Target Information
Target General Information | Top | |||||
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Target ID |
T29736
(Former ID: TTDR01057)
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Target Name |
Laminin beta-3 chain (LAMB3)
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Synonyms |
Nicein subunit beta; Laminin5beta3; Laminin-5 subunit beta; Laminin subunit beta-3; Laminin B1k chain; Laminin 5 beta 3; LAMNB1; Kalinin subunit beta; Kalinin B1 chain; Epiligrin subunit bata
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Gene Name |
LAMB3
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Epidermolysis bullosa [ICD-11: EC3Z] | |||||
Function |
Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
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UniProt ID | ||||||
Sequence |
MRPFFLLCFALPGLLHAQQACSRGACYPPVGDLLVGRTRFLRASSTCGLTKPETYCTQYG
EWQMKCCKCDSRQPHNYYSHRVENVASSSGPMRWWQSQNDVNPVSLQLDLDRRFQLQEVM MEFQGPMPAGMLIERSSDFGKTWRVYQYLAADCTSTFPRVRQGRPQSWQDVRCQSLPQRP NARLNGGKVQLNLMDLVSGIPATQSQKIQEVGEITNLRVNFTRLAPVPQRGYHPPSAYYA VSQLRLQGSCFCHGHADRCAPKPGASAGPSTAVQVHDVCVCQHNTAGPNCERCAPFYNNR PWRPAEGQDAHECQRCDCNGHSETCHFDPAVFAASQGAYGGVCDNCRDHTEGKNCERCQL HYFRNRRPGASIQETCISCECDPDGAVPGAPCDPVTGQCVCKEHVQGERCDLCKPGFTGL TYANPQGCHRCDCNILGSRRDMPCDEESGRCLCLPNVVGPKCDQCAPYHWKLASGQGCEP CACDPHNSLSPQCNQFTGQCPCREGFGGLMCSAAAIRQCPDRTYGDVATGCRACDCDFRG TEGPGCDKASGRCLCRPGLTGPRCDQCQRGYCNRYPVCVACHPCFQTYDADLREQALRFG RLRNATASLWSGPGLEDRGLASRILDAKSKIEQIRAVLSSPAVTEQEVAQVASAILSLRR TLQGLQLDLPLEEETLSLPRDLESLDRSFNGLLTMYQRKREQFEKISSADPSGAFRMLST AYEQSAQAAQQVSDSSRLLDQLRDSRREAERLVRQAGGGGGTGSPKLVALRLEMSSLPDL TPTFNKLCGNSRQMACTPISCPGELCPQDNGTACGSRCRGVLPRAGGAFLMAGQVAEQLR GFNAQLQRTRQMIRAAEESASQIQSSAQRLETQVSASRSQMEEDVRRTRLLIQQVRDFLT DPDTDAATIQEVSEAVLALWLPTDSATVLQKMNEIQAIAARLPNVDLVLSQTKQDIARAR RLQAEAEEARSRAHAVEGQVEDVVGNLRQGTVALQEAQDTMQGTSRSLRLIQDRVAEVQQ VLRPAEKLVTSMTKQLGDFWTRMEELRHQARQQGAEAVQAQQLAEGASEQALSAQEGFER IKQKYAELKDRLGQSSMLGEQGARIQSVKTEAEELFGETMEMMDRMKDMELELLRGSQAI MLRSADLTGLEKRVEQIRDHINGRVLYYATCK Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | AlphaFold |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | LAMB3-transduced autologous epidermal stem cells | Drug Info | Phase 1 | Epidermolysis bullosa | [2] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | LAMB3-transduced autologous epidermal stem cells | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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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
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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.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Focal adhesion | hsa04510 | Affiliated Target |
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Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
ECM-receptor interaction | hsa04512 | Affiliated Target |
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Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy |
Degree | 8 | Degree centrality | 8.59E-04 | Betweenness centrality | 3.25E-05 |
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Closeness centrality | 1.99E-01 | Radiality | 1.35E+01 | Clustering coefficient | 5.71E-01 |
Neighborhood connectivity | 2.13E+01 | Topological coefficient | 2.13E-01 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 7 KEGG Pathways | + | ||||
1 | PI3K-Akt signaling pathway | |||||
2 | Focal adhesion | |||||
3 | ECM-receptor interaction | |||||
4 | Toxoplasmosis | |||||
5 | Amoebiasis | |||||
6 | Pathways in cancer | |||||
7 | Small cell lung cancer | |||||
Panther Pathway | [+] 1 Panther Pathways | + | ||||
1 | Integrin signalling pathway | |||||
PID Pathway | [+] 3 PID Pathways | + | ||||
1 | Beta1 integrin cell surface interactions | |||||
2 | Alpha6 beta4 integrin-ligand interactions | |||||
3 | a6b1 and a6b4 Integrin signaling | |||||
Reactome | [+] 5 Reactome Pathways | + | ||||
1 | Degradation of the extracellular matrix | |||||
2 | Assembly of collagen fibrils and other multimeric structures | |||||
3 | Anchoring fibril formation | |||||
4 | Laminin interactions | |||||
5 | Non-integrin membrane-ECM interactions | |||||
WikiPathways | [+] 5 WikiPathways | + | ||||
1 | Focal Adhesion | |||||
2 | Assembly of collagen fibrils and other multimeric structures | |||||
3 | Alpha 6 Beta 4 signaling pathway | |||||
4 | Integrin cell surface interactions | |||||
5 | Cell junction organization |
References | Top | |||||
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REF 1 | Correction of junctional epidermolysis bullosa by transplantation of genetically modified epidermal stem cells. Nat Med. 2006 Dec;12(12):1397-402. | |||||
REF 2 | Long-Term Stability and Safety of Transgenic Cultured Epidermal Stem Cells in Gene Therapy of Junctional Epidermolysis Bullosa. Stem Cell Reports. 2014 January 14; 2(1): 1-8. |
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