AMPE_BITRH
ID AMPE_BITRH Reviewed; 955 AA.
AC D3UW23;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Glutamyl aminopeptidase {ECO:0000303|PubMed:20706583};
DE Short=EAP {ECO:0000305};
DE EC=3.4.11.7 {ECO:0000269|PubMed:20706583};
DE AltName: Full=Aminopeptidase A {ECO:0000303|PubMed:20706583};
DE Short=AP-A {ECO:0000303|PubMed:20706583};
DE AltName: Full=Rhiminopeptidase A {ECO:0000303|PubMed:20706583};
OS Bitis rhinoceros (West African gaboon viper) (Vipera rhinoceros).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Bitis.
OX NCBI_TaxID=715877;
RN [1] {ECO:0000312|EMBL:CBJ34330.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 653-663, IDENTIFICATION BY
RP MASS SPECTROMETRY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES,
RP GLYCOSYLATION, X-RAY CRYSTALLOGRAPHY (7.5 ANGSTROMS), AND 3D-STRUCTURE
RP MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=20706583; DOI=10.1371/journal.pntd.0000796;
RA Vaiyapuri S., Wagstaff S.C., Watson K.A., Harrison R.A., Gibbins J.M.,
RA Hutchinson E.G.;
RT "Purification and functional characterisation of rhiminopeptidase A, a
RT novel aminopeptidase from the venom of Bitis gabonica rhinoceros.";
RL PLoS Negl. Trop. Dis. 4:e796-e796(2010).
CC -!- FUNCTION: Venom protein that cleaves N-terminal acidic residues from
CC peptides with high potency in presence of calcium (PubMed:20706583). 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:P0DQU2, ECO:0000269|PubMed:20706583}.
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:20706583};
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: Substrate specificity is modulated by calcium
CC which enhances the enzymatic activity for cleavage of acidic residues
CC while reducing its activity with neutral and basic residues
CC (PubMed:20706583). Hydrolytic activity is inhibited by the
CC aminopeptidase inhibitor (Leu and acidic inhibitor) amastatin, but not
CC by bestatin (aminopeptidase inhibitor Leu inhibitor), leupeptin,
CC pepstatin A and PMSF (PubMed:20706583). Its hydrolytic activity is also
CC strongly reduced by zinc ions, with a complete inhibition at 0.5 mM,
CC and moderately inhibited by cobalt and cupper ions (PubMed:20706583).
CC {ECO:0000269|PubMed:20706583}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=703 uM for Glu-AMC (in presence of 1.2 mM Ca(2+))
CC {ECO:0000269|PubMed:20706583};
CC KM=2478 uM for Asp-AMC (in presence of 1.2 mM Ca(2+))
CC {ECO:0000269|PubMed:20706583};
CC KM=2235 uM for Glu-AMC (in absence of Ca(2+))
CC {ECO:0000269|PubMed:20706583};
CC KM=4119 uM for Asp-AMC (in absence Ca(2+))
CC {ECO:0000269|PubMed:20706583};
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 -!- PTM: N-glycosylated. Glycosylation counts for an increased mass of
CC about 32% of the protein mass (about 48 kDa).
CC {ECO:0000269|PubMed:20706583}.
CC -!- SIMILARITY: Belongs to the peptidase M1 family. {ECO:0000305}.
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DR EMBL; FN666431; CBJ34330.1; -; 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="Glutamyl aminopeptidase"
FT /evidence="ECO:0000305|PubMed:20706583"
FT /id="PRO_0000455654"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 18..38
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000305"
FT TOPO_DOM 39..955
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT ACT_SITE 389
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q07075,
FT ECO:0000255|PIRSR:PIRSR633508-1"
FT BINDING 218
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075,
FT ECO:0000255|PIRSR:PIRSR633508-2"
FT BINDING 352..356
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075,
FT 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:0000250|UniProtKB:Q07075,
FT 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:0000250|UniProtKB:Q07075,
FT 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:0000250|UniProtKB:Q07075,
FT ECO:0000255|PIRSR:PIRSR633508-4"
FT BINDING 882
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q07075,
FT ECO:0000255|PIRSR:PIRSR633508-2"
FT SITE 216
FT /note="Binds calcium which modulates its enzyme activity"
FT /evidence="ECO:0000250|UniProtKB:Q07075,
FT ECO:0000255|PIRSR:PIRSR633508-3"
FT SITE 474
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q07075,
FT ECO:0000255|PIRSR:PIRSR633508-3"
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 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 674
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 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; 109977 MW; 10B3A38226BB6331 CRC64;
MDIEDKTSKM HCMKGKHVVI ICGVVIAVGL ILGLGLGLGL DTKACNPPEV NGQVSTKSPI
SNTPDVTSPS GSSVFCSAKN DENGPWTHFR LPNYVHPVHY DLHLTPEMEA EVYTGMVNIS
IRLEEQTTKH LWLHLRETKI TEMPQLWTSS GQVIEIKRCF GYEPQEYVVI EAEEDLRPSN
YFLSMRFKGY LNGSLVGFYS TTYGENGKIK YIAATDHEPT DARKSFPCFD EPNKKATYTI
SITHEHDYEA ISNMPVEKTI SLDNKWTKTI FKKSVPMSTY LVAWAVHQFK YEERISSRGI
PLRIYAQPQQ INTAIYAANV TKVVFDYFEN YFNMNYSLPK LDKIAIPDFG TGAMENWGLI
TYRETNLLYD SQESAASNKQ RVAAVIAHEL VHQWFGNIVT MDWWDDLWLN EGFASFFEFM
GVNAKEEKWQ MLDQILISDL LPVLKEDSLV SSHPITVNVS SPDEITSVFD GISYSKGASI
LRMLEDWISP ECFRAGCEKY LKEHYFKNAK TDDFWKAMEE VSGKPVKEVM DTWTRQMGYP
VLKVDLNSTV TQQRFLLDPK ADPSKPSSQF SYKWNIPVKW KEGNTSNIIF YNKSELAGIT
ITRPSDLPLN SFLKVNKDHV GFYRVNYEPQ VWRALTDIMM KDHQNFNLAD RAGFIDDAFA
LARAGLLKYA DALNLTRYLQ NEAEYIPWQR AVVAISYIRN MFEDDKALYP KFQRYFGSLV
KPIASELKWE XDEDHIKSLL RTTVLEFACK MEDPEALGNA SLLFKKWMSG ISLDVNLRLL
VYRFGMQNSG DEQAWNYMFQ KYRTATLAQE KEKLLYGLAS VKNITLLNRF LSCIKNTSLI
RSQDVFTVLG YISLNSYGKT MAWDWVRLNW EYLVKRYTLN DRNLGRLISR LSGTFNTELQ
LWQMENFFER YPDAGAGEAS RKQALETTKS NIEWLKQYRD DVATWLENSE HSNFA
