STRINGSTRING
GSX2 GSX2 FZD3 FZD3 BBS2 BBS2 MKKS MKKS SMO SMO EMX1 EMX1 SLC6A4 SLC6A4 WNT5A WNT5A FBXW11 FBXW11 SLIT1 SLIT1 BBS4 BBS4 CDH2 CDH2 GDF7 GDF7 VPS51 VPS51 FANCD2 FANCD2 FANCC FANCC CTNNA1 CTNNA1 PROP1 PROP1 GBA GBA BBS1 BBS1 FGF8 FGF8 ZNF335 ZNF335 PSEN1 PSEN1 FOXO3 FOXO3 SPEF2 SPEF2 NF1 NF1 FZD6 FZD6 OTX1 OTX1 UCHL5 UCHL5 PAX2 PAX2 PTEN PTEN DUOX2 DUOX2 PAFAH1B1 PAFAH1B1 CTNNA2 CTNNA2 SOS1 SOS1 SLC4A10 SLC4A10 SHANK3 SHANK3 HESX1 HESX1 AKT3 AKT3
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:
GSX2GS homeobox 2; During telencephalic development, causes ventralization of pallial progenitors and, depending on the developmental stage, specifies different neuronal fates. At early stages, necessary and sufficient to correctly specify the ventral lateral ganglionic eminence (LGE) and its major derivatives, the striatal projection neurons. At later stages, may specify LGE progenitors toward dorsal LGE fates, including olfactory bulb interneurons (By similarity). Transcription factor that binds 5'-CNAATTAG-3' DNA sequence. Belongs to the Antp homeobox family. (304 aa)
FZD3Frizzled-3; Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to i [...] (666 aa)
BBS2Bardet-Biedl syndrome 2 protein; The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl ex [...] (721 aa)
MKKSMcKusick-Kaufman/Bardet-Biedl syndromes putative chaperonin; Probable molecular chaperone that assists the folding of proteins upon ATP hydrolysis. Plays a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. May play a role in protein processing in limb, cardiac and reproductive system development. May play a role in cytokinesis. Belongs to the TCP-1 chaperonin family. (570 aa)
SMOSmoothened homolog; G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity). (787 aa)
EMX1Homeobox protein EMX1; Transcription factor, which in cooperation with EMX2, acts to generate the boundary between the roof and archipallium in the developing brain. May function in combinations with OTX1/2 to specify cell fates in the developing central nervous system. (290 aa)
SLC6A4Sodium-dependent serotonin transporter; Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner. (630 aa)
WNT5AProtein Wnt-5a; Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta- catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur and inhibits tumor formation. Stimulates cell migration. Decre [...] (380 aa)
FBXW11F-box/WD repeat-containing protein 11; Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. SCF(FBXW11) mediates the ubiquitination of phosphorylated CTNNB1 and participates in Wnt signaling. SCF(FBXW11) mediates the ubiquitination of phosphorylated NFKBIA, which degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. SCF(FBXW11) mediat [...] (542 aa)
SLIT1Slit homolog 1 protein; Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions (By similarity). SLIT1 and SLIT2 together seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. (1534 aa)
BBS4Bardet-Biedl syndrome 4 protein; The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl ex [...] (519 aa)
CDH2Cadherin-2; Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence. CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic s [...] (906 aa)
GDF7Growth/differentiation factor 7; May play an active role in the motor area of the primate neocortex. (450 aa)
VPS51Vacuolar protein sorting-associated protein 51 homolog; Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome- derived carriers to the TGN. Acts as component of the EARP complex [...] (782 aa)
FANCD2Fanconi anemia group D2 protein; Required for maintenance of chromosomal stability. Promotes accurate and efficient pairing of homologs during meiosis. Involved in the repair of DNA double-strand breaks, both by homologous recombination and single-strand annealing. May participate in S phase and G2 phase checkpoint activation upon DNA damage. Plays a role in preventing breakage and loss of missegregating chromatin at the end of cell division, particularly after replication stress. Required for the targeting, or stabilization, of BLM to non-centromeric abnormal structures induced by rep [...] (1471 aa)
FANCCFanconi anemia group C protein; DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1. (558 aa)
CTNNA1Catenin alpha-1; Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and [...] (906 aa)
PROP1Homeobox protein prophet of Pit-1; Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes. (226 aa)
GBALysosomal acid glucosylceramidase; Glucosylceramidase that catalyzes, within the lysosomal compartment, the hydrolysis of glucosylceramide/GlcCer into free ceramide and glucose. Thereby, plays a central role in the degradation of complex lipids and the turnover of cellular membranes. Through the production of ceramides, participates to the PKC-activated salvage pathway of ceramide formation. Also plays a role in cholesterol metabolism. May either catalyze the glucosylation of cholesterol, through a transglucosylation reaction that transfers glucose from glucosylceramide to cholesterol. [...] (536 aa)
BBS1Bardet-Biedl syndrome 1 protein; The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl ex [...] (593 aa)
FGF8Fibroblast growth factor 8; Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryogenesis. Required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Plays a role in neurite outgrowth in hippocampal cells. Belongs to the heparin-binding growth factors family. (244 aa)
