G2Cdb::Gene report

Gene id
G00001641
Gene symbol
NPEPPS (HGNC)
Species
Homo sapiens
Description
aminopeptidase puromycin sensitive
Orthologue
G00000392 (Mus musculus)

Databases (7)

Gene
ENSG00000141279 (Ensembl human gene)
9520 (Entrez Gene)
769 (G2Cdb plasticity & disease)
NPEPPS (GeneCards)
Literature
606793 (OMIM)
Marker Symbol
HGNC:7900 (HGNC)
Protein Sequence
P55786 (UniProt)

Synonyms (2)

  • MP100
  • PSA

Literature (15)

Pubmed - other

  • Defining the human deubiquitinating enzyme interaction landscape.

    Sowa ME, Bennett EJ, Gygi SP and Harper JW

    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.

    Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel nonreciprocal proteomic data sets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, subcellular localization, and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway.

    Funded by: NIA NIH HHS: AG085011, R01 AG011085, R01 AG011085-16; NIGMS NIH HHS: GM054137, GM67945, R01 GM054137, R01 GM054137-14, R01 GM067945

    Cell 2009;138;2;389-403

  • Cobalt chloride-induced downregulation of puromycin-sensitive aminopeptidase suppresses the migration and invasion of PC-3 cells.

    Lee SH and Kim HG

    Division of Biological Sciences, Research Center of Bioactive Materials, Chonbuk National University, Chonju 561-756, Korea.

    Cobalt chloride (CoCl(2)) treatment of cells in vitro has been shown to induce cellular changes that are similar to those seen following hypoxia. To identify genes that are differentially expressed in response to treatment with CoCl(2), we compared the mRNA expression profiles of PC-3 cells that were treated with CoCl(2) with those of untreated PC-3 cells, using specific arbitrary primers and two anchored oligo(dT) primers provided in the ACP-based GeneFishing kits. The results of this study demonstrated that the puromycin-sensitive aminopeptidase (PSA) gene was downregulated in PC-3 cells that were treated with CoCl(2). This downregulation of PSA expression, in turn, suppressed the proliferation, migration, and invasion of PC-3 cells, as well as the secretion and expression of matrix metalloproteinase-9 (MMP-9).

    Journal of microbiology and biotechnology 2009;19;5;530-6

  • Large-scale mapping of human protein-protein interactions by mass spectrometry.

    Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T and Figeys D

    Protana, Toronto, Ontario, Canada.

    Mapping protein-protein interactions is an invaluable tool for understanding protein function. Here, we report the first large-scale study of protein-protein interactions in human cells using a mass spectrometry-based approach. The study maps protein interactions for 338 bait proteins that were selected based on known or suspected disease and functional associations. Large-scale immunoprecipitation of Flag-tagged versions of these proteins followed by LC-ESI-MS/MS analysis resulted in the identification of 24,540 potential protein interactions. False positives and redundant hits were filtered out using empirical criteria and a calculated interaction confidence score, producing a data set of 6463 interactions between 2235 distinct proteins. This data set was further cross-validated using previously published and predicted human protein interactions. In-depth mining of the data set shows that it represents a valuable source of novel protein-protein interactions with relevance to human diseases. In addition, via our preliminary analysis, we report many novel protein interactions and pathway associations.

    Molecular systems biology 2007;3;89

  • The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

    Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J and MGC Project Team

    The National Institutes of Health's Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues. Candidate clones were chosen based on 5'-EST sequences, and then fully sequenced to high accuracy and analyzed by algorithms developed for this project. Currently, more than 11,000 human and 10,000 mouse genes are represented in MGC by at least one clone with a full ORF. The random selection approach is now reaching a saturation point, and a transition to protocols targeted at the missing transcripts is now required to complete the mouse and human collections. Comparison of the sequence of the MGC clones to reference genome sequences reveals that most cDNA clones are of very high sequence quality, although it is likely that some cDNAs may carry missense variants as a consequence of experimental artifact, such as PCR, cloning, or reverse transcriptase errors. Recently, a rat cDNA component was added to the project, and ongoing frog (Xenopus) and zebrafish (Danio) cDNA projects were expanded to take advantage of the high-throughput MGC pipeline.

