P07711 (CATL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cathepsin L1
EC=3.4.22.15

Alternative name(s):
Major excreted protein
Short name=MEP

Cleaved into the following 2 chains:

1. Cathepsin L1 heavy chain
2. Cathepsin L1 light chain

Gene names

Name:	CTSL1
Synonyms:	CTSL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	333 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Important for the overall degradation of proteins in lysosomes.
Catalytic activity	Specificity close to that of papain. As compared to cathepsin B, cathepsin L exhibits higher activity toward protein substrates, but has little activity on Z-Arg-Arg-NHMec, and no peptidyl-dipeptidase activity.
Subunit structure	Dimer of a heavy and a light chain linked by disulfide bonds.
Subcellular location	Lysosome.
Sequence similarities	Belongs to the peptidase C1 family.

Ontologies

Keywords
Cellular component	Lysosome
Domain	Signal
Molecular function	Hydrolase Protease Thiol protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adaptive immune response Inferred from expression pattern PubMed 15196205. Source: UniProtKB antigen processing and presentation of exogenous peptide antigen via MHC class II Traceable author statement. Source: Reactome cellular response to thyroid hormone stimulus Inferred from expression pattern PubMed 21217776. Source: UniProtKB innate immune response Traceable author statement. Source: Reactome macrophage apoptotic process Non-traceable author statement PubMed 18495127. Source: BHF-UCL proteolysis Inferred from direct assay PubMed 8811434. Source: UniProtKB
Cellular_component	endolysosome lumen Traceable author statement. Source: Reactome extracellular region Non-traceable author statement PubMed 14718574. Source: UniProtKB nucleus Traceable author statement PubMed 21326229. Source: BHF-UCL
Molecular_function	cysteine-type endopeptidase activity Inferred from direct assay PubMed 14511383. Source: UniProtKB histone binding Inferred from direct assay PubMed 21326229. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
srp-6	G5EFH4	2	EBI-1220160,EBI-1549936	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Propeptide

18 – 113

96

Activation peptide

PRO_0000026244

Chain

114 – 288

175

Cathepsin L1 heavy chain

PRO_0000026245

Propeptide

289 – 291

3

PRO_0000026246

Chain

292 – 333

42

Cathepsin L1 light chain

PRO_0000026247

Sites

Active site

138

1

Active site

276

1

Active site

300

1

Amino acid modifications

Glycosylation

221

1

N-linked (GlcNAc...) Ref.10 Ref.11 Ref.12

Disulfide bond

135 ↔ 178

Disulfide bond

169 ↔ 211

Disulfide bond

269 ↔ 322

Interchain (between heavy and light chains)

Experimental info

Sequence conflict

56

1

M → V in AAH12612. Ref.6

Sequence conflict

268

1

D → N AA sequence Ref.7

Secondary structure

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333

Helix Strand Turn

Details...

