ITR2_MOMCO
ID ITR2_MOMCO Reviewed; 34 AA.
AC P82409;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2000, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Trypsin inhibitor 2 {ECO:0000305};
DE AltName: Full=MCoTI-II {ECO:0000303|PubMed:10801322};
DE AltName: Full=Trypsin inhibitor II {ECO:0000303|PubMed:10801322};
OS Momordica cochinchinensis (Spiny bitter cucumber) (Muricia
OS cochinchinensis).
OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC rosids; fabids; Cucurbitales; Cucurbitaceae; Momordiceae; Momordica.
OX NCBI_TaxID=3674;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION, SUCCINIMIDE CROSS-LINK AT ASP-4, ISOPEPTIDE
RP BOND AT ASP-4, AND MASS SPECTROMETRY.
RC TISSUE=Seed;
RX PubMed=10801322; DOI=10.1021/bi9929756;
RA Hernandez J.-F., Gagnon J., Chiche L., Nguyen T.M., Andrieu J.-P.,
RA Heitz A., Trinh T., Pham T.T.C., Le Nguyen D.;
RT "Squash trypsin inhibitors from Momordica cochinchinensis exhibit an
RT atypical macrocyclic structure.";
RL Biochemistry 39:5722-5730(2000).
RN [2]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=11434766; DOI=10.1021/bi0106639;
RA Heitz A., Hernandez J.F., Gagnon J., Hong T.T., Pham T.T., Nguyen T.M.,
RA Le-Nguyen D., Chiche L.;
RT "Solution structure of the squash trypsin inhibitor MCoTI-II. A new family
RT for cyclic knottins.";
RL Biochemistry 40:7973-7983(2001).
RN [3]
RP STRUCTURE BY NMR, AND DISULFIDE BONDS.
RX PubMed=11292835; DOI=10.1074/jbc.m101666200;
RA Felizmenio-Quimio M.E., Daly N.L., Craik D.J.;
RT "Circular proteins in plants: solution structure of a novel macrocyclic
RT trypsin inhibitor from Momordica cochinchinensis.";
RL J. Biol. Chem. 276:22875-22882(2001).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 6-21, AND DISULFIDE BONDS.
RX PubMed=16337652; DOI=10.1016/j.jmb.2005.11.005;
RA Niemann H.H., Schmoldt H.U., Wentzel A., Kolmar H., Heinz D.W.;
RT "Barnase fusion as a tool to determine the crystal structure of the small
RT disulfide-rich protein McoEeTI.";
RL J. Mol. Biol. 356:1-8(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS), AND DISULFIDE BONDS.
RX PubMed=24169696; DOI=10.1074/jbc.m113.528240;
RA Daly N.L., Thorstholm L., Greenwood K.P., King G.J., Rosengren K.J.,
RA Heras B., Martin J.L., Craik D.J.;
RT "Structural insights into the role of the cyclic backbone in a squash
RT trypsin inhibitor.";
RL J. Biol. Chem. 288:36141-36148(2013).
RN [6]
RP STRUCTURE BY NMR OF 8-34, AND DISULFIDE BONDS.
RX PubMed=26264857; DOI=10.1038/srep12974;
RA Huang Y.H., Henriques S.T., Wang C.K., Thorstholm L., Daly N.L., Kaas Q.,
RA Craik D.J.;
RT "Design of substrate-based BCR-ABL kinase inhibitors using the cyclotide
RT scaffold.";
RL Sci. Rep. 5:12974-12974(2015).
CC -!- FUNCTION: Inhibits trypsin; probably participates in a plant defense
CC mechanism. {ECO:0000305|PubMed:10801322}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC -!- DOMAIN: The presence of a 'disulfide through disulfide knot'
CC structurally defines this protein as a knottin. {ECO:0000250}.
CC -!- PTM: A cyclic succinimide probably forms by loss of water between Asp-4
CC and Gly-5, that can then rehydrate to either the original peptide bond
CC or to a beta-aspartyl isopeptide bond. Three isoforms of MCoTI-II are
CC detected, two with the parent molecular weight, corresponding to the
CC unmodified and proposed isopeptide forms, and one with a molecular
CC weight 18 Da lower, corresponding to a succinimide cross-linked form.
CC {ECO:0000269|PubMed:10801322}.
CC -!- PTM: This is a cyclic peptide. {ECO:0000269|PubMed:10801322}.
CC -!- MASS SPECTROMETRY: Mass=3453; Mass_error=0.2; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:10801322};
CC -!- SIMILARITY: Belongs to the protease inhibitor I7 (squash-type serine
CC protease inhibitor) family. {ECO:0000305}.
