GP63_LEIMA
ID GP63_LEIMA Reviewed; 602 AA.
AC P08148; P15906;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Leishmanolysin;
DE EC=3.4.24.36;
DE AltName: Full=Cell surface protease;
DE AltName: Full=Major surface glycoprotein;
DE AltName: Full=Major surface protease;
DE AltName: Full=Promastigote surface endopeptidase;
DE AltName: Full=Protein gp63;
DE Flags: Precursor;
GN Name=gp63;
OS Leishmania major.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5664;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 101-123.
RX PubMed=3346625; DOI=10.1084/jem.167.2.724;
RA Button L.L., McMaster W.R.;
RT "Molecular cloning of the major surface antigen of leishmania.";
RL J. Exp. Med. 167:724-729(1988).
RN [2]
RP SEQUENCE REVISION.
RA Button L.L., McMaster W.R.;
RL J. Exp. Med. 171:589-589(1990).
RN [3]
RP GPI-ANCHOR AT ASN-577, AND PROTEIN SEQUENCE OF 574-577.
RX PubMed=2145267; DOI=10.1016/s0021-9258(17)44853-8;
RA Schneider P., Ferguson M.A.J., McConville M.J., Mehlert A., Homans S.W.,
RA Bordier C.;
RT "Structure of the glycosyl-phosphatidylinositol membrane anchor of the
RT Leishmania major promastigote surface protease.";
RL J. Biol. Chem. 265:16955-16964(1990).
RN [4]
RP MUTAGENESIS OF TYR-254; HIS-264; GLU-265; HIS-268; ASN-300; ASN-407;
RP ASN-534 AND ASN-577.
RX PubMed=8626468; DOI=10.1074/jbc.271.14.7903;
RA McGwire B.S., Chang K.-P.;
RT "Posttranslational regulation of a Leishmania HEXXH metalloprotease (gp63).
RT The effects of site-specific mutagenesis of catalytic, zinc binding, N-
RT glycosylation, and glycosyl phosphatidylinositol addition sites on N-
RT terminal end cleavage, intracellular stability, and extracellular exit.";
RL J. Biol. Chem. 271:7903-7909(1996).
RN [5]
RP GLYCOSYLATION AT ASN-300 AND ASN-407.
RX PubMed=9041519; DOI=10.1016/s0166-6851(96)02780-6;
RA Funk V.A., Thomas-Oates J.E., Kielland S.L., Bates P.A., Olafson R.W.;
RT "A unique, terminally glucosylated oligosaccharide is a common feature on
RT Leishmania cell surfaces.";
RL Mol. Biochem. Parasitol. 84:33-48(1997).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), DISULFIDE BONDS, AND GLYCOSYLATION
RP AT ASN-300; ASN-407 AND ASN-534.
RX PubMed=7675788; DOI=10.1002/prot.340220109;
RA Schlagenhauf E., Etges R., Metcalf P.;
RT "Crystallization and preliminary X-ray diffraction studies of
RT leishmanolysin, the major surface metalloproteinase from Leishmania
RT major.";
RL Proteins 22:58-66(1995).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEX WITH ZINC, AND ACTIVE
RP SITE.
RX PubMed=9739094; DOI=10.1016/s0969-2126(98)00104-x;
RA Schlagenhauf E., Etges R., Metcalf P.;
RT "The crystal structure of the Leishmania major surface proteinase
RT leishmanolysin.";
RL Structure 6:1035-1046(1998).
CC -!- FUNCTION: Has an integral role during the infection of macrophages in
CC the mammalian host.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preference for hydrophobic residues at P1 and P1' and basic
CC residues at P2' and P3'. A model nonapeptide is cleaved at -Ala-
CC Tyr-|-Leu-Lys-Lys-.; EC=3.4.24.36;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:9739094};
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor.
CC -!- PTM: The phosphatidylinositol moiety of the GPI-anchor contains a fully
CC saturated, unbranched 1-O-alkyl chain (mainly C24:0) and a mixture of
CC fully saturated unbranched 2-O-acyl chains (C12:0, C14:0, C16:0, and
CC C18:0).
CC -!- SIMILARITY: Belongs to the peptidase M8 family. {ECO:0000305}.
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DR EMBL; Y00647; CAA68673.1; -; Genomic_DNA.
DR PIR; PL0221; PL0221.
DR PDB; 1LML; X-ray; 1.86 A; A=100-577.
DR PDBsum; 1LML; -.
DR AlphaFoldDB; P08148; -.
DR SMR; P08148; -.
DR MEROPS; M08.001; -.
DR GlyConnect; 335; 2 N-Linked glycans.
DR iPTMnet; P08148; -.
DR VEuPathDB; TriTrypDB:LmjF.10.0480; -.
DR VEuPathDB; TriTrypDB:LMJLV39_100010200; -.
DR VEuPathDB; TriTrypDB:LMJSD75_100010300; -.
DR eggNOG; KOG2556; Eukaryota.
DR BRENDA; 3.4.24.36; 2950.
DR EvolutionaryTrace; P08148; -.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:InterPro.
