P43251 (BTD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Biotinidase
Short name=Biotinase
EC=3.5.1.12

Gene names

Name:

BTD

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	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	Biotinidase deficiency (BTD deficiency) [MIM:253260]: 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. Biotinidase 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. Note: The disease is caused by mutations affecting the gene represented in this entry.
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 Reference proteome
Gene Ontology (GO)
Biological_process	central nervous system development Traceable author statement PubMed 7550325. Source: ProtInc epidermis development Traceable author statement PubMed 7550325. Source: ProtInc nitrogen compound metabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell nucleolus Inferred from electronic annotation. Source: Compara perikaryon Inferred from electronic annotation. Source: Compara
Molecular_function	biotin carboxylase activity Traceable author statement Ref.1. 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.7 Ref.8
	Glycosylation	150	1	N-linked (GlcNAc...) Ref.7 Ref.8
	Glycosylation	203	1	N-linked (GlcNAc...) Ref.7
	Glycosylation	349	1	N-linked (GlcNAc...) Ref.7 Ref.8
	Glycosylation	402	1	N-linked (GlcNAc...) Ref.7 Ref.8
	Glycosylation	489	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	128	1	F → V in BTD deficiency. Ref.10		VAR_005113
	Natural variant	171	1	A → T in BTD deficiency. Ref.10 Ref.11 Corresponds to variant rs13073139 [ dbSNP | Ensembl ].		VAR_005114
	Natural variant	228	1	D → Y in BTD deficiency. Ref.10		VAR_005115
	Natural variant	323	1	H → R in BTD deficiency; partial. Ref.10		VAR_005116
	Natural variant	391	1	P → S. Corresponds to variant rs35034250 [ dbSNP | Ensembl ].		VAR_056238
	Natural variant	444	1	D → H in BTD deficiency; profound and partial; 52% decrease in activity. Ref.10 Ref.11 Corresponds to variant rs13078881 [ dbSNP | Ensembl ].		VAR_005117
	Natural variant	451	1	G → D in BTD deficiency; partial. Ref.10		VAR_005118
	Natural variant	456	1	Q → H in BTD deficiency. Ref.10		VAR_005119
	Natural variant	532	1	T → M in BTD deficiency. Ref.10		VAR_005120
	Natural variant	538	1	R → C in BTD deficiency. Ref.9 Ref.10		VAR_005121

Sequences

	Sequence		Length	Mass (Da)
	P43251 [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"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: Pericardium.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	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].
[6]	"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: Kidney.
[7]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-119; ASN-150; ASN-203; ASN-349 AND ASN-402, MASS SPECTROMETRY. Tissue: Plasma.
[8]	"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] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-119; ASN-150; ASN-349 AND ASN-402, MASS SPECTROMETRY. Tissue: Liver.
[9]	"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] [Europe PMC] [Abstract] Cited for: VARIANT BTD DEFICIENCY CYS-538.
[10]	"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] [Europe PMC] [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.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS BTD DEFICIENCY THR-171 AND HIS-444.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	U03274 mRNA. Translation: AAC04318.1. AF018631, AF018630 Genomic DNA. Translation: AAC21679.1. AK313252 mRNA. Translation: BAG36062.1. AC027129 Genomic DNA. No translation available. CH471055 Genomic DNA. Translation: EAW64254.1. BC012099 mRNA. Translation: AAH12099.1.
IPI	IPI00218413.
PIR	A54362.
RefSeq	NP_000051.1. NM_000060.2.
UniGene	Hs.517830.
3D structure databases
ProteinModelPortal	P43251.
ModBase	Search...
Protein-protein interaction databases
IntAct	P43251. 1 interaction.
STRING	9606.ENSP00000306477.
PTM databases
PhosphoSite	P43251.
Polymorphism databases
DMDM	226693503.
Proteomic databases
PaxDb	P43251.
PRIDE	P43251.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000303498; ENSP00000306477; ENSG00000169814.
GeneID	686.
KEGG	hsa:686.
UCSC	uc003cah.3. human.
Organism-specific databases
CTD	686.
GeneCards	GC03P015621.
HGNC	HGNC:1122. BTD.
MIM	253260. phenotype. 609019. gene.
neXtProt	NX_P43251.
Orphanet	79241. Biotinidase deficiency.
PharmGKB	PA25443.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG270742.
HOGENOM	HOG000007627.
HOVERGEN	HBG003996.
InParanoid	P43251.
KO	K01435.
PhylomeDB	P43251.
Enzyme and pathway databases
SABIO-RK	P43251.
Gene expression databases
ArrayExpress	P43251.
Bgee	P43251.
CleanEx	HS_BTD.
Genevestigator	P43251.
GermOnline	ENSG00000169814. Homo sapiens.
Family and domain databases
Gene3D	3.60.110.10. 1 hit.
InterPro	IPR012101. Biotinidase_euk. IPR003010. C-N_Hydrolase. [Graphical view]
PANTHER	PTHR10609. PTHR10609. 1 hit.
Pfam	PF00795. CN_hydrolase. 1 hit. [Graphical view]
PIRSF	PIRSF011861. Biotinidase. 1 hit.
SUPFAM	SSF56317. Ntlse/CNhydtse. 1 hit.
PROSITE	PS50263. CN_HYDROLASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	686.
NextBio	2824.
SOURCE	Search...

Entry information

Entry name

BTD_HUMAN

Accession

Primary (citable) accession number: P43251
Secondary accession number(s): B2R865, Q96EM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	April 14, 2009
Last modified:	May 1, 2013
This is version 116 of the entry and version 2 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.