Full text data of XPNPEP1
XPNPEP1
(XPNPEPL, XPNPEPL1)
[Confidence: low (only semi-automatic identification from reviews)]
Xaa-Pro aminopeptidase 1; 3.4.11.9 (Aminoacylproline aminopeptidase; Cytosolic aminopeptidase P; Soluble aminopeptidase P; sAmp; X-Pro aminopeptidase 1; X-prolyl aminopeptidase 1, soluble)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Xaa-Pro aminopeptidase 1; 3.4.11.9 (Aminoacylproline aminopeptidase; Cytosolic aminopeptidase P; Soluble aminopeptidase P; sAmp; X-Pro aminopeptidase 1; X-prolyl aminopeptidase 1, soluble)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NQW7
ID XPP1_HUMAN Reviewed; 623 AA.
AC Q9NQW7; A8K071; G5E9Y2; O15250; Q53EX6; Q8N3Q0; Q96D23;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 114.
DE RecName: Full=Xaa-Pro aminopeptidase 1;
DE EC=3.4.11.9;
DE AltName: Full=Aminoacylproline aminopeptidase;
DE AltName: Full=Cytosolic aminopeptidase P;
DE AltName: Full=Soluble aminopeptidase P;
DE Short=sAmp;
DE AltName: Full=X-Pro aminopeptidase 1;
DE AltName: Full=X-prolyl aminopeptidase 1, soluble;
GN Name=XPNPEP1; Synonyms=XPNPEPL, XPNPEPL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=9465902;
RA Vanhoof G., Goossens F., Juliano M.A., Juliano L., Hendriks D.,
RA Schatteman K., Lin A.H., Scharpe S.;
RT "Isolation and sequence analysis of a human cDNA clone (XPNPEPL)
RT homologous to X-prolyl aminopeptidase (aminopeptidase P).";
RL Cytogenet. Cell Genet. 78:275-280(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10871044; DOI=10.1006/abbi.2000.1792;
RA Sprinkle T.J., Caldwell C., Ryan J.W.;
RT "Cloning, chromosomal sublocalization of the human soluble
RT aminopeptidase P gene (XPNPEP1) to 10q25.3 and conservation of the
RT putative proton shuttle and metal ligand binding sites with XPNPEP2.";
RL Arch. Biochem. Biophys. 378:51-56(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, COFACTOR,
RP ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC TISSUE=Pancreatic adenocarcinoma;
RX PubMed=11106490; DOI=10.1021/bi001585c;
RA Cottrell G.S., Hooper N.M., Turner A.J.;
RT "Cloning, expression, and characterization of human cytosolic
RT aminopeptidase P: a single manganese(II)-dependent enzyme.";
RL Biochemistry 39:15121-15128(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Ovary, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS,
RP COFACTOR, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP MUTAGENESIS OF GLU-41 AND TRP-477, AND SUBUNIT.
RX PubMed=18515364; DOI=10.1074/jbc.M710274200;
RA Li X., Lou Z., Li X., Zhou W., Ma M., Cao Y., Geng Y., Bartlam M.,
RA Zhang X.C., Rao Z.;
RT "Structure of human cytosolic X-prolyl aminopeptidase: a double
RT Mn(II)-dependent dimeric enzyme with a novel three-domain subunit.";
RL J. Biol. Chem. 283:22858-22866(2008).
CC -!- FUNCTION: Contributes to the degradation of bradykinin. Catalyzes
CC the removal of a penultimate prolyl residue from the N-termini of
CC peptides, such as Arg-Pro-Pro.
CC -!- CATALYTIC ACTIVITY: Release of any N-terminal amino acid,
CC including proline, that is linked to proline, even from a
CC dipeptide or tripeptide.
CC -!- COFACTOR: Binds 2 manganese ions per subunit.
CC -!- ENZYME REGULATION: Inhibited by apstatin and the metal ion
CC chelators EDTA and 1,10-phenanthroline. Partially inhibited by
CC dithiothreitol. Not inhibited by enalaprilat or amastatin.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100.6 uM for bradykinin;
CC KM=308 uM for the tripeptide Arg-Pro-Pro;
CC pH dependence:
CC Optimum pH is 8.2;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NQW7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQW7-2; Sequence=VSP_051752;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9NQW7-3; Sequence=VSP_045250;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, including
CC pancreas, heart, muscle, kidney, liver, lung and brain. Highest
CC levels in pancreas.
CC -!- SIMILARITY: Belongs to the peptidase M24B family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD38640.1; Type=Erroneous initiation;
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DR EMBL; X95762; CAA65068.1; -; mRNA.
DR EMBL; AF195530; AAF97866.1; -; mRNA.
DR EMBL; AF272981; AAF75795.1; -; mRNA.
DR EMBL; AK289436; BAF82125.1; -; mRNA.
DR EMBL; CR456922; CAG33203.1; -; mRNA.
DR EMBL; AK223513; BAD97233.1; -; mRNA.
DR EMBL; AL833411; CAD38640.1; ALT_INIT; mRNA.
DR EMBL; AL354951; CAI14248.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49577.1; -; Genomic_DNA.
DR EMBL; BC005126; AAH05126.1; -; mRNA.
DR EMBL; BC007579; AAH07579.1; -; mRNA.
DR EMBL; BC013417; AAH13417.4; -; mRNA.
