Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQVRPMQ)

• DOT Name: Phosphatidylinositol-binding clathrin assembly protein (PICALM)
• Synonyms: Clathrin assembly lymphoid myeloid leukemia protein
• Gene Name: PICALM
• Related Disease:
  Essential tremor
  Non-insulin dependent diabetes
  Acute leukaemia
  Acute lymphocytic leukaemia
  Acute megakaryoblastic leukemia
  Advanced cancer
  Alzheimer disease 3
  Amyloidosis
  Anxiety
  Anxiety disorder
  Arrhythmia
  B-cell lymphoma
  Catecholaminergic polymorphic ventricular tachycardia 1
  Cerebrovascular disease
  Chromosomal disorder
  Familial Alzheimer disease
  Frontotemporal dementia
  Haematological malignancy
  Long QT syndrome
  Lymphoblastic lymphoma
  Lymphoma
  Monocytic leukemia
  Obesity
  Paroxysmal familial ventricular fibrillation
  Progressive supranuclear palsy
  Schizophrenia
  T-cell acute lymphoblastic leukaemia
  Legius syndrome
  leukaemia
  Neurofibromatosis type 1
  Dementia
  Acute myelogenous leukaemia
  Childhood acute lymphoblastic leukemia
  Leukemia
  Myeloid leukaemia
• UniProt ID: PICAL_HUMAN
• Pfam ID: PF07651
• Sequence:
  MSGQSLTDRITAAQHSVTGSAVSKTVCKATTHEIMGPKKKHLDYLIQCTNEMNVNIPQLA
  DSLFERTTNSSWVVVFKSLITTHHLMVYGNERFIQYLASRNTLFNLSNFLDKSGLQGYDM
  STFIRRYSRYLNEKAVSYRQVAFDFTKVKRGADGVMRTMNTEKLLKTVPIIQNQMDALLD
  FNVNSNELTNGVINAAFMLLFKDAIRLFAAYNEGIINLLEKYFDMKKNQCKEGLDIYKKF
  LTRMTRISEFLKVAEQVGIDRGDIPDLSQAPSSLLDALEQHLASLEGKKIKDSTAASRAT
  TLSNAVSSLASTGLSLTKVDEREKQAALEEEQARLKALKEQRLKELAKKPHTSLTTAASP
  VSTSAGGIMTAPAIDIFSTPSSSNSTSKLPNDLLDLQQPTFHPSVHPMSTASQVASTWGD
  PFSATVDAVDDAIPSLNPFLTKSSGDVHLSISSDVSTFTTRTPTHEMFVGFTPSPVAQPH
  PSAGLNVDFESVFGNKSTNVIVDSGGFDELGGLLKPTVASQNQNLPVAKLPPSKLVSDDL
  DSSLANLVGNLGIGNGTTKNDVNWSQPGEKKLTGGSNWQPKVAPTTAWNAATMAPPVMAY
  PATTPTGMIGYGIPPQMGSVPVMTQPTLIYSQPVMRPPNPFGPVSGAQIQFM
• Function: Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly. Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8. In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors. Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF).
• Tissue Specificity: Expressed in all tissues examined.
• Reactome Pathway:
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  RND3 GTPase cycle (R-HSA-9696264)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

35 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Essential tremor	DIS7GBKQ	Definitive	Biomarker	[1]
Non-insulin dependent diabetes	DISK1O5Z	Definitive	Genetic Variation	[2]
Acute leukaemia	DISDQFDI	Strong	Genetic Variation	[3]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[4]
Acute megakaryoblastic leukemia	DIS0JX3M	Strong	Biomarker	[5]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[6]
Alzheimer disease 3	DISVT69G	Strong	Biomarker	[7]
Amyloidosis	DISHTAI2	Strong	Biomarker	[8]
Anxiety	DISIJDBA	Strong	Biomarker	[9]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[10]
Arrhythmia	DISFF2NI	Strong	Biomarker	[11]
B-cell lymphoma	DISIH1YQ	Strong	Biomarker	[3]
Catecholaminergic polymorphic ventricular tachycardia 1	DISKGB3F	Strong	Genetic Variation	[11]
Cerebrovascular disease	DISAB237	Strong	Genetic Variation	[12]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[13]
Familial Alzheimer disease	DISE75U4	Strong	Biomarker	[14]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[12]
Haematological malignancy	DISCDP7W	Strong	Biomarker	[15]
Long QT syndrome	DISMKWS3	Strong	Genetic Variation	[11]
Lymphoblastic lymphoma	DISB9ZYC	Strong	Altered Expression	[16]
Lymphoma	DISN6V4S	Strong	Genetic Variation	[17]
Monocytic leukemia	DIS8M755	Strong	Genetic Variation	[18]
Obesity	DIS47Y1K	Strong	Genetic Variation	[19]
Paroxysmal familial ventricular fibrillation	DISRM7IX	Strong	Biomarker	[11]
Progressive supranuclear palsy	DISO5KRQ	Strong	Genetic Variation	[12]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[20]
T-cell acute lymphoblastic leukaemia	DIS17AI2	Strong	Biomarker	[21]
Legius syndrome	DISO9AOZ	moderate	Biomarker	[22]
leukaemia	DISS7D1V	moderate	Biomarker	[23]
Neurofibromatosis type 1	DIS53JH9	moderate	Biomarker	[22]
Dementia	DISXL1WY	Disputed	Genetic Variation	[12]
Acute myelogenous leukaemia	DISCSPTN	Limited	Biomarker	[24]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Limited	Genetic Variation	[25]
Leukemia	DISNAKFL	Limited	Biomarker	[26]
Myeloid leukaemia	DISMN944	Limited	Genetic Variation	[27]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[28]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[29]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[30]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[31]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[32]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[34]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[35]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[36]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[37]
DNCB	DMDTVYC	Phase 2	DNCB increases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[39]
Eugenol	DM7US1H	Patented	Eugenol increases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[38]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[41]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[42]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[43]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[33]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[40]
Coumarin	DM0N8ZM	Investigative	Coumarin increases the phosphorylation of Phosphatidylinositol-binding clathrin assembly protein (PICALM).	[40]

References

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