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 26-NOV-2014, entry version 143. 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 IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. 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. {ECO:0000250}. 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. CC {ECO:0000255|PROSITE-ProRule:PRU10088}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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 BioGrid; 107111; 26. DR IntAct; Q13867; 11. DR MINT; MINT-1397729; -. DR STRING; 9606.ENSP00000261714; -. DR DrugBank; DB00290; Bleomycin. DR MEROPS; C01.084; -. DR PhosphoSite; Q13867; -. DR MaxQB; Q13867; -. 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 Orphanet; 364195; Resistance to bleomycine in the treatment of testicular cancer. DR PharmGKB; PA25370; -. DR eggNOG; COG3579; -. DR GeneTree; ENSGT00390000001735; -. DR HOGENOM; HOG000064089; -. DR HOVERGEN; HBG002388; -. DR InParanoid; Q13867; -. DR KO; K01372; -. DR OMA; PVRWRVQ; -. DR PhylomeDB; Q13867; -. DR TreeFam; TF323372; -. DR BRENDA; 3.4.22.40; 2681. DR Reactome; REACT_75842; Antigen processing: Ubiquitination & Proteasome degradation. 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 Bgee; Q13867; -. DR CleanEx; HS_BLMH; -. DR ExpressionAtlas; Q13867; baseline and differential. DR Genevestigator; Q13867; -. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProt. DR GO; GO:0005634; C:nucleus; IDA:UniProt. 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:0008234; F:cysteine-type peptidase 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; PS00139; THIOL_PROTEASE_CYS; 1. 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. {ECO:0000250}. FT MOD_RES 391 391 N6-acetyllysine. FT {ECO:0000269|PubMed:19608861}. FT VARIANT 443 443 I -> V (common polymorphism; FT dbSNP:rs1050565). FT {ECO:0000269|PubMed:8639621, FT ECO:0000269|Ref.8}. FT /FTId=VAR_010896. FT STRAND 4 6 {ECO:0000244|PDB:2CB5}. FT HELIX 8 19 {ECO:0000244|PDB:2CB5}. FT HELIX 22 31 {ECO:0000244|PDB:2CB5}. FT HELIX 36 40 {ECO:0000244|PDB:2CB5}. FT HELIX 43 48 {ECO:0000244|PDB:2CB5}. FT STRAND 54 56 {ECO:0000244|PDB:2CB5}. FT STRAND 69 71 {ECO:0000244|PDB:2CB5}. FT HELIX 73 89 {ECO:0000244|PDB:2CB5}. FT HELIX 99 123 {ECO:0000244|PDB:2CB5}. FT HELIX 131 138 {ECO:0000244|PDB:2CB5}. FT HELIX 147 157 {ECO:0000244|PDB:2CB5}. FT HELIX 162 164 {ECO:0000244|PDB:2CB5}. FT HELIX 170 172 {ECO:0000244|PDB:2CB5}. FT HELIX 175 197 {ECO:0000244|PDB:2CB5}. FT HELIX 202 224 {ECO:0000244|PDB:2CB5}. FT STRAND 229 236 {ECO:0000244|PDB:2CB5}. FT STRAND 242 248 {ECO:0000244|PDB:2CB5}. FT HELIX 250 257 {ECO:0000244|PDB:2CB5}. FT TURN 258 261 {ECO:0000244|PDB:2CB5}. FT HELIX 264 266 {ECO:0000244|PDB:2CB5}. FT STRAND 267 271 {ECO:0000244|PDB:2CB5}. FT STRAND 280 286 {ECO:0000244|PDB:2CB5}. FT STRAND 300 302 {ECO:0000244|PDB:2CB5}. FT HELIX 305 317 {ECO:0000244|PDB:2CB5}. FT STRAND 322 326 {ECO:0000244|PDB:2CB5}. FT TURN 328 331 {ECO:0000244|PDB:2CB5}. FT TURN 334 337 {ECO:0000244|PDB:2CB5}. FT HELIX 346 350 {ECO:0000244|PDB:2CB5}. FT HELIX 359 364 {ECO:0000244|PDB:2CB5}. FT STRAND 372 381 {ECO:0000244|PDB:2CB5}. FT STRAND 389 395 {ECO:0000244|PDB:2CB5}. FT STRAND 407 411 {ECO:0000244|PDB:2CB5}. FT HELIX 412 418 {ECO:0000244|PDB:2CB5}. FT STRAND 419 425 {ECO:0000244|PDB:2CB5}. FT HELIX 426 428 {ECO:0000244|PDB:2CB5}. FT HELIX 431 434 {ECO:0000244|PDB:2CB5}. FT HELIX 435 438 {ECO:0000244|PDB:2CB5}. FT STRAND 442 444 {ECO:0000244|PDB:2CB5}. FT HELIX 449 451 {ECO:0000244|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 //