Q11011 (PSA_MOUSE) 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

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	920 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. Ref.1
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+ By similarity.
Subunit structure	Monomer By similarity.
Subcellular location	Cytoplasm › cytosol. Nucleus Ref.1.
Tissue specificity	Widely expressed. Highest expression in brain, particularly the striatum and hippocampus. Expressed in Sertoli cells. Ref.1 Ref.6 Ref.8
Disruption phenotype	Mice exhibit dwarfism, increased anxiety, impaired pain responses and do not reproduce as well as wild-type mice. More MHC class I molecules are displayed on dendritic cell surfaces. Ref.6 Ref.7 Ref.8 Ref.10
Sequence similarities	Belongs to the peptidase M1 family.
Caution	It is uncertain whether Met-1 or Met-46 is the initiator.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding Zinc
Molecular function	Aminopeptidase Hydrolase Metalloprotease Protease
PTM	Acetylation Nitration
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	aminopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 920	920	Puromycin-sensitive aminopeptidase		PRO_0000095117
Regions
	Region	317 – 321	5	Substrate binding By similarity
	Motif	727 – 731	5	Nuclear localization signal Potential
Sites
	Active site	354	1	Proton acceptor By similarity
	Metal binding	353	1	Zinc; catalytic By similarity
	Metal binding	357	1	Zinc; catalytic By similarity
	Metal binding	376	1	Zinc; catalytic By similarity
	Binding site	181	1	Substrate By similarity
	Site	439	1	Transition state stabilizer By similarity
Amino acid modifications
	Modified residue	49	1	N6-acetyllysine By similarity
	Modified residue	465	1	Nitrated tyrosine Ref.9
Experimental info
	Sequence conflict	185	1	A → P in AAC52409. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q11011 [UniParc]. Last modified July 13, 2010. Version 2. Checksum: BECF4139F074A356	FASTA	920	103,325
	10 20 30 40 50 60 MWLAAAVPSL ARRLLLLGPP PPPLLLLLSR SSRRRRRLHS LGLAAMPEKR PFERLPAEVS 70 80 90 100 110 120 PINYSLCLKP DLLDFTFEGK LEAAAQVRQA TNQIVMNCAD IDIITASYAP EGDEEIHATG 130 140 150 160 170 180 FNYQNEDEKV TLSFPSTLQT GTGTLKIDFV GELNDKMKGF YRSRYTTPAG EVRYAAVTQF 190 200 210 220 230 240 EATDARRAFP CWDEPAIKAT FDISLVVPKD RVALSNMNVI DRKPYPDDEN LVEVKFARTP 250 260 270 280 290 300 VMSTYLVAFV VGEYDFVETR SKDGVCVRVY TPVGKAEQGK FALEVAAKTL PFYKDYFNVP 310 320 330 340 350 360 YPLPKIDLIA IADFAAGAME NWGLVTYRET ALLIDPKNSC SSSRQWVALV VGHELAHQWF 370 380 390 400 410 420 GNLVTMEWWT HLWLNEGFAS WIEYLCVDHC FPEYDIWTQF VSADYTRAQE LDALDNSHPI 430 440 450 460 470 480 EVSVGHPSEV DEIFDAISYS KGASVIRMLH DYIGDKDFKK GMNMYLTKFQ QKNAATEDLW 490 500 510 520 530 540 ESLESASGKP IAAVMNTWTK QMGFPLIYVE AEQVEDDRVL KLSQKKFCAS GPYGGEDCPQ 550 560 570 580 590 600 WMVPITISTS EDPNQAKLKI LMDKPEMSVV LKNVKPDQWV KLNLGTVGFY RTQYSSAMLE 610 620 630 640 650 660 SLLPGIRDLS LPPVDRLGLQ NDLFSLARAG IISTVEVLKV MEAFVNEPNY TVWSDLSCNL 670 680 690 700 710 720 GILSTLLSHT DFYEEIQEFV KDVFSPIGER LGWDPKPGEG HLDALLRGLV LGKLGKAGHK 730 740 750 760 770 780 ATLEEARRRF KEHVEGKQIL SADLRSPVYL TVLKHGDGAT LDIMLKLHKQ ADMQEEKNRI 790 800 810 820 830 840 ERVLGATLSP ELIQKVLTFA LSEEVRPQDT VSVIGGVAGG SKHGRKAAWK FIKDNWEELH 850 860 870 880 890 900 NRYQGGFLIS RLIKLSVEGF AVDKMAGEVK AFFESHPAPS AERTIQQCCE NILLNAAWLK 910 920 RDADSIHQYL LQRKTSPPSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Puromycin-sensitive aminopeptidase. Sequence analysis, expression, and functional characterization." Constam D.B., Tobler A.R., Rensing-Ehl A., Kemler I., Hersh L.B., Fontana A. J. Biol. Chem. 270:26931-26939(1995) [PubMed: 7592939] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6 and FVB/N. Tissue: Brain and Mammary tumor.