Helix

23 – 25

3

Helix

26 – 35

10

Helix

44 – 67

24

Beta strand

72 – 75

4

Turn

79 – 82

4

Helix

85 – 92

8

Beta strand

103 – 105

3

Helix

120 – 123

4

Beta strand

134 – 136

3

Helix

138 – 155

18

Helix

163 – 169

7

Turn

171 – 174

4

Helix

177 – 179

3

Helix

183 – 193

11

Beta strand

196 – 198

3

Turn

199 – 201

3

Helix

215 – 217

3

Beta strand

218 – 220

3

Beta strand

223 – 227

5

Helix

232 – 241

10

Beta strand

245 – 249

5

Helix

254 – 257

4

Beta strand

261 – 264

4

Helix

271 – 273

3

Beta strand

276 – 285

10

Beta strand

289 – 291

3

Beta strand

294 – 299

6

Beta strand

304 – 306

3

Beta strand

311 – 315

5

Beta strand

317 – 320

4

Helix

321 – 323

3

Turn

324 – 326

3

Beta strand

329 – 332

4

Sequences

	Sequence		Length	Mass (Da)
	P07711 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: 8CD17D00EF859D85	FASTA	333	37,564
	10 20 30 40 50 60 MNPTLILAAF CLGIASATLT FDHSLEAQWT KWKAMHNRLY GMNEEGWRRA VWEKNMKMIE 70 80 90 100 110 120 LHNQEYREGK HSFTMAMNAF GDMTSEEFRQ VMNGFQNRKP RKGKVFQEPL FYEAPRSVDW 130 140 150 160 170 180 REKGYVTPVK NQGQCGSCWA FSATGALEGQ MFRKTGRLIS LSEQNLVDCS GPQGNEGCNG 190 200 210 220 230 240 GLMDYAFQYV QDNGGLDSEE SYPYEATEES CKYNPKYSVA NDTGFVDIPK QEKALMKAVA 250 260 270 280 290 300 TVGPISVAID AGHESFLFYK EGIYFEPDCS SEDMDHGVLV VGYGFESTES DNNKYWLVKN 310 320 330 SWGEEWGMGG YVKMAKDRRN HCGIASAASY PTV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and sequence of a cDNA for human pro-(cathepsin L)." Gal S., Gottesman M.M. Biochem. J. 253:303-306(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts." Joseph L.J., Chang L.C., Stamenkovich D., Sukhatme V.P. J. Clin. Invest. 81:1621-1629(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon endothelium.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[7]	"Amino acid sequences of the human kidney cathepsins H and L." Ritonja A., Popovic T., Kotnik M., Machleidt W., Turk V. FEBS Lett. 228:341-345(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 114-288 AND 292-333.
[8]	"The major ras induced protein in NIH3T3 cells is cathepsin L." Joseph L.J., Lapid S., Sukhatme V.P. Nucleic Acids Res. 15:3186-3186(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 113-154.
[9]	"The N-terminal amino acid sequences of the heavy and light chains of human cathepsin L. Relationship to a cDNA clone for a major cysteine proteinase from a mouse macrophage cell line." Mason R.W., Walker J.E., Northrop F.D. Biochem. J. 240:373-377(1986) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 114-154 AND 292-333.
[10]	"Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry." Zhang H., Li X.-J., Martin D.B., Aebersold R. Nat. Biotechnol. 21:660-666(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-221.
[11]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221, MASS SPECTROMETRY. Tissue: Plasma.
[12]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221, MASS SPECTROMETRY. Tissue: Liver.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]	"Structure of human procathepsin L reveals the molecular basis of inhibition by the prosegment." Coulombe R., Grochulski P., Sivaraman J., Menard R., Mort J.S., Cygler M. EMBO J. 15:5492-5503(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 18-333.
[15]	"The crystal structure of human cathepsin L complexed with E-64." Fujishima A., Imai Y., Nomura T., Fujisawa Y., Yamamoto Y., Sugarawa T. FEBS Lett. 407:47-50(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 114-333.
[16]	Cygler M., Coulombe R. Submitted (AUG-1999) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 18-333.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X12451 mRNA. Translation: CAA30981.1.
M20496 mRNA. Translation: AAA66974.1.
CR457053 mRNA. Translation: CAG33334.1.
BX537395 mRNA. Translation: CAD97637.1.
AL160279 Genomic DNA. Translation: CAI16308.1.
BC012612 mRNA. Translation: AAH12612.1.
X05256 mRNA. Translation: CAA28877.1.

IPI

IPI00012887.

PIR

KHHUL. S01002.

RefSeq

NP_001244900.1. NM_001257971.1.
NP_001244901.1. NM_001257972.1.
NP_001903.1. NM_001912.4.
NP_666023.1. NM_145918.2.

