CATL2_HUMAN
ID CATL2_HUMAN Reviewed; 334 AA.
AC O60911; O60233; Q2TB86; Q5T1U0;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Cathepsin L2;
DE EC=3.4.22.43;
DE AltName: Full=Cathepsin U;
DE AltName: Full=Cathepsin V;
DE Flags: Precursor;
GN Name=CTSV; Synonyms=CATL2, CTSL2, CTSU; ORFNames=UNQ268/PRO305;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9563472;
RA Santamaria I., Velasco G., Cazorla M., Fueyo A., Campo E., Lopez-Otin C.;
RT "Cathepsin L2, a novel human cysteine proteinase produced by breast and
RT colorectal carcinomas.";
RL Cancer Res. 58:1624-1630(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Corneal epithelium;
RX PubMed=9727401;
RA Adachi W., Kawamoto S., Ohno I., Nishida K., Kinoshita S., Matsubara K.,
RA Okubo K.;
RT "Isolation and characterization of human cathepsin V: a major proteinase in
RT corneal epithelium.";
RL Invest. Ophthalmol. Vis. Sci. 39:1789-1796(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Kidney, and Thymus;
RX PubMed=10029531; DOI=10.1021/bi982175f;
RA Broemme D., Li Z., Barnes M., Mehler E.;
RT "Human cathepsin V functional expression, tissue distribution,
RT electrostatic surface potential, enzymatic characterization, and
RT chromosomal localization.";
RL Biochemistry 38:2377-2385(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10382972; DOI=10.1093/dnares/6.2.137;
RA Itoh R., Kawamoto S., Adachi W., Kinoshita S., Okubo K.;
RT "Genomic organization and chromosomal localization of the human cathepsin
RT L2 gene.";
RL DNA Res. 6:137-140(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP GLYCOSYLATION AT ASN-221 AND ASN-292.
RX PubMed=22967898; DOI=10.1016/j.febslet.2012.08.001;
RA Niwa Y., Suzuki T., Dohmae N., Umezawa K., Simizu S.;
RT "Determination of cathepsin V activity and intracellular trafficking by N-
RT glycosylation.";
RL FEBS Lett. 586:3601-3607(2012).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), ACTIVE SITE, AND DISULFIDE BONDS.
RX PubMed=11027133; DOI=10.1021/bi000951p;
RA Somoza J.R., Zhan H., Bowman K.K., Yu L., Mortara K.D., Palmer J.T.,
RA Clark J.M., McGrath M.E.;
RT "Crystal structure of human cathepsin V.";
RL Biochemistry 39:12543-12551(2000).
RN [11]
RP ERRATUM OF PUBMED:11027133.
RA Somoza J.R., Zhan H., Bowman K.K., Yu L., Mortara K.D., Palmer J.T.,
RA Clark J.M., McGrath M.E.;
RL Biochemistry 40:4200-4200(2001).
RN [12]
RP ACTIVITY REGULATION.
RX PubMed=30425301; DOI=10.1038/s41436-018-0355-3;
RA van den Bogaard E.H.J., van Geel M., van Vlijmen-Willems I.M.J.J.,
RA Jansen P.A.M., Peppelman M., van Erp P.E.J., Atalay S., Venselaar H.,
RA Simon M.E.H., Joosten M., Schalkwijk J., Zeeuwen P.L.J.M.;
RT "Deficiency of the human cysteine protease inhibitor cystatin M/E causes
RT hypotrichosis and dry skin.";
RL Genet. Med. 21:1559-1567(2019).
CC -!- FUNCTION: Cysteine protease. May have an important role in corneal
CC physiology. {ECO:0000269|PubMed:10029531, ECO:0000269|PubMed:9727401}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=The recombinant enzyme hydrolyzes proteins (serum albumin,
CC collagen) and synthetic substrates (Z-Phe-Arg-NHMec > Z-Leu-Arg-NHMec
CC > Z-Val-Arg-NHMec).; EC=3.4.22.43;
CC Evidence={ECO:0000269|PubMed:10029531};
CC -!- ACTIVITY REGULATION: Inhibited by CST6. {ECO:0000269|PubMed:30425301}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the thymus and testis.
