ID CATL1_HUMAN Reviewed; 333 AA.
AC P07711; Q6IAV1; Q96QJ0;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 29-MAY-2013, entry version 155.
DE RecName: Full=Cathepsin L1;
DE EC=3.4.22.15;
DE AltName: Full=Major excreted protein;
DE Short=MEP;
DE Contains:
DE RecName: Full=Cathepsin L1 heavy chain;
DE Contains:
DE RecName: Full=Cathepsin L1 light chain;
DE Flags: Precursor;
GN Name=CTSL1; Synonyms=CTSL;
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].
RX PubMed=3421948;
RA Gal S., Gottesman M.M.;
RT "Isolation and sequence of a cDNA for human pro-(cathepsin L).";
RL Biochem. J. 253:303-306(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2835398; DOI=10.1172/JCI113497;
RA Joseph L.J., Chang L.C., Stamenkovich D., Sukhatme V.P.;
RT "Complete nucleotide and deduced amino acid sequences of human and
RT murine preprocathepsin L. An abundant transcript induced by
RT transformation of fibroblasts.";
RL J. Clin. Invest. 81:1621-1629(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon endothelium;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [7]
RP PROTEIN SEQUENCE OF 114-288 AND 292-333.
RX PubMed=3342889; DOI=10.1016/0014-5793(88)80028-0;
RA Ritonja A., Popovic T., Kotnik M., Machleidt W., Turk V.;
RT "Amino acid sequences of the human kidney cathepsins H and L.";
RL FEBS Lett. 228:341-345(1988).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 113-154.
RX PubMed=3550705; DOI=10.1093/nar/15.7.3186;
RA Joseph L.J., Lapid S., Sukhatme V.P.;
RT "The major ras induced protein in NIH3T3 cells is cathepsin L.";
RL Nucleic Acids Res. 15:3186-3186(1987).
RN [9]
RP PROTEIN SEQUENCE OF 114-154 AND 292-333.
RX PubMed=3545185;
RA Mason R.W., Walker J.E., Northrop F.D.;
RT "The N-terminal amino acid sequences of the heavy and light chains of
RT human cathepsin L. Relationship to a cDNA clone for a major cysteine
RT proteinase from a mouse macrophage cell line.";
RL Biochem. J. 240:373-377(1986).
RN [10]
RP GLYCOSYLATION AT ASN-221.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221, AND MASS
RP SPECTROMETRY.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E.,
RA Moore R.J., Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [12]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 18-333.
RX PubMed=8896443;
RA Coulombe R., Grochulski P., Sivaraman J., Menard R., Mort J.S.,
RA Cygler M.;
RT "Structure of human procathepsin L reveals the molecular basis of
RT inhibition by the prosegment.";
RL EMBO J. 15:5492-5503(1996).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 114-333.
RX PubMed=9141479; DOI=10.1016/S0014-5793(97)00216-0;
RA Fujishima A., Imai Y., Nomura T., Fujisawa Y., Yamamoto Y.,
RA Sugarawa T.;
RT "The crystal structure of human cathepsin L complexed with E-64.";
RL FEBS Lett. 407:47-50(1997).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 18-333.
RA Cygler M., Coulombe R.;
RL Submitted (AUG-1999) to the PDB data bank.
CC -!- FUNCTION: Important for the overall degradation of proteins in
CC lysosomes.
CC -!- CATALYTIC ACTIVITY: Specificity close to that of papain. As
CC compared to cathepsin B, cathepsin L exhibits higher activity
CC toward protein substrates, but has little activity on Z-Arg-Arg-
CC NHMec, and no peptidyl-dipeptidase activity.
CC -!- SUBUNIT: Dimer of a heavy and a light chain linked by disulfide
CC bonds.
CC -!- INTERACTION:
CC G5EFH4:srp-6 (xeno); NbExp=2; IntAct=EBI-1220160, EBI-1549936;
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- SIMILARITY: Belongs to the peptidase C1 family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CTSL1ID40208ch9q21.html";
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DR EMBL; X12451; CAA30981.1; -; mRNA.
DR EMBL; M20496; AAA66974.1; -; mRNA.
DR EMBL; CR457053; CAG33334.1; -; mRNA.
DR EMBL; BX537395; CAD97637.1; -; mRNA.
DR EMBL; AL160279; CAI16308.1; -; Genomic_DNA.
DR EMBL; BC012612; AAH12612.1; -; mRNA.
DR EMBL; X05256; CAA28877.1; -; mRNA.
DR IPI; IPI00012887; -.
DR PIR; S01002; KHHUL.