DR RefSeq; NP_001161076.1; NM_001167604.1.
DR RefSeq; NP_065116.3; NM_020383.3.
DR UniGene; Hs.390623; -.
DR PDB; 3CTZ; X-ray; 1.60 A; A=1-623.
DR PDBsum; 3CTZ; -.
DR ProteinModelPortal; Q9NQW7; -.
DR SMR; Q9NQW7; 3-619.
DR IntAct; Q9NQW7; 7.
DR MINT; MINT-3039782; -.
DR STRING; 9606.ENSP00000358694; -.
DR BindingDB; Q9NQW7; -.
DR ChEMBL; CHEMBL3782; -.
DR MEROPS; M24.009; -.
DR PhosphoSite; Q9NQW7; -.
DR DMDM; 68566146; -.
DR PaxDb; Q9NQW7; -.
DR PRIDE; Q9NQW7; -.
DR DNASU; 7511; -.
DR Ensembl; ENST00000369680; ENSP00000358694; ENSG00000108039.
DR Ensembl; ENST00000502935; ENSP00000421566; ENSG00000108039.
DR GeneID; 7511; -.
DR KEGG; hsa:7511; -.
DR UCSC; uc001kyp.2; human.
DR CTD; 7511; -.
DR GeneCards; GC10M111614; -.
DR HGNC; HGNC:12822; XPNPEP1.
DR HPA; CAB025196; -.
DR HPA; HPA030419; -.
DR HPA; HPA030420; -.
DR HPA; HPA030422; -.
DR MIM; 602443; gene.
DR neXtProt; NX_Q9NQW7; -.
DR PharmGKB; PA37415; -.
DR eggNOG; COG0006; -.
DR HOGENOM; HOG000255713; -.
DR HOVERGEN; HBG002934; -.
DR InParanoid; Q9NQW7; -.
DR KO; K01262; -.
DR OMA; YRPGKWG; -.
DR BRENDA; 3.4.11.9; 2681.
DR ChiTaRS; XPNPEP1; human.
DR EvolutionaryTrace; Q9NQW7; -.
DR GeneWiki; XPNPEP1; -.
DR GenomeRNAi; 7511; -.
DR NextBio; 29395; -.
DR PRO; PR:Q9NQW7; -.
DR ArrayExpress; Q9NQW7; -.
DR Bgee; Q9NQW7; -.
DR CleanEx; HS_XPNPEP1; -.
DR Genevestigator; Q9NQW7; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0010815; P:bradykinin catabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR Gene3D; 3.90.230.10; -; 1.
DR InterPro; IPR000587; Creatinase.
DR InterPro; IPR000994; Pept_M24_structural-domain.
DR InterPro; IPR001131; Peptidase_M24B_aminopep-P_CS.
DR Pfam; PF01321; Creatinase_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR PROSITE; PS00491; PROLINE_PEPTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Aminopeptidase;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Manganese; Metal-binding; Metalloprotease; Protease;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 623 Xaa-Pro aminopeptidase 1.
FT /FTId=PRO_0000185083.
FT METAL 415 415 Manganese 1.
FT METAL 426 426 Manganese 1.
FT METAL 426 426 Manganese 2.
FT METAL 489 489 Manganese 2.
FT METAL 523 523 Manganese 2.
FT METAL 537 537 Manganese 1.
FT METAL 537 537 Manganese 2.
FT MOD_RES 304 304 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MAASRKPPRVRVNHQDFQLRNLRIIEPNEVTHSGDT
FT GVETDGRM (in isoform 3).
FT /FTId=VSP_045250.
FT VAR_SEQ 398 421 Missing (in isoform 2).
FT /FTId=VSP_051752.
FT MUTAGEN 41 41 E->A: Reduces activity by 10%.
FT MUTAGEN 477 477 W->E: Interferes with dimerization and
FT reduces activity by 94%.
FT CONFLICT 90 90 W -> C (in Ref. 10; AAH13417).
FT CONFLICT 131 131 K -> R (in Ref. 4; BAF82125).
FT CONFLICT 332 332 R -> P (in Ref. 1 and 2).
FT CONFLICT 496 496 N -> D (in Ref. 7).
FT CONFLICT 498 498 H -> R (in Ref. 7).
FT CONFLICT 572 572 I -> T (in Ref. 4; BAF82125).
