UniProtKB - P55786 (PSA_HUMAN)
Protein
Puromycin-sensitive aminopeptidase
Gene
NPEPPS
Organism
Homo sapiens (Human)
Status
Functioni
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.5 Publications
Caution
It is uncertain whether Met-1 or Met-45 is the initiator. N-terminal sequencing in PubMed:10978616 suggests that Met-45 is used, followed by methionine initiator removal.Curated
Catalytic activityi
- Release of an N-terminal amino acid, preferentially alanine, from a wide range of peptides, amides and arylamides. EC:3.4.11.14
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Activity regulationi
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+.3 Publications
Kineticsi
- KM=2.20 mM for Lys-p-NA2 Publications
- KM=0.25 mM for Leu-p-NA2 Publications
- KM=0.27 mM for Ala-p-NA2 Publications
- KM=0.80 mM for Met-p-NA2 Publications
- KM=0.47 mM for Pro-p-NA2 Publications
- KM=0.21 mM for Val-p-NA2 Publications
- KM=182 µM for Ala-MCA2 Publications
- KM=189 µM for Met-MCA2 Publications
- KM=220 µM for Lys-MCA2 Publications
- KM=91 µM for Leu-MCA2 Publications
- KM=167 µM for Phe-MCA2 Publications
pH dependencei
Optimum pH is 7.5. Stable from pH 5.0 to 8.0.2 Publications
Temperature dependencei
Stable up to 40 degrees Celsius.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 180 | SubstrateBy similarity | 1 | |
Metal bindingi | 352 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 353 | Proton acceptorPROSITE-ProRule annotation | 1 | |
Metal bindingi | 356 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 375 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Sitei | 438 | Transition state stabilizerBy similarity | 1 |
GO - Molecular functioni
- aminopeptidase activity Source: ProtInc
- metalloaminopeptidase activity Source: GO_Central
- peptide binding Source: GO_Central
- zinc ion binding Source: GO_Central
GO - Biological processi
- cellular response to hypoxia Source: UniProtKB
- peptide catabolic process Source: GO_Central
- positive regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
- protein polyubiquitination Source: Reactome
- proteolysis Source: GO_Central
Keywordsi
Molecular function | Aminopeptidase, Hydrolase, Metalloprotease, Protease |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P55786 |
Reactomei | R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
SABIO-RKi | P55786 |
Protein family/group databases
MEROPSi | M01.010 |
Names & Taxonomyi
Protein namesi | Recommended name: Puromycin-sensitive aminopeptidase (EC:3.4.11.14)Short name: PSA Alternative name(s): Cytosol alanyl aminopeptidase Short name: AAP-S |
Gene namesi | Name:NPEPPS Synonyms:PSA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000141279.15 |
HGNCi | HGNC:7900, NPEPPS |
MIMi | 606793, gene |
neXtProti | NX_P55786 |
Subcellular locationi
Cytosol
- cytosol Source: HPA
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 353 | E → A: Reduces catalytic activity by 25,000-fold to 100,000-fold. 1 Publication | 1 | |
Mutagenesisi | 353 | E → Q: Reduces catalytic activity by 5,000-fold to 15,000-fold. 1 Publication | 1 | |
Mutagenesisi | 353 | E → V: Reduces catalytic activity by 300,000-fold to 500,000-fold. 1 Publication | 1 | |
Mutagenesisi | 438 | Y → F: Reduces catalytic activity by 1,000-fold to 2,500-fold. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 9520 |
