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Database: UniProt
Entry: DNPEP_HUMAN
LinkDB: DNPEP_HUMAN
Original site: DNPEP_HUMAN 
ID   DNPEP_HUMAN             Reviewed;         475 AA.
AC   Q9ULA0; Q9BW44; Q9NUV5; Q9NV55;
DT   24-OCT-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   20-JUN-2018, entry version 161.
DE   RecName: Full=Aspartyl aminopeptidase;
DE            EC=3.4.11.21;
GN   Name=DNPEP; Synonyms=ASPEP, DAP;
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], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=9632644; DOI=10.1074/jbc.273.26.15961;
RA   Wilk S., Wilk E., Magnusson R.P.;
RT   "Purification, characterization, and cloning of a cytosolic aspartyl
RT   aminopeptidase.";
RL   J. Biol. Chem. 273:15961-15970(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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   [5]
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   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY
RP   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   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-468 IN COMPLEX WITH
RP   SUBSTRATE ANALOG, ZINC-BINDING SITES, SUBSTRATE-BINDING SITES, AND
RP   SUBUNIT.
RX   PubMed=22720794; DOI=10.1186/1472-6807-12-14;
RA   Chaikuad A., Pilka E.S., Riso A.D., Delft F.V., Kavanagh K.L.,
RA   Venien-Bryan C., Oppermann U., Yue W.W.;
RT   "Structure of human aspartyl aminopeptidase complexed with substrate
RT   analogue: insight into catalytic mechanism, substrate specificity and
RT   M18 peptidase family.";
RL   BMC Struct. Biol. 12:14-14(2012).
CC   -!- FUNCTION: Aminopeptidase with specificity towards an acidic amino
CC       acid at the N-terminus. Likely to play an important role in
CC       intracellular protein and peptide metabolism.
CC       {ECO:0000269|PubMed:9632644}.
CC   -!- CATALYTIC ACTIVITY: Release of an N-terminal aspartate or
CC       glutamate from a peptide, with a preference for aspartate.
CC       {ECO:0000269|PubMed:9632644}.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC         Evidence={ECO:0000269|PubMed:9632644};
CC       Note=Binds 2 Zn(2+) ions per subunit.
CC       {ECO:0000269|PubMed:9632644};
CC   -!- ENZYME REGULATION: One of the zinc ions is readily exchangeable
CC       with other divalent cations such as manganese, which strongly
CC       stimulates the enzymatic activity. {ECO:0000250}.
CC   -!- SUBUNIT: Tetrahedron-shaped homododecamer built from six
CC       homodimers. {ECO:0000269|PubMed:22720794}.
CC   -!- INTERACTION:
CC       Self; NbExp=3; IntAct=EBI-748356, EBI-748356;
CC       Q8TBB1:LNX1; NbExp=5; IntAct=EBI-748356, EBI-739832;
CC       Q00013:MPP1; NbExp=5; IntAct=EBI-748356, EBI-711788;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9632644}.
CC   -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:9632644}.
CC   -!- SIMILARITY: Belongs to the peptidase M18 family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-5 is the initiator.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA91903.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
CC       Sequence=BAA91903.1; Type=Frameshift; Positions=398; Evidence={ECO:0000305};
CC       Sequence=BAA92014.1; Type=Erroneous initiation; Evidence={ECO:0000305};
DR   EMBL; AF005050; AAD01211.2; -; mRNA.
DR   EMBL; AK001777; BAA91903.1; ALT_SEQ; mRNA.
DR   EMBL; AK001977; BAA92014.1; ALT_INIT; mRNA.
DR   EMBL; AC053503; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC000653; AAH00653.2; -; mRNA.
DR   RefSeq; NP_001306049.1; NM_001319120.1.
DR   RefSeq; NP_036232.2; NM_012100.3.
DR   UniGene; Hs.258551; -.
DR   UniGene; Hs.635110; -.
DR   PDB; 4DYO; X-ray; 2.20 A; A=1-468.
DR   PDBsum; 4DYO; -.
DR   ProteinModelPortal; Q9ULA0; -.
DR   SMR; Q9ULA0; -.
DR   BioGrid; 117093; 42.
DR   IntAct; Q9ULA0; 7.
DR   STRING; 9606.ENSP00000273075; -.
DR   BindingDB; Q9ULA0; -.
DR   ChEMBL; CHEMBL2761; -.
DR   DrugBank; DB00142; L-Glutamic Acid.
DR   GuidetoPHARMACOLOGY; 1559; -.
