RBCC Red Blood Cell Collection

BLMH [Confidence: low (only semi-automatic identification from reviews)]
Bleomycin hydrolase; BH; BLM hydrolase; BMH; 3.4.22.40
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt Q13867
ID BLMH_HUMAN Reviewed; 455 AA.
AC Q13867; B2R796; Q53F86; Q9UER9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-NOV-1996, sequence version 1.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Bleomycin hydrolase;
DE Short=BH;
DE Short=BLM hydrolase;
DE Short=BMH;
DE EC=3.4.22.40;
GN Name=BLMH;
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].
RC TISSUE=Brain;
RX PubMed=8620487;
RA Ferrando A.A., Velasco G., Campo E., Lopez-Otin C.;
RT "Cloning and expression analysis of human bleomycin hydrolase, a
RT cysteine proteinase involved in chemotherapy resistance.";
RL Cancer Res. 56:1746-1750(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANT
RP VAL-443.
RC TISSUE=Lung;
RX PubMed=8639621; DOI=10.1021/bi960092y;
RA Broemme D., Rossi A.B., Smeekens S.P., Anderson D.C., Payan D.G.;
RT "Human bleomycin hydrolase: molecular cloning, sequencing, functional
RT expression, and enzymatic characterization.";
RL Biochemistry 35:6706-6714(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 292-455, AND VARIANT
RP VAL-443.
RA Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F.;
RT "Full-insert sequence of mapped XREF EST.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-391, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
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 [11]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
RX PubMed=10404591; DOI=10.1016/S0969-2126(99)80083-5;
RA O'Farrell P.A., Gonzalez F., Zheng W., Johnston S.A., Joshua-Tor L.;
RT "Crystal structure of human bleomycin hydrolase, a self-
RT compartmentalizing cysteine protease.";
RL Structure 7:619-627(1999).
CC -!- FUNCTION: The normal physiological role of BLM hydrolase is
CC unknown, but it catalyzes the inactivation of the antitumor drug
CC BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-
CC aminoalaninamide moiety thus protecting normal and malignant cells
CC from BLM toxicity (By similarity).
CC -!- CATALYTIC ACTIVITY: Inactivates bleomycin B2 (a cytotoxic
CC glycometallopeptide) by hydrolysis of a carboxyamide bond of beta-
CC aminoalanine, but also shows general aminopeptidase activity. The
CC specificity varies somewhat with source, but amino acid arylamides
CC of Met, Leu and Ala are preferred.
CC -!- SUBUNIT: Homohexamer.
CC -!- INTERACTION:
CC P05067-4:APP; NbExp=2; IntAct=EBI-718504, EBI-302641;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the peptidase C1 family.
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DR EMBL; X92106; CAA63078.1; -; mRNA.
DR EMBL; BT007018; AAP35664.1; -; mRNA.
DR EMBL; AK223403; BAD97123.1; -; mRNA.
DR EMBL; AK312896; BAG35743.1; -; mRNA.
DR EMBL; CH471159; EAW51224.1; -; Genomic_DNA.
DR EMBL; BC003616; AAH03616.1; -; mRNA.
DR EMBL; AF091082; AAC72951.1; -; mRNA.
DR RefSeq; NP_000377.1; NM_000386.3.
DR UniGene; Hs.371914; -.
DR PDB; 1CB5; X-ray; 2.59 A; A/B/C=2-454.
DR PDB; 2CB5; X-ray; 1.85 A; A/B=2-454.
DR PDBsum; 1CB5; -.
DR PDBsum; 2CB5; -.
DR ProteinModelPortal; Q13867; -.
DR SMR; Q13867; 2-454.
DR IntAct; Q13867; 11.
DR MINT; MINT-1397729; -.
DR STRING; 9606.ENSP00000261714; -.
