Q13867 (BLMH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bleomycin hydrolase
Short name=BH
Short name=BLM hydrolase
Short name=BMH
EC=3.4.22.40

Gene names

Name:

BLMH

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	455 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity By similarity.
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.
Subunit structure	Homohexamer.
Subcellular location	Cytoplasm.
Sequence similarities	Belongs to the peptidase C1 family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Protease Thiol protease
PTM	Acetylation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	antigen processing and presentation of peptide antigen via MHC class I Traceable author statement. Source: Reactome protein polyubiquitination Traceable author statement. Source: Reactome proteolysis Traceable author statement PubMed 9546396. Source: ProtInc response to drug Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA
Molecular_function	aminopeptidase activity Traceable author statement PubMed 9546396. Source: ProtInc carboxypeptidase activity Traceable author statement PubMed 9546396. Source: ProtInc cysteine-type endopeptidase activity Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067-4	2	EBI-718504,EBI-302641

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 455

455

Bleomycin hydrolase

PRO_0000050550

Sites

Active site

73

1

Active site

372

1

Active site

396

1

Amino acid modifications

Modified residue

1

1

N-acetylmethionine By similarity

Modified residue

391

1

N6-acetyllysine Ref.9

Natural variations

Natural variant

443

1

I → V Common polymorphism. Ref.2 Ref.8
Corresponds to variant rs1050565 [ dbSNP | Ensembl ].

VAR_010896

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

455

Helix Strand Turn

Details...