CC Also expressed in corneal epithelium, and to a lesser extent in
CC conjunctival epithelium and skin. {ECO:0000269|PubMed:10029531,
CC ECO:0000269|PubMed:9563472, ECO:0000269|PubMed:9727401}.
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}.
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DR EMBL; Y14734; CAA75029.1; -; mRNA.
DR EMBL; AB001928; BAA25909.1; -; mRNA.
DR EMBL; AF070448; AAC23598.1; -; mRNA.
DR EMBL; AB019534; BAA34365.1; -; Genomic_DNA.
DR EMBL; AY358641; AAQ89004.1; -; mRNA.
DR EMBL; AL445670; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC023504; AAH23504.1; -; mRNA.
DR EMBL; BC110512; AAI10513.1; -; mRNA.
DR CCDS; CCDS6723.1; -.
DR RefSeq; NP_001188504.1; NM_001201575.1.
DR RefSeq; NP_001324.2; NM_001333.3.
DR PDB; 1FH0; X-ray; 1.60 A; A/B=114-334.
DR PDB; 3H6S; X-ray; 2.22 A; A/B/C/D=114-334.
DR PDB; 3KFQ; X-ray; 1.99 A; A/B=114-334.
DR PDBsum; 1FH0; -.
DR PDBsum; 3H6S; -.
DR PDBsum; 3KFQ; -.
DR AlphaFoldDB; O60911; -.
DR SMR; O60911; -.
DR BioGRID; 107895; 142.
DR IntAct; O60911; 35.
DR MINT; O60911; -.
DR STRING; 9606.ENSP00000445052; -.
DR BindingDB; O60911; -.
DR ChEMBL; CHEMBL3272; -.
DR DrugBank; DB02869; 3-amino-5-phenylpentane.
DR DrugBank; DB04451; 4-Methylpiperazin-1-Yl Carbonyl Group.
DR DrugCentral; O60911; -.
DR GuidetoPHARMACOLOGY; 2352; -.
DR MEROPS; C01.009; -.
DR MEROPS; I29.010; -.
DR GlyGen; O60911; 2 sites.
DR iPTMnet; O60911; -.
DR PhosphoSitePlus; O60911; -.
DR BioMuta; CTSV; -.
DR EPD; O60911; -.
DR jPOST; O60911; -.
DR MassIVE; O60911; -.
DR MaxQB; O60911; -.
DR PaxDb; O60911; -.
DR PeptideAtlas; O60911; -.
DR PRIDE; O60911; -.
DR ProteomicsDB; 49669; -.
DR Antibodypedia; 28731; 377 antibodies from 33 providers.
DR DNASU; 1515; -.
DR Ensembl; ENST00000259470.6; ENSP00000259470.5; ENSG00000136943.12.
DR Ensembl; ENST00000679661.1; ENSP00000506713.1; ENSG00000136943.12.
DR Ensembl; ENST00000681737.1; ENSP00000505681.1; ENSG00000136943.12.
DR Ensembl; ENST00000681927.1; ENSP00000505141.1; ENSG00000136943.12.
DR GeneID; 1515; -.
DR KEGG; hsa:1515; -.
DR MANE-Select; ENST00000259470.6; ENSP00000259470.5; NM_001333.4; NP_001324.2.
DR UCSC; uc004awt.4; human.
DR CTD; 1515; -.
DR DisGeNET; 1515; -.
DR GeneCards; CTSV; -.
DR HGNC; HGNC:2538; CTSV.
DR HPA; ENSG00000136943; Tissue enriched (lymphoid).
DR MIM; 603308; gene.
DR neXtProt; NX_O60911; -.
DR OpenTargets; ENSG00000136943; -.
DR PharmGKB; PA27036; -.
DR VEuPathDB; HostDB:ENSG00000136943; -.