    Funded by: PHS HHS: N01-C0-12400

    Genome research 2004;14;10B;2121-7

  • Complete sequencing and characterization of 21,243 full-length human cDNAs.

    Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T and Sugano S

    Helix Research Institute, 1532-3 Yana, Kisarazu, Chiba 292-0812, Japan.

    As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at approximately 58% compared with a peak at approximately 42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at approximately 42%, relatively low compared with that of protein-coding cDNAs.

    Nature genetics 2004;36;1;40-5

  • Analysis of conserved residues of the human puromycin-sensitive aminopeptidase.

    Thompson MW and Hersh LB

    Department of Cellular and Molecular Biochemistry, University of Kentucky, 800 Rose Street, MS607 Lexington, KY 40536-0298, USA.

    The puromycin-sensitive aminopeptidase (ApPS) is a zinc metallopeptidase involved in the degradation of neuropeptides. Putative catalytic residues of the enzyme, Cys146, Glu338, and Lys396 were mutated, and the resultant mutant enzymes characterized. ApPS C146S exhibited normal catalytic activity, ApPS E338A exhibited decreased substrate binding, and ApPS K396I exhibited decreases in both substrate binding and catalysis. ApPS K396I and ApPS Y394F were analyzed with respect to transition state inhibitor binding. No effect was seen with the K396I mutation, but ApPS Y394F exhibited a 3.3-fold lower affinity for RB-3014, a transition state inhibitor, indicating that Tyr394 is involved in transition state stabilization.

    Funded by: NIDA NIH HHS: DA 02243, DA 05736

    Peptides 2003;24;9;1359-65

  • Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence for a polymorphism at a.a. 140 and refined chromosomal localization to 17q21.

    Bauer WO, Nanda I, Beck G, Schmid M and Jakob F

    Department of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, Würzburg, Germany.

    Puromycin-sensitive aminopeptidase is a predominantly cytoplasmatic zinc-dependent exopeptidase. Its physiological function is not known to date. Here we report data on tissue distribution, a polymorphism within the coding region and the complete 3' UTR. The gene (NPEPPS alias PSA) was physically mapped to chromosome 17q21.2-->q21.32 using fluorescence in situ hybridization.

    Cytogenetics and cell genetics 2001;92;3-4;221-4

  • Ontogeny of puromycin-sensitive and insensitive aminopeptidase activities in several subcellular fractions of the rat brain.

    de Gandarias JM, Irazusta J, Gil J, Fernández D, Varona A and Casis L

    Department of Physiology, Medical School, University of the Basque Country, Bilbao, Spain.

    Puromycin-sensitive and insensitive aminopeptidase (aminopeptidase M) activities are measured in several subcellular fractions of the rat brain cortex and subcortex during the first postnatal month. Tyr-beta-naphthylamide has been used as substrate and 20 microM puromycin as selective inhibitor. We have found that puromycin-sensitive aminopeptidase activity increases twofold in the synaptosomal and mitochondrial fractions in the first 6-9 postnatal days, just during the period of axonal and dendritic growth. This enzyme also has significant age-related changes in the nuclear fraction. The developmental pattern is different, depending on the subcellular fraction analyzed. Significant developmental changes of puromycin-insensitive aminopeptidase (aminopeptidase M) are only found in the myelinic and microsomal fractions and they are less significant than those found in the puromycin-sensitive aminopeptidase. It has been suggested that these enzyme activities could be involved in processes of cell proliferation, differentiation, and maturation.

    Brain research bulletin 1999;50;4;283-90

  • Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase.

    Thompson MW, Tobler A, Fontana A and Hersh LB

    Department of Biochemistry, University of Kentucky, Lexington, Kentucky 40536, USA.

    The gene encoding the human puromycin-sensitive aminopeptidase (PSA) has been cloned and characterized. The human PSA gene is composed of 23 exons and 22 introns and spans approximately 40 kb of chromosome 17 at the interval 17q12-21. An analysis of the 5' end of the human PSA transcript reveals that the translational start site corresponds to nt 210 of the human PSA cDNA, as suggested by RT-PCR, 5' RACE, and computer analysis of expressed sequence tags. A comparison of the exon/exon boundaries of the human PSA gene with those of the human aminopeptidase N (APN) gene shows little conservation, suggesting that the two genes, which are closely related in protein sequence, diverged early during evolution.

