Target Information
| Target General Information | Top | |||||
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| Target ID |
T60631
(Former ID: TTDS00348)
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| Target Name |
Proto-oncogene c-Ret (RET)
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| Synonyms |
RET51; RET receptor tyrosine kinase; RET mutant Y791F; RET mutant V804M; RET mutant V804L; RET mutant S891A; RET mutant M918T; RET mutant G691S; Proto-oncogene tyrosine-protein kinase receptor Ret; PTC; Cadherin family member 12; CDHR16; CDHF12; C-ret
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| Gene Name |
RET
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 6 Target-related Diseases | + | ||||
| 1 | Colorectal cancer [ICD-11: 2B91] | |||||
| 2 | Lung cancer [ICD-11: 2C25] | |||||
| 3 | Mature B-cell lymphoma [ICD-11: 2A85] | |||||
| 4 | Solid tumour/cancer [ICD-11: 2A00-2F9Z] | |||||
| 5 | Thrombocytopenia [ICD-11: 3B64] | |||||
| 6 | Thyroid cancer [ICD-11: 2D10] | |||||
| Function |
Phosphorylates PTK2/FAK1. Regulates both cell death/survival balance and positional information. Required for the molecular mechanisms orchestration during intestine organogenesis; involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue. Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e. g. ITGB1 and ITGB3)-dependent manner. Involved in the development of the neural crest. Active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage. Acts as a dependence receptor; in the presence of the ligand GDNF in somatotrophs (within pituitary), promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF. Regulates nociceptor survival and size. Triggers the differentiation of rapidly adapting (RA) mechanoreceptors. Mediator of several diseases such as neuroendocrine cancers; these diseases are characterized by aberrant integrins-regulated cell migration. Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which induces inhibition of food-intake. Activates MAPK- and AKT-signaling pathways. Isoform 1 in complex with GFRAL induces higher activation of MAPK-signaling pathway than isoform 2 in complex with GFRAL. Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.10.1
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| Sequence |
MAKATSGAAGLRLLLLLLLPLLGKVALGLYFSRDAYWEKLYVDQAAGTPLLYVHALRDAP
EEVPSFRLGQHLYGTYRTRLHENNWICIQEDTGLLYLNRSLDHSSWEKLSVRNRGFPLLT VYLKVFLSPTSLREGECQWPGCARVYFSFFNTSFPACSSLKPRELCFPETRPSFRIRENR PPGTFHQFRLLPVQFLCPNISVAYRLLEGEGLPFRCAPDSLEVSTRWALDREQREKYELV AVCTVHAGAREEVVMVPFPVTVYDEDDSAPTFPAGVDTASAVVEFKRKEDTVVATLRVFD ADVVPASGELVRRYTSTLLPGDTWAQQTFRVEHWPNETSVQANGSFVRATVHDYRLVLNR NLSISENRTMQLAVLVNDSDFQGPGAGVLLLHFNVSVLPVSLHLPSTYSLSVSRRARRFA QIGKVCVENCQAFSGINVQYKLHSSGANCSTLGVVTSAEDTSGILFVNDTKALRRPKCAE LHYMVVATDQQTSRQAQAQLLVTVEGSYVAEEAGCPLSCAVSKRRLECEECGGLGSPTGR CEWRQGDGKGITRNFSTCSPSTKTCPDGHCDVVETQDINICPQDCLRGSIVGGHEPGEPR GIKAGYGTCNCFPEEEKCFCEPEDIQDPLCDELCRTVIAAAVLFSFIVSVLLSAFCIHCY HKFAHKPPISSAEMTFRRPAQAFPVSYSSSGARRPSLDSMENQVSVDAFKILEDPKWEFP RKNLVLGKTLGEGEFGKVVKATAFHLKGRAGYTTVAVKMLKENASPSELRDLLSEFNVLK QVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRGFLRESRKVGPGYLGSGGSRNSSSLDH PDERALTMGDLISFAWQISQGMQYLAEMKLVHRDLAARNILVAEGRKMKISDFGLSRDVY EEDSYVKRSQGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIPPERL FNLLKTGHRMERPDNCSEEMYRLMLQCWKQEPDKRPVFADISKDLEKMMVKRRDYLDLAA STPSDSLIYDDGLSEEETPLVDCNNAPLPRALPSTWIENKLYGMSDPNWPGESPVPLTRA DGTNTGFPRYPNDSVYANWMLSPSAAKLMDTFDS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T34WFL | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 6 Approved Drugs | + | ||||
