STRINGSTRING
DIO2 DIO2 SLC5A5 SLC5A5 CCND1 CCND1 BMP4 BMP4 PXDN PXDN TSHB TSHB KCNQ4 KCNQ4 PAX8 PAX8 PITX1 PITX1 DUOXA1 DUOXA1 NCOR1 NCOR1 PRL PRL HDAC3 HDAC3 TRH TRH SLC26A5 SLC26A5 PCSK1 PCSK1 TBX5 TBX5 DUOXA2 DUOXA2 SOX2 SOX2 NKX2-5 NKX2-5 ASCL2 ASCL2 GATA2 GATA2 PXDNL PXDNL RXRG RXRG IGSF1 IGSF1 RUNX2 RUNX2 LHX3 LHX3 NCOA3 NCOA3 DKK1 DKK1 MED12 MED12 FOXE1 FOXE1 LRP4 LRP4 IGFBP3 IGFBP3 DUOX2 DUOX2 IGF1 IGF1 GPS2 GPS2 THRB THRB POMC POMC NCOA1 NCOA1 CREB1 CREB1 MECP2 MECP2 NCOA2 NCOA2 TBL1XR1 TBL1XR1 BDNF BDNF RXRA RXRA TRHR TRHR NR4A1 NR4A1 TSHR TSHR NCOA4 NCOA4 SLC16A2 SLC16A2 SLC26A4 SLC26A4 PITX2 PITX2 CTNNB1 CTNNB1 TBL1X TBL1X
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:
DIO2Type II iodothyronine deiodinase; Responsible for the deiodination of T4 (3,5,3',5'- tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development. (273 aa)
SLC5A5Sodium/iodide cotransporter; Mediates iodide uptake in the thyroid gland; Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family. (643 aa)
CCND1G1/S-specific cyclin-D1; Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. A [...] (295 aa)
BMP4Bone morphogenetic protein 4; Induces cartilage and bone formation. Also acts in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). (408 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)
TSHBThyrotropin subunit beta; Indispensable for the control of thyroid structure and metabolism; Belongs to the glycoprotein hormones subunit beta family. (138 aa)
KCNQ4Potassium voltage-gated channel subfamily KQT member 4; Probably important in the regulation of neuronal excitability. May underlie a potassium current involved in regulating the excitability of sensory cells of the cochlea. KCNQ4 channels are blocked by linopirdin, XE991 and bepridil, whereas clofilium is without significant effect. Muscarinic agonist oxotremorine-M strongly suppress KCNQ4 current in CHO cells in which cloned KCNQ4 channels were coexpressed with M1 muscarinic receptors. (695 aa)
PAX8Paired box protein Pax-8; Transcription factor for the thyroid-specific expression of the genes exclusively expressed in the thyroid cell type, maintaining the functional differentiation of such cells. (450 aa)
PITX1Pituitary homeobox 1; Sequence-specific transcription factor that binds gene promoters and activates their transcription. May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb. Belongs to the paired homeobox family. Bicoid subfamily. (314 aa)
DUOXA1Dual oxidase maturation factor 1; May be required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX1. (483 aa)
NCOR1Nuclear receptor corepressor 1; Mediates transcriptional repression by certain nuclear receptors. Part of a complex which promotes histone deacetylation and the formation of repressive chromatin structures which may impede the access of basal transcription factors. Participates in the transcriptional repressor activity produced by BCL6. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation. Mediates the NR1D1-dependent repression and circadian regulation of TSHB expression (By [...] (2440 aa)
PRLProlactin; Prolactin acts primarily on the mammary gland by promoting lactation; Belongs to the somatotropin/prolactin family. (227 aa)
HDAC3Histone deacetylase 3; Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activi [...] (428 aa)
TRHPro-thyrotropin-releasing hormone; As a component of the hypothalamic-pituitary-thyroid axis, it controls the secretion of thyroid-stimulating hormone (TSH) and is involved in thyroid hormone synthesis regulation. It also operates as modulator of hair growth. It promotes hair-shaft elongation, prolongs the hair cycle growth phase (anagen) and antagonizes its termination (catagen) by TGFB2. It stimulates proliferation and inhibits apoptosis of hair matrix keratinocytes. (242 aa)
SLC26A5Prestin; Motor protein that converts auditory stimuli to length changes in outer hair cells and mediates sound amplification in the mammalian hearing organ. Prestin is a bidirectional voltage-to-force converter, it can operate at microsecond rates. It uses cytoplasmic anions as extrinsic voltage sensors, probably chloride and bicarbonate. After binding to a site with millimolar affinity, these anions are translocated across the membrane in response to changes in the transmembrane voltage. They move towards the extracellular surface following hyperpolarization, and towards the cytoplasm [...] (744 aa)
PCSK1Neuroendocrine convertase 1; Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP; Belongs to the peptidase S8 family. Furin subfamily. (753 aa)
