AMPE_GLOBR
ID AMPE_GLOBR Reviewed; 955 AA.
AC A5HUI5;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 03-AUG-2022, entry version 52.
DE RecName: Full=Aminopeptidase A {ECO:0000303|PubMed:17383704};
DE Short=AP-A {ECO:0000305};
DE Short=APA {ECO:0000303|PubMed:17383704};
DE EC=3.4.11.7 {ECO:0000269|PubMed:17383704};
DE AltName: Full=Glutamyl aminopeptidase {ECO:0000305};
DE Short=EAP {ECO:0000305};
OS Gloydius brevicaudus (Korean slamosa snake) (Agkistrodon halys
OS brevicaudus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Gloydius.
OX NCBI_TaxID=259325;
RN [1] {ECO:0000312|EMBL:BAF63164.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 211-223; 500-507; 544-559;
RP 594-613 AND 937-955, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Venom, and Venom gland;
RX PubMed=17383704; DOI=10.1016/j.toxicon.2007.02.012;
RA Ogawa Y., Murayama N., Fujita Y., Yanoshita R.;
RT "Characterization and cDNA cloning of aminopeptidase A from the venom of
RT Gloydius blomhoffi brevicaudus.";
RL Toxicon 49:1172-1181(2007).
CC -!- FUNCTION: Venom protein that cleaves N-terminal acidic residues from
CC peptides with high potency in presence of calcium (PubMed:17383704). It
CC may have several roles in venom including alteration of blood pressure
CC by cleaving circulating angiotensin-2, general degradation of host
CC tissue, increase of permeability to other venom components, and/or
CC processing of other toxins in the venom (By similarity).
CC {ECO:0000250|UniProtKB:D3UW23, ECO:0000250|UniProtKB:P0DQU2,
CC ECO:0000269|PubMed:17383704}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of N-terminal glutamate (and to a lesser extent
CC aspartate) from a peptide.; EC=3.4.11.7;
CC Evidence={ECO:0000269|PubMed:17383704};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q07075};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q07075};
CC -!- ACTIVITY REGULATION: The partially purified protein is inhibited by the
CC aminopeptidase competitive inhibitors amastatin (Leu and acidic
CC inhibitor), and bestatin (Leu inhibitor), by chelating agents EDTA, and
CC 1,10-Phenanthroline, as well as by Zn(2+) ions. Substrate specificity
CC is modulated by Ca(2+), Ba(2+), and Mn(2+) ions which enhances the
CC enzymatic activity for cleavage of acidic residues.
CC {ECO:0000269|PubMed:17383704}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.4 (measured only for partially purified enzyme).
CC {ECO:0000269|PubMed:17383704};
CC -!- SUBUNIT: Homodimer; disulfide-linked. {ECO:0000250|UniProtKB:Q07075}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q07075};
CC Single-pass type II membrane protein {ECO:0000255}. Note=Found in the
CC venom as transmembrane proteins in exosome-like vesicles.
CC {ECO:0000250|UniProtKB:P0DQU2}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAF63164.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB262071; BAF63164.1; ALT_INIT; mRNA.
DR MEROPS; M01.003; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070006; F:metalloaminopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd09601; M1_APN-Q_like; 1.
DR Gene3D; 1.10.390.10; -; 1.
DR Gene3D; 2.60.40.1730; -; 1.
DR InterPro; IPR033508; Aminopeptidase_A.
DR InterPro; IPR045357; Aminopeptidase_N-like_N.
DR InterPro; IPR042097; Aminopeptidase_N-like_N_sf.
DR InterPro; IPR024571; ERAP1-like_C_dom.
DR InterPro; IPR034016; M1_APN-typ.
DR InterPro; IPR001930; Peptidase_M1.
DR InterPro; IPR014782; Peptidase_M1_dom.
DR InterPro; IPR027268; Peptidase_M4/M1_CTD_sf.
DR PANTHER; PTHR11533:SF242; PTHR11533:SF242; 1.
DR Pfam; PF11838; ERAP1_C; 1.
DR Pfam; PF01433; Peptidase_M1; 1.
DR Pfam; PF17900; Peptidase_M1_N; 1.
DR PRINTS; PR00756; ALADIPTASE.
DR SUPFAM; SSF63737; SSF63737; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Aminopeptidase; Calcium; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Membrane; Metal-binding;
KW Metalloprotease; Protease; Signal-anchor; Transmembrane;
KW Transmembrane helix; Zinc.
FT CHAIN 1..955
FT /note="Aminopeptidase A"
FT /evidence="ECO:0000305|PubMed:17383704"
FT /id="PRO_0000455652"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 18..38
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..955
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-1"
FT BINDING 218
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-2"
FT BINDING 352..356
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-2"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-4"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-4"
FT BINDING 411
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-4"
FT BINDING 882
FT /ligand="substrate"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-2"
FT SITE 216
FT /note="Binds calcium which modulates its enzyme activity"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-3"
FT SITE 474
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PIRSR:PIRSR633508-3"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 118
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 312
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 319
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 547
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 584
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 592
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 647
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 674
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 681
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 759
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 766
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 823
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 836
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 955 AA; 109837 MW; 7962738BE564BFCB CRC64;
MDIEDKSSKM HCMKGKHVAI ICGVVIAVGL ILGLGLGLGL KPEACNPPED NGLLSTKPPT
TSTPNVTNPS GSSVFCSAKN DENGAWTNFR LPNYVQPVHY DLDLTPEMEA EVYTGMVNIS
IRLEEQTTRH LWLHLRETKI TEMPQLRTSS GQVIEIKRCF GYEPQEYVVI EAEEDLRPGN
YFLSMKFKGY LNGSLVGFYS TTYGENGKTK YIAATDHEPT DARKSFPCFD EPNKKATYTI
SITHEHDYEA ISNMPVEKTI SLDNKWTKTI FKKSVPMSTY LVAWAVHQFK YEERISSRGI
PLRVYAQPQQ INTTIYAANV TKVVFDYFEN YFNMNYSLPK LDKIAIPDFG TGAMENWGLI
TYRETNLLYD SQESAASNKQ RVAAVVAHEL VHQWFGNIVT MDWWDDLWLN EGFASFFEFM
GVNAKEEKWQ MLDQILIDDL LPVLKDDSLV SSHPITVNVS SPDEITSVFD GISYSKGASI
LRMLEDWISP DHFRAGCQKY LTDHYFKNAK TDDFWKAMEE VSGKPVREVM DTWTRQMGYP
VLKVDLNSTV TQQRFLLDPK ADPSKPSSQF SYKWNIPVKW KEGNTSSITF YNKSELAGIT
IMQPSDLPPD SFLKVNKDHV GFYRVNYEPQ VWRTLADIMM KDHQNFNLTD RAGFIDDAFA
LARAGLLKYA DALNLTRYLQ NETEYIPWQR AVVAVSYIGQ MVEDDKALYP KFQRYFGSLV
KPIASELKWE NDEDHIKSLL RTTVLEFACN MDDPEALGNA SLLFKNWTSG ISLDVNLRLL
VYRFGMQNSG DEQAWNYMFE KYRTATLAQE KEKLLYGLAS VKNITLLNRF LNCIKNTTLI
RSQDVFTVLR YISFNSYGKT MAWDWVRLNW EYLVKRYTLN DRNLGRLISR ISGTFNTELQ
LWQMENFFER YPDAGAGEAS RKQALETTKS NIEWLKQYRD DVATWLENSE QPNFV
