CATL_DROME
ID CATL_DROME Reviewed; 371 AA.
AC Q95029; O97431; Q5U121;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Cathepsin L;
DE EC=3.4.22.15;
DE AltName: Full=Cysteine proteinase 1;
DE Contains:
DE RecName: Full=Cathepsin L heavy chain;
DE Contains:
DE RecName: Full=Cathepsin L light chain;
DE Flags: Precursor;
GN Name=Cp1; Synonyms=fs(2)50Ca; ORFNames=CG6692;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Hemocyte;
RX PubMed=9099581; DOI=10.1111/j.1365-2583.1997.tb00085.x;
RA Tryselius Y., Hultmark D.;
RT "Cysteine proteinase 1 (CP1), a cathepsin L-like enzyme expressed in the
RT Drosophila melanogaster haemocyte cell line mbn-2.";
RL Insect Mol. Biol. 6:173-181(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=9662479; DOI=10.1046/j.1365-2583.1998.00070.x;
RA Gray Y.H.M., Sved J.A., Preston C.R., Engels W.R.;
RT "Structure and associated mutational effects of the cysteine proteinase
RT (CP1) gene of Drosophila melanogaster.";
RL Insect Mol. Biol. 7:291-293(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [4]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley; TISSUE=Larva, and Pupae;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 64-371, FUNCTION, TISSUE SPECIFICITY,
RP AND DEVELOPMENTAL STAGE.
RC STRAIN=Canton-S;
RX PubMed=7851441; DOI=10.1111/j.1432-1033.1995.tb20428.x;
RA Matsumoto I., Watanabe H., Abe K., Arai S., Emori Y.;
RT "A putative digestive cysteine proteinase from Drosophila melanogaster is
RT predominantly expressed in the embryonic and larval midgut.";
RL Eur. J. Biochem. 227:582-587(1995).
CC -!- FUNCTION: Important for the overall degradation of proteins in
CC lysosomes. Essential for adult male and female fertility. May play a
CC role in digestion. {ECO:0000269|PubMed:7851441,
CC ECO:0000269|PubMed:9099581, ECO:0000269|PubMed:9662479}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Specificity close to that of papain. As compared to cathepsin
CC B, cathepsin L exhibits higher activity toward protein substrates,
CC but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-
CC dipeptidase activity.; EC=3.4.22.15;
CC -!- SUBUNIT: Dimer of a heavy and a light chain linked by disulfide bonds.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:9099581}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=C;
CC IsoId=Q95029-1; Sequence=Displayed;
CC Name=A; Synonyms=B;
CC IsoId=Q95029-2; Sequence=VSP_021771;
CC -!- TISSUE SPECIFICITY: In the embryo, predominantly expressed in the
CC midgut. Also expressed in larval alimentary organs such as salivary
CC gland and midgut including gastric caeca. {ECO:0000269|PubMed:7851441}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryo, larva, pupa and adult.
CC {ECO:0000269|PubMed:7851441}.
CC -!- DISRUPTION PHENOTYPE: Flies exhibit wing and pigmentation defects.
CC Females are sterile, males are partially sterile.
CC {ECO:0000269|PubMed:9662479}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088, ECO:0000255|PROSITE-ProRule:PRU10089,
CC ECO:0000255|PROSITE-ProRule:PRU10090}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA06738.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; U75652; AAB18345.1; -; mRNA.
DR EMBL; AF012089; AAB65749.1; -; Genomic_DNA.
DR EMBL; AE013599; AAF58311.1; -; Genomic_DNA.
DR EMBL; AE013599; AAM68565.1; -; Genomic_DNA.
DR EMBL; BT016071; AAV36956.1; -; mRNA.
DR EMBL; D31970; BAA06738.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_523735.2; NM_079011.3. [Q95029-1]
DR RefSeq; NP_725347.1; NM_166026.3. [Q95029-2]
DR AlphaFoldDB; Q95029; -.
DR SMR; Q95029; -.
DR BioGRID; 62300; 43.
DR IntAct; Q95029; 2.
DR STRING; 7227.FBpp0086719; -.
DR MEROPS; C01.092; -.
DR GlyGen; Q95029; 1 site.
DR PaxDb; Q95029; -.
DR DNASU; 36546; -.
DR EnsemblMetazoa; FBtr0087592; FBpp0086718; FBgn0013770. [Q95029-2]
DR EnsemblMetazoa; FBtr0087593; FBpp0086719; FBgn0013770. [Q95029-1]
DR GeneID; 36546; -.
DR KEGG; dme:Dmel_CG6692; -.
