Targets

Cyclic peptides have a larger area of contact with targets than small-molecule drugs. Therefore, they have higher specificity, target-binding affinity, and fewer side effects.

T00001 Surface glycoproteins (Gn/Gc) 85

Organism :

Protein > Envelope glycoprotein> Surface glycoproteins (Gn/Gc)

Specific function: Peptide ligands that target a specific protein surface can have broad applications as therapeutics by blocking specific protein-protein interactions, such as preventing viral engagement of host cell receptors and thus preventing infection. Phage display libraries provide a powerful and inexpensive tool to identify such peptides. Here, we used selection of a cyclic nonapeptide-bearing phage library to identify peptides capable of binding the transmembrane surface glycoproteins of ANDV, Gn and Gc, and blocking infection in vitro.

T00002 1,3-beta-glucan synthase component FKS1 52

Organism :Aspergillus niger (strain CBS 513.88 / FGSC A1513)

Protein > Synthase> 1,3-beta-glucan synthase component FKS1

General function: 1,3-beta-d-glucan synthase activity

Specific function: Catalytic subunit of the 1,3-beta-glucan synthase. Synthesizes 1,3-beta-glucan, a major structural component of the cell wall. Involved in cell wall synthesis, maintenance and cell wall remodeling (By similarity).

Uniprot: A2QLK4

T00003 Somatostatin receptor type 2 8

Organism :Homo sapiens(Human)

Protein > Somatostatin receptor> Somatostatin receptor type 2

General function: Somatostatin receptor activity

Specific function: Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.

Uniprot: P30874 PDB: 7T10 7T11 7T10 7UL5 7T10 7T11 7T10 7WIC 7T10 7T11 7T10 7UL5 7T10 7T11 7T10

T00004 Somatostatin receptor type 5 6

Organism :Homo sapiens(Human)

Protein > Somatostatin receptor> Somatostatin receptor type 5

General function: Somatostatin receptor activity

Specific function: Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition activity of SSTR2 following heterodimerization.

Uniprot: P35346

T00005 Bacterial outer membrane 4

Organism :Bacteria

Group > Membrane> Bacterial outer membrane

T00006 Chitinase B 4

Organism :Serratia marcescens

Protein > Chitinase> Chitinase B

General function: Chitinase activity

Uniprot: P11797 PDB: 1E6N 1GOI 1E6N 1H0G 1E6N 1GOI 1E6N 1H0I 1E6N 1GOI 1E6N 1H0G 1E6N 1GOI 1E6N

T00007 Somatostatin receptor type 1 4

Organism :Homo sapiens(Human)

Protein > Somatostatin receptor> Somatostatin receptor type 1

General function: Somatostatin receptor activity

Specific function: Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.

Uniprot: P30872

T00008 Somatostatin receptor type 3 4

Organism :Homo sapiens(Human)

Protein > Somatostatin receptor> Somatostatin receptor type 3

General function: Somatostatin receptor activity

Specific function: Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase.

Uniprot: P32745

T00009 Chitinase 3

Organism :Serratia marcescens

Protein > Chitinase> Chitinase

General function: Chitinase activity

Uniprot: Q54276 PDB: 1E15 1E6P 1E15 1E6R 1E15 1E6P 1E15 1E6Z 1E15 1E6P 1E15 1E6R 1E15 1E6P 1E15

T00010 Follicle-stimulating hormone receptor 3

Organism :Homo sapiens(Human)

Protein > Hormone receptor> Follicle-stimulating hormone receptor

General function: G-protein coupled peptide receptor activity

Specific function: Receptor for follicle-stimulating hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Induces cAMP production through the activation of PI3K-AKT and SRC-ERK1/2 signaling pathways.

