Reviewed, UniProtKB/Swiss-Prot P07711 (CATL1_HUMAN)

Names and origin

Protein names

Recommended name:
    Cathepsin L1
    EC=3.4.22.15
Alternative name(s):
    Major excreted protein
      Short name(s)=MEP
Cleaved into 2 chains:
  Recommended name:
      Cathepsin L1 heavy chain
  Recommended name:
      Cathepsin L1 light chain

Gene names

Name:	CTSL1
Synonyms:	CTSL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular component	extracellular region Non-traceable author statement. Source: UniProtKB lysosome Non-traceable author statement. Source: UniProtKB
Molecular function	cathepsin L activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
srp-6	O01462	1	EBI-1220160,EBI-1549936	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Signal peptide

1 – 17

17

Potential

Propeptide

18 – 113

96

Activation peptide

Chain

114 – 288

175

Cathepsin L1 heavy chain

Propeptide

289 – 291

3

Chain

292 – 333

42

Cathepsin L1 light chain

Sites

Active site

138

1

Active site

276

1

Active site

300

1

Amino acid modifications

Glycosylation

221

1

N-linked (GlcNAc...)

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

1

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333

Helix Strand Turn

Details...

Turn

120 – 124

5

Helix

138 – 155

18

Helix

163 – 169

7

Helix

171 – 173

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

224 – 227

4

Helix

232 – 241

10

Beta strand

244 – 249

6

Helix

254 – 257

4

Beta strand

261 – 264

4

Beta strand

276 – 285

10

Beta strand

294 – 299

6

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)
	P07711-1 [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: 3421948] [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: 2835398] [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 German cDNA consortium Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases 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: 15164053] [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: 15489334] [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: 3342889] [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: 3550705] [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: 3545185] [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: 12754519] [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: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-221, MASS SPECTROMETRY. Tissue: Plasma.
[12]	"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: 8896443] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 18-333.
[13]	"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: 9141479] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 114-333.
[14]	Cygler M., Coulombe R. Submitted (AUG-1999) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 18-333.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

KHHUL. S01002.

RefSeq

NP_001903.1.
NP_666023.1.

UniGene

Hs.418123

3D structure databases

PDBMSD

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	[»]
3BC3	X-ray	2.20	A/B	114-333	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P07711.

Protein family/group databases

MEROPS

C01.032.
I29.001.

Proteomic databases

PeptideAtlas

P07711.

Genome annotation databases

Ensembl

ENSG00000135047. Homo sapiens. [Contig view]

GeneID

1514.

KEGG

hsa:1514.

Organism-specific databases

H-InvDB

HIX0008146.

HGNC

HGNC:2537. CTSL1.

HPA

CAB000459.

MIM

116880. gene.

PharmGKB

PA27035.

GenAtlas

Search...

GeneCards

Search...

GeneLynx

Search...

Phylogenomic databases

HOGENOM

P07711.

HOVERGEN

P07711.

Gene expression databases

ArrayExpress

P07711.

CleanEx

HS_CTSL1.

GermOnline

ENSG00000135047. Homo sapiens.

Family and domain databases

InterPro

IPR000169. Pept_cys_AS.
IPR013128. Peptidase_C1A.
IPR000668. Peptidase_C1A_C.
IPR013201. Prot_inhib_I29.
[Graphical view]

PANTHER

PTHR12411. Peptidase_C1A. 1 hit.

Pfam

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

PRINTS

PR00705. PAPAIN.

ProDom

PD000158. Peptidase_C1. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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]

BLOCKS

Search...

Other Resources

BindingDB

P07711.

DrugBank

DB00040. Glucagon recombinant.

LinkHub

P07711.

SOURCE

Search...

ProtoNet

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:	July 22, 2008
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)