ZNF335Zinc finger protein 335; Component or associated component of some histone methyltransferase complexes may regulate transcription through recruitment of those complexes on gene promoters. Enhances ligand- dependent transcriptional activation by nuclear hormone receptors. Plays an important role in neural progenitor cell proliferation and self-renewal through the regulation of specific genes involved brain development, including REST. Also controls the expression of genes involved in somatic development and regulates, for instance, lymphoblast proliferation. (1342 aa)
PSEN1Presenilin-1 CTF subunit; Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid- beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabili [...] (467 aa)
FOXO3Forkhead box protein O3; Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy. Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon [...] (673 aa)
SPEF2Sperm flagellar protein 2; Required for correct axoneme development in spermatozoa. Important for normal development of the manchette and sperm head morphology. Essential for male fertility. Plays a role in localization of the intraflagellar transport protein IFT20 to the manchette, suggesting function as an adapter for dynein-mediated protein transport during spermatogenesis. Also plays a role in bone growth where it seems to be required for normal osteoblast differentiation. (1822 aa)
NF1Neurofibromin truncated; Stimulates the GTPase activity of Ras. NF1 shows greater affinity for Ras GAP, but lower specific activity. May be a regulator of Ras activity. (2839 aa)
FZD6Frizzled-6; Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to i [...] (706 aa)
OTX1Homeobox protein OTX1; Probably plays a role in the development of the brain and the sense organs. Can bind to the BCD target sequence (BTS): 5'-TCTAATCCC- 3'. (354 aa)
UCHL5Ubiquitin carboxyl-terminal hydrolase isozyme L5; Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1. (355 aa)
PAX2Paired box protein Pax-2; Transcription factor that may have a role in kidney cell differentiation. Has a critical role in the development of the urogenital tract, the eyes, and the CNS. (396 aa)
PTENPhosphatase and tensin homolog; Tumor suppressor. Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine- phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4- diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5- tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4. The lipid phosphatase activity is critical for its tumor [...] (403 aa)
DUOX2Dual oxidase 2; Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain. (1548 aa)
PAFAH1B1Platelet-activating factor acetylhydrolase IB subunit alpha; Required for proper activation of Rho GTPases and actin polymerization at the leading edge of locomoting cerebellar neurons and postmigratory hippocampal neurons in response to calcium influx triggered via NMDA receptors. Non-catalytic subunit of an acetylhydrolase complex which inactivates platelet-activating factor (PAF) by removing the acetyl group at the SN-2 position (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule slidi [...] (410 aa)
CTNNA2Catenin alpha-2; May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system (By similarity). Required for proper regulation of cortical neuronal migration and neurite growth. It acts as negative regulator of Arp2/3 complex activity and Arp2/3- mediated actin polymerization. It thereby suppresses excessive actin branching which would impair neurite growth and stability. Regulates morphological plasticity of synapses and cerebellar and hippocampal lamination during development. Functions in th [...] (953 aa)
SOS1Son of sevenless homolog 1; Promotes the exchange of Ras-bound GDP by GTP. Probably by promoting Ras activation, regulates phosphorylation of MAP kinase MAPK3 in response to EGF. Catalytic component of a trimeric complex that participates in transduction of signals from Ras to Rac by promoting the Rac-specific guanine nucleotide exchange factor (GEF) activity (By similarity). (1333 aa)
SLC4A10Sodium-driven chloride bicarbonate exchanger; Sodium/bicarbonate cotransporter which plays an important role in regulating intracellular pH. Has been shown to act as a sodium/bicarbonate cotransporter in exchange for intracellular chloride (By similarity). Has also been shown to act as a sodium/biocarbonate cotransporter which does not couple net influx of bicarbonate to net efflux of chloride, with the observed chloride efflux being due to chloride self-exchange. Controls neuronal pH and may contribute to the secretion of cerebrospinal fluid (By similarity). Reduces the excitability o [...] (1118 aa)
SHANK3SH3 and multiple ankyrin repeat domains protein 3; Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex [...] (1724 aa)
HESX1Homeobox expressed in ES cells 1; Required for the normal development of the forebrain, eyes and other anterior structures such as the olfactory placodes and pituitary gland. Possible transcriptional repressor. Binds to the palindromic PIII sequence, 5'-AGCTTGAGTCTAATTGAATTAACTGTAC-3'. HESX1 and PROP1 bind as heterodimers on this palindromic site, and, in vitro, HESX1 can antagonize PROP1 activation; Belongs to the ANF homeobox family. (185 aa)
AKT3RAC-gamma serine/threonine-protein kinase; AKT3 is one of 3 closely related serine/threonine-protein kinases (AKT1, AKT2 and AKT3) called the AKT kinase, and which regulate many processes including metabolism, proliferation, cell survival, growth and angiogenesis. This is mediated through serine and/or threonine phosphorylation of a range of downstream substrates. Over 100 substrate candidates have been reported so far, but for most of them, no isoform specificity has been reported. AKT3 is the least studied AKT isoform. It plays an important role in brain development and is crucial fo [...] (479 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (18%) [HD]
STRING is a Core Data Resource as designated by Global Biodata Coalition and ELIXIR.