DR RefSeq; NP_001244900.1; NM_001257971.1.
DR RefSeq; NP_001244901.1; NM_001257972.1.
DR RefSeq; NP_001903.1; NM_001912.4.
DR RefSeq; NP_666023.1; NM_145918.2.
DR UniGene; Hs.731507; -.
DR UniGene; Hs.731952; -.
DR PDB; 1CJL; X-ray; 2.20 A; A=22-333.
DR PDB; 1CS8; X-ray; 1.80 A; A=19-333.
DR PDB; 1ICF; X-ray; 2.00 A; A/C=114-288, B/D=292-333.
DR PDB; 1MHW; X-ray; 1.90 A; A/B=114-288, C/D=292-333.
DR PDB; 2NQD; X-ray; 1.75 A; B=113-333.
DR PDB; 2VHS; X-ray; 1.50 A; A/B/C/D=114-333.
DR PDB; 2XU1; X-ray; 1.45 A; A/B/C/D=114-333.
DR PDB; 2XU3; X-ray; 0.90 A; A=114-333.
DR PDB; 2XU4; X-ray; 1.12 A; A=114-333.
DR PDB; 2XU5; X-ray; 1.60 A; A=114-333.
DR PDB; 2YJ2; X-ray; 1.15 A; A=114-333.
DR PDB; 2YJ8; X-ray; 1.30 A; A=114-333.
DR PDB; 2YJ9; X-ray; 1.35 A; A=114-333.
DR PDB; 2YJB; X-ray; 1.40 A; A=114-333.
DR PDB; 2YJC; X-ray; 1.14 A; A=114-333.
DR PDB; 3BC3; X-ray; 2.20 A; A/B=114-333.
DR PDB; 3H89; X-ray; 2.50 A; A/B/C/D/E/F=114-333.
DR PDB; 3H8B; X-ray; 1.80 A; A/B/C/D/E/F=114-333.
DR PDB; 3H8C; X-ray; 2.50 A; A/B=114-333.
DR PDB; 3HHA; X-ray; 1.27 A; A/B/C/D=114-333.
DR PDB; 3HWN; X-ray; 2.33 A; A/B/C/D=76-333.
DR PDB; 3IV2; X-ray; 2.20 A; A/B=114-333.
DR PDB; 3K24; X-ray; 2.50 A; A/B=114-333.
DR PDB; 3KSE; X-ray; 1.71 A; A/B/C=114-333.
DR PDB; 3OF8; X-ray; 2.20 A; A=113-333.
DR PDB; 3OF9; X-ray; 1.76 A; A=113-333.
DR PDBsum; 1CJL; -.
DR PDBsum; 1CS8; -.
DR PDBsum; 1ICF; -.
DR PDBsum; 1MHW; -.
DR PDBsum; 2NQD; -.
DR PDBsum; 2VHS; -.
DR PDBsum; 2XU1; -.
DR PDBsum; 2XU3; -.
DR PDBsum; 2XU4; -.
DR PDBsum; 2XU5; -.
DR PDBsum; 2YJ2; -.
DR PDBsum; 2YJ8; -.
DR PDBsum; 2YJ9; -.
DR PDBsum; 2YJB; -.
DR PDBsum; 2YJC; -.
DR PDBsum; 3BC3; -.
DR PDBsum; 3H89; -.
DR PDBsum; 3H8B; -.
DR PDBsum; 3H8C; -.
DR PDBsum; 3HHA; -.
DR PDBsum; 3HWN; -.
DR PDBsum; 3IV2; -.
DR PDBsum; 3K24; -.
DR PDBsum; 3KSE; -.
DR PDBsum; 3OF8; -.
DR PDBsum; 3OF9; -.
DR ProteinModelPortal; P07711; -.
DR IntAct; P07711; 11.
DR MINT; MINT-3005764; -.
DR STRING; 9606.ENSP00000345344; -.
DR MEROPS; I29.001; -.
DR PhosphoSite; P07711; -.
DR DMDM; 115741; -.
DR PaxDb; P07711; -.
DR PeptideAtlas; P07711; -.
DR PRIDE; P07711; -.
DR DNASU; 1514; -.
DR Ensembl; ENST00000340342; ENSP00000365061; ENSG00000135047.
DR Ensembl; ENST00000343150; ENSP00000345344; ENSG00000135047.
DR GeneID; 1514; -.
DR KEGG; hsa:1514; -.
DR UCSC; uc004aph.3; human.
DR CTD; 1514; -.
DR GeneCards; GC09P090341; -.
