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Q01532 (BLH1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cysteine proteinase 1, mitochondrial

EC=3.4.22.40
Alternative name(s):
Bleomycin hydrolase
Short name=BLM hydrolase
Homocysteine-thiolactonase
Short name=HTLase
Short name=Hcy-thiolactonase
Leucine aminopeptidase 3
Y3
Gene names
Name:LAP3
Synonyms:BLH1, GAL6, YCP1
Ordered Locus Names:YNL239W
ORF Names:N1118
OrganismSaccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]
Taxonomic identifier559292 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesSaccharomycetaceaeSaccharomyces

Protein attributes

Sequence length483 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

The normal physiological role of the enzyme is unknown, but it is not essential for the viability of yeast cells. Has aminopeptidase activity, shortening substrate peptides sequentially by 1 amino acid. Has bleomycin hydrolase activity, which can protect the cell from the toxic effects of bleomycin. Has homocysteine-thiolactonase activity, protecting the cell against homocysteine toxicity. Acts as a repressor in the GAL4 regulatory system, but this does not require either the peptidase or nucleic acid-binding activities. Ref.12 Ref.16

Catalytic activity

Inactivates bleomycin B2 (a cytotoxic glycometallopeptide) by hydrolysis of a carboxyamide bond of beta-aminoalanine, but also shows general aminopeptidase activity. The specificity varies somewhat with source, but amino acid arylamides of Met, Leu and Ala are preferred.

Enzyme regulation

Inhibited by E64, a specific inhibitor of cysteine proteases, N-ethylmaleimide, iodacetamide, and mercury and zinc ions. Ref.1 Ref.3

Subunit structure

Homohexamer. Binds to nucleic acids. Binds single-stranded DNA and RNA with higher affinity than double-stranded DNA. Ref.9

Subcellular location

Isoform Cytoplasmic: Cytoplasm Ref.11 Ref.13 Ref.15.

Isoform Mitochondrial: Mitochondrion Ref.11 Ref.13 Ref.15.

Post-translational modification

The N-terminus of isoform Cytoplasmic is blocked.

Miscellaneous

Present with 521 molecules/cell in log phase SD medium.

Sequence similarities

Belongs to the peptidase C1 family.

Biophysicochemical properties

Kinetic parameters:

N-terminal acetylation of lysine-4-methyl-7-coumarylamide (Ac-Lys-AMC) reduces the catalytic efficiency 50-fold towards this substrate.

KM=12.8 µM for arginine-4-methyl-7-coumarylamide Ref.1 Ref.3 Ref.10

KM=0.33 mM for glutamine-beta-naphthylamide

KM=228 µM for lysine-4-methyl-7-coumarylamide

Vmax=2.56 µmol/h/mg enzyme for arginine-4-methyl-7-coumarylamide

Vmax=370 nmol/min/mg enzyme for glutamine-beta-naphthylamide

pH dependence:

Optimum pH is 7.5.

Mass spectrometry

Molecular mass is 51830 Da from positions 31 - 482. Determined by ESI. Ref.7

Alternative products

This entry describes 2 isoforms produced by alternative initiation. [Align] [Select]
Isoform Mitochondrial (identifier: Q01532-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Cytoplasmic (identifier: Q01532-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: Missing.
Note: Produced by alternative initiation at Met-30 of isoform Mitochondrial.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3030Mitochondrion Potential
Chain31 – 482452Cysteine proteinase 1, mitochondrial
PRO_0000050554
Propeptide4831Removed in mature form; by autocatalysis
PRO_0000292865

Sites

Active site1021
Active site3981
Active site4211

Natural variations

Alternative sequence1 – 2929Missing in isoform Cytoplasmic.
VSP_026453

Experimental info

Mutagenesis1021C → A: Abolishes peptidase activity, which also hinders autocatalytic processing of the enzyme to the mature form. Ref.7
Mutagenesis271 – 2744KDKK → ADAA in GAL6DB; disrupts nucleic acid-binding activity, but retains normal peptidase activity. Ref.7
Mutagenesis3981H → A: Abolishes Hcy-thiolactonase activity. Ref.16
Mutagenesis4791G → A: Results in the abnormal cleavage of 3 C-terminal residues instead of only 1 during autocatalytic processing. Ref.19
Sequence conflict1871I → M in CAA48878. Ref.2

Secondary structure

.......................................................................... 483
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Mitochondrial [UniParc].