Uniprot: P23945 PDB: 1XWD 4AY9 1XWD 4MQW 1XWD 4AY9 1XWD 8I2G 1XWD 4AY9 1XWD 4MQW 1XWD 4AY9 1XWD

T00011 Liposomes 3

Organism :Unknown

Cell component> Liposomes

T00012 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA 2

Organism :Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)

Protein > Methyltransferase> 16S/23S rRNA (cytidine-2'-O)-methyltransferase TlyA

General function: Rna binding

Specific function: Acts as a host evasion factor, that significantly contributes to the pathogenesis of M.tuberculosis by modulating adaptive immune responses by inhibiting host-protective Th1 and Th17 cytokine responses as well as autophagy (PubMed:25847237). Catalyzes the 2'-O-methylation at nucleotides C1409 in 16S rRNA and C1920 in 23S rRNA (PubMed:16857584, PubMed:20854656). Is likely involved in ribosomal biogenesis (PubMed:21443791). Also exhibits hemolytic activity in vitro, by binding with and oligomerizing into host cell membranes (PubMed:20854656, PubMed:9611795).

Uniprot: P9WJ63 PDB: 5KS2 5KYG 5KS2

T00013 Alpha-2-macroglobulin 2

Organism :Homo sapiens(Human)

Protein> Alpha-2-macroglobulin

General function: Tumor necrosis factor binding

Specific function: Is able to inhibit all four classes of proteinases by a unique 'trapping' mechanism. This protein has a peptide stretch, called the 'bait region' which contains specific cleavage sites for different proteinases. When a proteinase cleaves the bait region, a conformational change is induced in the protein which traps the proteinase. The entrapped enzyme remains active against low molecular weight substrates (activity against high molecular weight substrates is greatly reduced). Following cleavage in the bait region a thioester bond is hydrolyzed and mediates the covalent binding of the protein to the proteinase.

Uniprot: P01023 PDB: 1BV8 2P9R 1BV8 6TAV 1BV8 2P9R 1BV8 7O7L 1BV8 2P9R 1BV8 6TAV 1BV8 2P9R 1BV8

T00014 C55-isoprenyl pyrophosphate 2

Organism :Gram positive and gram negative bacteria

Small molecule> C55-isoprenyl pyrophosphate

T00015 Calcineurin subunit B type 2 2

Organism :Homo sapiens(Human)

Protein > Calcineurin b homologous proteins> Calcineurin subunit B type 2

General function: Calcium ion binding

Specific function: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity (By similarity).

Uniprot: Q96LZ3

T00016 Calcium signal-modulating cyclophilin ligand 2

Organism :Homo sapiens(Human)

Protein> Calcium signal-modulating cyclophilin ligand

General function: Likely involved in the mobilization of calcium as a result of the TCR/CD3 complex interaction. Binds to cyclophilin B.

Specific function: Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (PubMed:23041287, PubMed:24392163, PubMed:27226539). Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol (PubMed:23041287, PubMed:24392163, PubMed:27226539). Required for the stability of GET1 (PubMed:32187542). Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium (PubMed:7522304). Essential for the survival of peripheral follicular B cells (By similarity)

Uniprot: P49069 PDB: 6SO5

T00017 DNA 2

Organism :Homo sapiens(Human)

Nucleotide > DNA> DNA

T00018 DNA topoisomerase 1 2

Organism :Homo sapiens(Human)

Protein > DNA topoisomerase> DNA topoisomerase 1

General function: Poly(a) rna binding

Specific function: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.

Uniprot: P11387 PDB: 1A31 1A35 1A31 1A36 1A31 1A35 1A31 1EJ9 1A31 1A35 1A31 1A36 1A31 1A35 1A31

T00019 DNA topoisomerase 2 2

Organism :Homo sapiens(Human)

Protein group > DNA topoisomerase> DNA topoisomerase 2

General function: Ubiquitin binding

Specific function: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segr...

