PSAP（prosaposin）是一種天然存在于體內(nèi)的神經(jīng)活性脂質(zhì)分解酵素前體，具有抗炎、神經(jīng)保護和骨代謝調(diào)節(jié)等多種生物學功能。最新研究表明，PSAP與各種人類疾病的發(fā)生、發(fā)展密切相關(guān)，例如神經(jīng)系統(tǒng)疾病、骨質(zhì)疏松、腫瘤等。

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).; 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.

1. Accumulating evidence suggests that PGRN is essential for proper lysosomal function, but the precise mechanisms involved are not known. Here, we show that PGRN facilitates neuronal uptake and lysosomal delivery of prosaposin (PSAP), the precursor of saposin peptides that are essential for lysosomal glycosphingolipid degradation. PMID: 28541286
2. Both PSAP reduction and overexpression lead to significantly elevated extracellular progranulin (PGRN) levels. Intriguingly, PSAP knockdown increases PGRN monomers, whereas PSAP overexpression increases PGRN oligomers, partly through a protein-protein interaction. PMID: 27356620
3. Study demonstrated that the binding of CST3 and PSAP decreased the inhibitory effects of CST3 on proteinase in vitro. The co-localization of both proteins was detected in cultured cells and in Bunina body-containing motor neurons from patients with amyotrophic lateral sclerosis, suggesting that they might be involved in the process of Bunina body formation. PMID: 29249381
4. This report documents the successful use of plasma lysoSLs profiling in the PSAP deficiency diagnosis, as a reliable and informative tool to obtain a preliminary information in infantile cases with complex traits displaying severe neurological signs and visceral involvement. PMID: 26831127
5. an extensive review of all the PSAP-causative variants published in the literature to date, accounting for a total of 10 PSAP allele types (review) PMID: 26462614
6. Our findings suggest a novel pharmacological approach to Sap C deficiency directed to treat major secondary pathological aspects in this disorder. PMID: 25926625
7. PSAP is a secreted biomarker. PMID: 26341737
8. Data suggested that the abundance of Psap in sperm sample may be a sensitive endpoint to predict PCB exposure. PMID: 26045750
9. Prosaposin facilitates sortilin-independent lysosomal trafficking of progranulin. PMID: 26370502
10. findings support a lung metastasis-promoting function of the miR-23b/27b/24 cluster of miRNAs, which functions in part through the direct inhibition of PSAP in breast cancer PMID: 24966325
11. Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H. PMID: 24657443
12. Saposin C protects glucocerebrosidase against alpha-synuclein inhibition. PMID: 24070323
13. Urine of patients with early prostate cancer contains lower levels of light chain fragments of inter-alpha-trypsin inhibitor and prosaposin fragment or saposin B. PMID: 23417432
14. These findings suggested that prosaposin might enhance estrogen receptor alpha-mediated signaling axis and play a role in breast cancer development and progression. PMID: 22738294
15. PSAP is a novel TFPI-2-interacting protein and that the binding sites are the KD2 of TFPI-2 and the C-terminus of PSAP. PMID: 21943334
16. novel esophageal squamous cell carcinoma marker PSAP was identified by mass spectrometry and immunohistochemical analysis PMID: 21743296
17. PSAP is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. PMID: 21555518
18. saposin C caused stimulation of androgen receptor expression and activity by associations with Src kinases PMID: 21328455
19. Saposin B(Sap B) is not a limiting factor of the coupled Sap B-arylsulfatase A reaction in mouse kidney cells even if sulfatide has accumulated to unphysiologically high levels PMID: 19224915
20. The biological properties of cells from four recently described Gaucher disease patients carrying mutations in the Sap C domain of the PSAP gene have been characterized. PMID: 20484222
21. PSAP is involved in prostate cancer invasion. PMID: 20132547
22. reconstruction of the order of internal duplications that gave rise to the four saposins by using phylogenetic tools PMID: 11734895