[5]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 26-920. Strain: C57BL/6J. Tissue: Embryo.
[6]	"Increased anxiety and impaired pain response in puromycin-sensitive aminopeptidase gene-deficient mice obtained by a mouse gene-trap method." Osada T., Ikegami S., Takiguchi-Hayashi K., Yamazaki Y., Katoh-Fukui Y., Higashinakagawa T., Sakaki Y., Takeuchi T. J. Neurosci. 19:6068-6078(1999) [PubMed: 10407043] [Abstract] Cited for: TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[7]	"Puromycin-sensitive aminopeptidase is essential for the maternal recognition of pregnancy in mice." Osada T., Watanabe G., Sakaki Y., Takeuchi T. Mol. Endocrinol. 15:882-893(2001) [PubMed: 11376108] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[8]	"Male reproductive defects caused by puromycin-sensitive aminopeptidase deficiency in mice." Osada T., Watanabe G., Kondo S., Toyoda M., Sakaki Y., Takeuchi T. Mol. Endocrinol. 15:960-971(2001) [PubMed: 11376114] [Abstract] Cited for: TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[9]	"Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease." Sacksteder C.A., Qian W.-J., Knyushko T.V., Wang H., Chin M.H., Lacan G., Melega W.P., Camp D.G. II, Smith R.D., Smith D.J., Squier T.C., Bigelow D.J. Biochemistry 45:8009-8022(2006) [PubMed: 16800626] [Abstract] Cited for: NITRATION [LARGE SCALE ANALYSIS] AT TYR-465, MASS SPECTROMETRY. Tissue: Brain.
[10]	"Puromycin-sensitive aminopeptidase limits MHC class I presentation in dendritic cells but does not affect CD8 T cell responses during viral infections." Towne C.F., York I.A., Neijssen J., Karow M.L., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Neefjes J.J., Rock K.L. J. Immunol. 180:1704-1712(2008) [PubMed: 18209067] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U35646 mRNA. Translation: AAC52409.1. AL627445 Genomic DNA. Translation: CAM26998.1. CH466556 Genomic DNA. Translation: EDL16075.1. BC009653 mRNA. Translation: AAH09653.1. BC086798 mRNA. Translation: AAH86798.1. BC098212 mRNA. Translation: AAH98212.1. AK133898 mRNA. Translation: BAE21917.1.
IPI	IPI00130000.
PIR	T10052.
RefSeq	NP_032968.2. NM_008942.2.
UniGene	Mm.29824.
3D structure databases
ProteinModelPortal	Q11011.
SMR	Q11011. Positions 48-916.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q11011. 1 interaction.
STRING	Q11011.
Protein family/group databases
MEROPS	M01.010.
PTM databases
PhosphoSite	Q11011.
Proteomic databases
PRIDE	Q11011.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000001480; ENSMUSP00000001480; ENSMUSG00000001441.
GeneID	19155.
KEGG	mmu:19155.
UCSC	uc007ldv.1. mouse.
Organism-specific databases
CTD	9520.
MGI	MGI:1101358. Npepps.
Phylogenomic databases
GeneTree	ENSGT00560000076993.
HOGENOM	HBG515894.
HOVERGEN	HBG106325.
InParanoid	Q11011.
OMA	LIGTQFE.
OrthoDB	EOG4S7JP9.
PhylomeDB	Q11011.
Gene expression databases
ArrayExpress	Q11011.
Bgee	Q11011.
CleanEx	MM_NPEPPS.
Genevestigator	Q11011.
GermOnline	ENSMUSG00000001441. Mus musculus.
Family and domain databases
InterPro	IPR001930. Peptidase_M1. IPR014782. Peptidase_M1_N. IPR015568. Peptidase_M1_puromycin-sens. [Graphical view]
KO	K08776.
PANTHER	PTHR11533:SF33. Pept_M1_puromysin-sens. 1 hit. PTHR11533. Peptidase_M1. 1 hit.
Pfam	PF01433. Peptidase_M1. 1 hit. [Graphical view]
PRINTS	PR00756. ALADIPTASE.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

PSA_MOUSE

Accession

Primary (citable) accession number: Q11011
Secondary accession number(s): Q3UZE0, Q5PR74, Q91VJ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 13, 2010
Last modified:	November 16, 2011
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program