Uniprot: P11388 PDB: 1ZXM 1ZXN 1ZXM 4FM9 1ZXM 1ZXN 1ZXM 4R1F 1ZXM 1ZXN 1ZXM 4FM9 1ZXM 1ZXN 1ZXM

T00020 Insulin-degrading enzyme 2

Organism :Homo sapiens(Human)

Protein > Metalloproteinase> Insulin-degrading enzyme

General function: Zinc ion binding

Specific function: Plays a role in the cellular breakdown of insulin, IAPP, glucagon, bradykinin, kallidin and other peptides, and thereby plays a role in intercellular peptide signaling. Degrades amyloid formed by APP and IAPP. May play a role in the degradation and clearance of naturally secreted amyloid beta-protein by neurons and microglia.(Microbial infection) The membrane-associated isoform acts as an entry receptor for varicella-zoster virus (VZV).

Uniprot: P14735 PDB: 2G47 2G48 2G47 2G49 2G47 2G48 2G47 2G54 2G47 2G48 2G47 2G49 2G47 2G48 2G47

T00021 Somatostatin receptor type 4 2

Organism :Homo sapiens(Human)

Protein > Somatostatin receptor> Somatostatin receptor type 4

General function: Neuropeptide binding

Specific function: Receptor for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibits adenylyl cyclase. It is functionally coupled not only to inhibition of adenylate cyclase, but also to activation of both arachidonate release and mitogen-activated protein (MAP) kinase cascade. Mediates antiproliferative action of somatostatin in tumor cells.

Uniprot: P31391 PDB: 7XMS 7XMT 7XMS

T00022 Streptogramin A acetyltransferase 2

Organism :Enterococcus faecium

Protein > Acetyltransferase> Streptogramin A acetyltransferase

General function: Transferase activity, transferring acyl groups

Specific function: Inactivates the A compounds of streptogramin antibiotics by acetylation, thus providing resistance to these antibiotics.

Uniprot: P50870 PDB: 1KHR 1KK4 1KHR 1KK5 1KHR 1KK4 1KHR 1KK6 1KHR 1KK4 1KHR 1KK5 1KHR 1KK4 1KHR

T00023 1,3-beta-glucan synthase component GSC2 1

Organism :Baker's yeast

Protein > Synthase> 1,3-beta-glucan synthase component GSC2

General function: 1,3-beta-d-glucan synthase activity

Specific function: Alternate catalytic subunit of the 1,3-beta-glucan synthase (GS). Synthesizes 1,3-beta-glucan, a major structural component of the yeast cell wall. Required for spore wall assembly. Negative regulation of activity by SMK1 is important for spore wall deposition. Activity is positively regulated by RHO1.

Uniprot: P40989

T00024 23S ribosomal RNA 1

Organism :Enteric bacteria and other eubacteria

Nucleotide > RNA> 23S ribosomal RNA

T00025 50S ribosomal protein L10 1

Organism :Shigella flexneri

Protein > Ribosomal protein> 50S ribosomal protein L10

General function: Structural constituent of ribosome

Specific function: Protein L10 is also a translational repressor protein. It controls the translation of the rplJL-rpoBC operon by binding to its mRNA (By similarity).Forms part of the ribosomal stalk, playing a central role in the interaction of the ribosome with GTP-bound translation factors.

Uniprot: P0A7J6

T00026 50S ribosomal protein L22 1

Organism :Escherichia coli O157:H7

Protein > Ribosomal protein> 50S ribosomal protein L22

General function: Structural constituent of ribosome

Specific function: This protein binds specifically to 23S rRNA; its binding is stimulated by other ribosomal proteins, e.g. L4, L17, and L20. It is important during the early stages of 50S assembly. It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (By similarity).The globular domain of the protein is located near the polypeptide exit tunnel on the outside of the subunit, while an extended beta-hairpin is found that lines the wall of the exit tunnel in the center of the 70S ribosome.

Uniprot: P61177

T00027 60S ribosomal protein L37 1

Organism :Homo sapiens(Human)

Protein > Ribosomal protein> 60S ribosomal protein L37

General function: Structural constituent of ribosome

Specific function: Binds to the 23S rRNA.