DR GO; GO:0008237; F:metallopeptidase activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0052028; P:induction by symbiont of host signal transduction pathway; IMP:ParkinsonsUK-UCL.
DR GO; GO:0052032; P:modulation by symbiont of host inflammatory response; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006508; P:proteolysis; IMP:ParkinsonsUK-UCL.
DR InterPro; IPR001577; Peptidase_M8.
DR PANTHER; PTHR10942; PTHR10942; 1.
DR Pfam; PF01457; Peptidase_M8; 1.
DR PRINTS; PR00782; LSHMANOLYSIN.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Cell membrane; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; GPI-anchor; Hydrolase; Lipoprotein; Membrane;
KW Metal-binding; Metalloprotease; Protease; Signal; Zinc; Zymogen.
FT SIGNAL 1..39
FT /evidence="ECO:0000255"
FT PROPEP 40..100
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:3346625"
FT /id="PRO_0000028667"
FT CHAIN 101..577
FT /note="Leishmanolysin"
FT /id="PRO_0000028668"
FT PROPEP 578..602
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:2145267"
FT /id="PRO_0000028669"
FT ACT_SITE 265
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:9739094"
FT BINDING 264
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:9739094"
FT BINDING 268
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:9739094"
FT BINDING 334
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:9739094"
FT LIPID 577
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000269|PubMed:2145267"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:7675788, ECO:0000269|PubMed:9041519"
FT CARBOHYD 407
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:7675788, ECO:0000269|PubMed:9041519"
FT CARBOHYD 534
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 125..142
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 191..230
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 314..386
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 393..455
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 406..425
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 415..489
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 466..510
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 515..565
FT /evidence="ECO:0000269|PubMed:7675788"
FT DISULFID 535..558
FT /evidence="ECO:0000269|PubMed:7675788"
FT MUTAGEN 254
FT /note="Y->D: No significant effect on protein expression
FT levels or catalytic activity."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 264
FT /note="H->F,Y: No detectable overexpression of mutant
FT protein and hence little catalytic activity."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 265
FT /note="E->D: No significant effect on protein expression
FT levels but almost abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 268
FT /note="H->N,Y: No detectable overexpression of mutant
FT protein and hence little catalytic activity."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 300
FT /note="N->Q: Increases electrophoretic mobility of the
FT protein."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 407
FT /note="N->Q: Increases electrophoretic mobility of the
FT protein."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 534
FT /note="N->Q: Increases electrophoretic mobility of the
FT protein."
FT /evidence="ECO:0000269|PubMed:8626468"
FT MUTAGEN 577
FT /note="N->L: Causes extracellular release of the protein."
FT /evidence="ECO:0000269|PubMed:8626468"
FT STRAND 111..114
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 160..169
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 177..181
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 198..202
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 226..232
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 238..244
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 247..249
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 256..269
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 274..279
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 320..322
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 328..332
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 333..335
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 356..364
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 372..374
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 380..383
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 386..390
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 393..395
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 402..404
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 435..437
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 450..454
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 458..465
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 475..477
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 478..480
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 487..494
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 506..516
FT /evidence="ECO:0007829|PDB:1LML"
FT TURN 517..520
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 521..525
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 548..550
FT /evidence="ECO:0007829|PDB:1LML"
FT STRAND 555..557
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 561..565
FT /evidence="ECO:0007829|PDB:1LML"
FT HELIX 569..572
FT /evidence="ECO:0007829|PDB:1LML"
SQ SEQUENCE 602 AA; 63953 MW; 982EF3245D87C43E CRC64;
MSVDSSSTHR RRCVAARLVR LAAAGAAVTV AVGTAAAWAH AGALQHRCVH DAMQARVRQS
VADHHKAPGA VSAVGLPYVT LDAAHTAAAA DPRPGSARSV VRDVNWGALR IAVSTEDLTD
PAYHCARVGQ HVKDHAGAIV TCTAEDILTN EKRDILVKHL IPQAVQLHTE RLKVQQVQGK
WKVTDMVGDI CGDFKVPQAH ITEGFSNTDF VMYVASVPSE EGVLAWATTC QTFSDGHPAV
GVINIPAANI ASRYDQLVTR VVTHEMAHAL GFSGPFFEDA RIVANVPNVR GKNFDVPVIN
SSTAVAKARE QYGCDTLEYL EVEDQGGAGS AGSHIKMRNA QDELMAPAAA AGYYTALTMA
IFQDLGFYQA DFSKAEVMPW GQNAGCAFLT NKCMEQSVTQ WPAMFCNESE DAIRCPTSRL
SLGACGVTRH PGLPPYWQYF TDPSLAGVSA FMDYCPVVVP YSDGSCTQRA SEAHASLLPF
NVFSDAARCI DGAFRPKATD GIVKSYAGLC ANVQCDTATR TYSVQVHGSN DYTNCTPGLR
VELSTVSNAF EGGGYITCPP YVEVCQGNVQ AAKDGGNTAA GRRGPRAAAT ALLVAALLAV
AL