DR   MEROPS; M18.002; -.
DR   iPTMnet; Q9ULA0; -.
DR   PhosphoSitePlus; Q9ULA0; -.
DR   BioMuta; DNPEP; -.
DR   DMDM; 17367145; -.
DR   EPD; Q9ULA0; -.
DR   MaxQB; Q9ULA0; -.
DR   PaxDb; Q9ULA0; -.
DR   PeptideAtlas; Q9ULA0; -.
DR   PRIDE; Q9ULA0; -.
DR   ProteomicsDB; 84965; -.
DR   DNASU; 23549; -.
DR   Ensembl; ENST00000273075; ENSP00000273075; ENSG00000123992.
DR   GeneID; 23549; -.
DR   KEGG; hsa:23549; -.
DR   UCSC; uc002vle.3; human.
DR   CTD; 23549; -.
DR   EuPathDB; HostDB:ENSG00000123992.18; -.
DR   GeneCards; DNPEP; -.
DR   HGNC; HGNC:2981; DNPEP.
DR   HPA; HPA036398; -.
DR   HPA; HPA044860; -.
DR   MIM; 611367; gene.
DR   neXtProt; NX_Q9ULA0; -.
DR   PharmGKB; PA27448; -.
DR   eggNOG; KOG2596; Eukaryota.
DR   eggNOG; COG1362; LUCA.
DR   HOGENOM; HOG000253244; -.
DR   HOVERGEN; HBG051386; -.
DR   InParanoid; Q9ULA0; -.
DR   KO; K01267; -.
DR   PhylomeDB; Q9ULA0; -.
DR   TreeFam; TF300487; -.
DR   GeneWiki; DNPEP; -.
DR   GenomeRNAi; 23549; -.
DR   PRO; PR:Q9ULA0; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000123992; -.
DR   CleanEx; HS_DAP; -.
DR   CleanEx; HS_DNPEP; -.
DR   ExpressionAtlas; Q9ULA0; baseline and differential.
DR   Genevisible; Q9ULA0; HS.
DR   GO; GO:0072562; C:blood microparticle; HDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR   GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0070006; F:metalloaminopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006518; P:peptide metabolic process; TAS:ProtInc.
DR   Gene3D; 2.30.250.10; -; 1.
DR   InterPro; IPR001948; Peptidase_M18.
DR   InterPro; IPR023358; Peptidase_M18_dom2.
DR   PANTHER; PTHR28570; PTHR28570; 1.
DR   Pfam; PF02127; Peptidase_M18; 1.
DR   PRINTS; PR00932; AMINO1PTASE.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Aminopeptidase; Complete proteome;
KW   Cytoplasm; Hydrolase; Metal-binding; Metalloprotease; Phosphoprotein;
KW   Protease; Reference proteome; Zinc.
FT   CHAIN         1    475       Aspartyl aminopeptidase.
FT                                /FTId=PRO_0000173451.
FT   METAL        94     94       Zinc 1. {ECO:0000269|PubMed:22720794}.
FT   METAL       264    264       Zinc 1. {ECO:0000269|PubMed:22720794}.
FT   METAL       264    264       Zinc 2. {ECO:0000269|PubMed:22720794}.
FT   METAL       302    302       Zinc 2. {ECO:0000269|PubMed:22720794}.
FT   METAL       346    346       Zinc 1. {ECO:0000269|PubMed:22720794}.
FT   METAL       440    440       Zinc 2. {ECO:0000269|PubMed:22720794}.
FT   BINDING     170    170       Substrate. {ECO:0000269|PubMed:22720794}.
FT   BINDING     301    301       Substrate. {ECO:0000269|PubMed:22720794}.
FT   BINDING     346    346       Substrate. {ECO:0000269|PubMed:22720794}.
FT   BINDING     349    349       Substrate. {ECO:0000269|PubMed:22720794}.
FT   BINDING     374    374       Substrate. {ECO:0000269|PubMed:22720794}.
FT   BINDING     381    381       Substrate. {ECO:0000269|PubMed:22720794}.
FT   MOD_RES       1      1       N-acetylmethionine.
FT                                {ECO:0000244|PubMed:22814378}.
FT   MOD_RES     203    203       Phosphothreonine.
FT                                {ECO:0000244|PubMed:24275569}.
FT   CONFLICT    119    119       E -> V (in Ref. 2; BAA92014).
FT                                {ECO:0000305}.
FT   HELIX         8     26       {ECO:0000244|PDB:4DYO}.