FT HELIX 7 16
FT TURN 20 22
FT STRAND 28 32
FT HELIX 45 47
FT HELIX 49 54
FT STRAND 62 68
FT STRAND 70 74
FT HELIX 76 78
FT HELIX 79 85
FT STRAND 90 94
FT HELIX 103 110
FT STRAND 116 119
FT HELIX 121 123
FT HELIX 126 138
FT STRAND 142 145
FT HELIX 150 154
FT HELIX 171 174
FT HELIX 178 190
FT TURN 191 193
FT STRAND 194 199
FT HELIX 202 209
FT STRAND 215 219
FT STRAND 225 231
FT STRAND 233 236
FT HELIX 240 243
FT HELIX 245 250
FT TURN 251 254
FT HELIX 259 261
FT STRAND 263 266
FT HELIX 268 270
FT HELIX 271 280
FT STRAND 287 291
FT HELIX 296 301
FT HELIX 304 306
FT STRAND 307 312
FT HELIX 314 320
FT HELIX 324 351
FT HELIX 352 354
FT HELIX 359 371
FT STRAND 376 381
FT STRAND 384 387
FT HELIX 388 392
FT HELIX 400 402
FT STRAND 412 416
FT STRAND 418 420
FT STRAND 427 431
FT HELIX 438 455
FT HELIX 465 472
FT HELIX 474 478
FT STRAND 487 490
FT STRAND 493 495
FT STRAND 519 522
FT STRAND 525 528
FT TURN 529 531
FT STRAND 532 535
FT STRAND 537 545
FT STRAND 552 554
FT STRAND 556 561
FT HELIX 569 571
FT HELIX 574 576
FT HELIX 579 602
FT HELIX 606 614
SQ SEQUENCE 623 AA; 69918 MW; DF4F5AF41E2F3876 CRC64;
MPPKVTSELL RQLRQAMRNS EYVTEPIQAY IIPSGDAHQS EYIAPCDCRR AFVSGFDGSA
GTAIITEEHA AMWTDGRYFL QAAKQMDSNW TLMKMGLKDT PTQEDWLVSV LPEGSRVGVD
PLIIPTDYWK KMAKVLRSAG HHLIPVKENL VDKIWTDRPE RPCKPLLTLG LDYTGISWKD
KVADLRLKMA ERNVMWFVVT ALDEIAWLFN LRGSDVEHNP VFFSYAIIGL ETIMLFIDGD
RIDAPSVKEH LLLDLGLEAE YRIQVHPYKS ILSELKALCA DLSPREKVWV SDKASYAVSE
TIPKDHRCCM PYTPICIAKA VKNSAESEGM RRAHIKDAVA LCELFNWLEK EVPKGGVTEI
SAADKAEEFR RQQADFVDLS FPTISSTGPN GAIIHYAPVP ETNRTLSLDE VYLIDSGAQY
KDGTTDVTRT MHFGTPTAYE KECFTYVLKG HIAVSAAVFP TGTKGHLLDS FARSALWDSG
LDYLHGTGHG VGSFLNVHEG PCGISYKTFS DEPLEAGMIV TDEPGYYEDG AFGIRIENVV
LVVPVKTKYN FNNRGSLTFE PLTLVPIQTK MIDVDSLTDK ECDWLNNYHL TCRDVIGKEL
QKQGRQEALE WLIRETQPIS KQH
//
ID XPP1_HUMAN Reviewed; 623 AA.
AC Q9NQW7; A8K071; G5E9Y2; O15250; Q53EX6; Q8N3Q0; Q96D23;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 114.
DE RecName: Full=Xaa-Pro aminopeptidase 1;
DE EC=3.4.11.9;
DE AltName: Full=Aminoacylproline aminopeptidase;
DE AltName: Full=Cytosolic aminopeptidase P;
DE AltName: Full=Soluble aminopeptidase P;
DE Short=sAmp;
DE AltName: Full=X-Pro aminopeptidase 1;
DE AltName: Full=X-prolyl aminopeptidase 1, soluble;
GN Name=XPNPEP1; Synonyms=XPNPEPL, XPNPEPL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Lymphocyte;
RX PubMed=9465902;
RA Vanhoof G., Goossens F., Juliano M.A., Juliano L., Hendriks D.,
RA Schatteman K., Lin A.H., Scharpe S.;
RT "Isolation and sequence analysis of a human cDNA clone (XPNPEPL)
RT homologous to X-prolyl aminopeptidase (aminopeptidase P).";
RL Cytogenet. Cell Genet. 78:275-280(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10871044; DOI=10.1006/abbi.2000.1792;
RA Sprinkle T.J., Caldwell C., Ryan J.W.;
RT "Cloning, chromosomal sublocalization of the human soluble
RT aminopeptidase P gene (XPNPEP1) to 10q25.3 and conservation of the
RT putative proton shuttle and metal ligand binding sites with XPNPEP2.";
RL Arch. Biochem. Biophys. 378:51-56(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, COFACTOR,
RP ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RC TISSUE=Pancreatic adenocarcinoma;
RX PubMed=11106490; DOI=10.1021/bi001585c;
RA Cottrell G.S., Hooper N.M., Turner A.J.;
RT "Cloning, expression, and characterization of human cytosolic
RT aminopeptidase P: a single manganese(II)-dependent enzyme.";
RL Biochemistry 39:15121-15128(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Adipose tissue;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Ovary, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-304, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH MANGANESE IONS,
RP COFACTOR, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP MUTAGENESIS OF GLU-41 AND TRP-477, AND SUBUNIT.
RX PubMed=18515364; DOI=10.1074/jbc.M710274200;
RA Li X., Lou Z., Li X., Zhou W., Ma M., Cao Y., Geng Y., Bartlam M.,
RA Zhang X.C., Rao Z.;
RT "Structure of human cytosolic X-prolyl aminopeptidase: a double
RT Mn(II)-dependent dimeric enzyme with a novel three-domain subunit.";
RL J. Biol. Chem. 283:22858-22866(2008).
CC -!- FUNCTION: Contributes to the degradation of bradykinin. Catalyzes
CC the removal of a penultimate prolyl residue from the N-termini of
CC peptides, such as Arg-Pro-Pro.
CC -!- CATALYTIC ACTIVITY: Release of any N-terminal amino acid,
CC including proline, that is linked to proline, even from a
CC dipeptide or tripeptide.