DR eggNOG; KOG1543; Eukaryota.
DR GeneTree; ENSGT00940000154367; -.
DR HOGENOM; CLU_012184_1_2_1; -.
DR InParanoid; O60911; -.
DR OMA; CSHPQGN; -.
DR OrthoDB; 1275401at2759; -.
DR PhylomeDB; O60911; -.
DR TreeFam; TF313739; -.
DR BRENDA; 3.4.22.43; 2681.
DR PathwayCommons; O60911; -.
DR Reactome; R-HSA-1236977; Endosomal/Vacuolar pathway.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-8939242; RUNX1 regulates transcription of genes involved in differentiation of keratinocytes.
DR SABIO-RK; O60911; -.
DR SignaLink; O60911; -.
DR BioGRID-ORCS; 1515; 12 hits in 1066 CRISPR screens.
DR ChiTaRS; CTSV; human.
DR EvolutionaryTrace; O60911; -.
DR GeneWiki; Cathepsin_L2; -.
DR GenomeRNAi; 1515; -.
DR Pharos; O60911; Tchem.
DR PRO; PR:O60911; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O60911; protein.
DR Bgee; ENSG00000136943; Expressed in thymus and 167 other tissues.
DR ExpressionAtlas; O60911; baseline and differential.
DR Genevisible; O60911; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0008234; F:cysteine-type peptidase activity; TAS:ProtInc.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Protease;
KW Reference proteome; Signal; Thiol protease; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..113
FT /note="Activation peptide"
FT /id="PRO_0000026277"
FT CHAIN 114..334
FT /note="Cathepsin L2"
FT /id="PRO_0000026278"
FT ACT_SITE 138
FT /evidence="ECO:0000269|PubMed:11027133"
FT ACT_SITE 277
FT /evidence="ECO:0000269|PubMed:11027133"
FT ACT_SITE 301
FT /evidence="ECO:0000269|PubMed:11027133"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22967898"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22967898"
FT DISULFID 135..178
FT /evidence="ECO:0000269|PubMed:11027133,
FT ECO:0007744|PDB:1FH0, ECO:0007744|PDB:3H6S,
FT ECO:0007744|PDB:3KFQ"
FT DISULFID 169..211
FT /evidence="ECO:0000269|PubMed:11027133,
FT ECO:0007744|PDB:1FH0, ECO:0007744|PDB:3H6S,
FT ECO:0007744|PDB:3KFQ"
FT DISULFID 270..323
FT /evidence="ECO:0000269|PubMed:11027133,
FT ECO:0007744|PDB:1FH0, ECO:0007744|PDB:3H6S,
FT ECO:0007744|PDB:3KFQ"
FT CONFLICT 81
FT /note="G -> P (in Ref. 1; CAA75029)"
FT /evidence="ECO:0000305"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 138..155
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 163..169
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 183..193
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:1FH0"
FT TURN 199..201
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 215..217
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 255..258
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:3H6S"
FT STRAND 277..289
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 293..300
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:1FH0"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:1FH0"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:1FH0"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:1FH0"
SQ SEQUENCE 334 AA; 37329 MW; CD2DE51AC5F242C8 CRC64;
MNLSLVLAAF CLGIASAVPK FDQNLDTKWY QWKATHRRLY GANEEGWRRA VWEKNMKMIE
LHNGEYSQGK HGFTMAMNAF GDMTNEEFRQ MMGCFRNQKF RKGKVFREPL FLDLPKSVDW
RKKGYVTPVK NQKQCGSCWA FSATGALEGQ MFRKTGKLVS LSEQNLVDCS RPQGNQGCNG
GFMARAFQYV KENGGLDSEE SYPYVAVDEI CKYRPENSVA NDTGFTVVAP GKEKALMKAV
ATVGPISVAM DAGHSSFQFY KSGIYFEPDC SSKNLDHGVL VVGYGFEGAN SNNSKYWLVK
NSWGPEWGSN GYVKIAKDKN NHCGIATAAS YPNV