FT   HELIX        31     44       {ECO:0000244|PDB:4DYO}.
FT   STRAND       63     68       {ECO:0000244|PDB:4DYO}.
FT   TURN         69     71       {ECO:0000244|PDB:4DYO}.
FT   STRAND       72     78       {ECO:0000244|PDB:4DYO}.
FT   STRAND       88     94       {ECO:0000244|PDB:4DYO}.
FT   STRAND       99    110       {ECO:0000244|PDB:4DYO}.
FT   STRAND      113    123       {ECO:0000244|PDB:4DYO}.
FT   HELIX       126    129       {ECO:0000244|PDB:4DYO}.
FT   STRAND      134    143       {ECO:0000244|PDB:4DYO}.
FT   TURN        145    147       {ECO:0000244|PDB:4DYO}.
FT   STRAND      150    156       {ECO:0000244|PDB:4DYO}.
FT   HELIX       169    171       {ECO:0000244|PDB:4DYO}.
FT   TURN        173    177       {ECO:0000244|PDB:4DYO}.
FT   TURN        183    186       {ECO:0000244|PDB:4DYO}.
FT   STRAND      190    193       {ECO:0000244|PDB:4DYO}.
FT   HELIX       194    200       {ECO:0000244|PDB:4DYO}.
FT   HELIX       218    228       {ECO:0000244|PDB:4DYO}.
FT   HELIX       232    234       {ECO:0000244|PDB:4DYO}.
FT   STRAND      235    244       {ECO:0000244|PDB:4DYO}.
FT   STRAND      249    251       {ECO:0000244|PDB:4DYO}.
FT   TURN        252    255       {ECO:0000244|PDB:4DYO}.
FT   STRAND      257    260       {ECO:0000244|PDB:4DYO}.
FT   HELIX       263    279       {ECO:0000244|PDB:4DYO}.
FT   TURN        283    288       {ECO:0000244|PDB:4DYO}.
FT   STRAND      291    299       {ECO:0000244|PDB:4DYO}.
FT   HELIX       301    303       {ECO:0000244|PDB:4DYO}.
FT   HELIX       315    324       {ECO:0000244|PDB:4DYO}.
FT   HELIX       332    336       {ECO:0000244|PDB:4DYO}.
FT   HELIX       337    339       {ECO:0000244|PDB:4DYO}.
FT   STRAND      341    345       {ECO:0000244|PDB:4DYO}.
FT   HELIX       356    358       {ECO:0000244|PDB:4DYO}.
FT   STRAND      372    374       {ECO:0000244|PDB:4DYO}.
FT   TURN        377    380       {ECO:0000244|PDB:4DYO}.
FT   HELIX       385    398       {ECO:0000244|PDB:4DYO}.
FT   STRAND      403    405       {ECO:0000244|PDB:4DYO}.
FT   HELIX       417    425       {ECO:0000244|PDB:4DYO}.
FT   STRAND      428    433       {ECO:0000244|PDB:4DYO}.
FT   STRAND      435    438       {ECO:0000244|PDB:4DYO}.
FT   STRAND      441    448       {ECO:0000244|PDB:4DYO}.
FT   HELIX       449    468       {ECO:0000244|PDB:4DYO}.
SQ   SEQUENCE   475 AA;  52428 MW;  A02BDCFB516BD081 CRC64;
     MQVAMNGKAR KEAVQTAAKE LLKFVNRSPS PFHAVAECRN RLLQAGFSEL KETEKWNIKP
     ESKYFMTRNS STIIAFAVGG QYVPGNGFSL IGAHTDSPCL RVKRRSRRSQ VGFQQVGVET
     YGGGIWSTWF DRDLTLAGRV IVKCPTSGRL EQQLVHVERP ILRIPHLAIH LQRNINENFG
     PNTEMHLVPI LATAIQEELE KGTPEPGPLN AVDERHHSVL MSLLCAHLGL SPKDIVEMEL
     CLADTQPAVL GGAYDEFIFA PRLDNLHSCF CALQALIDSC AGPGSLATEP HVRMVTLYDN
     EEVGSESAQG AQSLLTELVL RRISASCQHP TAFEEAIPKS FMISADMAHA VHPNYLDKHE
     ENHRPLFHKG PVIKVNSKQR YASNAVSEAL IREVANKVKV PLQDLMVRND TPCGTTIGPI
     LASRLGLRVL DLGSPQLAMH SIREMACTTG VLQTLTLFKG FFELFPSLSH NLLVD
//
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