Beta strand

4 – 6

3

Helix

8 – 19

12

Helix

22 – 31

10

Helix

36 – 40

5

Helix

43 – 48

6

Beta strand

54 – 56

3

Beta strand

69 – 71

3

Helix

73 – 89

17

Helix

99 – 123

25

Helix

131 – 138

8

Helix

147 – 157

11

Helix

162 – 164

3

Helix

170 – 172

3

Helix

175 – 197

23

Helix

202 – 224

23

Beta strand

229 – 236

8

Beta strand

242 – 248

7

Helix

250 – 257

8

Turn

258 – 261

4

Helix

264 – 266

3

Beta strand

267 – 271

5

Beta strand

280 – 286

7

Beta strand

300 – 302

3

Helix

305 – 317

13

Beta strand

322 – 326

5

Turn

328 – 331

4

Turn

334 – 337

4

Helix

346 – 350

5

Helix

359 – 364

6

Beta strand

372 – 381

10

Beta strand

389 – 395

7

Beta strand

407 – 411

5

Helix

412 – 418

7

Beta strand

419 – 425

7

Helix

426 – 428

3

Helix

431 – 434

4

Helix

435 – 438

4

Beta strand

442 – 444

3

Helix

449 – 451

3

Sequences

	Sequence		Length	Mass (Da)
	Q13867 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 577E86241EB0D460	FASTA	455	52,562
	10 20 30 40 50 60 MSSSGLNSEK VAALIQKLNS DPQFVLAQNV GTTHDLLDIC LKRATVQRAQ HVFQHAVPQE 70 80 90 100 110 120 GKPITNQKSS GRCWIFSCLN VMRLPFMKKL NIEEFEFSQS YLFFWDKVER CYFFLSAFVD 130 140 150 160 170 180 TAQRKEPEDG RLVQFLLMNP ANDGGQWDML VNIVEKYGVI PKKCFPESYT TEATRRMNDI 190 200 210 220 230 240 LNHKMREFCI RLRNLVHSGA TKGEISATQD VMMEEIFRVV CICLGNPPET FTWEYRDKDK 250 260 270 280 290 300 NYQKIGPITP LEFYREHVKP LFNMEDKICL VNDPRPQHKY NKLYTVEYLS NMVGGRKTLY 310 320 330 340 350 360 NNQPIDFLKK MVAASIKDGE AVWFGCDVGK HFNSKLGLSD MNLYDHELVF GVSLKNMNKA 370 380 390 400 410 420 ERLTFGESLM THAMTFTAVS EKDDQDGAFT KWRVENSWGE DHGHKGYLCM TDEWFSEYVY 430 440 450 EVVVDRKHVP EEVLAVLEQE PIILPAWDPM GALAE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression analysis of human bleomycin hydrolase, a cysteine proteinase involved in chemotherapy resistance." Ferrando A.A., Velasco G., Campo E., Lopez-Otin C. Cancer Res. 56:1746-1750(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Human bleomycin hydrolase: molecular cloning, sequencing, functional expression, and enzymatic characterization." Broemme D., Rossi A.B., Smeekens S.P., Anderson D.C., Payan D.G. Biochemistry 35:6706-6714(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANT VAL-443. Tissue: Lung.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala.
[5]	Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lymph.
[8]	"Full-insert sequence of mapped XREF EST." Barrow I.K.-P., Boguski M.S., Touchman J.W., Spencer F. Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 292-455, VARIANT VAL-443.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-391, MASS SPECTROMETRY.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Crystal structure of human bleomycin hydrolase, a self-compartmentalizing cysteine protease." O'Farrell P.A., Gonzalez F., Zheng W., Johnston S.A., Joshua-Tor L. Structure 7:619-627(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X92106 mRNA. Translation: CAA63078.1.
BT007018 mRNA. Translation: AAP35664.1.
AK223403 mRNA. Translation: BAD97123.1.
AK312896 mRNA. Translation: BAG35743.1.
CH471159 Genomic DNA. Translation: EAW51224.1.
BC003616 mRNA. Translation: AAH03616.1.
AF091082 mRNA. Translation: AAC72951.1.

IPI

IPI00219575.

RefSeq

NP_000377.1. NM_000386.3.

UniGene

Hs.371914.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CB5	X-ray	2.59	A/B/C	2-454	[»]
2CB5	X-ray	1.85	A/B	2-454	[»]

ProteinModelPortal

Q13867.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13867. 10 interactions.

MINT

MINT-1397729.

STRING

9606.ENSP00000261714.

Protein family/group databases

MEROPS

C01.084.

PTM databases

PhosphoSite

Q13867.

Polymorphism databases

DMDM

3023394.

Proteomic databases

PaxDb

Q13867.

PeptideAtlas

Q13867.

PRIDE

Q13867.

Protocols and materials databases

DNASU

642.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261714; ENSP00000261714; ENSG00000108578.

GeneID

642.

KEGG

hsa:642.

UCSC

uc002hez.2. human.

Organism-specific databases

CTD

642.

GeneCards

GC17M028575.

HGNC

HGNC:1059. BLMH.

HPA

HPA039548.

MIM

602403. gene.

neXtProt

NX_Q13867.

PharmGKB

PA25370.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3579.

HOGENOM

HOG000064089.

HOVERGEN

HBG002388.

InParanoid

Q13867.

KO

K01372.

OMA

TQDAMME.

OrthoDB

EOG4J3WGT.

PhylomeDB

Q13867.

Enzyme and pathway databases

BRENDA

3.4.22.40. 2681.

Reactome

REACT_6900. Immune System.

SABIO-RK

Q13867.

Gene expression databases

ArrayExpress

Q13867.

Bgee

Q13867.

CleanEx

HS_BLMH.

Genevestigator

Q13867.

GermOnline

ENSG00000108578. Homo sapiens.

Family and domain databases

InterPro

IPR000169. Pept_cys_AS.
IPR004134. Peptidase_C1B.
[Graphical view]

PANTHER

PTHR10363. PTHR10363. 1 hit.

Pfam

PF03051. Peptidase_C1_2. 1 hit.
[Graphical view]

PIRSF

PIRSF005700. PepC. 1 hit.

PROSITE

PS00640. THIOL_PROTEASE_ASN. False negative.
PS00139. THIOL_PROTEASE_CYS. 1 hit.
PS00639. THIOL_PROTEASE_HIS. False negative.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BLMH. human.

EvolutionaryTrace

Q13867.

GenomeRNAi

642.

NextBio

2604.

SOURCE

Search...

Entry information

Entry name

BLMH_HUMAN

Accession

Primary (citable) accession number: Q13867
Secondary accession number(s): B2R796, Q53F86, Q9UER9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 128 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.