CC -!- COFACTOR: Binds 2 manganese ions per subunit.
CC -!- ENZYME REGULATION: Inhibited by apstatin and the metal ion
CC chelators EDTA and 1,10-phenanthroline. Partially inhibited by
CC dithiothreitol. Not inhibited by enalaprilat or amastatin.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100.6 uM for bradykinin;
CC KM=308 uM for the tripeptide Arg-Pro-Pro;
CC pH dependence:
CC Optimum pH is 8.2;
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NQW7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQW7-2; Sequence=VSP_051752;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q9NQW7-3; Sequence=VSP_045250;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in all tissues tested, including
CC pancreas, heart, muscle, kidney, liver, lung and brain. Highest
CC levels in pancreas.
CC -!- SIMILARITY: Belongs to the peptidase M24B family.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD38640.1; Type=Erroneous initiation;
CC -----------------------------------------------------------------------
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DR EMBL; X95762; CAA65068.1; -; mRNA.
DR EMBL; AF195530; AAF97866.1; -; mRNA.
DR EMBL; AF272981; AAF75795.1; -; mRNA.
DR EMBL; AK289436; BAF82125.1; -; mRNA.
DR EMBL; CR456922; CAG33203.1; -; mRNA.
DR EMBL; AK223513; BAD97233.1; -; mRNA.
DR EMBL; AL833411; CAD38640.1; ALT_INIT; mRNA.
DR EMBL; AL354951; CAI14248.1; -; Genomic_DNA.
DR EMBL; CH471066; EAW49577.1; -; Genomic_DNA.
DR EMBL; BC005126; AAH05126.1; -; mRNA.
DR EMBL; BC007579; AAH07579.1; -; mRNA.
DR EMBL; BC013417; AAH13417.4; -; mRNA.
DR RefSeq; NP_001161076.1; NM_001167604.1.
DR RefSeq; NP_065116.3; NM_020383.3.
DR UniGene; Hs.390623; -.
DR PDB; 3CTZ; X-ray; 1.60 A; A=1-623.
DR PDBsum; 3CTZ; -.
DR ProteinModelPortal; Q9NQW7; -.
DR SMR; Q9NQW7; 3-619.
DR IntAct; Q9NQW7; 7.
DR MINT; MINT-3039782; -.
DR STRING; 9606.ENSP00000358694; -.
DR BindingDB; Q9NQW7; -.
DR ChEMBL; CHEMBL3782; -.
DR MEROPS; M24.009; -.
DR PhosphoSite; Q9NQW7; -.
DR DMDM; 68566146; -.
DR PaxDb; Q9NQW7; -.
DR PRIDE; Q9NQW7; -.
DR DNASU; 7511; -.
DR Ensembl; ENST00000369680; ENSP00000358694; ENSG00000108039.
DR Ensembl; ENST00000502935; ENSP00000421566; ENSG00000108039.
DR GeneID; 7511; -.
DR KEGG; hsa:7511; -.
DR UCSC; uc001kyp.2; human.
DR CTD; 7511; -.
DR GeneCards; GC10M111614; -.
DR HGNC; HGNC:12822; XPNPEP1.
DR HPA; CAB025196; -.
DR HPA; HPA030419; -.
DR HPA; HPA030420; -.
DR HPA; HPA030422; -.
DR MIM; 602443; gene.
DR neXtProt; NX_Q9NQW7; -.
DR PharmGKB; PA37415; -.
DR eggNOG; COG0006; -.
DR HOGENOM; HOG000255713; -.
DR HOVERGEN; HBG002934; -.
DR InParanoid; Q9NQW7; -.
DR KO; K01262; -.
DR OMA; YRPGKWG; -.
DR BRENDA; 3.4.11.9; 2681.
DR ChiTaRS; XPNPEP1; human.
DR EvolutionaryTrace; Q9NQW7; -.
DR GeneWiki; XPNPEP1; -.
DR GenomeRNAi; 7511; -.
DR NextBio; 29395; -.
DR PRO; PR:Q9NQW7; -.
DR ArrayExpress; Q9NQW7; -.
DR Bgee; Q9NQW7; -.
DR CleanEx; HS_XPNPEP1; -.
DR Genevestigator; Q9NQW7; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IDA:UniProtKB.
DR GO; GO:0010815; P:bradykinin catabolic process; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR Gene3D; 3.90.230.10; -; 1.
DR InterPro; IPR000587; Creatinase.
DR InterPro; IPR000994; Pept_M24_structural-domain.
DR InterPro; IPR001131; Peptidase_M24B_aminopep-P_CS.
DR Pfam; PF01321; Creatinase_N; 1.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR PROSITE; PS00491; PROLINE_PEPTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Aminopeptidase;
KW Complete proteome; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Manganese; Metal-binding; Metalloprotease; Protease;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 623 Xaa-Pro aminopeptidase 1.
FT /FTId=PRO_0000185083.
FT METAL 415 415 Manganese 1.
FT METAL 426 426 Manganese 1.
FT METAL 426 426 Manganese 2.
FT METAL 489 489 Manganese 2.
FT METAL 523 523 Manganese 2.
FT METAL 537 537 Manganese 1.
FT METAL 537 537 Manganese 2.
