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 13-FEB-2019, entry version 185. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Lopez-Otin C.; RT "Cathepsin L2, a novel human cysteine proteinase produced by breast RT and 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., RA Matsubara K., Okubo K.; RT "Isolation and characterization of human cathepsin V: a major RT proteinase in 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 RT cathepsin 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., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics 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., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA 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., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA 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., RA Rogers J., 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 RT project: 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 RT by N-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., RA Ayoub D., 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 RP 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. 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). CC -!- FUNCTION: Cysteine protease. May have an important role in corneal CC physiology. {ECO:0000269|PubMed:10029531, CC ECO:0000269|PubMed:9727401}. CC -!- CATALYTIC ACTIVITY: CC Reaction=The recombinant enzyme hydrolyzes proteins (serum CC albumin, collagen) and synthetic substrates (Z-Phe-Arg-NHMec > CC Z-Leu-Arg-NHMec > Z-Val-Arg-NHMec).; EC=3.4.22.43; CC Evidence={ECO:0000269|PubMed:10029531}; CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in the thymus and CC testis. Also expressed in corneal epithelium, and to a lesser CC extent in conjunctival epithelium and skin. CC {ECO:0000269|PubMed:10029531, ECO:0000269|PubMed:9563472, CC ECO:0000269|PubMed:9727401}. CC -!- SIMILARITY: Belongs to the peptidase C1 family. CC {ECO:0000255|PROSITE-ProRule:PRU10088, ECO:0000255|PROSITE- CC ProRule:PRU10089, ECO:0000255|PROSITE-ProRule:PRU10090}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- 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 UniGene; Hs.610096; -. 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 ProteinModelPortal; O60911; -. DR SMR; O60911; -. DR BioGrid; 107895; 32. DR IntAct; O60911; 15. DR MINT; O60911; -. DR STRING; 9606.ENSP00000259470; -. DR BindingDB; O60911; -. DR ChEMBL; CHEMBL3272; -. DR DrugBank; DB02869; 3-amino-5-phenylpentane. DR DrugBank; DB04451; 4-Methylpiperazin-1-Yl Carbonyl Group. DR GuidetoPHARMACOLOGY; 2352; -. DR MEROPS; I29.010; -. DR iPTMnet; O60911; -. DR PhosphoSitePlus; O60911; -. DR BioMuta; CTSV; -. DR EPD; O60911; -. DR jPOST; O60911; -. DR MaxQB; O60911; -. DR PaxDb; O60911; -. DR PeptideAtlas; O60911; -. DR PRIDE; O60911; -. DR ProteomicsDB; 49669; -. DR Ensembl; ENST00000259470; ENSP00000259470; ENSG00000136943. DR Ensembl; ENST00000538255; ENSP00000445052; ENSG00000136943. DR GeneID; 1515; -. DR KEGG; hsa:1515; -. DR UCSC; uc004awt.4; human. DR CTD; 1515; -. DR DisGeNET; 1515; -. DR EuPathDB; HostDB:ENSG00000136943.10; -. DR GeneCards; CTSV; -. DR HGNC; HGNC:2538; CTSV. DR HPA; CAB017112; -. DR MIM; 603308; gene. DR neXtProt; NX_O60911; -. DR OpenTargets; ENSG00000136943; -. DR PharmGKB; PA27036; -. DR eggNOG; KOG1543; Eukaryota. DR eggNOG; COG4870; LUCA. DR GeneTree; ENSGT00940000154367; -. DR HOGENOM; HOG000230774; -. DR HOVERGEN; HBG011513; -. DR InParanoid; O60911; -. DR KO; K01375; -. DR OMA; FEGANSD; -. DR OrthoDB; 1224404at2759; -. DR PhylomeDB; O60911; -. DR TreeFam; TF313739; -. DR BRENDA; 3.4.22.43; 2681. 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 ChiTaRS; CTSV; human. DR EvolutionaryTrace; O60911; -. DR GeneWiki; Cathepsin_L2; -. DR GenomeRNAi; 1515; -. DR PRO; PR:O60911; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; ENSG00000136943; Expressed in 175 organ(s), highest expression level in hair follicle. DR ExpressionAtlas; O60911; baseline and differential. DR Genevisible; O60911; HS. