ID   DNPEP_BOVIN             Reviewed;         471 AA.
AC   Q2HJH1;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   03-AUG-2022, entry version 100.
DE   RecName: Full=Aspartyl aminopeptidase {ECO:0000250|UniProtKB:Q9ULA0};
DE            EC=3.4.11.21 {ECO:0000250|UniProtKB:Q9ULA0};
GN   Name=DNPEP {ECO:0000250|UniProtKB:Q9ULA0};
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 3-471, ELECTRON MICROSCOPY (22
RP   ANGSTROMS), ZINC-BINDING SITES, AND ACTIVITY REGULATION.
RX   PubMed=22356908; DOI=10.1074/jbc.m112.347518;
RA   Chen Y., Farquhar E.R., Chance M.R., Palczewski K., Kiser P.D.;
RT   "Insights into substrate specificity and metal activation of mammalian
RT   tetrahedral aspartyl aminopeptidase.";
RL   J. Biol. Chem. 287:13356-13370(2012).
CC   -!- FUNCTION: Aminopeptidase with specificity towards an acidic amino acid
CC       at the N-terminus. Likely to play an important role in intracellular
CC       protein and peptide metabolism (By similarity). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of an N-terminal aspartate or glutamate from a
CC         peptide, with a preference for aspartate.; EC=3.4.11.21;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 2 Zn(2+) ions per subunit.;
CC   -!- ACTIVITY REGULATION: One of the zinc ions is readily exchangeable with
CC       other divalent cations such as manganese, which strongly stimulates the
CC       enzymatic activity. {ECO:0000269|PubMed:22356908}.
CC   -!- SUBUNIT: Tetrahedron-shaped homododecamer built from six homodimers.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- SIMILARITY: Belongs to the peptidase M18 family. {ECO:0000305}.
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DR   EMBL; BC105402; AAI05403.1; -; mRNA.
DR   RefSeq; NP_001039417.1; NM_001045952.1.
DR   PDB; 3VAR; X-ray; 2.25 A; A=3-471.
DR   PDB; 3VAT; X-ray; 2.10 A; A=3-471.
DR   PDBsum; 3VAR; -.
DR   PDBsum; 3VAT; -.
DR   AlphaFoldDB; Q2HJH1; -.
DR   SMR; Q2HJH1; -.
DR   STRING; 9913.ENSBTAP00000028671; -.
DR   MEROPS; M18.002; -.
DR   PaxDb; Q2HJH1; -.
DR   PeptideAtlas; Q2HJH1; -.
DR   PRIDE; Q2HJH1; -.
DR   Ensembl; ENSBTAT00000028671; ENSBTAP00000028671; ENSBTAG00000021514.
DR   GeneID; 506882; -.
DR   KEGG; bta:506882; -.
DR   CTD; 23549; -.
DR   VEuPathDB; HostDB:ENSBTAG00000021514; -.
DR   VGNC; VGNC:28148; DNPEP.
DR   eggNOG; KOG2596; Eukaryota.
DR   GeneTree; ENSGT00390000003164; -.
DR   HOGENOM; CLU_019532_2_0_1; -.
DR   InParanoid; Q2HJH1; -.
DR   OMA; GPILKVN; -.
DR   OrthoDB; 769270at2759; -.
DR   TreeFam; TF300487; -.
DR   Proteomes; UP000009136; Chromosome 2.
DR   Bgee; ENSBTAG00000021514; Expressed in spermatid and 106 other tissues.
DR   ExpressionAtlas; Q2HJH1; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 2.30.250.10; -; 1.
DR   InterPro; IPR014720; dsRBD_dom.
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; Aminopeptidase; Cytoplasm; Hydrolase; Metal-binding;
KW   Metalloprotease; Phosphoprotein; Protease; Reference proteome; Zinc.
FT   CHAIN           1..471
FT                   /note="Aspartyl aminopeptidase"
FT                   /id="PRO_0000284910"
FT   BINDING         90
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         166
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         260
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         260
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   BINDING         297
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         298
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   BINDING         342
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         342
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         345
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         370
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         377
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         436
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT   MOD_RES         199
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ULA0"
FT   HELIX           5..22
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           27..40
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          59..64
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   TURN            65..67
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          68..74
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          84..90
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          95..106
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          109..119
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           122..125
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          130..139
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   TURN            141..143
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          146..152
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           165..167
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   TURN            169..173
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   TURN            179..183
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          186..189
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           190..196
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           214..224
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           228..230
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          231..240
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          245..247
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   TURN            248..251
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          253..256
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           259..275
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           279..284
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          287..295
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           297..299
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          303..306
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           311..320
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           328..332
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           333..335
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          337..341
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           352..354
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          368..370
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   TURN            373..376
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           381..394
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          399..401
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           413..421
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          424..429
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          431..434
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   STRAND          437..444
FT                   /evidence="ECO:0007829|PDB:3VAT"
FT   HELIX           445..466
FT                   /evidence="ECO:0007829|PDB:3VAT"
SQ   SEQUENCE   471 AA;  51828 MW;  35BD6BBAE2D5158C CRC64;
     MSGRARKEAV QAAARELLKF VNRSPSPFHA VAECRSRLLQ AGFHELKETE SWDIKPESKY
     FLTRNSSTII AFAVGGQYVP GNGFSLIGAH TDSPCLRVKR RSRRSQVGFQ QVGVETYGGG
     IWSTWFDRDL TLAGRVIVKC PTSGRLEQRL VHVDRPILRI PHLAIHLQRN VNENFGPNME
     MHLVPILATS IQEELEKGTP EPGPLNATDE RHHSVLTSLL CAHLGLSPED ILEMELCLAD
     TQPAVLGGAY EEFIFAPRLD NLHSCFCALQ ALIDSCSAPA SLAADPHVRM IALYDNEEVG
     SESAQGAQSL LTELVLRRIS ASPQHLTAFE EAIPKSYMIS ADMAHAVHPN YLDKHEENHR
     PLFHKGPVIK VNSKQRYASN AVSEALIREV ASSVGVPLQD LMVRNDSPCG TTIGPILASR
     LGLRVLDLGS PQLAMHSIRE TACTTGVLQT ITLFKGFFEL FPSLSRSLLV D