    Funded by: NIDA NIH HHS: DA05764-03, NIDA02243

    Biochemical and biophysical research communications 1999;258;2;234-40

  • cDNA cloning and molecular characterization of human brain metalloprotease MP100: a beta-secretase candidate?

    Huber G, Thompson A, Grüninger F, Mechler H, Hochstrasser R, Hauri HP and Malherbe P

    Pharma Division, Preclinical CNS Research, F. Hoffmann-La Roche Ltd., Basel, Switzerland.

    Metalloprotease MP100 was originally isolated as a beta-secretase candidate from human brain using a beta-amyloid precursor protein (beta-APP)-derived p-nitroanilide (pNA) peptide substrate. Peptide sequences from purified MP100 were now found to resemble sequences reported for a puromycin-sensitive aminopeptidase (PSA) highly enriched in brain, and cDNA cloning revealed nearly complete homology of MP100 to PSA, with only a single bp difference resulting in an amino acid change at position 184. Another MP100 cDNA encoded a protein with a 36-amino acid deletion (positions 180-217) and a two-amino acid insertion after Val533. Purified recombinant human MP100 cleaved the original pNA substrate as well as a free beta-site-spanning amyloid beta (A beta) peptide (A beta(-10/+10)), generating A beta(1-10). The latter substrate, however, remained uncleaved, if N- and C-terminally blocked, and also purified beta-APP was not cleaved. Double immunoimaging revealed partial, patchy, colocalization of beta-APP and MP100 in doubly transfected human embryonic kidney cells (HEK cells) and in normal neuroblastoma cells, and both proteins could be coimmunoprecipitated from rat brain extracts, suggesting their close vicinity in vivo. Coexpression of MP100 and beta-APP695, however, did not boost A beta levels in HEK cells, although active enzyme was produced. Thus, MP100 does not exert true beta-secretase-like function in cells, although it may well act as a secondary exoprotease in a complex beta-APP/A beta metabolism.

    Journal of neurochemistry 1999;72;3;1215-23

  • Cloning of the human puromycin-sensitive aminopeptidase and evidence for expression in neurons.

    Tobler AR, Constam DB, Schmitt-Gräff A, Malipiero U, Schlapbach R and Fontana A

    Department of Internal Medicine, University Hospital of Zürich, Switzerland.

    The puromycin-sensitive aminopeptidase (PSA) is thought to contribute to the degradation of enkephalins. Besides being the most abundant aminopeptidase in the brain, PSA is expressed in other organs as well. From a human fetal brain cDNA library, we have isolated a cDNA encoding the human PSA (huPSA) protein. The isolated cDNA gave rise to a protein with a molecular mass of 99 kDa. Compared with mouse PSA, homology at the amino acid and cDNA level was 98 and 93%, respectively. Translation of the huPSA was found to be initiated at the second of two possible start codons, as shown by studies with antibodies directed against peptide sequences of both potential N-terminal regions. Northern blot analysis with RNA isolated from different human organs demonstrated that the huPSA transcript is strongest but not exclusively expressed in the brain. Vesicular stomatitis virus epitope-tagged huPSA protein was expressed in HeLa cells and found to be localized in the cytoplasm, especially in the perinuclear region. By in situ hybridization, huPSA transcript could be identified in cortical and cerebellar neurons, whereas glial cells and blood vessels remained negative.

    Journal of neurochemistry 1997;68;3;889-97

  • Puromycin-sensitive aminopeptidase. Sequence analysis, expression, and functional characterization.

    Constam DB, Tobler AR, Rensing-Ehl A, Kemler I, Hersh LB and Fontana A

    University Hospital of Zürich, Department of Internal Medicine, Switzerland.