Uniprot: P61927 PDB: 4UG0 4V6X 4UG0 5AJ0 4UG0 4V6X 4UG0 5LKS 4UG0 4V6X 4UG0 5AJ0 4UG0 4V6X 4UG0

T00028 Atrial natriuretic peptide receptor 1 1

Organism :Homo sapiens(Human)

Protein > Natriuretic peptide receptor> Atrial natriuretic peptide receptor 1

General function: Protein kinase activity

Specific function: Receptor for the atrial natriuretic peptide NPPA/ANP and the brain natriuretic peptide NPPB/BNP which are potent vasoactive hormones playing a key role in cardiovascular homeostasis. Has guanylate cyclase activity upon binding of the ligand.

Uniprot: P16066

T00029 B-lymphocyte antigen CD20 1

Organism :Homo sapiens(Human)

Protein > Membrane protein> B-lymphocyte antigen CD20

General function: Mhc class ii protein complex binding

Specific function: in this study we analyzed the ability of C2H7 to bind the same 25-mer peptide used for the structural analysis of Rituximab specificity. After confirmation of the relatively strong binding of C2H7 to the peptide, we determined the crystal structure of the C2H7 Fab in complex with the peptide to reveal the details of C2H7 binding with the possible epitope region of CD20. The results not only reveal the molecular basis for the fine specificity of C2H7 to CD20 but also provide useful hints for further development of 2H7 derived mAb drugs.

Uniprot: P11836 PDB: 3BKY

T00030 Calcineurin subunit B type 1 1

Organism :Homo sapiens(Human)

Protein > Calcineurin b homologous proteins> Calcineurin subunit B type 1

General function: Protein domain specific binding

Specific function: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.

Uniprot: P63098 PDB: 1AUI 1M63 1AUI 1MF8 1AUI 1M63 1AUI 2P6B 1AUI 1M63 1AUI 1MF8 1AUI 1M63 1AUI

T00031 Calcitonin receptor 1

Organism :Homo sapiens(Human)

Protein > Calcitonin receptor> Calcitonin receptor

General function: Receptor activity

Specific function: This is a receptor for calcitonin. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The calcitonin receptor is thought to couple to the heterotrimeric guanosine triphosphate-binding protein that is sensitive to cholera toxin.

Uniprot: P30988 PDB: 5II0 5UZ7 5II0 6NIY 5II0 5UZ7 5II0 6PFO 5II0 5UZ7 5II0 6NIY 5II0 5UZ7 5II0

T00032 Carboxypeptidase A1 1

Organism :Homo sapiens(Human)

Protein > Hydrolase> Carboxypeptidase A1

General function: Zinc ion binding

Specific function: Carboxypeptidase that catalyzes the release of a C-terminal amino acid, but has little or no action with -Asp, -Glu, -Arg, -Lys or -Pro.

Uniprot: P15085 PDB: 2V77 3FJU 2V77 4UEE 2V77 3FJU 2V77 4UEZ 2V77 3FJU 2V77 4UEE 2V77 3FJU 2V77

T00033 Chitotriosidase-1 1

Organism :Homo sapiens(Human)

Protein > Hydrolase> Chitotriosidase-1

General function: Endochitinase activity

Specific function: Degrades chitin, chitotriose and chitobiose. May participate in the defense against nematodes and other pathogens. Isoform 3 has no enzymatic activity.

Uniprot: Q13231 PDB: 1GUV 1HKI 1GUV 1HKJ 1GUV 1HKI 1GUV 1HKK 1GUV 1HKI 1GUV 1HKJ 1GUV 1HKI 1GUV

T00034 Elongation factor 1-alpha 2 1

Organism :Homo sapiens(Human)

Protein> Elongation factor 1-alpha 2

General function: Gtp binding

Specific function: This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.

Uniprot: Q05639 PDB: 3C5J 8B6Z 3C5J

T00035 Heat-stable enterotoxin receptor 1

Organism :Homo sapiens(Human)

Protein > Enterotoxin receptor> Heat-stable enterotoxin receptor

General function: Toxic substance binding

Specific function: Receptor for the E.coli heat-stable enterotoxin (E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GC-C). Also activated by the endogenous peptides guanylin and uroguanylin.

