Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain. (updated: March 4, 2015)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 0%
No model available.
(right-click above to access to more options from the contextual menu)
The reference OMIM entry for this protein is 606793
Aminopeptidase, puromycin-sensitive; npepps
Psa
Metalloprotease mp100; mp100
DESCRIPTION
Aminopeptidases are a group of exopeptidases that hydrolyze amino acids from the N terminus of a peptide substrate. Puromycin-sensitive aminopeptidase (EC 3.4.11.14) contains the zinc-binding domain characteristic of the gluzincin group of zinc metalloproteases (see
605896).
CLONING
Tobler et al. (1997) cloned PSA from a human fetal brain cDNA library using the mouse PSA cDNA as probe. They established that translation is initiated at the second of 2 possible start codons, resulting in a deduced 875-amino acid protein with a molecular mass of 99 kD by SDS-PAGE. PSA contains a zinc-binding motif conserved among gluzincin aminopeptidases and shares 98% sequence identity with the mouse protein. Northern blot analysis detected ubiquitous expression of a 4.8-kb transcript, with highest expression in brain. By in situ hybridization of adult human brain sections, expression was localized to the perikaryon of neurons of the cortex and cerebellum. Using immunofluorescence localization of transfected HeLa cells, Tobler et al. (1997) found that PSA localizes to the perinuclear cytoplasm and shows a filamentous staining pattern. Bauer et al. (2001) cloned PSA cDNA from a human skeletal muscle library. Northern blot analysis detected major and minor transcripts of 4.8 and 4.2 kb, respectively. Huber et al. (1999) determined that PSA is identical to the metalloprotease MP100 that was originally isolated as a beta-secretase candidate from human brain by Schonlein et al. (1994).
GENE FUNCTION
Huber et al. (1999) were able to colocalize and coimmunoprecipitate PSA with beta-amyloid precursor protein (
104760); however, PSA did not increase production of the amyloid-beta peptide in cotransfected cells. By RT-PCR, but not by Northern blot analysis, Bauer et al. (2001) found that PSA was upregulated in human leukemic cells following vitamin D stimulation.
GENE STRUCTURE
Thompson et al. (1999) determined that the PSA gene contains 23 exons spanning approximately 40 kb. They found that the active site motif iis split between exons 9 and 10. Analysis of the 5-prime flanking region indicated that the gene lacks a TATA box, is GC rich, and contains 5 putative SP1 (
189906)-binding sites.
MAPPING
By FISH, Bauer et al. (2001) mapped the PSA gene to chromosome 17q21. Osada et al. (1999) mapped the mouse Psa gene to a region of syntenic homology on chromosome 11.
POPULATION GENETICS
By analyzing short-read mapping depth for 159 human genomes, Sudmant et al. (2010) demonstrated accurate estimation of absolute copy number for duplications as small as 1.9 kb pairs, ranging from 0 to 48 copies. Sudmant et al. (2010) identified 4.1 million 'singly unique nucleotide' positions informative in distinguishing specific copies and used them to genotype the copy and content of specific paralogs within highly duplicated gene families. These data identified human-specific expansions in genes associated with brain development, such as GPRIN2 (
611240) and SRGAP2 (
606524), which have been implicated in neurite outgrowth and branching. Also included were the brain-specific HYDIN2 gene (
610813), associated with micro- and macrocephaly; DRD5 (
126453), a dopamine D5 receptor; and the GTF2I (
601679) transcription factors, whose deletion has been associated with visual-spatial and sociability deficits among Williams-Beuren syndrome (
194050) patients, among others. The data of Sudmant et al. (2010) also revealed e ...
More on the omim web site
Subscribe to this protein entry history
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 606793 was added.