FT MOD_RES 304 304 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MAASRKPPRVRVNHQDFQLRNLRIIEPNEVTHSGDT
FT GVETDGRM (in isoform 3).
FT /FTId=VSP_045250.
FT VAR_SEQ 398 421 Missing (in isoform 2).
FT /FTId=VSP_051752.
FT MUTAGEN 41 41 E->A: Reduces activity by 10%.
FT MUTAGEN 477 477 W->E: Interferes with dimerization and
FT reduces activity by 94%.
FT CONFLICT 90 90 W -> C (in Ref. 10; AAH13417).
FT CONFLICT 131 131 K -> R (in Ref. 4; BAF82125).
FT CONFLICT 332 332 R -> P (in Ref. 1 and 2).
FT CONFLICT 496 496 N -> D (in Ref. 7).
FT CONFLICT 498 498 H -> R (in Ref. 7).
FT CONFLICT 572 572 I -> T (in Ref. 4; BAF82125).
FT HELIX 7 16
FT TURN 20 22
FT STRAND 28 32
FT HELIX 45 47
FT HELIX 49 54
FT STRAND 62 68
FT STRAND 70 74
FT HELIX 76 78
FT HELIX 79 85
FT STRAND 90 94
FT HELIX 103 110
FT STRAND 116 119
FT HELIX 121 123
FT HELIX 126 138
FT STRAND 142 145
FT HELIX 150 154
FT HELIX 171 174
FT HELIX 178 190
FT TURN 191 193
FT STRAND 194 199
FT HELIX 202 209
FT STRAND 215 219
FT STRAND 225 231
FT STRAND 233 236
FT HELIX 240 243
FT HELIX 245 250
FT TURN 251 254
FT HELIX 259 261
FT STRAND 263 266
FT HELIX 268 270
FT HELIX 271 280
FT STRAND 287 291
FT HELIX 296 301
FT HELIX 304 306
FT STRAND 307 312
FT HELIX 314 320
FT HELIX 324 351
FT HELIX 352 354
FT HELIX 359 371
FT STRAND 376 381
FT STRAND 384 387
FT HELIX 388 392
FT HELIX 400 402
FT STRAND 412 416
FT STRAND 418 420
FT STRAND 427 431
FT HELIX 438 455
FT HELIX 465 472
FT HELIX 474 478
FT STRAND 487 490
FT STRAND 493 495
FT STRAND 519 522
FT STRAND 525 528
FT TURN 529 531
FT STRAND 532 535
FT STRAND 537 545
FT STRAND 552 554
FT STRAND 556 561
FT HELIX 569 571
FT HELIX 574 576
FT HELIX 579 602
FT HELIX 606 614
SQ SEQUENCE 623 AA; 69918 MW; DF4F5AF41E2F3876 CRC64;
MPPKVTSELL RQLRQAMRNS EYVTEPIQAY IIPSGDAHQS EYIAPCDCRR AFVSGFDGSA
GTAIITEEHA AMWTDGRYFL QAAKQMDSNW TLMKMGLKDT PTQEDWLVSV LPEGSRVGVD
PLIIPTDYWK KMAKVLRSAG HHLIPVKENL VDKIWTDRPE RPCKPLLTLG LDYTGISWKD
KVADLRLKMA ERNVMWFVVT ALDEIAWLFN LRGSDVEHNP VFFSYAIIGL ETIMLFIDGD
RIDAPSVKEH LLLDLGLEAE YRIQVHPYKS ILSELKALCA DLSPREKVWV SDKASYAVSE
TIPKDHRCCM PYTPICIAKA VKNSAESEGM RRAHIKDAVA LCELFNWLEK EVPKGGVTEI
SAADKAEEFR RQQADFVDLS FPTISSTGPN GAIIHYAPVP ETNRTLSLDE VYLIDSGAQY
KDGTTDVTRT MHFGTPTAYE KECFTYVLKG HIAVSAAVFP TGTKGHLLDS FARSALWDSG
LDYLHGTGHG VGSFLNVHEG PCGISYKTFS DEPLEAGMIV TDEPGYYEDG AFGIRIENVV
LVVPVKTKYN FNNRGSLTFE PLTLVPIQTK MIDVDSLTDK ECDWLNNYHL TCRDVIGKEL
QKQGRQEALE WLIRETQPIS KQH
//
MIM
602443
*RECORD*
*FIELD* NO
602443
*FIELD* TI
*602443 X-PROLYL AMINOPEPTIDASE 1; XPNPEP1
;;X-PROLYL AMINOPEPTIDASE-LIKE; XPNPEPL;;
read moreAMINOPEPTIDASE P-LIKE;;
AMINOPEPTIDASE P, SOLUBLE; SAMP;;
AMINOPEPTIDASE P, CYTOSOLIC;;
APP1
*FIELD* TX
DESCRIPTION
X-prolyl aminopeptidase (EC 3.4.11.9) is a proline-specific
metalloaminopeptidase that specifically catalyzes the removal of any
unsubstituted N-terminal amino acid that is adjacent to a penultimate
proline residue. Because of its specificity toward proline, it has been
suggested that X-prolyl aminopeptidase is important in the maturation
and degradation of peptide hormones, neuropeptides, and tachykinins, as
well as in the digestion of otherwise resistant dietary protein
fragments, thereby complementing the pancreatic peptidases. Deficiency
of X-prolyl aminopeptidase results in excretion of large amounts of
imino-oligopeptides in urine (Blau et al., 1988).
