BLMH_RAT
ID BLMH_RAT Reviewed; 454 AA.
AC P70645;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 141.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 44-62; 165-175 AND
RP 283-296.
RC TISSUE=Spleen;
RX PubMed=8889821; DOI=10.1093/oxfordjournals.jbchem.a021420;
RA Takeda A., Masuda Y., Yamamoto T., Hirabayashi T., Nakamura Y., Nakaya K.;
RT "Cloning and analysis of cDNA encoding rat bleomycin hydrolase, a DNA-
RT binding cysteine protease.";
RL J. Biochem. 120:353-359(1996).
RN [2]
RP PROTEIN SEQUENCE OF 1-10, ACETYLATION AT MET-1, AND CHARACTERIZATION.
RC TISSUE=Skin;
RX PubMed=8907172; DOI=10.1093/oxfordjournals.jbchem.a021212;
RA Takeda A., Higuchi D., Yamamoto T., Nakamura Y., Masuda Y., Hirabayashi T.,
RA Nakaya K.;
RT "Purification and characterization of bleomycin hydrolase, which represents
RT a new family of cysteine proteases, from rat skin.";
RL J. Biochem. 119:29-36(1996).
CC -!- FUNCTION: The normal physiological role of BLM hydrolase is unknown,
CC but it catalyzes the inactivation of the antitumor drug BLM (a
CC glycopeptide) by hydrolyzing the carboxamide bond of its B-
CC aminoalaninamide moiety thus protecting normal and malignant cells from
CC BLM toxicity (By similarity). Binds single-stranded DNA with higher
CC affinity than double-stranded DNA. May play an important role in the
CC metabolism of antibiotics. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Inactivates bleomycin B2 (a cytotoxic glycometallopeptide) by
CC hydrolysis of a carboxyamide bond of beta-aminoalanine, but also
CC shows general aminopeptidase activity. The specificity varies
CC somewhat with source, but amino acid arylamides of Met, Leu and Ala
CC are preferred.; EC=3.4.22.40;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5.;
CC -!- SUBUNIT: Homohexamer (By similarity). Interacts with NUDT12 (via ANK
CC repeats) (By similarity). {ECO:0000250|UniProtKB:Q13867}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13867}.
CC Cytoplasmic granule {ECO:0000250|UniProtKB:Q13867}. Note=Co-localizes
CC with NUDT12 in the cytoplasmic granules.
CC {ECO:0000250|UniProtKB:Q13867}.
CC -!- TISSUE SPECIFICITY: Expressed at relatively higher levels in the
CC stomach, esophagus, spleen, thymus and testis, and at lower levels in
CC the skin, lung and skeletal muscle.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088}.
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DR EMBL; D87336; BAA13333.1; -; mRNA.
DR PIR; JC4886; JC4886.
DR AlphaFoldDB; P70645; -.
DR SMR; P70645; -.
DR IntAct; P70645; 1.
DR STRING; 10116.ENSRNOP00000005125; -.
DR MEROPS; C01.084; -.
DR iPTMnet; P70645; -.
DR PhosphoSitePlus; P70645; -.
DR jPOST; P70645; -.
DR PaxDb; P70645; -.
DR PeptideAtlas; P70645; -.
DR PRIDE; P70645; -.
DR RGD; 1304668; Blmh.
DR eggNOG; KOG4128; Eukaryota.
DR InParanoid; P70645; -.
DR OMA; WDMIVNL; -.
DR BRENDA; 3.4.22.40; 5301.
DR Reactome; R-RNO-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR PRO; PR:P70645; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; ISO:RGD.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0043418; P:homocysteine catabolic process; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0009636; P:response to toxic substance; ISO:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:RGD.
DR CDD; cd00585; Peptidase_C1B; 1.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
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 SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS00139; THIOL_PROTEASE_CYS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase; Protease;
KW Reference proteome; Thiol protease.
FT CHAIN 1..454
FT /note="Bleomycin hydrolase"
FT /id="PRO_0000050553"
FT ACT_SITE 73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 372
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT ACT_SITE 396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10088"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:8907172"
FT MOD_RES 391
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q13867"
SQ SEQUENCE 454 AA; 52323 MW; 30BAC4A1A89DC1DC CRC64;
MNNAGLNSEK VAALIQKLNS DPQFVLAQNV GTTHDLLDIC LKRATVQGAQ HVFQHVVPQE
GKPVTNQKSS GRCWIFSCLN VMRLPFMKKF NIEEFEFSQS YLFFWDKVER CYFFLNAFVD
TAQKKEPEDG RLVQYLLMNP TNDGGQWDML VNIVEKYGVV PKKCFPESHT TEATRRMNDI
LNHKMREFCI RLRNLVHSGA TKGEISSTQD AMMEEIFRVV CICLGNPPET FTWEYRDKDK
NYHKVGPITP LQFYKEHVKP LFNMEDKICF VNDPRPQHKY NKLYTVDYLS NMVGGRKTLY
NNQPIDFLKK MVAASIRDGE AVWFGCDVGK HFNGKLGLSD MNVYDHELVF GVSLKNMNKA
ERLAFGESLM THAMTFTAVS EKDDQEGAFV KWRVENSWGE DHGHKGYLCM TDEWFSEYVY
EVVVDKKHVP EEVLAVLEQE PIVLPAWDPM GALA
