P55786 (PSA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Puromycin-sensitive aminopeptidase
Short name=PSA
EC=3.4.11.14

Alternative name(s):
Cytosol alanyl aminopeptidase
Short name=AAP-S

Gene names

Name:	NPEPPS
Synonyms:	PSA

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	919 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11
Catalytic activity	Release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Strongly inhibited by bestatin, leuhistin, actinonin, amastatin, 1,10-phenanthroline, DFP, PCMBS, Zn2+, Cd2+, Co2+, Cu2+, Hg2+, EDTA and puromycin. Not inhibited by PMSF, and only slightly inhibited by leupeptin and aprotinin. Activity is increased by Mg2+ and Ca2+. Ref.6 Ref.9 Ref.10
Subunit structure	Monomer. Ref.6
Subcellular location	Cytoplasm › cytosol. Nucleus Potential Ref.6.
Tissue specificity	Detected in liver, epithelium of renal tubules, epithelium of small and large intestine, gastric epithelial cells, and alveoli of the lung (at protein level). Ref.6
Sequence similarities	Belongs to the peptidase M1 family.
Caution	It is uncertain whether Met-1 or Met-45 is the initiator. N-terminal sequencing in Ref.6 suggests that Met-45 is used, followed by methionine initiator removal.
Biophysicochemical properties	Kinetic parameters: KM=2.20 mM for Lys-p-NA Ref.6 Ref.9 KM=0.25 mM for Leu-p-NA KM=0.27 mM for Ala-p-NA KM=0.80 mM for Met-p-NA KM=0.47 mM for Pro-p-NA KM=0.21 mM for Val-p-NA KM=182 µM for Ala-MCA KM=189 µM for Met-MCA KM=220 µM for Lys-MCA KM=91 µM for Leu-MCA KM=167 µM for Phe-MCA pH dependence: Optimum pH is 7.5. Stable from pH 5.0 to 8.0. Temperature dependence: Stable up to 40 degrees Celsius.
Sequence caution	The sequence AAH65294.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAA68964.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding Zinc
Molecular function	Aminopeptidase Hydrolase Metalloprotease Protease
PTM	Nitration
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of peptide antigen via MHC class I Traceable author statement. Source: Reactome cellular response to hypoxia Inferred from direct assay PubMed 21056661. Source: UniProtKB protein polyubiquitination Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	aminopeptidase activity Traceable author statement Ref.5. Source: ProtInc metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF6	P56537	1	EBI-1046129,EBI-372243