CC -!- CAUTION: The genomic sequence for this protein is not available, so
CC Asp-4 may possibly be an asparagine which is known to be more labile
CC when immediately followed by a glycine. {ECO:0000305}.
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DR PDB; 1HA9; NMR; -; A=1-34.
DR PDB; 1IB9; NMR; -; A=1-34.
DR PDB; 2C4B; X-ray; 1.30 A; A/B=6-21.
DR PDB; 2IT8; NMR; -; A=6-34.
DR PDB; 2MT8; NMR; -; A=14-34.
DR PDB; 2PO8; NMR; -; A=8-34.
DR PDB; 4GUX; X-ray; 1.80 A; D/E/F=1-34.
DR PDBsum; 1HA9; -.
DR PDBsum; 1IB9; -.
DR PDBsum; 2C4B; -.
DR PDBsum; 2IT8; -.
DR PDBsum; 2MT8; -.
DR PDBsum; 2PO8; -.
DR PDBsum; 4GUX; -.
DR AlphaFoldDB; P82409; -.
DR BMRB; P82409; -.
DR SMR; P82409; -.
DR MEROPS; I07.004; -.
DR EvolutionaryTrace; P82409; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IMP:CAFA.
DR GO; GO:0006952; P:defense response; IEA:UniProtKB-KW.
DR GO; GO:1900004; P:negative regulation of serine-type endopeptidase activity; IMP:CAFA.
DR CDD; cd00150; PlantTI; 1.
DR InterPro; IPR000737; Prot_inh_squash.
DR InterPro; IPR011052; Proteinase_amylase_inhib_sf.
DR Pfam; PF00299; Squash; 1.
DR SUPFAM; SSF57027; SSF57027; 1.
DR PROSITE; PS00286; SQUASH_INHIBITOR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Isopeptide bond;
KW Knottin; Plant defense; Protease inhibitor; Secreted;
KW Serine protease inhibitor.
FT PEPTIDE 1..34
FT /note="Trypsin inhibitor 2"
FT /id="PRO_0000044858"
FT SITE 10..11
FT /note="Reactive bond"
FT DISULFID 8..25
FT /evidence="ECO:0000269|PubMed:11292835,
FT ECO:0000269|PubMed:11434766, ECO:0000269|PubMed:16337652,
FT ECO:0000269|PubMed:24169696, ECO:0000269|PubMed:26264857,
FT ECO:0007744|PDB:1HA9, ECO:0007744|PDB:1IB9,
FT ECO:0007744|PDB:2C4B, ECO:0007744|PDB:2MT8,
FT ECO:0007744|PDB:4GUX"
FT DISULFID 15..27
FT /evidence="ECO:0000269|PubMed:11292835,
FT ECO:0000269|PubMed:11434766, ECO:0000269|PubMed:16337652,
FT ECO:0000269|PubMed:24169696, ECO:0000269|PubMed:26264857,
FT ECO:0007744|PDB:1HA9, ECO:0007744|PDB:1IB9,
FT ECO:0007744|PDB:2C4B, ECO:0007744|PDB:2MT8,
FT ECO:0007744|PDB:4GUX"
FT DISULFID 21..33
FT /evidence="ECO:0000269|PubMed:11292835,
FT ECO:0000269|PubMed:11434766, ECO:0000269|PubMed:16337652,
FT ECO:0000269|PubMed:24169696, ECO:0000269|PubMed:26264857,
FT ECO:0007744|PDB:1HA9, ECO:0007744|PDB:1IB9,
FT ECO:0007744|PDB:2C4B, ECO:0007744|PDB:2MT8,
FT ECO:0007744|PDB:4GUX"
FT CROSSLNK 1..34
FT /note="Cyclopeptide (Ser-Gly)"
FT /evidence="ECO:0000269|PubMed:10801322"
FT CROSSLNK 4..5
FT /note="(2-aminosuccinimidyl)acetic acid (Asp-Gly);
FT alternate"
FT /evidence="ECO:0000269|PubMed:10801322"
FT CROSSLNK 4..5
FT /note="Isoaspartyl glycine isopeptide (Asp-Gly); alternate"
FT /evidence="ECO:0000269|PubMed:10801322"
FT STRAND 11..14
FT /evidence="ECO:0007829|PDB:2MT8"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:2C4B"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:2PO8"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:4GUX"
SQ SEQUENCE 34 AA; 3477 MW; 8F7D0B4C048BB93A CRC64;
SGSDGGVCPK ILKKCRRDSD CPGACICRGN GYCG
