Target Information
Target General Information | Top | |||||
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Target ID |
T77594
(Former ID: TTDI02087)
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Target Name |
Endoplasmic reticulum chaperone BiP (HSPA5)
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Synonyms |
Immunoglobulin heavy chainbinding protein; Immunoglobulin heavy chain-binding protein; Heat shock protein family A member 5; Heat shock protein 70 family protein 5; Heat shock 70 kDa protein 5; HSP70 family protein 5; GRP78; GRP-78; Endoplasmic reticulum lumenal Ca(2+)binding protein grp78; Binding-immunoglobulin protein; BiP; 78 kDa glucose-regulated protein
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Gene Name |
HSPA5
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Target Type |
Clinical trial target
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[1] | ||||
Disease | [+] 2 Target-related Diseases | + | ||||
1 | Melanoma [ICD-11: 2C30] | |||||
2 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
Function |
Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate. Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1. Plays an auxiliary role in post-translational transport of small presecretory proteins across endoplasmic reticulum (ER). May function as an allosteric modulator for SEC61 channel-forming translocon complex, likely cooperating with SEC62 to enable the productive insertion of these precursors into SEC61 channel. Appears to specifically regulate translocation of precursors having inhibitory residues in their mature region that weaken channel gating. Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen.
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BioChemical Class |
Acid anhydride hydrolase
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UniProt ID | ||||||
EC Number |
EC 3.6.4.10
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Sequence |
MKLSLVAAMLLLLSAARAEEEDKKEDVGTVVGIDLGTTYSCVGVFKNGRVEIIANDQGNR
ITPSYVAFTPEGERLIGDAAKNQLTSNPENTVFDAKRLIGRTWNDPSVQQDIKFLPFKVV EKKTKPYIQVDIGGGQTKTFAPEEISAMVLTKMKETAEAYLGKKVTHAVVTVPAYFNDAQ RQATKDAGTIAGLNVMRIINEPTAAAIAYGLDKREGEKNILVFDLGGGTFDVSLLTIDNG VFEVVATNGDTHLGGEDFDQRVMEHFIKLYKKKTGKDVRKDNRAVQKLRREVEKAKRALS SQHQARIEIESFYEGEDFSETLTRAKFEELNMDLFRSTMKPVQKVLEDSDLKKSDIDEIV LVGGSTRIPKIQQLVKEFFNGKEPSRGINPDEAVAYGAAVQAGVLSGDQDTGDLVLLDVC PLTLGIETVGGVMTKLIPRNTVVPTKKSQIFSTASDNQPTVTIKVYEGERPLTKDNHLLG TFDLTGIPPAPRGVPQIEVTFEIDVNGILRVTAEDKGTGNKNKITITNDQNRLTPEEIER MVNDAEKFAEEDKKLKERIDTRNELESYAYSLKNQIGDKEKLGGKLSSEDKETMEKAVEE KIEWLESHQDADIEDFKAKKKELEEIVQPIISKLYGSAGPPPTGEEDTAEKDEL Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
ADReCS ID | BADD_A01759 ; BADD_A04698 | |||||
HIT2.0 ID | T54SZZ |
Drugs and Modes of Action | Top | |||||
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Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
1 | IT-139 | Drug Info | Phase 1 | Solid tumour/cancer | [2] | |
2 | NKP-1339 | Drug Info | Phase 1 | Solid tumour/cancer | [3] | |
3 | SAM-6 | Drug Info | Phase 1 | Melanoma | [4] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Inhibitor | [+] 2 Inhibitor drugs | + | ||||
1 | IT-139 | Drug Info | [1] | |||
2 | NKP-1339 | Drug Info | [1] |
Chemical Structure based Activity Landscape of Target | Top |
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Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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KEGG Pathway | [+] 5 KEGG Pathways | + | ||||
1 | Protein export | |||||
2 | Protein processing in endoplasmic reticulum | |||||
3 | Antigen processing and presentation | |||||
4 | Thyroid hormone synthesis | |||||
5 | Prion diseases | |||||
NetPath Pathway | [+] 2 NetPath Pathways | + | ||||
1 | TSH Signaling Pathway | |||||
2 | TCR Signaling Pathway | |||||
Panther Pathway | [+] 2 Panther Pathways | + | ||||
1 | Apoptosis signaling pathway | |||||
2 | Parkinson disease | |||||
Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
1 | Retinol Metabolism | |||||
Reactome | [+] 2 Reactome Pathways | + | ||||
1 | Platelet degranulation | |||||
2 | Regulation of HSF1-mediated heat shock response | |||||
WikiPathways | [+] 6 WikiPathways | + | ||||
1 | MAPK Signaling Pathway | |||||
2 | Apoptosis-related network due to altered Notch3 in ovarian cancer | |||||
3 | Activation of Chaperone Genes by ATF6-alpha | |||||
4 | Parkin-Ubiquitin Proteasomal System pathway | |||||
5 | Unfolded Protein Response | |||||
6 | Response to elevated platelet cytosolic Ca2+ |
References | Top | |||||
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REF 1 | NKP-1339, a first-in-class anticancer drug showing mild side effects and activity in patients suffering from advanced refractory cancer. BMC Pharmacol Toxicol. 2012; 13(Suppl 1): A82. | |||||
REF 2 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800034247) | |||||
REF 3 | ClinicalTrials.gov (NCT01415297) Dose Escalation Study of NKP-1339 to Treat Advanced Solid Tumors. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT01727778) Safety and Preliminary Efficacy Study of the Antibody PAT-SM6 in Patients With Relapsed or Refractory Multiple Myeloma. U.S. National Institutes of Health. | |||||
REF 5 | A new tumor-specific variant of GRP78 as target for antibody-based therapy. Lab Invest. 2008 Apr;88(4):375-86. |
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