homolog; The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to DDX58/RIG-I and recruits RNF125 to promote ubiquitination [...] (608 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (14%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.