CLONING
X-prolyl aminopeptidase has been isolated from different tissues and
species. Vergas Romero et al. (1995) reported the complete amino acid
sequence of the pig kidney enzyme. The nucleotide sequences of the
X-prolyl aminopeptidase-encoding genes (pepP) from several
microorganisms have been reported. By RT-PCR of
phytohemagglutinin-stimulated lymphocyte mRNA, Vanhoof et al. (1997)
isolated a novel human cDNA, named XPNPEPL, that encodes a 623-amino
acid protein exhibiting 44% sequence identity and 62% sequence
similarity to pig kidney X-prolyl aminopeptidase and high sequence
homology to proteins in S. pombe and S. cerevisiae. Northern blot
analysis indicated ubiquitous expression of XPNPEPL as a 2.7-kb
transcript, with the highest expression in pancreas, followed by heart
and muscle.
Sprinkle et al. (2000) cloned XPNPEPL, which they termed soluble
aminopeptidase P (SAMP), or XPNPEP1. They noted the presence of 4 blocks
of sequences homologous to E. coli methionine aminopeptidase, which is
part of the 'pita-bread fold' family. Like the bacteria enzyme, XPNPEPL
contains a putative proton shuttle (residue 395) and 5 divalent metal
ligands (residues 415, 426, 485, 523, and 537). Sprinkle et al. (2000)
proposed that the enzyme inactivates bradykinin and is part of an
intracellular kallikrein-kinin system, possibly in secretory vesicles.
Cottrell et al. (2000) cloned and characterized XPNPEPL, which they
designated cytosolic APP. They identified an arg residue at position 332
instead of the pro residue reported by Vanhoof et al. (1997) and
determined that the cytosolic protein is 43% identical to membrane
aminopeptidase P (XPNPEP2; 300145). The cytosolic enzyme lacks the
hydrophobic signal sequences for an N-terminal signal peptide and a
C-terminal GPI anchor found in the membrane-bound enzyme. Immunoblot
analysis showed expression of a 71-kD homodimer protein capable of
hydrolyzing bradykinin in a divalent cation-dependent manner, similar to
XPNPEP2. The principal metal in the purified recombinant protein was
manganese, at an approximately 1:1 molar ratio.
Using RT-PCR, Ersahin et al. (2005) detected APP1 expression in all
human tissues examined with high expression in pancreas, liver, kidney,
and testis. There was fairly uniform expression in T cells, B cells, and
monocytes. APP1 functions as a soluble cytosolic homodimer of about 70
kD and exhibits broad substrate specificity.
GENE FUNCTION
Oh et al. (2004) described a hypothesis-driven, systems biology approach
to identifying a small subset of proteins induced at the tissue-blood
interface that are inherently accessible to antibodies injected
intravenously. They used subcellular fractionation, subtractive
proteomics, and bioinformatics to identify endothelial cell surface
proteins exhibiting restricted tissue distribution and apparent tissue
modulation. Expression profiling and gamma-scintigraphic imaging with
antibodies established 2 of these proteins, aminopeptidase-P and annexin
A1 (151690), as selective in vivo targets for antibodies in lung and
solid tumors, respectively. Radioimmunotherapy to annexin A1 destroyed
tumors and increased animal survival.
MAPPING
Using FISH and somatic hybrid analysis, Sprinkle et al. (2000) mapped
the XPNPEPL gene to chromosome 10q25.3, distinct from the Xq25
localization of XPNPEP2.
MOLECULAR GENETICS
- Associations Pending Confirmation
To identify loci contributing to susceptibility to biliary atresia
(210500), characterized by the progressive fibrosclerosing obliteration
of the extrahepatic biliary system during the first few weeks of life,
Garcia-Barcelo et al. (2010) carried out a genomewide association study
(GWAS) using nearly 500,000 single-nucleotide polymorphisms (SNPs) in
200 Chinese biliary atresia patients and 481 ethnically matched control
subjects. The 10 most associated SNPs from the GWAS were genotyped in an
independent set of 124 BA and 90 control subjects. The strongest overall
association was found for dbSNP rs17095355 on chromosome 10q24, 68 kb
downstream from XPNPEP1.
*FIELD* RF
1. Blau, N.; Niederwieser, A.; Shmerling, D. H.: Peptiduria presumably
caused by aminopeptidase-P deficiency: a new inborn error of metabolism. J.
Inherit. Metab. Dis. 11 (suppl): 240-242, 1988.
2. Cottrell, G. S.; Hooper, N. M.; Turner, A. J.: Cloning, expression,
and characterization of human cytosolic aminopeptidase P: a single
manganese(II)-dependent enzyme. Biochemistry 39: 15121-15128, 2000.
3. Ersahin, C.; Szpaderska, A. M.; Orawski, A. T.; Simmons, W. H.
: Aminopeptidase P isozyme expression in human tissues and peripheral
blood mononuclear cell fractions. Arch. Biochem. Biophys. 435: 303-310,
2005.
4. Garcia-Barcelo, M.-M.; Yeung, M.-Y.; Miao, X.-P.; Tang, C. S.-M.;
Chen, G.; So, M.-T.; Ngan, E. S.-W.; Lui, V. C.-H.; Chen, Y.; Liu,
X.-L.; Hui, K.-J. W. S.; Li, L.; and 13 others: Genome-wide association
study identifies a susceptibility locus for biliary atresia on 10q24.2. Hum.