Uniprot: P25092

T00036 HER2(Human epidermal growth factor receptor 2) 1

Organism :Homo sapiens(Human), Camelus dromedarius

Protein > Growth factor receptor> HER2(Human epidermal growth factor receptor 2)

General function: Ubiquitin protein ligase binding

Specific function: This modified phage transduced HER2-expressing cells with very high specificity (more than 1000-fold that of parental HER2-negative cells) and with an efficiency comparable to that of chemical transfection protocols.

Uniprot: P04626 PDB: 5MY6

T00037 Histone deacetylase 1

Organism :Homo sapiens(Human)

Protein group > Histone deacetylase> Histone deacetylase

General function: Transcription regulatory region sequence-specific dna binding

Uniprot: Q13547 PDB: 4BKX 5ICN 4BKX 6Z2J 4BKX 5ICN 4BKX 6Z2K 4BKX 5ICN 4BKX 6Z2J 4BKX 5ICN 4BKX

T00038 Histone deacetylase 1 1

Organism :Homo sapiens(Human)

Protein > Histone deacetylase> Histone deacetylase 1

General function: Transcription regulatory region sequence-specific dna binding

Specific function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). 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. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation.

Uniprot: Q13547 PDB: 4BKX 5ICN 4BKX 6Z2J 4BKX 5ICN 4BKX 6Z2K 4BKX 5ICN 4BKX 6Z2J 4BKX 5ICN 4BKX

T00039 Histone deacetylase 2 1

Organism :Homo sapiens(Human)

Protein > Histone deacetylase> Histone deacetylase 2

General function: Transcription factor binding

Specific function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). 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. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A.

Uniprot: Q92769 PDB: 3MAX 4LXZ 3MAX 4LY1 3MAX 4LXZ 3MAX 5IWG 3MAX 4LXZ 3MAX 4LY1 3MAX 4LXZ 3MAX

T00040 Histone deacetylase 4 1

Organism :Homo sapiens(Human)

Protein > Histone deacetylase> Histone deacetylase 4

General function: Zinc ion binding

Uniprot: P56524 PDB: 2H8N 2O94 2H8N 2VQJ 2H8N 2O94 2H8N 2VQM 2H8N 2O94 2H8N 2VQJ 2H8N 2O94 2H8N

T00041 Histone deacetylase 6 1

Organism :Homo sapiens(Human)

Protein > Histone deacetylase> Histone deacetylase 6

General function: Zinc ion binding

Specific function: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). 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 (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy.

Uniprot: Q9UBN7 PDB: 3C5K 3GV4 3C5K 3PHD 3C5K 3GV4 3C5K 5B8D 3C5K 3GV4 3C5K 3PHD 3C5K 3GV4 3C5K

T00042 Insulin receptor 1

Organism :Homo sapiens(Human)