23. procathepsin D interacts with prosaposin in human breast and ovarian cancer cells. PMID: 12083803
24. crystal structure reveals a dimeric shell for lipid binding PMID: 12518053
25. data indicate that saposin C is required for acid beta-glucosidase resistance to proteolytic degradation in the cell PMID: 12813057
26. The structure of saposin C compared to other saposin-fold family members provides an explanation for function variability of this protein family. PMID: 14674747
27. model proposed in which saposin C exposes lipid antigens from intralysosomal membranes for loading onto CD1b PMID: 14716313
28. There might be a potential pleuripotent regulatory function for prosaposin in prostate cancer. PMID: 15305334
29. Amplification and overexpression of PSAP was studied in prostatic neoplasms. PMID: 16080200
30. determination of crystal structure of human saposins A and C to 2.0 Angstroms and 2.4 Angstroms, respectively and both reveal the compact, monomeric saposin fold PMID: 16823039
31. FSAP (Factor VII-activating protease) can cleave and inactivate PDGF-BB (platelet-derived growth factor-BB) and thereby inhibits VSMC (vascular smooth-muscle cell) proliferation. PMID: 17300216
32. saposin B may facilitate lipid binding to CD1d molecules throughout the endocytic pathway PMID: 17372201
33. an unglycosylated Sap-B variant, Asn215His, which causes a fatal sphingolipid storage disease, lost the ability to extract membrane lipids at acidic pH in the presence of BMP PMID: 17561962
34. Expression of saposin C-originated saposin C may upregulate AR gene expression and activate the androgen receptor transcriptional function in an androgen-independent manner in prostate cancer cells. PMID: 17712477
35. These data for the first time demonstrate that not only saposin C or PSAP regulates AR expression/activity, but also function as an androgen-regulated gene in prostate stromal cells. PMID: 18481277
36. findings point to the role of lipid rafts in the prosaposin-triggered signalling pathway, thus supporting a role for this factor as a new component of the multimolecular signalling complex involved in the neurotrophic response. PMID: 18761669
37. two new patients with PSAP gene defects; one, with pSap-d, who had a severe neurovisceral dystrophy and died as a neonate, and the other with SapB-d, who presented with a metachromatic leukodystrophy-like disorder but had normal arylsulfatase activity PMID: 19267410
38. Report the up-regulation of prosaposin in the senescent fibroblasts and endothelial cells. PMID: 19471889
39. Prosaposin functions in a paracrine and endocrine fashion by stimulating the expression of thrombospondin-1 (Tsp-1) in fibroblasts present in both primary tumors and distant organs, doing so in a p53-dependent manner. PMID: 19581582
40. Saposin C or its precursor (PSAP) function as an androgen-agonist and upregulate androgen receptor and prostate-specific antigen expression/activity in androgen-responsive prostate cancer cells LNCaP, TRAMP-C1 and -C2., and CWR 22RV1. PMID: 17044040
41. Prosaposin is an androgen-target gene and its expression in androgen-responsive prostate cancer cells can be upregulated by male hormones. PMID: 17171640
42. Cloning of prosaposin gene from androgen-independent (AI) prostate cancer (PCa) cells and it genomic amplification in human metastatic AI PCa cell lines and punch biopsy samples of prostate cancer xenografts and lymph node metastases. PMID: 16080200
43. Saposin C stimulates prostate cancer and stromal cells growth and invasion and uPA/uPAR expression, and activates p42/44 and SAPK/JNK signaling pathways of MAPK. PMID: 15897971
44. Prosaposin and/or saposin C via modulation of caspases expression/activity and/or PI3K/Akt signaling pathway act as a survival and anti-apoptotic factor for prostate cancer cells. PMID: 15548330

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Lysosome.; [Prosaposin]: Secreted.

HGNC: 9498

OMIM: 176801

KEGG: hsa:5660

STRING: 9606.ENSP00000378394

UniGene: Hs.523004