CPI2_BRUMA
ID CPI2_BRUMA Reviewed; 161 AA.
AC A0A0K0IP23; O16159;
DT 05-JUN-2019, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 2.
DT 03-AUG-2022, entry version 20.
DE RecName: Full=Cystatin cpi-2 {ECO:0000305};
DE Flags: Precursor;
GN Name=cpi-2 {ECO:0000303|PubMed:9233676};
OS Brugia malayi (Filarial nematode worm).
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Spirurina; Spiruromorpha; Filarioidea; Onchocercidae; Brugia.
OX NCBI_TaxID=6279 {ECO:0000312|Proteomes:UP000006672};
RN [1] {ECO:0000312|EMBL:AAB69857.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9233676; DOI=10.1016/s0166-6851(97)00050-9;
RA Gregory W.F., Blaxter M.L., Maizels R.M.;
RT "Differentially expressed, abundant trans-spliced cDNAs from larval Brugia
RT malayi.";
RL Mol. Biochem. Parasitol. 87:85-95(1997).
RN [2] {ECO:0000312|EMBL:AAD51086.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Gregory W.F., Maizels R.M.;
RT "Two distinct cystatin-type cysteine protease inhibitors from the parasitic
RT nematode Brugia malayi.";
RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000312|Proteomes:UP000006672}
RP NUCLEOTIDE SEQUENCE.
RC STRAIN=FR3 {ECO:0000312|Proteomes:UP000006672};
RX PubMed=17885136; DOI=10.1126/science.1145406;
RA Ghedin E., Wang S., Spiro D., Caler E., Zhao Q., Crabtree J., Allen J.E.,
RA Delcher A.L., Guiliano D.B., Miranda-Saavedra D., Angiuoli S.V., Creasy T.,
RA Amedeo P., Haas B., El-Sayed N.M., Wortman J.R., Feldblyum T., Tallon L.,
RA Schatz M., Shumway M., Koo H., Salzberg S.L., Schobel S., Pertea M.,
RA Pop M., White O., Barton G.J., Carlow C.K.S., Crawford M.J., Daub J.,
RA Dimmic M.W., Estes C.F., Foster J.M., Ganatra M., Gregory W.F.,
RA Johnson N.M., Jin J., Komuniecki R., Korf I., Kumar S., Laney S., Li B.-W.,
RA Li W., Lindblom T.H., Lustigman S., Ma D., Maina C.V., Martin D.M.,
RA McCarter J.P., McReynolds L., Mitreva M., Nutman T.B., Parkinson J.,
RA Peregrin-Alvarez J.M., Poole C., Ren Q., Saunders L., Sluder A.E.,
RA Smith K., Stanke M., Unnasch T.R., Ware J., Wei A.D., Weil G.,
RA Williams D.J., Zhang Y., Williams S.A., Fraser-Liggett C., Slatko B.,
RA Blaxter M.L., Scott A.L.;
RT "Draft genome of the filarial nematode parasite Brugia malayi.";
RL Science 317:1756-1760(2007).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=11301256; DOI=10.1016/s0960-9822(01)00118-x;
RA Manoury B., Gregory W.F., Maizels R.M., Watts C.;
RT "Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia
RT malayi, inhibits class II MHC-restricted antigen processing.";
RL Curr. Biol. 11:447-451(2001).
RN [5] {ECO:0000305}
RP FUNCTION, MOTIF, AND MUTAGENESIS OF ASN-77.
RX PubMed=15664654; DOI=10.1016/j.molbiopara.2004.11.008;
RA Murray J., Manoury B., Balic A., Watts C., Maizels R.M.;
RT "Bm-CPI-2, a cystatin from Brugia malayi nematode parasites, differs from
RT Caenorhabditis elegans cystatins in a specific site mediating inhibition of
RT the antigen-processing enzyme AEP.";
RL Mol. Biochem. Parasitol. 139:197-203(2005).