Molec. Genet. 19: 2917-2925, 2010.
5. Oh, P.; Li, Y.; Yu, J.; Durr, E.; Krasinska, K. M.; Carver, L.
A.; Testa, J. E.; Schnitzer, J. E.: Subtractive proteomic mapping
of the endothelial surface in lung and solid tumours for tissue-specific
therapy. Nature 429: 629-635, 2004.
6. Sprinkle, T. J.; Caldwell, C.; Ryan, J. W.: Cloning, chromosomal
sublocalization of the human soluble aminopeptidase P gene (XPNPEP1)
to 10q25.3 and conservation of the putative proton shuttle and metal
ligand binding sites with XPNPEP2. Arch. Biochem. Biophys. 378:
51-56, 2000.
7. Vanhoof, G.; Goossens, F.; Juliano, M. A.; Juliano, L.; Hendriks,
D.; Schatteman, K.; Lin, A. H.; Scharpe, S.: Isolation and sequence
analysis of a human cDNA clone (XPNPEPL) homologous to X-prolyl aminopeptidase
(aminopeptidase P). Cytogenet. Cell Genet. 78: 275-280, 1997.
8. Vergas Romero, C.; Neudorfer, I.; Mann, K.; Schafer, W.: Purification
and amino acid sequence of aminopeptidase P from pig kidney. Europ.
J. Biochem. 229: 262-269, 1995.
*FIELD* CN
George E. Tiller - updated: 09/06/2013
Patricia A. Hartz - updated: 9/7/2010
Ada Hamosh - updated: 7/26/2004
Paul J. Converse - updated: 6/24/2002
*FIELD* CD
Victor A. McKusick: 3/16/1998
*FIELD* ED
alopez: 09/06/2013
wwang: 9/7/2010
alopez: 7/26/2004
terry: 7/26/2004
alopez: 11/3/2003
mgross: 6/24/2002
mgross: 6/21/2002
dholmes: 4/1/1998
psherman: 3/16/1998
*RECORD*
*FIELD* NO
602443
*FIELD* TI
*602443 X-PROLYL AMINOPEPTIDASE 1; XPNPEP1
;;X-PROLYL AMINOPEPTIDASE-LIKE; XPNPEPL;;
read moreAMINOPEPTIDASE P-LIKE;;
AMINOPEPTIDASE P, SOLUBLE; SAMP;;
AMINOPEPTIDASE P, CYTOSOLIC;;
APP1
*FIELD* TX
DESCRIPTION
X-prolyl aminopeptidase (EC 3.4.11.9) is a proline-specific
metalloaminopeptidase that specifically catalyzes the removal of any
unsubstituted N-terminal amino acid that is adjacent to a penultimate
proline residue. Because of its specificity toward proline, it has been
suggested that X-prolyl aminopeptidase is important in the maturation
and degradation of peptide hormones, neuropeptides, and tachykinins, as
well as in the digestion of otherwise resistant dietary protein
fragments, thereby complementing the pancreatic peptidases. Deficiency
of X-prolyl aminopeptidase results in excretion of large amounts of
imino-oligopeptides in urine (Blau et al., 1988).
CLONING
X-prolyl aminopeptidase has been isolated from different tissues and
species. Vergas Romero et al. (1995) reported the complete amino acid
sequence of the pig kidney enzyme. The nucleotide sequences of the
X-prolyl aminopeptidase-encoding genes (pepP) from several
microorganisms have been reported. By RT-PCR of
phytohemagglutinin-stimulated lymphocyte mRNA, Vanhoof et al. (1997)
isolated a novel human cDNA, named XPNPEPL, that encodes a 623-amino
acid protein exhibiting 44% sequence identity and 62% sequence
similarity to pig kidney X-prolyl aminopeptidase and high sequence
homology to proteins in S. pombe and S. cerevisiae. Northern blot
analysis indicated ubiquitous expression of XPNPEPL as a 2.7-kb
transcript, with the highest expression in pancreas, followed by heart
and muscle.
Sprinkle et al. (2000) cloned XPNPEPL, which they termed soluble
aminopeptidase P (SAMP), or XPNPEP1. They noted the presence of 4 blocks
of sequences homologous to E. coli methionine aminopeptidase, which is
part of the 'pita-bread fold' family. Like the bacteria enzyme, XPNPEPL
contains a putative proton shuttle (residue 395) and 5 divalent metal
ligands (residues 415, 426, 485, 523, and 537). Sprinkle et al. (2000)
proposed that the enzyme inactivates bradykinin and is part of an
intracellular kallikrein-kinin system, possibly in secretory vesicles.
Cottrell et al. (2000) cloned and characterized XPNPEPL, which they
designated cytosolic APP. They identified an arg residue at position 332
instead of the pro residue reported by Vanhoof et al. (1997) and
determined that the cytosolic protein is 43% identical to membrane
aminopeptidase P (XPNPEP2; 300145). The cytosolic enzyme lacks the
hydrophobic signal sequences for an N-terminal signal peptide and a
C-terminal GPI anchor found in the membrane-bound enzyme. Immunoblot
analysis showed expression of a 71-kD homodimer protein capable of
hydrolyzing bradykinin in a divalent cation-dependent manner, similar to
XPNPEP2. The principal metal in the purified recombinant protein was
manganese, at an approximately 1:1 molar ratio.