OpenTargetsi | ENSG00000141279 |
PharmGKBi | PA31703 |
Miscellaneous databases
Pharosi | P55786, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2264 |
DrugBanki | DB11638, Artenimol DB11781, Tosedostat |
GuidetoPHARMACOLOGYi | 1575 |
Polymorphism and mutation databases
BioMutai | NPEPPS |
DMDMi | 51704228 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000095116 | 1 – 919 | Puromycin-sensitive aminopeptidaseAdd BLAST | 919 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 464 | 3'-nitrotyrosineBy similarity | 1 |
Keywords - PTMi
NitrationProteomic databases
CPTACi | CPTAC-415 CPTAC-416 |
EPDi | P55786 |
jPOSTi | P55786 |
MassIVEi | P55786 |
MaxQBi | P55786 |
PaxDbi | P55786 |
PeptideAtlasi | P55786 |
PRIDEi | P55786 |
ProteomicsDBi | 56864 [P55786-1] 6572 |
PTM databases
iPTMneti | P55786 |
MetOSitei | P55786 |
PhosphoSitePlusi | P55786 |
SwissPalmi | P55786 |
Expressioni
Tissue specificityi
Detected in liver, epithelium of renal tubules, epithelium of small and large intestine, gastric epithelial cells, and alveoli of the lung (at protein level).1 Publication
Gene expression databases
Bgeei | ENSG00000141279, Expressed in right hemisphere of cerebellum and 246 other tissues |
ExpressionAtlasi | P55786, baseline and differential |
Genevisiblei | P55786, HS |
Organism-specific databases
HPAi | ENSG00000141279, Low tissue specificity |
Interactioni
Subunit structurei
Monomer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 114897, 103 interactors |
IntActi | P55786, 24 interactors |
MINTi | P55786 |
STRINGi | 9606.ENSP00000320324 |
Chemistry databases
BindingDBi | P55786 |
Miscellaneous databases
RNActi | P55786, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 316 – 320 | Substrate bindingBy similarity | 5 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 726 – 730 | Nuclear localization signalSequence analysis | 5 |
Sequence similaritiesi
Belongs to the peptidase M1 family.Curated
Phylogenomic databases
eggNOGi | KOG1046, Eukaryota |
GeneTreei | ENSGT00940000155246 |
HOGENOMi | CLU_003705_0_1_1 |
InParanoidi | P55786 |
OMAi | MMEYVAI |
OrthoDBi | 1136568at2759 |
PhylomeDBi | P55786 |
TreeFami | TF300395 |
Family and domain databases
CDDi | cd09601, M1_APN-Q_like, 1 hit |
Gene3Di | 2.60.40.1730, 1 hit |
InterProi | View protein in InterPro IPR042097, Aminopeptidase_N-like_N IPR024571, ERAP1-like_C_dom IPR034016, M1_APN-typ IPR001930, Peptidase_M1 IPR014782, Peptidase_M1_dom |
Pfami | View protein in Pfam PF11838, ERAP1_C, 1 hit PF01433, Peptidase_M1, 1 hit |
PRINTSi | PR00756, ALADIPTASE |
SUPFAMi | SSF63737, SSF63737, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P55786-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MWLAAAAPSL ARRLLFLGPP PPPLLLLVFS RSSRRRLHSL GLAAMPEKRP
60 70 80 90 100
FERLPADVSP INYSLCLKPD LLDFTFEGKL EAAAQVRQAT NQIVMNCADI
110 120 130 140 150
DIITASYAPE GDEEIHATGF NYQNEDEKVT LSFPSTLQTG TGTLKIDFVG
160 170 180 190 200
ELNDKMKGFY RSKYTTPSGE VRYAAVTQFE ATDARRAFPC WDEPAIKATF
210 220 230 240 250
DISLVVPKDR VALSNMNVID RKPYPDDENL VEVKFARTPV MSTYLVAFVV
260 270 280 290 300
GEYDFVETRS KDGVCVRVYT PVGKAEQGKF ALEVAAKTLP FYKDYFNVPY
310 320 330 340 350
PLPKIDLIAI ADFAAGAMEN WGLVTYRETA LLIDPKNSCS SSRQWVALVV
360 370 380 390 400