Last modified June 26, 2007. Version 3.
Checksum: BF92A6049F98DD3D

FASTA48355,483
        10         20         30         40         50         60 
MLPTSVSRSL YLKTFRSHLL RAPQIVLKRM SSSIDISKIN SWNKEFQSDL THQLATTVLK 

        70         80         90        100        110        120 
NYNADDALLN KTRLQKQDNR VFNTVVSTDS TPVTNQKSSG RCWLFAATNQ LRLNVLSELN 

       130        140        150        160        170        180 
LKEFELSQAY LFFYDKLEKA NYFLDQIVSS ADQDIDSRLV QYLLAAPTED GGQYSMFLNL 

       190        200        210        220        230        240 
VKKYGLIPKD LYGDLPYSTT ASRKWNSLLT TKLREFAETL RTALKERSAD DSIIVTLREQ 

       250        260        270        280        290        300 
MQREIFRLMS LFMDIPPVQP NEQFTWEYVD KDKKIHTIKS TPLEFASKYA KLDPSTPVSL 

       310        320        330        340        350        360 
INDPRHPYGK LIKIDRLGNV LGGDAVIYLN VDNETLSKLV VKRLQNNKAV FFGSHTPKFM 

       370        380        390        400        410        420 
DKKTGVMDIE LWNYPAIGYN LPQQKASRIR YHESLMTHAM LITGCHVDET SKLPLRYRVE 

       430        440        450        460        470        480 
NSWGKDSGKD GLYVMTQKYF EEYCFQIVVD INELPKELAS KFTSGKEEPI VLPIWDPMGA 


LAK 

« Hide

Isoform Cytoplasmic [UniParc].

Checksum: 2F4B6236AEE3BABF
Show »

FASTA45452,089

References

« Hide 'large scale' references
[1]"Cloning and characterization of a cysteine proteinase from Saccharomyces cerevisiae."
Kambouris N.G., Burke D.J., Creutz C.E.
J. Biol. Chem. 267:21570-21576(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[2]"A yeast gene (BLH1) encodes a polypeptide with high homology to vertebrate bleomycin hydrolase, a family member of thiol proteinases."
Magdolen U., Mueller G., Magdolen V., Bandlow W.
Biochim. Biophys. Acta 1171:299-303(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 228-250 AND 367-387.
[3]"BLH1 codes for a yeast thiol aminopeptidase, the equivalent of mammalian bleomycin hydrolase."
Enenkel C., Wolf D.H.
J. Biol. Chem. 268:7036-7043(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[4]"The DNA sequence of cosmid 14-5 from chromosome XIV reveals 21 open reading frames including a novel gene encoding a globin-like domain."
Pandolfo D., de Antoni A., Lanfranchi G., Valle G.
Yeast 12:1071-1076(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications."
Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., Beinhauer J.D., Boskovic J., Buitrago M.J. expand/collapse author list , Bussereau F., Coster F., Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J.
Nature 387:93-98(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 204508 / S288c.
[6]"The reference genome sequence of Saccharomyces cerevisiae: Then and now."
Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.
G3 (Bethesda) 4:389-398(2014) [PubMed] [Europe PMC] [Abstract]
Cited for: GENOME REANNOTATION.
Strain: ATCC 204508 / S288c.
[7]"The cysteine-peptidase bleomycin hydrolase is a member of the galactose regulon in yeast."
Zheng W., Xu H.E., Johnston S.A.
J. Biol. Chem. 272:30350-30355(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-58, MASS SPECTROMETRY, MUTAGENESIS OF CYS-102 AND 271-LYS--LYS-274.
[8]"Calcium-dependent secretory vesicle-binding and lipid-binding proteins of Saccharomyces cerevisiae."
Creutz C.E., Snyder S.L., Kambouris N.G.
Yeast 7:229-244(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 228-251 AND 367-387.
[9]"Crystal structure of a conserved protease that binds DNA: the bleomycin hydrolase, Gal6."
Joshua-Tor L., Xu H.E., Johnston S.A., Rees D.C.
Science 269:945-950(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF C-TERMINUS, X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 30-483, SUBUNIT.
[10]"Yeast bleomycin hydrolase is a DNA-binding cysteine protease. Identification, purification, biochemical characterization."
Xu H.E., Johnston S.A.
J. Biol. Chem. 269:21177-21183(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, BIOPHYSICOCHEMICAL PROPERTIES.
[11]"The nucleic acid binding activity of bleomycin hydrolase is involved in bleomycin detoxification."
Zheng W., Johnston S.A.
Mol. Cell. Biol. 18:3580-3585(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, SUBCELLULAR LOCATION.
[12]"Cellular resistance to bleomycin in Saccharomyces cerevisiae is not affected by changes in bleomycin hydrolase levels."
Wang H., Ramotar D.
Biochem. Cell Biol. 80:789-796(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"Global analysis of protein localization in budding yeast."
Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K.
Nature 425:686-691(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[14]"Global analysis of protein expression in yeast."
Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.
Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[15]"The proteome of Saccharomyces cerevisiae mitochondria."
Sickmann A., Reinders J., Wagner Y., Joppich C., Zahedi R.P., Meyer H.E., Schoenfisch B., Perschil I., Chacinska A., Guiard B., Rehling P., Pfanner N., Meisinger C.
Proc. Natl. Acad. Sci. U.S.A. 100:13207-13212(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
Strain: ATCC 76625 / YPH499.
[16]"Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase."
Zimny J., Sikora M., Guranowski A., Jakubowski H.
J. Biol. Chem. 281:22485-22492(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF HIS-398.
[17]"A large-scale full-length cDNA analysis to explore the budding yeast transcriptome."
Miura F., Kawaguchi N., Sese J., Toyoda A., Hattori M., Morishita S., Ito T.
Proc. Natl. Acad. Sci. U.S.A. 103:17846-17851(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: ALTERNATIVE INITIATION.
[18]"A multidimensional chromatography technology for in-depth phosphoproteome analysis."
Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.
Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"The unusual active site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase, and peptide ligase."
Zheng W., Johnston S.A., Joshua-Tor L.
Cell 93:103-109(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 30-483 OF MUTANT ALA-102, MUTAGENESIS OF GLY-479.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M97910 Genomic DNA. Translation: AAA35231.1.
X69124 Genomic DNA. Translation: CAA48878.1.
X68228 Genomic DNA. Translation: CAA48309.1.
Z71515 Genomic DNA. Translation: CAA96144.1.
Z69381 Genomic DNA. Translation: CAA93359.1.
U74299 Genomic DNA. Translation: AAB18260.1.
BK006947 Genomic DNA. Translation: DAA10320.1.
PIRS25606. A46093.
RefSeqNP_014160.2. NM_001183077.1. [Q01532-2]