Protein > Insulin receptor> Insulin receptor

General function: Receptor signaling protein tyrosine kinase activity

Specific function: Receptor tyrosine kinase which mediates the pleiotropic actions of insulin. Binding of insulin leads to phosphorylation of several intracellular substrates, including, insulin receptor substrates (IRS1, 2, 3, 4), SHC, GAB1, CBL and other signaling intermediates. Each of these phosphorylated proteins serve as docking proteins for other signaling proteins that contain Src-homology-2 domains (SH2 domain) that specifically recognize different phosphotyrosines residues, including the p85 regulatory subunit of PI3K and SHP2. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway, which is responsible for most of the metabolic actions of insulin, and the Ras-MAPK pathway, which regulates expression of some genes and cooperates with the PI3K pathway to control cell growth and differentiation. Binding of the SH2 domains of PI3K to phosphotyrosines on IRS1 leads to the activation of PI3K and the generation of phosphatidylinositol-(3, 4, 5)-triphosphate (PIP3), a lipid second messenger, which activates several PIP3-dependent serine/threonine kinases, such as PDPK1 and subsequently AKT/PKB. The net effect of this pathway is to produce a translocation of the glucose transporter SLC2A4/GLUT4 from cytoplasmic vesicles to the cell membrane to facilitate glucose transport. Moreover, upon insulin stimulation, activated AKT/PKB is responsible for: anti-apoptotic effect of insulin by inducing phosphorylation of BAD; regulates the expression of gluconeogenic and lipogenic enzymes by controlling the activity of the winged helix or forkhead (FOX) class of transcription factors. Another pathway regulated by PI3K-AKT/PKB activation is mTORC1 signaling pathway which regulates cell growth and metabolism and integrates signals from insulin. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 thereby activating mTORC1 pathway. The Ras/RAF/MAP2K/MAPK pathway is mainly involved in mediating cell growth, survival and cellular differentiation of insulin. Phosphorylated IRS1 recruits GRB2/SOS complex, which triggers the activation of the Ras/RAF/MAP2K/MAPK pathway. In addition to binding insulin, the insulin receptor can bind insulin-like growth factors (IGFI and IGFII). Isoform Short has a higher affinity for IGFII binding. When present in a hybrid receptor with IGF1R, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.

Uniprot: P06213 PDB: 1GAG 1I44 1GAG 1IR3 1GAG 1I44 1GAG 1IRK 1GAG 1I44 1GAG 1IR3 1GAG 1I44 1GAG

T00043 Insulin-like growth factor 1 receptor 1

Organism :Homo sapiens(Human)

Protein > Growth factor receptor> Insulin-like growth factor 1 receptor

General function: Protein tyrosine kinase activity

Specific function: Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R.When present in a hybrid receptor with INSR, binds IGF1. PubMed:12138094 shows that hybrid receptors composed of IGF1R and INSR isoform Long are activated with a high affinity by IGF1, with low affinity by IGF2 and not significantly activated by insulin, and that hybrid receptors composed of IGF1R and INSR isoform Short are activated by IGF1, IGF2 and insulin. In contrast, PubMed:16831875 shows that hybrid receptors composed of IGF1R and INSR isoform Long and hybrid receptors composed of IGF1R and INSR isoform Short have similar binding characteristics, both bind IGF1 and have a low affinity for insulin.

Uniprot: P08069 PDB: 1IGR 1JQH 1IGR 1K3A 1IGR 1JQH 1IGR 1M7N 1IGR 1JQH 1IGR 1K3A 1IGR 1JQH 1IGR

T00044 Integrin beta-3 1

Organism :Homo sapiens(Human)

Protein > Membrane protein> Integrin beta-3

General function: Virus receptor activity

Specific function: Integrin alpha-V/beta-3 (ITGAV:ITGB3) is a receptor for cytotactin, fibronectin, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, vitronectin and von Willebrand factor. Integrin alpha-IIb/beta-3 (ITGA2B:ITGB3) is a receptor for fibronectin, fibrinogen, plasminogen, prothrombin, thrombospondin and vitronectin. Integrins alpha-IIb/beta-3 and alpha-V/beta-3 recognize the sequence R-G-D in a wide array of ligands. Integrin alpha-IIb/beta-3 recognizes the sequence H-H-L-G-G-G-A-K-Q-A-G-D-V in fibrinogen gamma chain. Following activation integrin alpha-IIb/beta-3 brings about platelet/platelet interaction through binding of soluble fibrinogen. This step leads to rapid platelet aggregation which physically plugs ruptured endothelial surface. Fibrinogen binding enhances SELP expression in activated platelets (By similarity).(Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for herpes virus 8/HHV-8 (PubMed:18045938). Integrin ITGAV:ITGB3 acts as a receptor for coxsackievirus A9 (PubMed:7519807). Acts as a receptor for Hantaan virus (PubMed:9618541). Integrin ITGAV:ITGB3 acts as a receptor for cytomegalovirus/HHV-5 (PubMed:15834425). Integrin ITGA5:ITGB3 acts as a receptor for human metapneumovirus (PubMed:24478423). Integrin ITGAV:ITGB3 acts aP05556s a receptor for human parechovirus 1 (PubMed:11160695). Integrin ITGAV:ITGB3 acts as a receptor for west nile virus (PubMed:23658209). In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions (PubMed:10397733).