RN [6] {ECO:0000305}
RP DEVELOPMENTAL STAGE.
RX PubMed=18249028; DOI=10.1016/j.biocel.2007.11.012;
RA Gregory W.F., Maizels R.M.;
RT "Cystatins from filarial parasites: evolution, adaptation and function in
RT the host-parasite relationship.";
RL Int. J. Biochem. Cell Biol. 40:1389-1398(2008).
CC -!- FUNCTION: Cysteine protease inhibitor which inhibits members of the
CC peptidase C1 family. Also acts as an asparaginyl endopeptidase
CC inhibitor (PubMed:11301256, PubMed:15664654). In the human host,
CC inhibits CTSL/cathepsin L, CTSS/cathepsin S, CTSB/cathepsin B and
CC asparaginyl endopeptidase LGMN/AEP which may cause defects in both
CC antigen and MHC class II invariant chain CD74/Ii processing
CC (PubMed:11301256). {ECO:0000269|PubMed:11301256,
CC ECO:0000269|PubMed:15664654}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all life cycle stages.
CC {ECO:0000269|PubMed:18249028}.
CC -!- SIMILARITY: Belongs to the cystatin family. {ECO:0000255,
CC ECO:0000255|RuleBase:RU362130}.
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DR EMBL; AF015263; AAB69857.1; -; mRNA.
DR EMBL; AF177193; AAD51086.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A0K0IP23; -.
DR SMR; A0A0K0IP23; -.
DR STRING; 6279.A0A0K0IP23; -.
DR MEROPS; I25.044; -.
DR EnsemblMetazoa; Bm10669a.1; Bm10669a.1; WBGene00230930.
DR WBParaSite; Bm10669a.1; Bm10669a.1; WBGene00230930.
DR Proteomes; UP000006672; Unassembled WGS sequence.
DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR CDD; cd00042; CY; 1.
DR InterPro; IPR000010; Cystatin_dom.
DR InterPro; IPR046350; Cystatin_sf.
DR InterPro; IPR018073; Prot_inh_cystat_CS.
DR Pfam; PF00031; Cystatin; 1.
DR SMART; SM00043; CY; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
DR PROSITE; PS00287; CYSTATIN; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Protease inhibitor; Reference proteome;
KW Signal; Thiol protease inhibitor.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..161
FT /note="Cystatin cpi-2"
FT /evidence="ECO:0000255"
FT /id="PRO_5008442636"
FT MOTIF 76..78
FT /note="Important for interaction with host LGMN"
FT /evidence="ECO:0000305|PubMed:15664654"
FT MOTIF 93..97
FT /note="Secondary area of contact"
FT /evidence="ECO:0000305"
FT SITE 49
FT /note="Reactive site"
FT /evidence="ECO:0000305"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 111..124
FT /evidence="ECO:0000250|UniProtKB:P01038"
FT MUTAGEN 77
FT /note="N->D: Reduces inhibition of human LGMN/AEP without
FT affecting the catalytic activity of cathepsins CTSL, CTSS
FT and CTSB."
FT /evidence="ECO:0000269|PubMed:15664654"
FT MUTAGEN 77
FT /note="N->K: Abolishes inhibition of human LGMN/AEP without
FT affecting the catalytic activity of cathepsins CTSL, CTSS
FT and CTSB."
FT /evidence="ECO:0000269|PubMed:15664654"
FT CONFLICT 89
FT /note="N -> K (in Ref. 1; AAB69857/AAD51086)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 161 AA; 18392 MW; 84D4641AEB736EB5 CRC64;
MMSTMSIKEG LLVILLSLFL FDTTALIHRR EIPHMESKGQ MQRGQVLLGG WQERSPEDNE
ILELLPSVLT KVNQQSNDEY HLMPIKLLNV SSQVVAGVKY KMEVQVARSE CKKSASEQVN
LKTCKKLEGH PDQVMTLEVW EKPWEDFLQV NILETKVLSS V