GHELAHQWFG NLVTMEWWTH LWLNEGFASW IEYLCVDHCF PEYDIWTQFV
410 420 430 440 450
SADYTRAQEL DALDNSHPIE VSVGHPSEVD EIFDAISYSK GASVIRMLHD
460 470 480 490 500
YIGDKDFKKG MNMYLTKFQQ KNAATEDLWE SLENASGKPI AAVMNTWTKQ
510 520 530 540 550
MGFPLIYVEA EQVEDDRLLR LSQKKFCAGG SYVGEDCPQW MVPITISTSE
560 570 580 590 600
DPNQAKLKIL MDKPEMNVVL KNVKPDQWVK LNLGTVGFYR TQYSSAMLES
610 620 630 640 650
LLPGIRDLSL PPVDRLGLQN DLFSLARAGI ISTVEVLKVM EAFVNEPNYT
660 670 680 690 700
VWSDLSCNLG ILSTLLSHTD FYEEIQEFVK DVFSPIGERL GWDPKPGEGH
710 720 730 740 750
LDALLRGLVL GKLGKAGHKA TLEEARRRFK DHVEGKQILS ADLRSPVYLT
760 770 780 790 800
VLKHGDGTTL DIMLKLHKQA DMQEEKNRIE RVLGATLLPD LIQKVLTFAL
810 820 830 840 850
SEEVRPQDTV SVIGGVAGGS KHGRKAAWKF IKDNWEELYN RYQGGFLISR
860 870 880 890 900
LIKLSVEGFA VDKMAGEVKA FFESHPAPSA ERTIQQCCEN ILLNAAWLKR
910
DAESIHQYLL QRKASPPTV
Computationally mapped potential isoform sequencesi
There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE9PLK3 | E9PLK3_HUMAN | Aminopeptidase | NPEPPS | 915 | Annotation score: | ||
E9PJ74 | E9PJ74_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 158 | Annotation score: | ||
E9PI82 | E9PI82_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 127 | Annotation score: | ||
E9PRQ5 | E9PRQ5_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 172 | Annotation score: | ||
H0YDG0 | H0YDG0_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 169 | Annotation score: | ||
H0YCQ5 | H0YCQ5_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 65 | Annotation score: | ||
E9PP11 | E9PP11_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 201 | Annotation score: | ||
E9PJF9 | E9PJF9_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 134 | Annotation score: | ||
E9PJY4 | E9PJY4_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 141 | Annotation score: | ||
E9PPZ2 | E9PPZ2_HUMAN | Puromycin-sensitive aminopeptidase | NPEPPS | 178 | Annotation score: | ||
There is more potential isoformShow all |
Sequence cautioni
The sequence AAH65294 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence CAA68964 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 184 | A → P in CAA68964 (PubMed:9048733).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056446 | 1 – 44 | Missing in isoform 2. 1 PublicationAdd BLAST | 44 | |
Alternative sequenceiVSP_056447 | 181 – 216 | Missing in isoform 2. 1 PublicationAdd BLAST | 36 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y07701 mRNA Translation: CAA68964.1 Different initiation. AK296887 mRNA Translation: BAH12449.1 AC025682 Genomic DNA No translation available. BC065294 mRNA Translation: AAH65294.2 Different initiation. AJ132583 mRNA Translation: CAA10709.1 AF252387 Genomic DNA Translation: AAF70086.1 |
CCDSi | CCDS45721.1 [P55786-1] |
RefSeqi | NP_001317186.1, NM_001330257.1 NP_006301.3, NM_006310.3 [P55786-1] |
Genome annotation databases
Ensembli | ENST00000322157; ENSP00000320324; ENSG00000141279 [P55786-1] |
GeneIDi | 9520 |
KEGGi | hsa:9520 |
UCSCi | uc002ilr.5, human [P55786-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | Y07701 mRNA Translation: CAA68964.1 Different initiation. AK296887 mRNA Translation: BAH12449.1 AC025682 Genomic DNA No translation available. BC065294 mRNA Translation: AAH65294.2 Different initiation. AJ132583 mRNA Translation: CAA10709.1 AF252387 Genomic DNA Translation: AAF70086.1 |