DR H-InvDB; HIX0058839; -.
DR H-InvDB; HIX0170314; -.
DR HGNC; HGNC:2537; CTSL1.
DR HPA; CAB000459; -.
DR MIM; 116880; gene.
DR neXtProt; NX_P07711; -.
DR PharmGKB; PA162382890; -.
DR eggNOG; COG4870; -.
DR HOGENOM; HOG000230774; -.
DR HOVERGEN; HBG011513; -.
DR InParanoid; P07711; -.
DR KO; K01365; -.
DR OMA; REPLFAQ; -.
DR OrthoDB; EOG48PMKF; -.
DR PhylomeDB; P07711; -.
DR BRENDA; 3.4.22.15; 2681.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR Reactome; REACT_6900; Immune System.
DR BindingDB; P07711; -.
DR ChEMBL; CHEMBL3837; -.
DR ChiTaRS; CTSL1; human.
DR DrugBank; DB00040; Glucagon recombinant.
DR EvolutionaryTrace; P07711; -.
DR GenomeRNAi; 1514; -.
DR NextBio; 6271; -.
DR PMAP-CutDB; P07711; -.
DR ArrayExpress; P07711; -.
DR Bgee; P07711; -.
DR CleanEx; HS_CTSL1; -.
DR Genevestigator; P07711; -.
DR GermOnline; ENSG00000135047; Homo sapiens.
DR GO; GO:0036021; C:endolysosome lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; TAS:BHF-UCL.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:BHF-UCL.
DR GO; GO:0002250; P:adaptive immune response; IEP:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IEP:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; TAS:Reactome.
DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0071888; P:macrophage apoptotic process; NAS:BHF-UCL.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome.
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; 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 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; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Hydrolase; Lysosome; Protease;
KW Reference proteome; Signal; Thiol protease; Zymogen.
FT SIGNAL 1 17 Potential.
FT PROPEP 18 113 Activation peptide.
FT /FTId=PRO_0000026244.
FT CHAIN 114 288 Cathepsin L1 heavy chain.
FT /FTId=PRO_0000026245.
FT PROPEP 289 291
FT /FTId=PRO_0000026246.
FT CHAIN 292 333 Cathepsin L1 light chain.
FT /FTId=PRO_0000026247.
FT ACT_SITE 138 138
FT ACT_SITE 276 276
FT ACT_SITE 300 300
FT CARBOHYD 221 221 N-linked (GlcNAc...).
FT DISULFID 135 178
FT DISULFID 169 211
FT DISULFID 269 322 Interchain (between heavy and light
FT chains).
FT CONFLICT 56 56 M -> V (in Ref. 6; AAH12612).
FT CONFLICT 268 268 D -> N (in Ref. 7; AA sequence).
FT HELIX 23 25
FT HELIX 26 35
FT HELIX 44 67
FT STRAND 72 75
FT TURN 79 82
FT HELIX 85 92
FT STRAND 103 105
FT HELIX 120 123
FT STRAND 134 136
FT HELIX 138 155
FT HELIX 163 169
FT TURN 171 174
FT HELIX 177 179
FT HELIX 183 193
FT STRAND 196 198
FT TURN 199 201
FT HELIX 215 217
FT STRAND 218 220
FT STRAND 223 227
FT HELIX 232 241
FT STRAND 245 249
FT HELIX 254 257
FT STRAND 261 264
FT HELIX 271 273
FT STRAND 276 285
FT STRAND 289 291
FT STRAND 294 299
FT STRAND 304 306
FT STRAND 311 315
FT STRAND 317 320
FT HELIX 321 323
FT TURN 324 326
FT STRAND 329 332
SQ SEQUENCE 333 AA; 37564 MW; 8CD17D00EF859D85 CRC64;
MNPTLILAAF CLGIASATLT FDHSLEAQWT KWKAMHNRLY GMNEEGWRRA VWEKNMKMIE
LHNQEYREGK HSFTMAMNAF GDMTSEEFRQ VMNGFQNRKP RKGKVFQEPL FYEAPRSVDW
REKGYVTPVK NQGQCGSCWA FSATGALEGQ MFRKTGRLIS LSEQNLVDCS GPQGNEGCNG
GLMDYAFQYV QDNGGLDSEE SYPYEATEES CKYNPKYSVA NDTGFVDIPK QEKALMKAVA
TVGPISVAID AGHESFLFYK EGIYFEPDCS SEDMDHGVLV VGYGFESTES DNNKYWLVKN
SWGEEWGMGG YVKMAKDRRN HCGIASAASY PTV
//