| 1 | Ponatinib | Drug Info | Approved | Acute lymphoblastic leukaemia | [2], [3] | |
| 2 | Pralsetinib | Drug Info | Approved | Non-small-cell lung cancer | [4] | |
| 3 | Regorafenib | Drug Info | Approved | Metastatic colorectal cancer | [3], [5] | |
| 4 | Romiplostim | Drug Info | Approved | Thrombocytopenia | [6], [7] | |
| 5 | Selpercatinib | Drug Info | Approved | Non-small-cell lung cancer | [8] | |
| 6 | Vandetanib | Drug Info | Approved | Solid tumour/cancer | [9], [10] | |
| Clinical Trial Drug(s) | [+] 4 Clinical Trial Drugs | + | ||||
| 1 | MGCD516 | Drug Info | Phase 2/3 | Solid tumour/cancer | [11] | |
| 2 | CEP-32496 | Drug Info | Phase 1/2 | Solid tumour/cancer | [13], [14] | |
| 3 | GSK3179106 | Drug Info | Phase 1 | Inflammatory bowel disease | [17] | |
| 4 | tamatinib | Drug Info | Clinical trial | Solid tumour/cancer | [18] | |
| Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
| 1 | CEP-751 | Drug Info | Terminated | Neurodegenerative disorder | [19] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 2 Modulator drugs | + | ||||
| 1 | Ponatinib | Drug Info | [20] | |||
| 2 | Regorafenib | Drug Info | [20] | |||
| Inhibitor | [+] 44 Inhibitor drugs | + | ||||
| 1 | Pralsetinib | Drug Info | [4] | |||
| 2 | Romiplostim | Drug Info | [1] | |||
| 3 | Selpercatinib | Drug Info | [8] | |||
| 4 | Vandetanib | Drug Info | [21], [22] | |||
| 5 | MGCD516 | Drug Info | [23] | |||
| 6 | MGCD516 | Drug Info | [24] | |||
| 7 | CEP-32496 | Drug Info | [25] | |||
| 8 | GSK3179106 | Drug Info | [17] | |||
| 9 | tamatinib | Drug Info | [18] | |||
| 10 | Benzo(b)carbazol-11-one compound 1 | Drug Info | [26] | |||
| 11 | Benzo(b)carbazol-11-one compound 2 | Drug Info | [26] | |||
| 12 | Carboxamide derivative 4 | Drug Info | [26] | |||
| 13 | Dihydropyridine compound 1 | Drug Info | [26] | |||
| 14 | Dihydropyridine compound 2 | Drug Info | [26] | |||
| 15 | Dihydropyridine compound 4 | Drug Info | [26] | |||
| 16 | Dihydropyridine compound 6 | Drug Info | [26] | |||
| 17 | Pyrazolo[3,4-d]pyrimidine derivative 5 | Drug Info | [26] | |||
| 18 | Pyrazolo[3,4-d]pyrimidine derivative 6 | Drug Info | [26] | |||
| 19 | Pyrazolo[3,4-d]pyrimidine derivative 7 | Drug Info | [26] | |||
| 20 | Pyrazolo[3,4-d]pyrimidine derivative 8 | Drug Info | [26] | |||
| 21 | Pyridine derivative 18 | Drug Info | [26] | |||
| 22 | Pyridine derivative 19 | Drug Info | [26] | |||
| 23 | Pyridine derivative 20 | Drug Info | [26] | |||
| 24 | Pyridine derivative 21 | Drug Info | [26] | |||
| 25 | Pyridine derivative 22 | Drug Info | [26] | |||
| 26 | Pyrrolo-pyridinone derivative 2 | Drug Info | [26] | |||
| 27 | Pyrrolo-pyridinone derivative 3 | Drug Info | [26] | |||
| 28 | Pyrrolo-pyridinone derivative 4 | Drug Info | [26] | |||
| 29 | Pyrrolo-pyrimidine derivative 2 | Drug Info | [26] | |||
| 30 | Pyrrolo-pyrimidine derivative 3 | Drug Info | [26] | |||
| 31 | Pyrrolo-pyrimidine derivative 4 | Drug Info | [26] | |||
| 32 | Pyrrolo-pyrimidine derivative 5 | Drug Info | [26] | |||
| 33 | Pyrrolo-pyrimidine derivative 6 | Drug Info | [26] | |||
| 34 | Quinazoline derivative 14 | Drug Info | [26] | |||
| 35 | Quinazoline derivative 15 | Drug Info | [26] | |||
| 36 | Quinazoline derivative 16 | Drug Info | [26] | |||
| 37 | CEP-751 | Drug Info | [27] | |||
| 38 | (Z)-3-((1H-pyrrol-2-yl)methylene)indolin-2-one | Drug Info | [1] | |||
| 39 | AST-487 | Drug Info | [28] | |||
| 40 | GW-559768X | Drug Info | [23] | |||
| 41 | ITRI-305 | Drug Info | [23] | |||
| 42 | PMID21493067C1d | Drug Info | [29] | |||
| 43 | PMID21561767C8h | Drug Info | [30] | |||