CCDSi | CCDS45721.1 [P55786-1] |
RefSeqi | NP_001317186.1, NM_001330257.1 NP_006301.3, NM_006310.3 [P55786-1] |
3D structure databases
SMRi | P55786 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 114897, 103 interactors |
IntActi | P55786, 24 interactors |
MINTi | P55786 |
STRINGi | 9606.ENSP00000320324 |
Chemistry databases
BindingDBi | P55786 |
ChEMBLi | CHEMBL2264 |
DrugBanki | DB11638, Artenimol DB11781, Tosedostat |
GuidetoPHARMACOLOGYi | 1575 |
Protein family/group databases
MEROPSi | M01.010 |
PTM databases
iPTMneti | P55786 |
MetOSitei | P55786 |
PhosphoSitePlusi | P55786 |
SwissPalmi | P55786 |
Polymorphism and mutation databases
BioMutai | NPEPPS |
DMDMi | 51704228 |
Proteomic databases
CPTACi | CPTAC-415 CPTAC-416 |
EPDi | P55786 |
jPOSTi | P55786 |
MassIVEi | P55786 |
MaxQBi | P55786 |
PaxDbi | P55786 |
PeptideAtlasi | P55786 |
PRIDEi | P55786 |
ProteomicsDBi | 56864 [P55786-1] 6572 |
Protocols and materials databases
Antibodypediai | 8552, 272 antibodies |
Genome annotation databases
Ensembli | ENST00000322157; ENSP00000320324; ENSG00000141279 [P55786-1] |
GeneIDi | 9520 |
KEGGi | hsa:9520 |
UCSCi | uc002ilr.5, human [P55786-1] |
Organism-specific databases
CTDi | 9520 |
DisGeNETi | 9520 |
EuPathDBi | HostDB:ENSG00000141279.15 |
GeneCardsi | NPEPPS |
HGNCi | HGNC:7900, NPEPPS |
HPAi | ENSG00000141279, Low tissue specificity |
MIMi | 606793, gene |
neXtProti | NX_P55786 |
OpenTargetsi | ENSG00000141279 |
PharmGKBi | PA31703 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1046, Eukaryota |
GeneTreei | ENSGT00940000155246 |
HOGENOMi | CLU_003705_0_1_1 |
InParanoidi | P55786 |
OMAi | MMEYVAI |
OrthoDBi | 1136568at2759 |
PhylomeDBi | P55786 |
TreeFami | TF300395 |
Enzyme and pathway databases
PathwayCommonsi | P55786 |
Reactomei | R-HSA-983168, Antigen processing: Ubiquitination & Proteasome degradation |
SABIO-RKi | P55786 |
Miscellaneous databases
BioGRID-ORCSi | 9520, 255 hits in 847 CRISPR screens |
ChiTaRSi | NPEPPS, human |
GeneWikii | NPEPPS |
GenomeRNAii | 9520 |
Pharosi | P55786, Tchem |
PROi | PR:P55786 |
RNActi | P55786, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000141279, Expressed in right hemisphere of cerebellum and 246 other tissues |
ExpressionAtlasi | P55786, baseline and differential |
Genevisiblei | P55786, HS |
Family and domain databases
CDDi | cd09601, M1_APN-Q_like, 1 hit |
Gene3Di | 2.60.40.1730, 1 hit |
InterProi | View protein in InterPro IPR042097, Aminopeptidase_N-like_N IPR024571, ERAP1-like_C_dom IPR034016, M1_APN-typ IPR001930, Peptidase_M1 IPR014782, Peptidase_M1_dom |
Pfami | View protein in Pfam PF11838, ERAP1_C, 1 hit PF01433, Peptidase_M1, 1 hit |
PRINTSi | PR00756, ALADIPTASE |
SUPFAMi | SSF63737, SSF63737, 1 hit |
PROSITEi | View protein in PROSITE PS00142, ZINC_PROTEASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PSA_HUMAN | |
Accessioni | P55786Primary (citable) accession number: P55786 Secondary accession number(s): B7Z463 Q9UEM2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | August 31, 2004 | |
Last modified: | December 2, 2020 | |
This is version 192 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Peptidase families
Classification of peptidase families and list of entries