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A6RX-ray2.05A32-483[»]
1GCBX-ray2.20A30-483[»]
2DZYX-ray2.57A30-482[»]
2DZZX-ray2.15A30-482[»]
2E00X-ray2.00A30-482[»]
2E01X-ray1.73A30-482[»]
2E02X-ray2.20A30-482[»]
2E03X-ray2.13A30-482[»]
3GCBX-ray1.87A30-482[»]
ProteinModelPortalQ01532.
SMRQ01532. Positions 30-482.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid35600. 16 interactions.
DIPDIP-2941N.
IntActQ01532. 11 interactions.
MINTMINT-513897.
STRING4932.YNL239W.

Protein family/group databases

MEROPSC01.085.

Proteomic databases

MaxQBQ01532.
PaxDbQ01532.
PeptideAtlasQ01532.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID855482.
KEGGsce:YNL239W.

Organism-specific databases

CYGDYNL239w.
SGDS000005183. LAP3.

Phylogenomic databases

eggNOGCOG3579.
HOGENOMHOG000064089.
KOK01372.
OMANIFFNHI.
OrthoDBEOG7X0VS5.

Enzyme and pathway databases

BioCycYEAST:G3O-33237-MONOMER.
BRENDA3.4.22.40. 984.
SABIO-RKQ01532.

Gene expression databases

GenevestigatorQ01532.

Family and domain databases

InterProIPR000169. Pept_cys_AS.
IPR025660. Pept_his_AS.
IPR004134. Peptidase_C1B.
[Graphical view]
PANTHERPTHR10363. PTHR10363. 1 hit.
PfamPF03051. Peptidase_C1_2. 1 hit.
[Graphical view]
PIRSFPIRSF005700. PepC. 1 hit.
PROSITEPS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ01532.
NextBio979451.
PROQ01532.

Entry information

Entry nameBLH1_YEAST
AccessionPrimary (citable) accession number: Q01532
Secondary accession number(s): D6W0V4
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: June 26, 2007
Last modified: July 9, 2014
This is version 146 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

Yeast chromosome XIV

Yeast (Saccharomyces cerevisiae) chromosome XIV: entries and gene names

Yeast

Yeast (Saccharomyces cerevisiae): entries, gene names and cross-references to SGD

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references