Reviewed, UniProtKB/Swiss-Prot P43251 (BTD_HUMAN)

Names and origin

Protein names

Recommended name:
    Biotinidase
      Short name=Biotinase
    EC=3.5.1.12

Gene names

Name:

BTD

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	543 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.
Catalytic activity	Biotin amide + H2O = biotin + NH3.
Subcellular location	Secreted › extracellular space.
Involvement in disease	Defects in BTD are the cause of biotinidase deficiency (BTD deficiency) [MIM:253260]; also called late-onset multiple carboxylase deficiency. BTD deficiency is a juvenile form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. BTD deficiency is characterized by seizures, hypotonia, skin rash, alopecia, ataxia, hearing loss, and optic atrophy. If untreated, symptoms usually become progressively worse, and coma and death may occur.
Sequence similarities	Belongs to the CN hydrolase family. BTD/VNN subfamily. Contains 1 CN hydrolase domain.
Caution	It is uncertain whether Met-1 or Met-21 is the initiator.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Signal
Molecular function	Hydrolase
PTM	Glycoprotein
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	central nervous system development Traceable author statement. Source: ProtInc epidermis development Traceable author statement. Source: ProtInc nitrogen compound metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	biotin carboxylase activity Ref.1 Traceable author statement. Source: ProtInc biotinidase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 41	41
	Chain	42 – 543	502	Biotinidase		PRO_0000019707
Regions
	Domain	57 – 363	307	CN hydrolase
Sites
	Active site	112	1	Proton acceptor Potential
	Active site	212	1	Potential
	Active site	245	1	Nucleophile By similarity
Amino acid modifications
	Glycosylation	119	1	N-linked (GlcNAc...) Ref.5 Ref.6
	Glycosylation	150	1	N-linked (GlcNAc...) Ref.5 Ref.6
	Glycosylation	203	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	349	1	N-linked (GlcNAc...) Ref.5 Ref.6
	Glycosylation	402	1	N-linked (GlcNAc...) Ref.5 Ref.6
	Glycosylation	489	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	128	1	F → V in BTD deficiency. Ref.8		VAR_005113
	Natural variant	171	1	A → T in BTD deficiency. dbSNP rs13073139.		VAR_005114
	Natural variant	228	1	D → Y in BTD deficiency. Ref.8		VAR_005115
	Natural variant	323	1	H → R in BTD deficiency; partial. Ref.8		VAR_005116
	Natural variant	391	1	P → S: dbSNP rs35034250.		VAR_056238
	Natural variant	444	1	D → H in BTD deficiency; profound and partial; 52% decrease in activity. dbSNP rs13078881. Ref.8 Ref.9		VAR_005117
	Natural variant	451	1	G → D in BTD deficiency; partial. Ref.8		VAR_005118
	Natural variant	456	1	Q → H in BTD deficiency. Ref.8		VAR_005119
	Natural variant	532	1	T → M in BTD deficiency. Ref.8		VAR_005120
	Natural variant	538	1	R → C in BTD deficiency. Ref.8 Ref.7		VAR_005121