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0009897; C:external side of plasma membrane; IEA:Ensembl. 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:0005902; C:microvillus; IEA:Ensembl. DR GO; GO:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0043204; C:perikaryon; IEA:Ensembl. DR GO; GO:0030141; C:secretory granule; IEA:Ensembl. DR GO; GO:0004177; F:aminopeptidase activity; IEA:Ensembl. 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:0030984; F:kininogen binding; IEA:Ensembl. DR GO; GO:0042277; F:peptide binding; IEA:Ensembl. DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl. 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:0048102; P:autophagic cell death; IEA:Ensembl. DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl. DR GO; GO:0046697; P:decidualization; IEA:Ensembl. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0010259; P:multicellular organism aging; IEA:Ensembl. DR GO; GO:0021675; P:nerve development; IEA:Ensembl. DR GO; GO:0051603; P:proteolysis involved in cellular protein catabolic process; IBA:GO_Central. DR GO; GO:0045616; P:regulation of keratinocyte differentiation; TAS:Reactome. DR GO; GO:0051384; P:response to glucocorticoid; IEA:Ensembl. DR GO; GO:0009749; P:response to glucose; IEA:Ensembl. DR GO; GO:0034698; P:response to gonadotropin; IEA:Ensembl. DR GO; GO:1990834; P:response to odorant; IEA:Ensembl. DR GO; GO:0060008; P:Sertoli cell differentiation; IEA:Ensembl. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. 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; IPR013128; Peptidase_C1A. DR InterPro; IPR000668; Peptidase_C1A_C. DR InterPro; IPR039417; Peptidase_C1A_papain-like. DR InterPro; IPR013201; Prot_inhib_I29. DR PANTHER; PTHR12411; PTHR12411; 1. 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; Complete proteome; Disulfide bond; Glycoprotein; KW Hydrolase; Lysosome; Protease; Reference proteome; Signal; KW Thiol protease; Zymogen. FT SIGNAL 1 17 {ECO:0000255}. FT PROPEP 18 113 Activation peptide. FT /FTId=PRO_0000026277. FT CHAIN 114 334 Cathepsin L2. FT /FTId=PRO_0000026278. FT ACT_SITE 138 138 {ECO:0000269|PubMed:11027133}. FT ACT_SITE 277 277 {ECO:0000269|PubMed:11027133}. FT ACT_SITE 301 301 {ECO:0000269|PubMed:11027133}. FT CARBOHYD 221 221 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22967898}. FT CARBOHYD 292 292 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22967898}. FT DISULFID 135 178 {ECO:0000244|PDB:1FH0, FT ECO:0000244|PDB:3H6S, FT ECO:0000244|PDB:3KFQ, FT ECO:0000269|PubMed:11027133}. FT DISULFID 169 211 {ECO:0000244|PDB:1FH0, FT ECO:0000244|PDB:3H6S, FT ECO:0000244|PDB:3KFQ, FT ECO:0000269|PubMed:11027133}. FT DISULFID 270 323 {ECO:0000244|PDB:1FH0, FT ECO:0000244|PDB:3H6S, FT ECO:0000244|PDB:3KFQ, FT ECO:0000269|PubMed:11027133}. FT CONFLICT 81 81 G -> P (in Ref. 1; CAA75029). FT {ECO:0000305}. FT HELIX 120 123 {ECO:0000244|PDB:1FH0}. FT HELIX 138 155 {ECO:0000244|PDB:1FH0}. FT HELIX 163 169 {ECO:0000244|PDB:1FH0}. FT HELIX 171 173 {ECO:0000244|PDB:1FH0}. FT HELIX 177 179 {ECO:0000244|PDB:1FH0}. FT HELIX 183 193 {ECO:0000244|PDB:1FH0}. FT STRAND 196 198 {ECO:0000244|PDB:1FH0}. FT TURN 199 201 {ECO:0000244|PDB:1FH0}. FT HELIX 215 217 {ECO:0000244|PDB:1FH0}. FT STRAND 218 220 {ECO:0000244|PDB:1FH0}. FT STRAND 225 227 {ECO:0000244|PDB:1FH0}. FT HELIX 233 242 {ECO:0000244|PDB:1FH0}. FT STRAND 246 250 {ECO:0000244|PDB:1FH0}. FT HELIX 255 258 {ECO:0000244|PDB:1FH0}. FT STRAND 262 265 {ECO:0000244|PDB:1FH0}. FT STRAND 272 274 {ECO:0000244|PDB:3H6S}. FT STRAND 277 289 {ECO:0000244|PDB:1FH0}. FT STRAND 293 300 {ECO:0000244|PDB:1FH0}. FT STRAND 312 316 {ECO:0000244|PDB:1FH0}. FT STRAND 318 321 {ECO:0000244|PDB:1FH0}. FT HELIX 322 324 {ECO:0000244|PDB:1FH0}. FT TURN 325 327 {ECO:0000244|PDB:1FH0}. FT STRAND 330 332 {ECO:0000244|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 //