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 919	919	Puromycin-sensitive aminopeptidase		PRO_0000095116
Regions
	Region	316 – 320	5	Substrate binding By similarity
	Motif	726 – 730	5	Nuclear localization signal Potential
Sites
	Active site	353	1	Proton acceptor By similarity
	Metal binding	352	1	Zinc; catalytic By similarity
	Metal binding	356	1	Zinc; catalytic By similarity
	Metal binding	375	1	Zinc; catalytic By similarity
	Binding site	180	1	Substrate By similarity
	Site	438	1	Transition state stabilizer By similarity
Amino acid modifications
	Modified residue	464	1	Nitrated tyrosine By similarity
Experimental info
	Mutagenesis	353	1	E → A: Reduces catalytic activity by 25,000-fold to 100,000-fold. Ref.8
	Mutagenesis	353	1	E → Q: Reduces catalytic activity by 5,000-fold to 15,000-fold. Ref.8
	Mutagenesis	353	1	E → V: Reduces catalytic activity by 300,000-fold to 500,000-fold. Ref.8
	Mutagenesis	438	1	Y → F: Reduces catalytic activity by 1,000-fold to 2,500-fold. Ref.8
	Sequence conflict	184	1	A → P in CAA68964. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P55786 [UniParc]. Last modified August 31, 2004. Version 2. Checksum: 873C9BF75494A057	FASTA	919	103,276
	10 20 30 40 50 60 MWLAAAAPSL ARRLLFLGPP PPPLLLLVFS RSSRRRLHSL GLAAMPEKRP FERLPADVSP 70 80 90 100 110 120 INYSLCLKPD LLDFTFEGKL EAAAQVRQAT NQIVMNCADI DIITASYAPE GDEEIHATGF 130 140 150 160 170 180 NYQNEDEKVT LSFPSTLQTG TGTLKIDFVG ELNDKMKGFY RSKYTTPSGE VRYAAVTQFE 190 200 210 220 230 240 ATDARRAFPC WDEPAIKATF DISLVVPKDR VALSNMNVID RKPYPDDENL VEVKFARTPV 250 260 270 280 290 300 MSTYLVAFVV GEYDFVETRS KDGVCVRVYT PVGKAEQGKF ALEVAAKTLP FYKDYFNVPY 310 320 330 340 350 360 PLPKIDLIAI ADFAAGAMEN WGLVTYRETA LLIDPKNSCS SSRQWVALVV GHELAHQWFG 370 380 390 400 410 420 NLVTMEWWTH LWLNEGFASW IEYLCVDHCF PEYDIWTQFV SADYTRAQEL DALDNSHPIE 430 440 450 460 470 480 VSVGHPSEVD EIFDAISYSK GASVIRMLHD YIGDKDFKKG MNMYLTKFQQ KNAATEDLWE 490 500 510 520 530 540 SLENASGKPI AAVMNTWTKQ MGFPLIYVEA EQVEDDRLLR LSQKKFCAGG SYVGEDCPQW 550 560 570 580 590 600 MVPITISTSE DPNQAKLKIL MDKPEMNVVL KNVKPDQWVK LNLGTVGFYR TQYSSAMLES 610 620 630 640 650 660 LLPGIRDLSL PPVDRLGLQN DLFSLARAGI ISTVEVLKVM EAFVNEPNYT VWSDLSCNLG 670 680 690 700 710 720 ILSTLLSHTD FYEEIQEFVK DVFSPIGERL GWDPKPGEGH LDALLRGLVL GKLGKAGHKA 730 740 750 760 770 780 TLEEARRRFK DHVEGKQILS ADLRSPVYLT VLKHGDGTTL DIMLKLHKQA DMQEEKNRIE 790 800 810 820 830 840 RVLGATLLPD LIQKVLTFAL SEEVRPQDTV SVIGGVAGGS KHGRKAAWKF IKDNWEELYN 850 860 870 880 890 900 RYQGGFLISR LIKLSVEGFA VDKMAGEVKA FFESHPAPSA ERTIQQCCEN ILLNAAWLKR 910 DAESIHQYLL QRKASPPTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the human puromycin-sensitive aminopeptidase and evidence for expression in neurons." Tobler A.R., Constam D.B., Schmitt-Graeff A., Malipiero U., Schlapbach R., Fontana A. J. Neurochem. 68:889-897(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage." Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C. Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 31-919. Tissue: Lung.
[4]	"Human puromycin-sensitive aminopeptidase: cloning of 3' UTR, evidence for a polymorphism at a.a. 140 and refined chromosomal localization to 17q21." Bauer W.O., Nanda I., Beck G., Schmid M., Jakob F. Cytogenet. Cell Genet. 92:221-224(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-919. Tissue: Skeletal muscle.
[5]	"Cloning and analysis of the gene for the human puromycin-sensitive aminopeptidase." Thompson M.W., Tobler A., Fontana A., Hersh L.B. Biochem. Biophys. Res. Commun. 258:234-240(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 45-85.