    Among the molecular mechanisms that control the cell division cycle, proteolysis has emerged as a key regulatory process enabling cells to pass critical check points. Such proteolysis involves a cascade of enzymes including a multisubunit complex termed 26S proteasome. Here we report on the analysis of a novel mouse cDNA encoding the puromycin-sensitive aminopeptidase (PSA) and on its expression in COS cells and 3T3 fibroblasts. PSA is 27-40% homologous to several known Zn(2+)-binding aminopeptidases including aminopeptidase N. Immunohistochemical analysis revealed that PSA is localized to the cytoplasm and to the nucleus and associates with microtubules of the spindle apparatus during mitosis. Furthermore, puromycin and bestatin both arrested the cell cycle, leading to an accumulation of cells in G2/M phase, and ultimately induced cells to undergo apoptosis at concentrations that inhibit PSA. Control experiments including cycloheximide further suggested that the induction of apoptosis by puromycin was not attributable to inhibition of protein synthesis. Taken together, these data favor the novel idea that PSA participates in proteolytic events essential for cell growth and viability.

    Funded by: NIDA NIH HHS: DA 02243

    The Journal of biological chemistry 1995;270;45;26931-9

  • Immunocytochemical comparison of cultured normal epithelial prostatic cells with prostatic tissue sections.

    Cussenot O, Berthon P, Cochand-Priollet B, Maitland NJ and Le Duc A

    Département de Recherche en Urologie, Hôpital Saint Louis, Paris, France.

    By analyzing a culture system of human prostatic epithelial cells (HPEC) and human prostatic fibroblasts (HPF) for expression of several determinants by immunocytochemistry, we have shown that long-term cultures are able to preserve the phenotypic characteristics of the normal tissue from which they are derived. The cytoskeletal elements, prostate-specific proteins, and steroid receptor profiles were compared to those of prostatic epithelium and stroma in situ. When cultured in low serum and low calcium medium, the adult HPEC grew as two layers of cells, the upper one of which retained the differentiation characteristics observed in the luminal fraction of normal prostatic epithelium. This cell type is the likely origin of prostatic neoplasia, with expression of CK8, 18, and 19 but not CK14. Androgen receptors, prostatic-specific antigen, and prostatic acid phosphatase are also expressed in vitro but at lower level than in situ. The lower cell layer expressed most of the same determinants but at a much lower level, suggestive of a stem-cell type. The HPF cultured in RPMI serum supplemented media retained the stromal pattern of the cells observed in situ. Culture systems which conserve the characteristics of their normal counterparts in vivo should provide useful models for studying in vitro genetic and epigenetic factors associated with differentiation and proliferation, but also with tumorigenic progression in the prostatic gland.

    Experimental cell research 1994;214;1;83-92

  • Studies on the tissue distribution of the puromycin-sensitive enkephalin-degrading aminopeptidases.

    McLellan S, Dyer SH, Rodriguez G and Hersh LB

    Department of Biochemistry, University of Texas, Southwestern Medical Center, Dallas 75235.

    An antiserum generated to the soluble form of the rat brain puromycin-sensitive enkephalin-degrading aminopeptidase was used to determine the tissue distribution of the soluble and membrane-associated forms of this enzyme. All tissues examined contained significant levels of the soluble enzyme form, with this enzyme accounting for greater than 90% of the arylamidase activity in brain, heart, and skeletal muscle. Native gel electrophoresis coupled with activity staining as well as inhibition studies were used to confirm the presence of this enzyme in various tissues. Serum was found not to contain this particular aminopeptidase. In contrast to the results obtained with the soluble enzyme form, brain was the only tissue found to contain the membrane-associated enzyme form. Although all tissues contained membrane-associated aminopeptidase activity only the brain enzyme could be maintained in solution in the absence of detergent. In addition, the brain membrane-associated enzyme could be distinguished from the membrane-associated aminopeptidase activity in other tissues on the basis of its sensitivity to inhibition by puromycin.

    Funded by: NIDA NIH HHS: DA 02243

    Journal of neurochemistry 1988;51;5;1552-9

Gene lists (4)

Gene List Source Species Name Description Gene count
L00000009 G2C Homo sapiens Human PSD Human orthologues of mouse PSD adapted from Collins et al (2006) 1080
L00000016 G2C Homo sapiens Human PSP Human orthologues of mouse PSP adapted from Collins et al (2006) 1121
L00000059 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-CONSENSUS Human cortex PSD consensus 748
L00000069 G2C Homo sapiens BAYES-COLLINS-HUMAN-PSD-FULL Human cortex biopsy PSD full list 1461
© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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