| 44 | TG-100435 | Drug Info | [31] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine | Ligand Info | |||||
| Structure Description | Crystal structure of RET tyrosine kinase domain bound to adenosine | PDB:4CKJ | ||||
| Method | X-ray diffraction | Resolution | 1.65 Å | Mutation | No | [32] |
| PDB Sequence |
GPLSLSVDAF
709 KILEDPKWEF719 PRKNLVLGKT729 LGEGEFGKVV739 KATAFHLKGR749 AGYTTVAVKM 759 LKENASPSEL769 RDLLSEFNVL779 KQVNHPHVIK789 LYGACSQDGP799 LLLIVEYAKY 809 GSLRGFLRES819 RKVRALTMGD850 LISFAWQISQ860 GMQYLAEMKL870 VHRDLAARNI 880 LVAEGRKMKI890 SDFGLSRDVY900 EEDSVKRSQG911 RIPVKWMAIE921 SLFDHIYTTQ 931 SDVWSFGVLL941 WEIVTLGGNP951 YPGIPPERLF961 NLLKTGHRME971 RPDNCSEEMY 981 RLMLQCWKQE991 PDKRPVFADI1001 SKDLEKMMVK1011 RR
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Intedanib | Ligand Info | |||||
| Structure Description | STRUCTURE OF RET PROTEIN TYROSINE KINASE DOMAIN IN COMPLEX WITH NINTEDANIB | PDB:6NEC | ||||
| Method | X-ray diffraction | Resolution | 1.87 Å | Mutation | No | [33] |
| PDB Sequence |
EDPKWEFPRK
722 NLVLGKTLGE732 GEFGKVVKAT742 AFHLKGRAGY752 TTVAVKMLKE762 NASPSELRDL 772 LSEFNVLKQV782 NHPHVIKLYG792 ACSQDGPLLL802 IVEYAKYGSL812 RGFLRESRKV 822 GPGYLGDERA845 LTMGDLISFA855 WQISQGMQYL865 AEMKLVHRDL875 AARNILVAEG 885 RKMKISDFGL895 SRDVYEEDSY905 VKRSQGRIPV915 KWMAIESLFD925 HIYTTQSDVW 935 SFGVLLWEIV945 TLGGNPYPGI955 PPERLFNLLK965 TGHRMERPDN975 CSEEMYRLML 985 QCWKQEPDKR995 PVFADISKDL1005 EKMMVKR
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LYS728
4.582
THR729
3.807
LEU730
3.700
GLY731
3.636
GLU732
4.250
VAL738
3.805
ALA756
3.471
LYS758
2.805
GLU775
3.429
LEU779
3.361
ILE788
3.474
VAL804
3.535
GLU805
2.801
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| 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 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 Pathway Affiliation
Biological Network Descriptors
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Calcium signaling pathway | hsa04020 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Degree | 28 | Degree centrality | 3.01E-03 | Betweenness centrality | 2.35E-03 |
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| Closeness centrality | 2.43E-01 | Radiality | 1.43E+01 | Clustering coefficient | 1.61E-01 |
| Neighborhood connectivity | 4.09E+01 | Topological coefficient | 7.58E-02 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| 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) | ||||||
| Drug Resistance Mutation (DRM) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 4 KEGG Pathways | + | ||||
| 1 | Endocytosis | |||||
| 2 | Pathways in cancer | |||||
| 3 | Thyroid cancer | |||||
| 4 | Central carbon metabolism in cancer | |||||
| PID Pathway | [+] 2 PID Pathways | + | ||||
| 1 | Signaling events regulated by Ret tyrosine kinase | |||||
| 2 | Posttranslational regulation of adherens junction stability and dissassembly | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | SIDS Susceptibility Pathways | |||||
| 2 | Dopaminergic Neurogenesis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors. Bioorg Med Chem. 2010 Feb 15;18(4):1482-96. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5890). | |||||
| REF 3 | Nat Rev Drug Discov. 2013 Feb;12(2):87-90. | |||||
| REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 5 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5891). | |||||
| REF 6 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6974). | |||||
| REF 7 | 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6. | |||||
| REF 8 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020 | |||||
