Target Information
| Target General Information | Top | |||||
|---|---|---|---|---|---|---|
| Target ID |
T57034
(Former ID: TTDI02155)
|
|||||
| Target Name |
Protein tyrosine phosphatase beta (PTPRB)
|
|||||
| Synonyms |
Vascular endothelial protein tyrosine phosphatase; VE-PTP; Receptor-type tyrosine-protein phosphatase beta; R-PTP-beta; PTPRB
Click to Show/Hide
|
|||||
| Gene Name |
PTPRB
|
|||||
| Target Type |
Clinical trial target
|
[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Chronic arterial occlusive disease [ICD-11: BD4Z] | |||||
| 2 | Retinopathy [ICD-11: 9B71] | |||||
| Function |
Plays an important role in blood vessel remodeling and angiogenesis. Not necessary for the initial formation of blood vessels, but is essential for their maintenance and remodeling. Can induce dephosphorylation of TEK/TIE2, CDH5/VE-cadherin and KDR/VEGFR-2. Regulates angiopoietin-TIE2 signaling in endothelial cells. Acts as a negative regulator of TIE2, and controls TIE2 driven endothelial cell proliferation, which in turn affects blood vessel remodeling during embryonic development and determines blood vessel size during perinatal growth. Essential for the maintenance of endothelial cell contact integrity and for the adhesive function of VE-cadherin in endothelial cells and this requires the presence of plakoglobin.
Click to Show/Hide
|
|||||
| BioChemical Class |
Phosphoric monoester hydrolase
|
|||||
| UniProt ID | ||||||
| EC Number |
EC 3.1.3.48
|
|||||
| Sequence |
MLSHGAGLALWITLSLLQTGLAEPERCNFTLAESKASSHSVSIQWRILGSPCNFSLIYSS
DTLGAALCPTFRIDNTTYGCNLQDLQAGTIYNFRIISLDEERTVVLQTDPLPPARFGVSK EKTTSTSLHVWWTPSSGKVTSYEVQLFDENNQKIQGVQIQESTSWNEYTFFNLTAGSKYN IAITAVSGGKRSFSVYTNGSTVPSPVKDIGISTKANSLLISWSHGSGNVERYRLMLMDKG ILVHGGVVDKHATSYAFHGLTPGYLYNLTVMTEAAGLQNYRWKLVRTAPMEVSNLKVTND GSLTSLKVKWQRPPGNVDSYNITLSHKGTIKESRVLAPWITETHFKELVPGRLYQVTVSC VSGELSAQKMAVGRTFPDKVANLEANNNGRMRSLVVSWSPPAGDWEQYRILLFNDSVVLL NITVGKEETQYVMDDTGLVPGRQYEVEVIVESGNLKNSERCQGRTVPLAVLQLRVKHANE TSLSIMWQTPVAEWEKYIISLADRDLLLIHKSLSKDAKEFTFTDLVPGRKYMATVTSISG DLKNSSSVKGRTVPAQVTDLHVANQGMTSSLFTNWTQAQGDVEFYQVLLIHENVVIKNES ISSETSRYSFHSLKSGSLYSVVVTTVSGGISSRQVVVEGRTVPSSVSGVTVNNSGRNDYL SVSWLLAPGDVDNYEVTLSHDGKVVQSLVIAKSVRECSFSSLTPGRLYTVTITTRSGKYE NHSFSQERTVPDKVQGVSVSNSARSDYLRVSWVHATGDFDHYEVTIKNKNNFIQTKSIPK SENECVFVQLVPGRLYSVTVTTKSGQYEANEQGNGRTIPEPVKDLTLRNRSTEDLHVTWS GANGDVDQYEIQLLFNDMKVFPPFHLVNTATEYRFTSLTPGRQYKILVLTISGDVQQSAF IEGFTVPSAVKNIHISPNGATDSLTVNWTPGGGDVDSYTVSAFRHSQKVDSQTIPKHVFE HTFHRLEAGEQYQIMIASVSGSLKNQINVVGRTVPASVQGVIADNAYSSYSLIVSWQKAA GVAERYDILLLTENGILLRNTSEPATTKQHKFEDLTPGKKYKIQILTVSGGLFSKEAQTE GRTVPAAVTDLRITENSTRHLSFRWTASEGELSWYNIFLYNPDGNLQERAQVDPLVQSFS FQNLLQGRMYKMVIVTHSGELSNESFIFGRTVPASVSHLRGSNRNTTDSLWFNWSPASGD FDFYELILYNPNGTKKENWKDKDLTEWRFQGLVPGRKYVLWVVTHSGDLSNKVTAESRTA PSPPSLMSFADIANTSLAITWKGPPDWTDYNDFELQWLPRDALTVFNPYNNRKSEGRIVY GLRPGRSYQFNVKTVSGDSWKTYSKPIFGSVRTKPDKIQNLHCRPQNSTAIACSWIPPDS DFDGYSIECRKMDTQEVEFSRKLEKEKSLLNIMMLVPHKRYLVSIKVQSAGMTSEVVEDS TITMIDRPPPPPPHIRVNEKDVLISKSSINFTVNCSWFSDTNGAVKYFTVVVREADGSDE LKPEQQHPLPSYLEYRHNASIRVYQTNYFASKCAENPNSNSKSFNIKLGAEMESLGGKCD PTQQKFCDGPLKPHTAYRISIRAFTQLFDEDLKEFTKPLYSDTFFSLPITTESEPLFGAI EGVSAGLFLIGMLVAVVALLICRQKVSHGRERPSARLSIRRDRPLSVHLNLGQKGNRKTS CPIKINQFEGHFMKLQADSNYLLSKEYEELKDVGRNQSCDIALLPENRGKNRYNNILPYD ATRVKLSNVDDDPCSDYINASYIPGNNFRREYIVTQGPLPGTKDDFWKMVWEQNVHNIVM VTQCVEKGRVKCDHYWPADQDSLYYGDLILQMLSESVLPEWTIREFKICGEEQLDAHRLI RHFHYTVWPDHGVPETTQSLIQFVRTVRDYINRSPGAGPTVVHCSAGVGRTGTFIALDRI LQQLDSKDSVDIYGAVHDLRLHRVHMVQTECQYVYLHQCVRDVLRARKLRSEQENPLFPI YENVNPEYHRDPVYSRH Click to Show/Hide