Using RT-PCR, Ersahin et al. (2005) detected APP1 expression in all
human tissues examined with high expression in pancreas, liver, kidney,
and testis. There was fairly uniform expression in T cells, B cells, and
monocytes. APP1 functions as a soluble cytosolic homodimer of about 70
kD and exhibits broad substrate specificity.
GENE FUNCTION
Oh et al. (2004) described a hypothesis-driven, systems biology approach
to identifying a small subset of proteins induced at the tissue-blood
interface that are inherently accessible to antibodies injected
intravenously. They used subcellular fractionation, subtractive
proteomics, and bioinformatics to identify endothelial cell surface
proteins exhibiting restricted tissue distribution and apparent tissue
modulation. Expression profiling and gamma-scintigraphic imaging with
antibodies established 2 of these proteins, aminopeptidase-P and annexin
A1 (151690), as selective in vivo targets for antibodies in lung and
solid tumors, respectively. Radioimmunotherapy to annexin A1 destroyed
tumors and increased animal survival.
MAPPING
Using FISH and somatic hybrid analysis, Sprinkle et al. (2000) mapped
the XPNPEPL gene to chromosome 10q25.3, distinct from the Xq25
localization of XPNPEP2.
MOLECULAR GENETICS
- Associations Pending Confirmation
To identify loci contributing to susceptibility to biliary atresia
(210500), characterized by the progressive fibrosclerosing obliteration
of the extrahepatic biliary system during the first few weeks of life,
Garcia-Barcelo et al. (2010) carried out a genomewide association study
(GWAS) using nearly 500,000 single-nucleotide polymorphisms (SNPs) in
200 Chinese biliary atresia patients and 481 ethnically matched control
subjects. The 10 most associated SNPs from the GWAS were genotyped in an
independent set of 124 BA and 90 control subjects. The strongest overall
association was found for dbSNP rs17095355 on chromosome 10q24, 68 kb
downstream from XPNPEP1.
*FIELD* RF
1. Blau, N.; Niederwieser, A.; Shmerling, D. H.: Peptiduria presumably
caused by aminopeptidase-P deficiency: a new inborn error of metabolism. J.
Inherit. Metab. Dis. 11 (suppl): 240-242, 1988.
2. Cottrell, G. S.; Hooper, N. M.; Turner, A. J.: Cloning, expression,
and characterization of human cytosolic aminopeptidase P: a single
manganese(II)-dependent enzyme. Biochemistry 39: 15121-15128, 2000.
3. Ersahin, C.; Szpaderska, A. M.; Orawski, A. T.; Simmons, W. H.
: Aminopeptidase P isozyme expression in human tissues and peripheral
blood mononuclear cell fractions. Arch. Biochem. Biophys. 435: 303-310,
2005.
4. Garcia-Barcelo, M.-M.; Yeung, M.-Y.; Miao, X.-P.; Tang, C. S.-M.;
Chen, G.; So, M.-T.; Ngan, E. S.-W.; Lui, V. C.-H.; Chen, Y.; Liu,
X.-L.; Hui, K.-J. W. S.; Li, L.; and 13 others: Genome-wide association
study identifies a susceptibility locus for biliary atresia on 10q24.2. Hum.
Molec. Genet. 19: 2917-2925, 2010.
5. Oh, P.; Li, Y.; Yu, J.; Durr, E.; Krasinska, K. M.; Carver, L.
A.; Testa, J. E.; Schnitzer, J. E.: Subtractive proteomic mapping
of the endothelial surface in lung and solid tumours for tissue-specific
therapy. Nature 429: 629-635, 2004.
6. Sprinkle, T. J.; Caldwell, C.; Ryan, J. W.: Cloning, chromosomal
sublocalization of the human soluble aminopeptidase P gene (XPNPEP1)
to 10q25.3 and conservation of the putative proton shuttle and metal
ligand binding sites with XPNPEP2. Arch. Biochem. Biophys. 378:
51-56, 2000.
7. Vanhoof, G.; Goossens, F.; Juliano, M. A.; Juliano, L.; Hendriks,
D.; Schatteman, K.; Lin, A. H.; Scharpe, S.: Isolation and sequence
analysis of a human cDNA clone (XPNPEPL) homologous to X-prolyl aminopeptidase
(aminopeptidase P). Cytogenet. Cell Genet. 78: 275-280, 1997.
8. Vergas Romero, C.; Neudorfer, I.; Mann, K.; Schafer, W.: Purification
and amino acid sequence of aminopeptidase P from pig kidney. Europ.
J. Biochem. 229: 262-269, 1995.
*FIELD* CN
George E. Tiller - updated: 09/06/2013
Patricia A. Hartz - updated: 9/7/2010
Ada Hamosh - updated: 7/26/2004
Paul J. Converse - updated: 6/24/2002
*FIELD* CD
Victor A. McKusick: 3/16/1998
*FIELD* ED
alopez: 09/06/2013
wwang: 9/7/2010
alopez: 7/26/2004
terry: 7/26/2004
alopez: 11/3/2003
mgross: 6/24/2002
mgross: 6/21/2002
dholmes: 4/1/1998
psherman: 3/16/1998