UniGene

Hs.731507.
Hs.731952.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CJL	X-ray	2.20	A	22-333	[»]
1CS8	X-ray	1.80	A	19-333	[»]
1ICF	X-ray	2.00	A/C	114-288	[»]
			B/D	292-333	[»]
1MHW	X-ray	1.90	A/B	114-288	[»]
			C/D	292-333	[»]
2NQD	X-ray	1.75	B	113-333	[»]
2VHS	X-ray	1.50	A/B/C/D	114-333	[»]
2XU1	X-ray	1.45	A/B/C/D	114-333	[»]
2XU3	X-ray	0.90	A	114-333	[»]
2XU4	X-ray	1.12	A	114-333	[»]
2XU5	X-ray	1.60	A	114-333	[»]
2YJ2	X-ray	1.15	A	114-333	[»]
2YJ8	X-ray	1.30	A	114-333	[»]
2YJ9	X-ray	1.35	A	114-333	[»]
2YJB	X-ray	1.40	A	114-333	[»]
2YJC	X-ray	1.14	A	114-333	[»]
3BC3	X-ray	2.20	A/B	114-333	[»]
3H89	X-ray	2.50	A/B/C/D/E/F	114-333	[»]
3H8B	X-ray	1.80	A/B/C/D/E/F	114-333	[»]
3H8C	X-ray	2.50	A/B	114-333	[»]
3HHA	X-ray	1.27	A/B/C/D	114-333	[»]
3HWN	X-ray	2.33	A/B/C/D	76-333	[»]
3IV2	X-ray	2.20	A/B	114-333	[»]
3K24	X-ray	2.50	A/B	114-333	[»]
3KSE	X-ray	1.71	A/B/C	114-333	[»]
3OF8	X-ray	2.20	A	113-333	[»]
3OF9	X-ray	1.76	A	113-333	[»]

ProteinModelPortal

P07711.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07711. 11 interactions.

STRING

9606.ENSP00000345344.

Protein family/group databases

MEROPS

I29.001.

PTM databases

PhosphoSite

P07711.

Polymorphism databases

DMDM

115741.

Proteomic databases

PaxDb

P07711.

PeptideAtlas

P07711.

PRIDE

P07711.

Protocols and materials databases

DNASU

1514.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000340342; ENSP00000365061; ENSG00000135047.
ENST00000343150; ENSP00000345344; ENSG00000135047.

GeneID

1514.

KEGG

hsa:1514.

UCSC

uc004aph.3. human.

Organism-specific databases

CTD

1514.

GeneCards

GC09P090341.

H-InvDB

HIX0058839.
HIX0170314.

HGNC

HGNC:2537. CTSL1.

HPA

CAB000459.

MIM

116880. gene.

neXtProt

NX_P07711.

PharmGKB

PA162382890.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4870.

HOGENOM

HOG000230774.

HOVERGEN

HBG011513.

InParanoid

P07711.

KO

K01365.

OMA

REPLFAQ.

OrthoDB

EOG48PMKF.

PhylomeDB

P07711.

Enzyme and pathway databases

BRENDA

3.4.22.15. 2681.

Reactome

REACT_118779. Extracellular matrix organization.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P07711.

Bgee

P07711.

CleanEx

HS_CTSL1.

Genevestigator

P07711.

GermOnline

ENSG00000135047. Homo sapiens.

Family and domain databases

InterPro

IPR025661. Pept_asp_AS.
IPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR013201. Prot_inhib_I29.
[Graphical view]

PANTHER

PTHR12411. PTHR12411. 1 hit.

Pfam

PF08246. Inhibitor_I29. 1 hit.
PF00112. Peptidase_C1. 1 hit.
[Graphical view]

PRINTS

PR00705. PAPAIN.

SMART

SM00848. Inhibitor_I29. 1 hit.
SM00645. Pept_C1. 1 hit.
[Graphical view]

PROSITE

PS00640. THIOL_PROTEASE_ASN. 1 hit.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P07711.

ChEMBL

CHEMBL3837.

ChiTaRS

CTSL1. human.

DrugBank

DB00040. Glucagon recombinant.

EvolutionaryTrace

P07711.

GenomeRNAi

1514.

NextBio

6271.

PMAP-CutDB

P07711.

SOURCE

Search...

Entry information

Entry name

CATL1_HUMAN

Accession

Primary (citable) accession number: P07711
Secondary accession number(s): Q6IAV1, Q96QJ0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 154 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.