[6]	"Puromycin-sensitive alanyl aminopeptidase from human liver cytosol: purification and characterization." Yamamoto Y., Li Y.H., Ushiyama I., Nishimura A., Ohkubo I., Nishi K. Forensic Sci. Int. 113:143-146(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 46-105, FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Liver.
[7]	"Two new proteases in the MHC class I processing pathway." Stoltze L., Schirle M., Schwarz G., Schroter C., Thompson M.W., Hersh L.B., Kalbacher H., Stevanovic S., Rammensee H.G., Schild H. Nat. Immunol. 1:413-418(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Mutation of active site residues of the puromycin-sensitive aminopeptidase: conversion of the enzyme into a catalytically inactive binding protein." Thompson M.W., Govindaswami M., Hersh L.B. Arch. Biochem. Biophys. 413:236-242(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF GLU-353 AND TYR-438, ACTIVE SITE.
[9]	"Degradation of tau protein by puromycin-sensitive aminopeptidase in vitro." Sengupta S., Horowitz P.M., Karsten S.L., Jackson G.R., Geschwind D.H., Fu Y., Berry R.W., Binder L.I. Biochemistry 45:15111-15119(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[10]	"Puromycin-sensitive aminopeptidase is the major peptidase responsible for digesting polyglutamine sequences released by proteasomes during protein degradation." Bhutani N., Venkatraman P., Goldberg A.L. EMBO J. 26:1385-1396(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[11]	"Cytosolic aminopeptidases influence MHC class I-mediated antigen presentation in an allele-dependent manner." Kim E., Kwak H., Ahn K. J. Immunol. 183:7379-7387(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y07701 mRNA. Translation: CAA68964.1. Different initiation. AC025682 Genomic DNA. No translation available. BC065294 mRNA. Translation: AAH65294.2. Different initiation. AJ132583 mRNA. Translation: CAA10709.1. AF252387 Genomic DNA. Translation: AAF70086.1.
IPI	IPI00026216.
RefSeq	NP_006301.3. NM_006310.3.
UniGene	Hs.740414.
3D structure databases
ProteinModelPortal	P55786.
ModBase	Search...
Protein-protein interaction databases
IntAct	P55786. 6 interactions.
STRING	9606.ENSP00000320324.
Protein family/group databases
MEROPS	M01.010.
PTM databases
PhosphoSite	P55786.
Polymorphism databases
DMDM	51704228.
Proteomic databases
PaxDb	P55786.
PeptideAtlas	P55786.
PRIDE	P55786.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322157; ENSP00000320324; ENSG00000141279.
GeneID	9520.
KEGG	hsa:9520.
UCSC	uc002ilr.4. human.
Organism-specific databases
CTD	9520.
GeneCards	GC17P045608.
H-InvDB	HIX0013922.
HGNC	HGNC:7900. NPEPPS.
HPA	HPA021453. HPA045649.
MIM	606793. gene.
neXtProt	NX_P55786.
PharmGKB	PA31703.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0308.
HOGENOM	HOG000106482.
HOVERGEN	HBG106325.
InParanoid	P55786.
KO	K08776.
OMA	NVVEVKF.
OrthoDB	EOG4S7JP9.
PhylomeDB	P55786.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	P55786.
Bgee	P55786.
CleanEx	HS_NPEPPS.
Genevestigator	P55786.
Family and domain databases
InterPro	IPR024571. DUF3358. IPR001930. Peptidase_M1. IPR014782. Peptidase_M1_N. IPR015568. Peptidase_M1_puromycin-sens. [Graphical view]
PANTHER	PTHR11533. PTHR11533. 1 hit. PTHR11533:SF33. PTHR11533:SF33. 1 hit.
Pfam	PF11838. DUF3358. 1 hit. PF01433. Peptidase_M1. 1 hit. [Graphical view]
PRINTS	PR00756. ALADIPTASE.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P55786.
ChEMBL	CHEMBL2264.
ChiTaRS	NPEPPS. human.
GenomeRNAi	9520.
NextBio	35678.
PMAP-CutDB	P55786.
SOURCE	Search...

Entry information

Entry name

PSA_HUMAN

Accession

Primary (citable) accession number: P55786
Secondary accession number(s): Q6P145, Q9NP16, Q9UEM2

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	August 31, 2004
Last modified:	May 1, 2013
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.