Sequences

	Sequence		Length	Mass (Da)
	P43251-1 [UniParc]. Last modified April 14, 2009. Version 2. Checksum: 1A999893A0784944	FASTA	543	61,133
	10 20 30 40 50 60 MAHAHIQGGR RAKSRFVVCI MSGARSKLAL FLCGCYVVAL GAHTGEESVA DHHEAEYYVA 70 80 90 100 110 120 AVYEHPSILS LNPLALISRQ EALELMNQNL DIYEQQVMTA AQKDVQIIVF PEDGIHGFNF 130 140 150 160 170 180 TRTSIYPFLD FMPSPQVVRW NPCLEPHRFN DTEVLQRLSC MAIRGDMFLV ANLGTKEPCH 190 200 210 220 230 240 SSDPRCPKDG RYQFNTNVVF SNNGTLVDRY RKHNLYFEAA FDVPLKVDLI TFDTPFAGRF 250 260 270 280 290 300 GIFTCFDILF FDPAIRVLRD YKVKHVVYPT AWMNQLPLLA AIEIQKAFAV AFGINVLAAN 310 320 330 340 350 360 VHHPVLGMTG SGIHTPLESF WYHDMENPKS HLIIAQVAKN PVGLIGAENA TGETDPSHSK 370 380 390 400 410 420 FLKILSGDPY CEKDAQEVHC DEATKWNVNA PPTFHSEMMY DNFTLVPVWG KEGYLHVCSN 430 440 450 460 470 480 GLCCYLLYER PTLSKELYAL GVFDGLHTVH GTYYIQVCAL VRCGGLGFDT CGQEITEATG 490 500 510 520 530 540 IFEFHLWGNF STSYIFPLFL TSGMTLEVPD QLGWENDHYF LRKSRLSSGL VTAALYGRLY ERD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human serum biotinidase. cDNA cloning, sequence, and characterization." Cole H., Reynolds T.R., Lockyer J.M., Buck G.A., Denson T., Spence J.E., Hymes J., Wolf B. J. Biol. Chem. 269:6566-6570(1994) [PubMed: 7509806] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[2]	"Structure of the human biotinidase gene." Knight H.C., Reynolds T.R., Meyers G.A., Pomponio R.J., Buck G.A., Wolf B. Mamm. Genome 9:327-330(1998) [PubMed: 9530634] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry." Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D. J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-119; ASN-150; ASN-203; ASN-349 AND ASN-402, MASS SPECTROMETRY. Tissue: Plasma.
[6]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-119; ASN-150; ASN-349 AND ASN-402, MASS SPECTROMETRY. Tissue: Liver.
[7]	"Arg538 to Cys mutation in a CpG dinucleotide of the human biotinidase gene is the second most common cause of profound biotinidase deficiency in symptomatic children." Pomponio R.J., Norrgard K.J., Hymes J., Reynolds T.R., Buck G.A., Baumgartner R., Suormala T., Wolf B. Hum. Genet. 99:506-512(1997) [PubMed: 9099842] [Abstract] Cited for: VARIANT BTD DEFICIENCY CYS-538.
[8]	"Partial biotinidase deficiency is usually due to the D444H mutation in the biotinidase gene." Swango K.L., Demirkol M., Huener G., Pronicka E., Sykut-Cegielska J., Schulze A., Mayatepek E., Wolf B. Hum. Genet. 102:571-575(1998) [PubMed: 9654207] [Abstract] Cited for: VARIANTS BTD DEFICIENCY VAL-128; THR-171; TYR-228; ARG-323; HIS-444; ASP-451; HIS-456; MET-532 AND CYS-538.
[9]	"Double mutation (A171T and D444H) is a common cause of profound biotinidase deficiency in children ascertained by newborn screening in the United States." Norrgard K.J., Pomponio R.J., Swango K.L., Hymes J., Reynolds T., Buck G.A., Wolf B. Hum. Mutat. 11:410-410(1998) [PubMed: 10206677] [Abstract] Cited for: VARIANTS BTD DEFICIENCY THR-171 AND HIS-444.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	U03274 mRNA. Translation: AAC04318.1. AF018631, AF018630 Genomic DNA. Translation: AAC21679.1. AC027129 Genomic DNA. No translation available. BC012099 mRNA. Translation: AAH12099.1.
IPI	IPI00218413.
PIR	A54362.
RefSeq	NP_000051.1.
UniGene	Hs.517830
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P43251.
Proteomic databases
PRIDE	P43251.
Genome annotation databases
Ensembl	ENST00000303498; ENSP00000306477; ENSG00000169814; Homo sapiens. [Genome view]
GeneID	686.
KEGG	hsa:686.
UCSC	uc003cah.1. human.
Organism-specific databases
CTD	686.
GeneCards	GC03P015621.
H-InvDB	HIX0003104.
HGNC	HGNC:1122. BTD.
MIM	253260. phenotype. 609019. gene.
Orphanet	148. Multiple carboxylase deficiency.
PharmGKB	PA25443.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P43251.
HOVERGEN	P43251.
Enzyme and pathway databases
BRENDA	3.5.1.12. 247.
Gene expression databases
ArrayExpress	P43251.
Bgee	P43251.
CleanEx	HS_BTD.
Genevestigator	P43251.
GermOnline	ENSG00000169814. Homo sapiens.
Family and domain databases
InterPro	IPR012101. Biotinidase_euk. IPR003010. Ntlse/CNhydtse. [Graphical view]
Gene3D	G3DSA:3.60.110.10. Ntlse/CNhydtse. 1 hit.
PANTHER	PTHR10609. Biotinidase_euk. 1 hit.
Pfam	PF00795. CN_hydrolase. 1 hit. [Graphical view]
PIRSF	PIRSF011861. Biotinidase. 1 hit.
PROSITE	PS50263. CN_HYDROLASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	2824.
SOURCE	Search...

Entry information

Entry name

BTD_HUMAN

Accession

Primary (citable) accession number: P43251
Secondary accession number(s): Q96EM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	April 14, 2009
Last modified:	November 24, 2009
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.