DR CTD; 36546; -.
DR FlyBase; FBgn0013770; Cp1.
DR VEuPathDB; VectorBase:FBgn0013770; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000153321; -.
DR InParanoid; Q95029; -.
DR PhylomeDB; Q95029; -.
DR Reactome; R-DME-1474228; Degradation of the extracellular matrix.
DR Reactome; R-DME-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-DME-2132295; MHC class II antigen presentation.
DR Reactome; R-DME-5683826; Surfactant metabolism.
DR Reactome; R-DME-6798695; Neutrophil degranulation.
DR Reactome; R-DME-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR SignaLink; Q95029; -.
DR BioGRID-ORCS; 36546; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 36546; -.
DR PRO; PR:Q95029; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0013770; Expressed in seminal fluid secreting gland and 46 other tissues.
DR ExpressionAtlas; Q95029; baseline and differential.
DR Genevisible; Q95029; DM.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0045169; C:fusome; IDA:FlyBase.
DR GO; GO:0005764; C:lysosome; IDA:FlyBase.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:FlyBase.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IDA:FlyBase.
DR GO; GO:0008233; F:peptidase activity; IDA:FlyBase.
DR GO; GO:0007586; P:digestion; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IBA:GO_Central.
DR CDD; cd02248; Peptidase_C1A; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR025661; Pept_asp_AS.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR025660; Pept_his_AS.
DR InterPro; IPR000668; Peptidase_C1A_C.
DR InterPro; IPR039417; Peptidase_C1A_papain-like.
DR InterPro; IPR013201; Prot_inhib_I29.
DR Pfam; PF08246; Inhibitor_I29; 1.
DR Pfam; PF00112; Peptidase_C1; 1.
DR PRINTS; PR00705; PAPAIN.
DR SMART; SM00848; Inhibitor_I29; 1.
DR SMART; SM00645; Pept_C1; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Developmental protein; Digestion; Disulfide bond;
KW Glycoprotein; Hydrolase; Lysosome; Protease; Reference proteome; Signal;
KW Thiol protease; Zymogen.
FT SIGNAL 1..48
FT /evidence="ECO:0000255"
FT PROPEP 49..153
FT /note="Activation peptide"
FT /id="PRO_0000026265"
FT CHAIN 154..326
FT /note="Cathepsin L heavy chain"
FT /id="PRO_0000026266"
FT PROPEP 327..329
FT /id="PRO_0000026267"
FT CHAIN 330..371
FT /note="Cathepsin L light chain"
FT /id="PRO_0000026268"
FT ACT_SITE 178
FT /evidence="ECO:0000250"
FT ACT_SITE 317
FT /evidence="ECO:0000250"
FT ACT_SITE 338
FT /evidence="ECO:0000250"
FT CARBOHYD 127
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 175..218
FT /evidence="ECO:0000250"
FT DISULFID 209..251
FT /evidence="ECO:0000250"
FT DISULFID 310..360
FT /note="Interchain (between heavy and light chains)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 2..31
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:9099581, ECO:0000303|Ref.5"
FT /id="VSP_021771"
FT CONFLICT 228
FT /note="R -> P (in Ref. 6; BAA06738)"
FT /evidence="ECO:0000305"
FT CONFLICT 255..257
FT /note="KGT -> RAQ (in Ref. 6; BAA06738)"
FT /evidence="ECO:0000305"
FT CONFLICT 277..281
FT /note="AEAVA -> PEPVP (in Ref. 6; BAA06738)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="A -> P (in Ref. 6; BAA06738)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 371 AA; 41601 MW; 01955EB4735316D7 CRC64;
MNHLGVFETR FRPRTRHKSQ RAQLIPEQIT MRTAVLLPLL ALLAVAQAVS FADVVMEEWH
TFKLEHRKNY QDETEERFRL KIFNENKHKI AKHNQRFAEG KVSFKLAVNK YADLLHHEFR
QLMNGFNYTL HKQLRAADES FKGVTFISPA HVTLPKSVDW RTKGAVTAVK DQGHCGSCWA
FSSTGALEGQ HFRKSGVLVS LSEQNLVDCS TKYGNNGCNG GLMDNAFRYI KDNGGIDTEK
SYPYEAIDDS CHFNKGTVGA TDRGFTDIPQ GDEKKMAEAV ATVGPVSVAI DASHESFQFY
SEGVYNEPQC DAQNLDHGVL VVGFGTDESG EDYWLVKNSW GTTWGDKGFI KMLRNKENQC
GIASASSYPL V