Uniprot: P05106 PDB: 1JV2 1KUP 1JV2 1KUZ 1JV2 1KUP 1JV2 1L5G 1JV2 1KUP 1JV2 1KUZ 1JV2 1KUP 1JV2

T00045 Iron(3+)-hydroxamate-binding protein FhuD 1

Organism :Escherichia coli (strain K12)

Protein> Iron(3+)-hydroxamate-binding protein FhuD

Specific function: Part of the ABC transporter complex FhuCDB involved in iron(3+)-hydroxamate import. Binds the iron(3+)-hydroxamate complex and transfers it to the membrane-bound permease. Required for the transport of all iron(3+)-hydroxamate siderophores such as ferrichrome, gallichrome, desferrioxamine, coprogen, aerobactin, shizokinen, rhodotorulic acid and the antibiotic albomycin.

Uniprot: P07822 PDB: 1EFD 1ESZ 1EFD 1K2V 1EFD 1ESZ 1EFD 1K7S 1EFD 1ESZ 1EFD 1K2V 1EFD 1ESZ 1EFD

T00046 Multidrug resistance-associated protein 1 1

Organism :Homo sapiens(Human)

Protein > Membrane protein> Multidrug resistance-associated protein 1

General function: Transporter activity

Specific function: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency.

Uniprot: P33527 PDB: 2CBZ 4C3Z 2CBZ

T00047 Mycocyclosin synthase 1

Organism :Mycobacterium tuberculosis

Protein > Synthase> Mycocyclosin synthase

General function: Carbon monoxide binding

Specific function: Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate.

Uniprot: P9WPP7 PDB: 1N40 1N4G 1N40 2IJ5 1N40 1N4G 1N40 2IJ7 1N40 1N4G 1N40 2IJ5 1N40 1N4G 1N40

T00048 Neurokinin 1 receptor 1

Organism :Homo sapiens(Human)

Protein > Neuropeptide receptor> Neurokinin 1 receptor

General function: Tachykinin receptor activity

Specific function: This is a receptor for the tachykinin neuropeptide substance P. It is probably associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance P > substance K > neuromedin-K.

Uniprot: P25103 PDB: 2KS9 2KSA 2KS9 2KSB 2KS9 2KSA 2KS9 6E59 2KS9 2KSA 2KS9 2KSB 2KS9 2KSA 2KS9

T00049 Peptidyl-prolyl cis-trans isomerase A 1

Organism :Homo sapiens(Human)

Protein > Peptidyl-prolyl isomerase> Peptidyl-prolyl cis-trans isomerase A

General function: Virion binding

Specific function: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.

Uniprot: P62937 PDB: 1AK4 1AWQ 1AK4 1AWR 1AK4 1AWQ 1AK4 1AWS 1AK4 1AWQ 1AK4 1AWR 1AK4 1AWQ 1AK4

T00050 Peptidyl-prolyl cis-trans isomerase F 1

Organism :Homo sapiens(Human)

Protein > Peptidyl-prolyl isomerase> Peptidyl-prolyl cis-trans isomerase F

General function: Peptidyl-prolyl cis-trans isomerase activity

Specific function: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Involved in regulation of the mitochondrial permeability transition pore (mPTP). It is proposed that its association with the mPTP is masking a binding site for inhibiting inorganic phosphate (Pi) and promotes the open probability of the mPTP leading to apoptosis or necrosis; the requirement of the PPIase activity for this function is debated. In cooperation with mitochondrial TP53 is involved in activating oxidative stress-induced necrosis. Involved in modulation of mitochondrial membrane F(1)F(0) ATP synthase activity and regulation of mitochondrial matrix adenine nucleotide levels. Has anti-apoptotic activity independently of mPTP and in cooperation with BCL2 inhibits cytochrome c-dependent apoptosis.