TBX5T-box transcription factor TBX5; DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation. Binds to the core DNA motif of NPPA promoter. (518 aa)
DUOXA2Dual oxidase maturation factor 2; Required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX2. May play a role in thyroid hormone synthesis. (320 aa)
SOX2Transcription factor SOX-2; Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206 (By similarity). Binds to the proximal enhancer region of NANOG (By similarity). Critical for early embryogenesis and for embryonic stem cell pluripotency. Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differen [...] (317 aa)
NKX2-5Homeobox protein Nkx-2.5; Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity). Binds to the core DNA motif of NPPA promoter. It is transcriptionally controlled by PBX1 and acts as a transcriptional repressor of CDKN2B (By similarity). It is required for spleen development. (324 aa)
ASCL2Achaete-scute homolog 2; AS-C proteins are involved in the determination of the neuronal precursors in the peripheral nervous system and the central nervous system. (193 aa)
GATA2Endothelial transcription factor GATA-2; Transcriptional activator which regulates endothelin-1 gene expression in endothelial cells. Binds to the consensus sequence 5'- AGATAG-3'. (480 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)
RXRGRetinoic acid receptor RXR-gamma; Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity). (463 aa)
IGSF1Immunoglobulin superfamily member 1; Seems to be a coreceptor in inhibin signaling, but seems not to be a high-affinity inhibin receptor. Antagonizes activin A signaling in the presence or absence of inhibin B (By similarity). Necessary to mediate a specific antagonistic effect of inhibin B on activin- stimulated transcription. (1341 aa)
RUNX2Runt-related transcription factor 2; Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2- media [...] (521 aa)
LHX3LIM/homeobox protein Lhx3; Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (By similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system. Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1. (402 aa)
NCOA3Nuclear receptor coactivator 3; Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone- dependent fashion. Plays a central role in creating a multisubunit coactivator complex, which probably acts via remodeling of chromatin. Involved in the coactivation of different nuclear receptors, such as for steroids (GR and ER), retinoids (RARs and RXRs), thyroid hormone (TRs), vitamin D3 (VDR) and prostanoids (PPARs). Displays histone acetyltransferase activity. Also involved in the coactivation of the NF-kappa-B pathway via [...] (1424 aa)
DKK1Dickkopf-related protein 1; Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease. Inhibits the pro-apoptotic function of KREMEN1 in a Wnt-independent manner [...] (266 aa)
MED12Mediator of RNA polymerase II transcription subunit 12; Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. This subunit may specifi [...] (2177 aa)
FOXE1Forkhead box protein E1; Transcription factor that binds consensus sites on a variety of gene promoters and activate their transcription. Involved in proper palate formation, most probably through the expression of MSX1 and TGFB3 genes which are direct targets of this transcription factor. Also implicated in thyroid gland morphogenesis. May indirectly play a role in cell growth and migration through the regulation of WNT5A expression. (373 aa)
LRP4Low-density lipoprotein receptor-related protein 4; Mediates SOST-dependent inhibition of bone formation. Functions as a specific facilitator of SOST-mediated inhibition of Wnt signaling. Plays a key role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between motor neuron and skeletal muscle. Directly binds AGRIN and recruits it to the MUSK signaling complex. Mediates the AGRIN-induced phosphorylation of MUSK, the kinase of the complex. The activation of MUSK in myotubes induces the formation of NMJ by regulating different processes including the [...] (1905 aa)
IGFBP3Insulin-like growth factor-binding protein 3; IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. (297 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)
IGF1Insulin-like growth factor I; The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]- 2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exo [...] (158 aa)
GPS2G protein pathway suppressor 2; Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'- linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context. Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and [...] (327 aa)
THRBThyroid hormone receptor beta; Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine. (461 aa)