DR MEROPS; C01.084; -.
DR PhosphoSite; Q13867; -.
DR DMDM; 3023394; -.
DR PaxDb; Q13867; -.
DR PeptideAtlas; Q13867; -.
DR PRIDE; Q13867; -.
DR DNASU; 642; -.
DR Ensembl; ENST00000261714; ENSP00000261714; ENSG00000108578.
DR GeneID; 642; -.
DR KEGG; hsa:642; -.
DR UCSC; uc002hez.2; human.
DR CTD; 642; -.
DR GeneCards; GC17M028575; -.
DR HGNC; HGNC:1059; BLMH.
DR HPA; HPA039548; -.
DR MIM; 602403; gene.
DR neXtProt; NX_Q13867; -.
DR PharmGKB; PA25370; -.
DR eggNOG; COG3579; -.
DR HOGENOM; HOG000064089; -.
DR HOVERGEN; HBG002388; -.
DR InParanoid; Q13867; -.
DR KO; K01372; -.
DR OMA; PVRWRVQ; -.
DR PhylomeDB; Q13867; -.
DR BRENDA; 3.4.22.40; 2681.
DR Reactome; REACT_6900; Immune System.
DR SABIO-RK; Q13867; -.
DR ChiTaRS; BLMH; human.
DR EvolutionaryTrace; Q13867; -.
DR GeneWiki; Bleomycin_hydrolase; -.
DR GeneWiki; BLMH; -.
DR GenomeRNAi; 642; -.
DR NextBio; 2604; -.
DR PRO; PR:Q13867; -.
DR ArrayExpress; Q13867; -.
DR Bgee; Q13867; -.
DR CleanEx; HS_BLMH; -.
DR Genevestigator; Q13867; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0004177; F:aminopeptidase activity; TAS:ProtInc.
DR GO; GO:0004180; F:carboxypeptidase activity; TAS:ProtInc.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; TAS:Reactome.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0042493; P:response to drug; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR InterPro; IPR000169; Pept_cys_AS.
DR InterPro; IPR004134; Peptidase_C1B.
DR PANTHER; PTHR10363; PTHR10363; 1.
DR Pfam; PF03051; Peptidase_C1_2; 1.
DR PIRSF; PIRSF005700; PepC; 1.
DR PROSITE; PS00640; THIOL_PROTEASE_ASN; FALSE_NEG.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
DR PROSITE; PS00639; THIOL_PROTEASE_HIS; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Polymorphism; Protease;
KW Reference proteome; Thiol protease.
FT CHAIN 1 455 Bleomycin hydrolase.
FT /FTId=PRO_0000050550.
FT ACT_SITE 73 73
FT ACT_SITE 372 372
FT ACT_SITE 396 396
FT MOD_RES 1 1 N-acetylmethionine (By similarity).
FT MOD_RES 391 391 N6-acetyllysine.
FT VARIANT 443 443 I -> V (common polymorphism;
FT dbSNP:rs1050565).
FT /FTId=VAR_010896.
FT STRAND 4 6
FT HELIX 8 19
FT HELIX 22 31
FT HELIX 36 40
FT HELIX 43 48
FT STRAND 54 56
FT STRAND 69 71
FT HELIX 73 89
FT HELIX 99 123
FT HELIX 131 138
FT HELIX 147 157
FT HELIX 162 164
FT HELIX 170 172
FT HELIX 175 197
FT HELIX 202 224
FT STRAND 229 236
FT STRAND 242 248
FT HELIX 250 257
FT TURN 258 261
FT HELIX 264 266
FT STRAND 267 271
FT STRAND 280 286
FT STRAND 300 302
FT HELIX 305 317
FT STRAND 322 326
FT TURN 328 331
FT TURN 334 337
FT HELIX 346 350
FT HELIX 359 364
FT STRAND 372 381
FT STRAND 389 395
FT STRAND 407 411
FT HELIX 412 418
FT STRAND 419 425
FT HELIX 426 428
FT HELIX 431 434
FT HELIX 435 438
FT STRAND 442 444
FT HELIX 449 451
SQ SEQUENCE 455 AA; 52562 MW; 577E86241EB0D460 CRC64;
MSSSGLNSEK VAALIQKLNS DPQFVLAQNV GTTHDLLDIC LKRATVQRAQ HVFQHAVPQE
GKPITNQKSS GRCWIFSCLN VMRLPFMKKL NIEEFEFSQS YLFFWDKVER CYFFLSAFVD
TAQRKEPEDG RLVQFLLMNP ANDGGQWDML VNIVEKYGVI PKKCFPESYT TEATRRMNDI
LNHKMREFCI RLRNLVHSGA TKGEISATQD VMMEEIFRVV CICLGNPPET FTWEYRDKDK
NYQKIGPITP LEFYREHVKP LFNMEDKICL VNDPRPQHKY NKLYTVEYLS NMVGGRKTLY
NNQPIDFLKK MVAASIKDGE AVWFGCDVGK HFNSKLGLSD MNLYDHELVF GVSLKNMNKA
ERLTFGESLM THAMTFTAVS EKDDQDGAFT KWRVENSWGE DHGHKGYLCM TDEWFSEYVY
EVVVDRKHVP EEVLAVLEQE PIILPAWDPM GALAE
//

