BLMH_HUMAN
ID BLMH_HUMAN Reviewed; 455 AA.
AC Q13867; B2R796; Q53F86; Q9UER9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 201.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 cysteine
RT proteinase involved in chemotherapy resistance.";
RL Cancer Res. 56:1746-1750(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND VARIANT 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 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., 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 project:
RT 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 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 IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA 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., Buerckstuemmer T.,
RA 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 SUBUNIT, INTERACTION WITH NUDT12, AND SUBCELLULAR LOCATION.
RX PubMed=31875550; DOI=10.1016/j.celrep.2019.11.108;
RA Wu H., Li L., Chen K.M., Homolka D., Gos P., Fleury-Olela F.,
RA McCarthy A.A., Pillai R.S.;
RT "Decapping Enzyme NUDT12 Partners with BLMH for Cytoplasmic Surveillance of
RT NAD-Capped RNAs.";
RL Cell Rep. 29:4422-4434(2019).
RN [12]
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-compartmentalizing
RT cysteine protease.";
RL Structure 7:619-627(1999).
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. {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 -!- SUBUNIT: Homohexamer (PubMed:31875550). Interacts with NUDT12 (via ANK
CC repeats) (PubMed:31875550). {ECO:0000269|PubMed:31875550}.
CC -!- INTERACTION:
CC Q13867; Q06481-5: APLP2; NbExp=3; IntAct=EBI-718504, EBI-25646567;
CC Q13867; P05067: APP; NbExp=3; IntAct=EBI-718504, EBI-77613;
CC Q13867; P05067-4: APP; NbExp=2; IntAct=EBI-718504, EBI-302641;
CC Q13867; Q13867: BLMH; NbExp=6; IntAct=EBI-718504, EBI-718504;
CC Q13867; P29466-3: CASP1; NbExp=3; IntAct=EBI-718504, EBI-12248206;
CC Q13867; Q9UBU7: DBF4; NbExp=3; IntAct=EBI-718504, EBI-372690;
CC Q13867; Q07954-2: LRP1; NbExp=3; IntAct=EBI-718504, EBI-25833471;
CC Q13867; Q96HA8: NTAQ1; NbExp=4; IntAct=EBI-718504, EBI-741158;
CC Q13867; Q9BQG2: NUDT12; NbExp=8; IntAct=EBI-718504, EBI-10230612;
CC Q13867; Q9UBU9: NXF1; NbExp=3; IntAct=EBI-718504, EBI-398874;
CC Q13867; O95336: PGLS; NbExp=3; IntAct=EBI-718504, EBI-11307753;
CC Q13867; P04271: S100B; NbExp=3; IntAct=EBI-718504, EBI-458391;
CC Q13867; P43405-2: SYK; NbExp=3; IntAct=EBI-718504, EBI-25892332;
CC Q13867; O14787-2: TNPO2; NbExp=3; IntAct=EBI-718504, EBI-12076664;
CC Q13867; Q9Y5L0: TNPO3; NbExp=3; IntAct=EBI-718504, EBI-1042571;
CC Q13867; Q96LD4-2: TRIM47; NbExp=3; IntAct=EBI-718504, EBI-12371725;
CC Q13867; Q9BVJ6: UTP14A; NbExp=3; IntAct=EBI-718504, EBI-473284;
CC Q13867; Q9UBQ0-2: VPS29; NbExp=3; IntAct=EBI-718504, EBI-11141397;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31875550}.
CC Cytoplasmic granule {ECO:0000269|PubMed:31875550}. Note=Co-localizes
CC with NUDT12 in the cytoplasmic granules. {ECO:0000269|PubMed:31875550}.
CC -!- SIMILARITY: Belongs to the peptidase C1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU10088}.
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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 CCDS; CCDS32604.1; -.
DR RefSeq; NP_000377.1; NM_000386.3.
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 AlphaFoldDB; Q13867; -.
DR SMR; Q13867; -.
DR BioGRID; 107111; 125.
DR IntAct; Q13867; 64.
DR MINT; Q13867; -.
DR STRING; 9606.ENSP00000261714; -.
DR ChEMBL; CHEMBL4295818; -.
DR DrugBank; DB00290; Bleomycin.
DR MEROPS; C01.084; -.
DR GlyGen; Q13867; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13867; -.
DR PhosphoSitePlus; Q13867; -.
DR SwissPalm; Q13867; -.
DR BioMuta; BLMH; -.
