Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUOEKY7)

• DOT Name: Prosaposin (PSAP)
• Synonyms: Proactivator polypeptide
• Gene Name: PSAP
• Related Disease:
  Combined PSAP deficiency
  Gaucher disease due to saposin C deficiency
  Krabbe disease due to saposin A deficiency
  Metachromatic leukodystrophy due to saposin B deficiency
  Ovarian neoplasm
  Breast cancer
  Breast carcinoma
  Candidiasis
  Colitis
  Fibrosarcoma
  Frontotemporal dementia
  Gastric cancer
  Gaucher disease
  Glioblastoma multiforme
  Glioma
  Hepatitis B virus infection
  Hepatocellular carcinoma
  HIV infectious disease
  Inflammatory bowel disease
  Lysosomal storage disease
  Metachromatic leukodystrophy
  Metachromatic leukodystrophy, juvenile form
  Metastatic prostate carcinoma
  Neoplasm
  Neuronal ceroid lipofuscinosis
  Parkinson disease
  Progressive multifocal leukoencephalopathy
  Prostate neoplasm
  Psoriasis
  Sphingolipidosis
  Stomach cancer
  Vulvovaginal Candidiasis
  Breast neoplasm
  Castration-resistant prostate carcinoma
  Krabbe disease
  Movement disorder
  Plasma cell myeloma
  Malaria
  Amyotrophic lateral sclerosis
  Gallbladder cancer
  Gallbladder carcinoma
  Oral candidiasis
  Parkinson disease 24, autosomal dominant, susceptibility to
  Prostate cancer
  Prostate carcinoma
• UniProt ID: SAP_HUMAN
• PDB ID: 1M12; 1N69; 1SN6; 2DOB; 2GTG; 2QYP; 2R0R; 2R1Q; 2RB3; 2Z9A; 3BQP; 3BQQ; 4DDJ; 4UEX; 4V2O; 6SLR; 8EQU
• Pfam ID: PF02199 ; PF05184 ; PF03489
• Sequence:
  MYALFLLASLLGAALAGPVLGLKECTRGSAVWCQNVKTASDCGAVKHCLQTVWNKPTVKS
  LPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDI
  IKGEMSRPGEVCSALNLCESLQKHLAELNHQKQLESNKIPELDMTEVVAPFMANIPLLLY
  PQDGPRSKPQPKDNGDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADI
  CKNYISQYSEIAIQMMMHMQPKEICALVGFCDEVKEMPMQTLVPAKVASKNVIPALELVE
  PIKKHEVPAKSDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEV
  VDTYGSSILSILLEEVSPELVCSMLHLCSGTRLPALTVHVTQPKDGGFCEVCKKLVGYLD
  RNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIG
  ACPSAHKPLLGTEKCIWGPSYWCQNTETAAQCNAVEHCKRHVWN
• Function: Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.; Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.; Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).; [Prosaposin]: Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling; Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.
• KEGG Pathway:
  Sphingolipid metabolism (hsa00600)
  Lysosome (hsa04142)
• Reactome Pathway:
  Peptide ligand-binding receptors (R-HSA-375276)
  G alpha (i) signalling events (R-HSA-418594)
  Neutrophil degranulation (R-HSA-6798695)
  Glycosphingolipid catabolism (R-HSA-9840310)
  Platelet degranulation (R-HSA-114608)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Combined PSAP deficiency	DISB6MVK	Definitive	Autosomal recessive	[1]
Gaucher disease due to saposin C deficiency	DISPIVDC	Definitive	Autosomal recessive	[1]
Krabbe disease due to saposin A deficiency	DISK0BQA	Definitive	Autosomal recessive	[2]
Metachromatic leukodystrophy due to saposin B deficiency	DISCWKVO	Definitive	Autosomal recessive	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Candidiasis	DISIRYMU	Strong	Biomarker	[5]
Colitis	DISAF7DD	Strong	Biomarker	[6]
Fibrosarcoma	DISWX7MU	Strong	Biomarker	[7]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Gaucher disease	DISTW5JG	Strong	Biomarker	[10]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[11]
Glioma	DIS5RPEH	Strong	Altered Expression	[11]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[13]
HIV infectious disease	DISO97HC	Strong	Biomarker	[14]
Inflammatory bowel disease	DISGN23E	Strong	Biomarker	[6]
Lysosomal storage disease	DIS6QM6U	Strong	Genetic Variation	[15]
Metachromatic leukodystrophy	DIS3OMWS	Strong	Genetic Variation	[16]
Metachromatic leukodystrophy, juvenile form	DISAI38Z	Strong	GermlineCausalMutation	[17]
Metastatic prostate carcinoma	DISVBEZ9	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Biomarker	[19]
Neuronal ceroid lipofuscinosis	DIS9A4K4	Strong	Biomarker	[20]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[21]
Progressive multifocal leukoencephalopathy	DISX02WS	Strong	Biomarker	[22]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[18]
Psoriasis	DIS59VMN	Strong	Altered Expression	[23]
Sphingolipidosis	DISEC08E	Strong	Genetic Variation	[24]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Vulvovaginal Candidiasis	DISRCR6D	Strong	Biomarker	[25]
Breast neoplasm	DISNGJLM	moderate	Altered Expression	[26]
Castration-resistant prostate carcinoma	DISVGAE6	moderate	Biomarker	[27]
Krabbe disease	DIS6H1IB	moderate	Genetic Variation	[28]
Movement disorder	DISOJJ2D	moderate	CausalMutation	[29]
Plasma cell myeloma	DIS0DFZ0	moderate	Biomarker	[30]
Malaria	DISQ9Y50	Disputed	Genetic Variation	[31]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[32]
Gallbladder cancer	DISXJUAF	Limited	Biomarker	[33]
Gallbladder carcinoma	DISD6ACL	Limited	Biomarker	[33]
Oral candidiasis	DISAVKAH	Limited	Altered Expression	[34]
Parkinson disease 24, autosomal dominant, susceptibility to	DISRD6P5	Limited	Unknown	[35]
Prostate cancer	DISF190Y	Limited	Biomarker	[36]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[36]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Prosaposin (PSAP) affects the response to substance of Methotrexate.	[56]

19 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 Prosaposin (PSAP).	[37]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Prosaposin (PSAP).	[38]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Prosaposin (PSAP).	[39]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Prosaposin (PSAP).	[40]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Prosaposin (PSAP).	[41]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Prosaposin (PSAP).	[42]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Prosaposin (PSAP).	[43]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prosaposin (PSAP).	[44]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Prosaposin (PSAP).	[39]
Selenium	DM25CGV	Approved	Selenium increases the expression of Prosaposin (PSAP).	[45]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Prosaposin (PSAP).	[46]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Prosaposin (PSAP).	[47]
Piroxicam	DMTK234	Approved	Piroxicam decreases the expression of Prosaposin (PSAP).	[48]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Prosaposin (PSAP).	[49]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Prosaposin (PSAP).	[45]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prosaposin (PSAP).	[52]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Prosaposin (PSAP).	[53]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Prosaposin (PSAP).	[54]
PP-242	DM2348V	Investigative	PP-242 increases the expression of Prosaposin (PSAP).	[55]

1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
DNCB	DMDTVYC	Phase 2	DNCB affects the binding of Prosaposin (PSAP).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Prosaposin (PSAP).	[51]

References

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