MIM 602403
*RECORD*
*FIELD* NO
602403
*FIELD* TI
*602403 BLEOMYCIN HYDROLASE; BLMH
;;BMH
*FIELD* TX

CLONING

The gene encoding bleomycin hydrolase (BMH) was cloned and found to
read moreencode a 455-amino acid protein containing the signature active site
residues of the cysteine protease papain superfamily (Bromme et al.,
1996; Ferrando et al., 1996). The protein had aminopeptidase activity
that was blocked by the irreversible cysteine protease inhibitor E-64.
Ferrando et al. (1996) found the BMH protein to be approximately 40%
identical to that of the yeast homolog Gal6. Both yeast and human BMH
also possess endopeptidase activity. The gene is expressed in many human
tissues with elevated expression levels found in testis, skeletal
muscle, and pancreas, and low levels of expression in colon and
peripheral blood leukocytes (Bromme et al., 1996).

MAPPING

Montoya et al. (1997) mapped the BLMH gene to chromosome 17 using a
human/rodent hybrid mapping panel and localized it to 17q11.1-q11.2 by
linkage analysis using the CEPH reference database. By fluorescence in
situ hybridization, Ferrando et al. (1997) mapped the BLMH gene to
17q11.2, very close to the locus of the NF1 gene (613113).

GENE STRUCTURE

Montoya et al. (1997) found that the BLMH gene contains 11 exons ranging
in size from 69 to 198 bp separated by introns of approximately 1 kb,
reflecting the archetypal genomic structure of the cysteine protease
family. Ferrando et al. (1997) concluded that BLMH contains 12 coding
exons and spans more than 30 kb. They also concluded that the number and
distribution of exons and introns differ from those reported for other
human cysteine proteinases, indicating that these genes are only
distantly related. The nuclear sequence of the 5-prime flanking region
of the gene had characteristics of housekeeping genes, consistent with
the widespread expression of bleomycin hydrolase in human tissues. The
5-prime flanking region of the gene also contains a polymorphic CCG
trinucleotide repeat that may be a target of genetic instability events
and affect its transcriptional activity.

GENE FUNCTION

Bleomycin hydrolase is highly conserved through evolution; however, the
only known activity of the enzyme is metabolic inactivation of the
glycopeptide bleomycin (BLM), a component of combination chemotherapy
regimens for cancer. Even in low doses, bleomycin has the unfortunate
property of inducing pulmonary toxicity in approximately 3 to 5% of
patients; cumulative doses greater than 450 mg induced potentially
lethal pulmonary toxicity in up to 10% of patients. Lazo and Humphreys
(1983) considered the BMH gene to be a primary candidate for protection
against potential fatal bleomycin-induced pulmonary fibrosis and
bleomycin resistance in tumors. Haston et al. (1996) presented evidence
for a genetic basis for susceptibility to BMH-induced pulmonary
fibrosis.

The yeast Gal6 protein forms a barrel structure with the active sites
embedded in a channel as in the proteasome. The C termini lie in the
active site clefts. Zheng et al. (1998) showed that Gal6 acts as a
carboxypeptidase on its C terminus to convert itself to an
aminopeptidase and peptide ligase. The substrate specificity of the
peptidase activity is determined by the position of the C terminus of
Gal6 rather than the sequence of the substrate. The authors proposed a
model to explain these diverse activities and the ability of yeast Gal6
to inactivate bleomycin.