DR EPD; Q13867; -.
DR jPOST; Q13867; -.
DR MassIVE; Q13867; -.
DR MaxQB; Q13867; -.
DR PaxDb; Q13867; -.
DR PeptideAtlas; Q13867; -.
DR PRIDE; Q13867; -.
DR ProteomicsDB; 59703; -.
DR ABCD; Q13867; 4 sequenced antibodies.
DR Antibodypedia; 15119; 271 antibodies from 32 providers.
DR DNASU; 642; -.
DR Ensembl; ENST00000261714.11; ENSP00000261714.6; ENSG00000108578.15.
DR GeneID; 642; -.
DR KEGG; hsa:642; -.
DR MANE-Select; ENST00000261714.11; ENSP00000261714.6; NM_000386.4; NP_000377.1.
DR UCSC; uc002hez.3; human.
DR CTD; 642; -.
DR DisGeNET; 642; -.
DR GeneCards; BLMH; -.
DR HGNC; HGNC:1059; BLMH.
DR HPA; ENSG00000108578; Tissue enhanced (skin).
DR MIM; 602403; gene.
DR neXtProt; NX_Q13867; -.
DR OpenTargets; ENSG00000108578; -.
DR Orphanet; 364195; Prediction of resistance to bleomycine in the treatment of testicular cancer.
DR PharmGKB; PA25370; -.
DR VEuPathDB; HostDB:ENSG00000108578; -.
DR eggNOG; KOG4128; Eukaryota.
DR GeneTree; ENSGT00390000001735; -.
DR HOGENOM; CLU_038600_0_0_1; -.
DR InParanoid; Q13867; -.
DR OMA; WDMIVNL; -.
DR OrthoDB; 649145at2759; -.
DR PhylomeDB; Q13867; -.
DR TreeFam; TF323372; -.
DR BRENDA; 3.4.22.40; 2681.
DR PathwayCommons; Q13867; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SABIO-RK; Q13867; -.
DR SignaLink; Q13867; -.
DR BioGRID-ORCS; 642; 14 hits in 1083 CRISPR screens.
DR ChiTaRS; BLMH; human.
DR EvolutionaryTrace; Q13867; -.
DR GeneWiki; Bleomycin_hydrolase; -.
DR GeneWiki; BLMH; -.
DR GenomeRNAi; 642; -.
DR Pharos; Q13867; Tbio.
DR PRO; PR:Q13867; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q13867; protein.
DR Bgee; ENSG00000108578; Expressed in upper arm skin and 185 other tissues.
DR ExpressionAtlas; Q13867; baseline and differential.
DR Genevisible; Q13867; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0004177; F:aminopeptidase activity; EXP:Reactome.
DR GO; GO:0004180; F:carboxypeptidase activity; TAS:ProtInc.
DR GO; GO:0004197; F:cysteine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0043418; P:homocysteine catabolic process; IBA:GO_Central.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:Reactome.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0009636; P:response to toxic substance; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
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 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Protease; Reference proteome; Thiol protease.
FT CHAIN 1..455
FT /note="Bleomycin hydrolase"
FT /id="PRO_0000050550"
FT ACT_SITE 73
FT ACT_SITE 372
FT ACT_SITE 396
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P70645"
FT MOD_RES 391
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 443
FT /note="I -> V (in dbSNP:rs1050565)"
FT /evidence="ECO:0000269|PubMed:8639621, ECO:0000269|Ref.8"
FT /id="VAR_010896"
FT STRAND 4..6
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 8..19
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 22..31
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 36..40
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 43..48
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 73..89
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 99..123
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 131..138
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 175..197
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 202..224
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 229..236
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 250..257
FT /evidence="ECO:0007829|PDB:2CB5"
FT TURN 258..261
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 264..266
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 280..286
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 300..302
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 305..317
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 322..326
FT /evidence="ECO:0007829|PDB:2CB5"
FT TURN 328..331
FT /evidence="ECO:0007829|PDB:2CB5"
FT TURN 334..337
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 346..350
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 359..364
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 372..381
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 389..395
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 407..411
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 412..418
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 419..425
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 426..428
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 431..434
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 435..438
FT /evidence="ECO:0007829|PDB:2CB5"
FT STRAND 442..444
FT /evidence="ECO:0007829|PDB:2CB5"
FT HELIX 449..451
FT /evidence="ECO:0007829|PDB:1CB5"
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