Uniprot: P30405 PDB: 2BIT 2BIU 2BIT 2Z6W 2BIT 2BIU 2BIT 3QYU 2BIT 2BIU 2BIT 2Z6W 2BIT 2BIU 2BIT

T00051 Prothrombin 1

Organism :Homo sapiens(Human)

Protein> Prothrombin

General function: Thrombospondin receptor activity

Specific function: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.

Uniprot: P00734 PDB: 1A2C 1A3B 1A2C 1A3E 1A2C 1A3B 1A2C 1A46 1A2C 1A3B 1A2C 1A3E 1A2C 1A3B 1A2C

T00052 Serine/threonine-protein phosphatase PP1-gamma catalytic subunit 1

Organism :Homo sapiens(Human)

Protein > Phosphatase> Serine/threonine-protein phosphatase PP1-gamma catalytic subunit

General function: Protein serine/threonine phosphatase activity

Specific function: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).

Uniprot: P36873 PDB: 1IT6 1JK7 1IT6 1U32 1IT6 1JK7 1IT6 2BCD 1IT6 1JK7 1IT6 1U32 1IT6 1JK7 1IT6

T00053 SH2 domain of Grb2(1) 1

Organism :Homo sapiens(Human)

Protein > Protein domain> SH2 domain of Grb2(1)

General function: Sh3/sh2 adaptor activity

Specific function: The growth factor receptor-binding (Grb2) adaptor protein plays a central role in signaling by receptor tyrosine kinases. Grb2 is necessary for activation of the Ras pathway via complex formation with the Ras exchange factor Sos. 2 The Src homology (SH2) domain of Grb2 binds preferentially to phosphotyrosines (Y*s) with the sequence motif Y*XNX. The two SH3 domains of Grb2 bind to Sos, which catalyzes GTP/GDP exchange on Ras, thereby activating the GTPase and downstream kinase cascade.

Uniprot: P62993 PDB: 1BM2 1BMB

T00054 Somatostatin receptor 1

Organism :Homo sapiens(Human)

Group > Somatostatin receptor> Somatostatin receptor

T00055 Trypsin-1 1

Organism :Homo sapiens(Human)

Protein > Hydrolase> Trypsin-1

General function: Serine-type endopeptidase activity

Specific function: Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.

Uniprot: P07477 PDB: 1FXY 1TRN 1FXY 2RA3 1FXY 1TRN 1FXY 4WWY 1FXY 1TRN 1FXY 2RA3 1FXY 1TRN 1FXY

T00056 Voltage-dependent N-type calcium channel 1

Organism :Homo sapiens(Human)

Protein group > Membrane protein> Voltage-dependent N-type calcium channel

General function: Voltage-gated calcium channel activity

Specific function: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents.

Uniprot: A0A024R8I1

T00057 Opioid receptor delta (oprd1) 1

Organism :Homo sapiens(Human)

Protein> Opioid receptor delta (oprd1)

General function: G-protein coupled receptor

Specific function: G-protein coupled receptor that functions as receptor for endogenous enkephalins and for a subset of other opioids. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain and in opiate-mediated analgesia. Plays a role in developing analgesic tolerance to morphine.

Uniprot: P41143 PDB: 4N6H 4RWA 4RWD 6PT2 6PT3 8F7S

T00058 Opioid receptor mu (mop) 1

Organism :Homo sapiens(Human)

Protein> Opioid receptor mu (mop)

General function: G-protein coupled receptor

Specific function: Receptor for endogenous opioids such as beta-endorphin and endomorphin

Uniprot: P35372 PDB: 8EF5 8EF6 8EFB 8EFL 8EFO 8EFQ 8F7Q 8F7R

T00059 Subtilisin/kexin-like protease PC9 1

Organism :Homo sapiens(Human)

Protein > Proprotein convertase> Subtilisin/kexin-like protease PC9

General function: regulation of plasma cholesterol homeostasis

Specific function: Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway.

Uniprot: Q8NBP7 PDB: 2P4E 2PMW