Southern blot analysis of DNA from leukocytes and autologous breast
tumors showed that the bleomycin hydrolase gene is not a frequent target
of amplification in human breast carcinomas (Ferrando et al., 1997).

Susceptibility to bleomycin-induced chromatid breaks in cultured
peripheral blood lymphocytes may reflect the way a person deals with
carcinogenic challenges (Hsu et al., 1989). This susceptibility, also
referred to as mutagen sensitivity (see 610452), has been found to be
increased in patients with environmentally related cancers, including
cancers of the head and neck, lung, and colon. In combination with
carcinogenic exposure, this susceptibility can greatly influence cancer
risk.

MOLECULAR GENETICS

Using PCR-SSCP, Bromme et al. (1996) and Montoya et al. (1997) found a
1450A-G polymorphism of the BMH gene that resulted in an ile443-to-val
(I443V) conserved amino acid substitution in the carboxy terminus of the
protein (602403.0001). BMH is suspected of being the unknown beta
secretase that cleaves off the amyloid beta fragment from the amyloid
precursor protein (APP; 104760) associated with Alzheimer disease (AD).
In pooled AD cases and controls, the frequency of the 1450A and 1450G
alleles were statistically indistinguishable. The G/G homozygote
genotype distribution, however, was significantly different between AD
cases (12.7%) and controls (6.6%); (P less than 0.001). Significant
differences were not seen in the A/A homozygote and A/G heterozygote
genotype distributions. Further studies by Montoya et al. (1998)
indicated that the frequency of the G/G homozygote was significantly
higher in AD cases than in controls only in the non-APOE4 (see 107741)
group (15.9% in cases vs 4.7% in controls). The odds ratio for
developing AD with BMH G/G genotype in the absence of an APOE4 allele
was 3.81; in the presence of an APOE4 allele, the odds ratio was 0.98.
Farrer et al. (1998) were unable to confirm this association in a sample
of 621 Caucasian Alzheimer patients drawn from 4 North American
university-based research centers.

ANIMAL MODEL

In mouse strains differing in susceptibility to bleomycin-induced lung
fibrosis, Haston et al. (2002) showed highly significant linkage to only
2 loci. The first locus, on chromosome 17 in the major
histocompatibility complex (MHC) (lod = 17.4), named BLM-induced
pulmonary fibrosis-1 (Blmpf1), was highly significant in both males and
females, and accounted for approximately 20% of the phenotypic variance.
The authors confirmed the presence of Blmpf1 in MHC congenic mice and
narrowed the region to 2.7 cM in a reduced MHC congenic strain. The
second locus, on chromosome 11 (lod = 5.6) (Blmpf2), was significant in
males only. Functional studies demonstrated that bleomycin hydrolase
activity modulated bleomycin-induced pulmonary fibrosis, suggesting that
it may be a candidate gene for Blmpf2. The authors suggested
sex-specific models of susceptibility to bleomycin-induced lung
fibrosis, with an interaction between Blmpf2 and Blmpf1 for the more
susceptible males and Blmpf1 as the major locus in females.

*FIELD* AV
.0001
BLEOMYCIN HYDROLASE POLYMORPHISM
BLMH, ILE443VAL

Polymorphism in the bleomycin hydrolase gene in the form of a 1450A-G
nucleotide change resulting in an ile443-to-val amino acid substitution
was identified in the carboxy terminus of the bleomycin hydrolase gene
by Bromme et al. (1996). As indicated earlier, an increased frequency of
G/G homozygotes was found among non-APOE4 cases of Alzheimer disease
(see 104300).

*FIELD* RF
1. Bromme, D.; Rossi, A. B.; Smeekens, S. P.; Anderson, D. C.; Payan,
D. G.: Human bleomycin hydrolase: molecular cloning, sequencing,
functional expression, and enzymatic characterization. Biochemistry 35:
6706-6714, 1996.