| REF 9 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5717). | |||||
| REF 10 | 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4. | |||||
| REF 11 | ClinicalTrials.gov (NCT04887870) Study of Sitravatinib With or Without Other Anticancer Therapies Receiving Clinical Benefit From Parent Study. U.S. National Institutes of Health. | |||||
| REF 12 | ClinicalTrials.gov (NCT04161391) Study of TPX-0046, A RET/SRC Inhibitor in Adult Subjects With Advanced Solid Tumors Harboring RET Fusions or Mutations. U.S. National Institutes of Health. | |||||
| REF 13 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7880). | |||||
| REF 14 | ClinicalTrials.gov (NCT01877811) CEP-32496 in Patients With Advanced Solid Tumors in Phase 1 and Advanced Melanoma and Metastatic Colorectal Cancer in Phase 2. U.S. National Institutes of Health. | |||||
| REF 15 | ClinicalTrials.gov (NCT03780517) Safety, Efficacy, and Tolerability of BOS172738 in Patients With Advanced Rearranged During Transfection (RET) Gene-Altered Tumors. U.S. National Institutes of Health. | |||||
| REF 16 | Clinical pipeline report, company report or official report of Klus Pharma | |||||
| REF 17 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 18 | Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing. Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):130-6. | |||||
| REF 19 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800008742) | |||||
| REF 20 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 21 | A comparison of physicochemical property profiles of marketed oral drugs and orally bioavailable anti-cancer protein kinase inhibitors in clinical development. Curr Top Med Chem. 2007;7(14):1408-22. | |||||
| REF 22 | Clinical pipeline report, company report or official report of AstraZeneca (2009). | |||||
| REF 23 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2185). | |||||
| REF 24 | Role and relevance of TrkB mutations and expression in non-small cell lung cancer. Clin Cancer Res. 2011 May 1;17(9):2638-45. | |||||
| REF 25 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 26 | RET kinase inhibitors: a review of recent patents (2012-2015).Expert Opin Ther Pat. 2017 Jan;27(1):91-99. | |||||
| REF 27 | CEP-701 and CEP-751 inhibit constitutively activated RET tyrosine kinase activity and block medullary thyroid carcinoma cell growth. Cancer Res. 2003 Sep 1;63(17):5559-63. | |||||
| REF 28 | The RET kinase inhibitor NVP-AST487 blocks growth and calcitonin gene expression through distinct mechanisms in medullary thyroid cancer cells. Cancer Res. 2007 Jul 15;67(14):6956-64. | |||||
| REF 29 | In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg Med Chem Lett. 2011 May 15;21(10):2958-61. | |||||
| REF 30 | Discovery of 5-(arenethynyl) hetero-monocyclic derivatives as potent inhibitors of BCR-ABL including the T315I gatekeeper mutant. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3743-8. | |||||
| REF 31 | Discovery of [7-(2,6-dichlorophenyl)-5-methylbenzo [1,2,4]triazin-3-yl]-[4-(2-pyrrolidin-1-ylethoxy)phenyl]amine--a potent, orally active Src kinas... Bioorg Med Chem Lett. 2007 Feb 1;17(3):602-8. | |||||
| REF 32 | Oncogenic RET kinase domain mutations perturb the autophosphorylation trajectory by enhancing substrate presentation in trans. Mol Cell. 2014 Mar 6;53(5):738-51. | |||||
| REF 33 | Structural basis of resistance of mutant RET protein-tyrosine kinase to its inhibitors nintedanib and vandetanib. J Biol Chem. 2019 Jul 5;294(27):10428-10437. | |||||
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