|
|||||
| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | AKB-9778 | Drug Info | Phase 2 | Peripheral arterial disease | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | AKB-9778 | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
|---|---|---|---|---|---|---|
| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
|---|---|---|---|---|---|---|
| Ligand Name: N-(Tert-butoxycarbonyl)-L-tyrosyl-N-methyl-4-(sulfoamino)-L-phenylalaninamide | Ligand Info | |||||
| Structure Description | Structural studies of protein tyrosine phosphatase beta catalytic domain in complex with a sulfamic acid (soaking experiment) | PDB:2I4G | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [3] |
| PDB Sequence |
KTSCPIKINQ
1687 FEGHFMKLQA1697 DSNYLLSKEY1707 EELKDVGRNQ1717 SCDIALLPEN1727 RGKNRYNNIL 1737 PYDATRVKLS1747 NVCSDYINAS1761 YIPGNNFRRE1771 YIVTQGPLPG1781 TKDDFWKMVW 1791 EQNVHNIVMV1801 TQCVEKGRVK1811 CDHYWPADQD1821 SLYYGDLILQ1831 MLSESVLPEW 1841 TIREFKICGE1851 EQLDAHRLIR1861 HFHYTVWPDH1871 GVPETTQSLI1881 QFVRTVRDYI 1891 NRSPGAGPTV1901 VHCSAGVGRT1911 GTFIALDRIL1921 QQLDSKDSVD1931 IYGAVHDLRL 1941 HRVHMVQTEC1951 QYVYLHQCVR1961 DVLRARKLR
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: (4-Ethylphenyl)sulfamic acid | Ligand Info | |||||
| Structure Description | Engineering the PTPbeta catalytic domain with improved crystallization properties | PDB:2I5X | ||||
| Method | X-ray diffraction | Resolution | 1.70 Å | Mutation | No | [3] |
| PDB Sequence |
KTSCPIKINQ
1687 FEGHFMKLQA1697 DSNYLLSKEY1707 EELKDVGRNQ1717 SCDIALLPEN1727 RGKNRYNNIL 1737 PYDATRVKLS1747 NPCSDYINAS1761 YIPGNNFRRE1771 YIVTQGPLPG1781 TKDDFWKMVW 1791 EQNVHNIVMV1801 TQCVEKGRVK1811 CDHYWPADQD1821 SLYYGDLILQ1831 MLSESVLPEW 1841 TIREFKICGH1857 RLIRHFHYTV1867 WPDHGVPETT1877 QSLIQFVRTV1887 RDYINRSPGA 1897 GPTVVHCSAG1907 VGRTGTFIAL1917 DRILQQLDSK1927 DSVDIYGAVH1937 DLRLHRVHMV 1947 QTECQYVYLH1957 QCVRDVLRAR1967
|
|||||
|
|
||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
|---|---|
|
Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
|
|
|
Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
|
| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
|---|---|---|---|
| Adherens junction | hsa04520 | Affiliated Target |
|
| Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 3.65E-06 |
|---|---|---|---|---|---|
| Closeness centrality | 1.92E-01 | Radiality | 1.33E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 9.50E+00 | Topological coefficient | 5.00E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
|---|---|
| Target Poor or Non Binders | Top | |||||
|---|---|---|---|---|---|---|
| Target Poor or Non Binders | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | Effects of vascular-endothelial protein tyrosine phosphatase inhibition on breast cancer vasculature and metastatic progression.J Natl Cancer Inst.2013 Aug 21;105(16):1188-201. | |||||
| REF 2 | ClinicalTrials.gov (NCT02387788) Open Label Study to Assess the Efficacy and Safety of AKB-9778 in Subjects With Macular Edema Due to RVO. U.S. National Institutes of Health. | |||||
| REF 3 | Engineering the catalytic domain of human protein tyrosine phosphatase beta for structure-based drug discovery. Acta Crystallogr D Biol Crystallogr. 2006 Dec;62(Pt 12):1435-45. | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.