POMCCorticotropin-like intermediary peptide; [Corticotropin]: Stimulates the adrenal glands to release cortisol. [Melanocyte-stimulating hormone beta]: Increases the pigmentation of skin by increasing melanin production in melanocytes. [Met-enkephalin]: Endogenous opiate; Belongs to the POMC family. (267 aa)
NCOA1Nuclear receptor coactivator 1; Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone- dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating m [...] (1441 aa)
CREB1Cyclic AMP-responsive element-binding protein 1; Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells; Belongs to the bZIP family. (341 aa)
MECP2Methyl-CpG-binding protein 2; Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)- containing DNA, with a preference for 5-methylcytosine (5mC). (498 aa)
NCOA2Nuclear receptor coactivator 2; Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required with NCOA1 to control energy balance between white and brown adipose tissues. Critical regulator of glucose metabolism regulation, acts as RORA coactivator to specifically modulate G6PC expression. Involved in the positive regulation of the transcriptional activity of the glucocorticoid receptor NR3C1 by sumoylation enhancer RWDD3. Positively regulates the circadian clock by [...] (1464 aa)
TBL1XR1F-box-like/WD repeat-containing protein TBL1XR1; F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of the N-Cor corepressor complex that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of N-Cor complex, thereby allowing cofactor exchange, and transcription activation; Belongs to the WD repeat EBI family. (514 aa)
BDNFBrain-derived neurotrophic factor; Important signaling molecule that activates signaling cascades downstream of NTRK2. During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentia [...] (329 aa)
RXRARetinoic acid receptor RXR-alpha; Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (RARs) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 to regulate transcription. The high affinity ligand for retinoid X receptors (RXRs) is 9-cis retinoic acid. In the absence of ligand, th [...] (462 aa)
TRHRThyrotropin-releasing hormone receptor; Receptor for thyrotropin-releasing hormone. This receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system; Belongs to the G-protein coupled receptor 1 family. (398 aa)
NR4A1Nuclear receptor subfamily 4 group A member 1; Orphan nuclear receptor. May act concomitantly with NURR1 in regulating the expression of delayed-early genes during liver regeneration. Binds the NGFI-B response element (NBRE) 5'-AAAAGGTCA-3' (By similarity). May inhibit NF-kappa-B transactivation of IL2. Participates in energy homeostasis by sequestrating the kinase STK11 in the nucleus, thereby attenuating cytoplasmic AMPK activation. Plays a role in the vascular response to injury (By similarity). ECO:0000250|UniProtKB:P12813. (652 aa)
TSHRThyrotropin receptor; Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Plays a central role in controlling thyroid cell metabolism (By similarity); Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily. (764 aa)
NCOA4Nuclear receptor coactivator 4; Enhances the androgen receptor transcriptional activity in prostate cancer cells. Ligand-independent coactivator of the peroxisome proliferator-activated receptor (PPAR) gamma. (650 aa)
SLC16A2Monocarboxylate transporter 8; Very active and specific thyroid hormone transporter. Stimulates cellular uptake of thyroxine (T4), triiodothyronine (T3), reverse triiodothyronine (rT3) and diidothyronine. Does not transport Leu, Phe, Trp or Tyr; Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family. (539 aa)
SLC26A4Pendrin; Sodium-independent transporter of chloride and iodide. Belongs to the SLC26A/SulP transporter (TC 2.A.53) family. (780 aa)
PITX2Pituitary homeobox 2; Controls cell proliferation in a tissue-specific manner and is involved in morphogenesis. During embryonic development, exerts a role in the expansion of muscle progenitors. May play a role in the proper localization of asymmetric organs such as the heart and stomach. Isoform PTX2C is involved in left-right asymmetry the developing embryo (By similarity); Belongs to the paired homeobox family. Bicoid subfamily. (324 aa)
CTNNB1Catenin beta-1; Key downstream component of the canonical Wnt signaling pathway. In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an [...] (781 aa)
TBL1XF-box-like/WD repeat-containing protein TBL1X; F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange. (577 aa)
Your Current Organism:
Homo sapiens
NCBI taxonomy Id: 9606
Other names: H. sapiens, human, man
Server load: low (36%) [HD]