2. Farrer, L. A.; Abraham, C. R.; Haines, J. L.; Rogaeva, E. A.; Song,
Y.; McGraw, W. T.; Brindle, N.; Premkumar, S.; Scott, W. K.; Yamaoka,
L. H.; Saunders, A. M.; Roses, A. D.; Auerbach, S. A.; Sorbi, S.;
Duara, R.; Pericak-Vance, M. A.; St. George-Hyslop, P. H.: Association
between bleomycin hydrolase and Alzheimer's disease in Caucasians. Ann.
Neurol. 44: 808-811, 1998.

3. Ferrando, A. A.; Pendas, A. M.; Llano, E.; Velasco, G.; Lidereau,
R.; Lopez-Otin, C.: Gene characterization, promoter analysis, and
chromosomal localization of human bleomycin hydrolase. J. Biol. Chem. 272:
33298-33304, 1997.

4. Ferrando, A. A.; Velasco, G.; Campo, E.; Lopez-Otin, C.: Cloning
and expression analysis of human bleomycin hydrolase, a cysteine proteinase
involved in chemotherapy resistance. Cancer Res. 56: 1746-1750,
1996.

5. Haston, C. K.; Amos, C. I.; King, T. M.; Travis, E. L.: Inheritance
of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse. Cancer
Res. 56: 2596-2601, 1996.

6. Haston, C. K.; Wang, M.; Dejournett, R. E.; Zhou, X.; Ni, D.; Gu,
X.; King, T. M.; Weil, M. M.; Newman, R. A.; Amos, C. I.; Travis,
E. L.: Bleomycin hydrolase and a genetic locus within the MHC affect
risk for pulmonary fibrosis in mice. Hum. Molec. Genet. 11: 1855-1863,
2002.

7. Hsu, T. C.; Johnston, D. A.; Cherry, L. M.; Ramkissoon, D.; Schantz,
S. P.; Jessup, J. M.; Winn, R. J.; Shirley, L.; Furlong, C.: Sensitivity
to genotoxic effects of bleomycin in humans: possible relationship
to environmental carcinogenesis. Int. J. Cancer 43: 403-409, 1989.

8. Lazo, J. S.; Humphreys, C. J.: Lack of metabolism as the biochemical
basis of bleomycin-induced pulmonary toxicity. Proc. Nat. Acad. Sci. 80:
3064-3068, 1983.

9. Montoya, S. E.; Aston, C. E.; DeKosky, S. T.; Kamboh, M. I.; Lazo,
J. S.; Ferrell, R. E.: Bleomycin hydrolase is associated with risk
of sporadic Alzheimer's disease. (Letter) Nature Genet. 18: 211-212,
1998. Note: Erratum: Nature Genet. 19: 404 only, 1998.

10. Montoya, S. E.; Ferrell, R. E.; Lazo, J. S.: Genomic structure
and genetic mapping of the human neutral cysteine protease bleomycin
hydrolase. Cancer Res. 57: 4191-4195, 1997.

11. Zheng, W.; Johnston, S. A.; Joshua-Tor, L.: The unusual active
site of Gal6/bleomycin hydrolase can act as a carboxypeptidase, aminopeptidase,
and peptide ligase. Cell 93: 103-109, 1998.

*FIELD* CN
George E. Tiller - updated: 7/8/2003
Victor A. McKusick - updated: 9/30/1999
Orest Hurko - updated: 8/25/1999
Stylianos E. Antonarakis - updated: 5/18/1998
Victor A. McKusick - updated: 3/3/1998

*FIELD* CD
Victor A. McKusick: 2/27/1998

*FIELD* ED
joanna: 11/23/2009
carol: 9/28/2006
joanna: 12/2/2005
cwells: 7/8/2003
alopez: 5/16/2001
alopez: 11/15/1999
alopez: 10/5/1999
terry: 9/30/1999
carol: 8/25/1999
carol: 5/20/1998
carol: 5/18/1998
joanna: 5/15/1998
alopez: 4/7/1998
dholmes: 4/1/1998
alopez: 3/16/1998
alopez: 3/6/1998
terry: 3/3/1998
alopez: 2/27/1998