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UniProtKB - P50747 (BPL1_HUMAN)

Entry version 196 (07 Apr 2021)
Sequence version 1 (01 Oct 1996)
Previous versions | rss
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Protein

Biotin--protein ligase

Gene

HLCS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Biotin--protein ligase catalyzing the biotinylation of the 4 biotin-dependent carboxylases acetyl-CoA-carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase.3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=224 nM for biotin1 Publication
  1. Vmax=143.9 pmol/min/mg enzyme1 Publication

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionLigase, Multifunctional enzyme
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P50747

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-196780, Biotin transport and metabolism
R-HSA-3371599, Defective HLCS causes multiple carboxylase deficiency

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		P50747

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Biotin--protein ligase (EC:6.3.4.-1 Publication)
Alternative name(s):
Biotin apo-protein ligase
Including the following 4 domains:
Biotin--[methylmalonyl-CoA-carboxytransferase] ligase (EC:6.3.4.91 Publication)
Biotin--[propionyl-CoA-carboxylase [ATP-hydrolyzing]] ligase (EC:6.3.4.101 Publication)
Alternative name(s):
Holocarboxylase synthetase
Short name:
HCS
Biotin--[methylcrotonoyl-CoA-carboxylase] ligase (EC:6.3.4.111 Publication)
Biotin--[acetyl-CoA-carboxylase] ligase (EC:6.3.4.151 Publication)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HLCSImported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 21

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:4976, HLCS

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		609018, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P50747

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000159267.14

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Mitochondrion

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Holocarboxylase synthetase deficiency (HLCS deficiency)12 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA neonatal form of multiple carboxylase deficiency, an autosomal recessive disorder of biotin metabolism, characterized by ketoacidosis, hyperammonemia, excretion of abnormal organic acid metabolites, and dermatitis. In holocarboxylase synthetase deficiency, clinical and biochemical symptoms improve dramatically with administration of biotin.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_03580042E → D in HLCS deficiency; benign variant; conserves enzymatic wild-type activity. 2 PublicationsCorresponds to variant dbSNP:rs61732504Ensembl.1
Natural variantiVAR_046507183R → P in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant). 1 Publication1
Natural variantiVAR_021218216L → R in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant); growth of patients' fibroblasts is compromised compared with normal fibroblasts; patients cells are not sensitive to biotin-depletion from the media; growth rates cannot be restored by re-administration of biotin; enzyme activity is severely compromised and cannot be increased by additional biotin; turn-over rate for the mutant protein is double that of wild-type enzyme. 4 PublicationsCorresponds to variant dbSNP:rs28934602Ensembl.1
Natural variantiVAR_005084237L → P in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant). 5 PublicationsCorresponds to variant dbSNP:rs119103227Ensembl.1
Natural variantiVAR_073074241G → W in HLCS deficiency. 1 Publication1
Natural variantiVAR_009196333V → E in HLCS deficiency; <10% activity; has normal or low KM values for biotin (non-KM mutant). 3 PublicationsCorresponds to variant dbSNP:rs1198548955Ensembl.1
Natural variantiVAR_046508360R → S in HLCS deficiency; 22% activity; shows elevated KM values for biotin (KM mutant) compared with that of the wild-type form. 1 PublicationCorresponds to variant dbSNP:rs1230666123Ensembl.1
Natural variantiVAR_046509363V → D in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant). 2 PublicationsCorresponds to variant dbSNP:rs769499327Ensembl.1
Natural variantiVAR_046510456Y → C in HLCS deficiency; 0.2% activity. 1 PublicationCorresponds to variant dbSNP:rs781603756Ensembl.1
Natural variantiVAR_009197462T → I in HLCS deficiency; <10% activity. 1 PublicationCorresponds to variant dbSNP:rs1256356959Ensembl.1
Natural variantiVAR_046511470L → S in HLCS deficiency; 4.3% activity. 1 PublicationCorresponds to variant dbSNP:rs1261821166Ensembl.1
Natural variantiVAR_073075505G → R in HLCS deficiency. 1 PublicationCorresponds to variant dbSNP:rs1555885056Ensembl.1
Natural variantiVAR_013009508R → W in HLCS deficiency. 4 PublicationsCorresponds to variant dbSNP:rs119103229Ensembl.1
Natural variantiVAR_021219511N → K in HLCS deficiency. 1 Publication1
Natural variantiVAR_046512518G → E in HLCS deficiency. 1 Publication1
Natural variantiVAR_046513547V → G in HLCS deficiency; 3.4% activity. 1 Publication1
Natural variantiVAR_009198550V → M in HLCS deficiency. 4 PublicationsCorresponds to variant dbSNP:rs119103231Ensembl.1
Natural variantiVAR_009199571D → N in HLCS deficiency; almost no activity. 2 PublicationsCorresponds to variant dbSNP:rs119103228Ensembl.1
Natural variantiVAR_009200581G → S in HLCS deficiency; <10% activity. 4 PublicationsCorresponds to variant dbSNP:rs119103230Ensembl.1
Natural variantiVAR_021220582G → R in HLCS deficiency. 1 PublicationCorresponds to variant dbSNP:rs376899782Ensembl.1
Natural variantiVAR_009201610Missing in HLCS deficiency; 14% of activity; shows elevated KM values for biotin (KM mutant) compared with that of the wild-type form. 3 Publications1
Natural variantiVAR_046514615D → Y in HLCS deficiency. 1 Publication1
Natural variantiVAR_046515634D → N in HLCS deficiency. 1 PublicationCorresponds to variant dbSNP:rs149399432Ensembl.1
Natural variantiVAR_046516634D → Y in HLCS deficiency; 12% activity. 1 Publication1
Natural variantiVAR_046517715D → G in HLCS deficiency. 1 Publication1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		3141

MalaCards human disease database

More...MalaCardsi		HLCS
MIMi253270, phenotype

Open Targets

More...OpenTargetsi		ENSG00000159267

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		79242, Holocarboxylase synthetase deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA29310

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P50747, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL2062354

Drug and drug target database

More...DrugBanki		DB00121, Biotin

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		HLCS

Domain mapping of disease mutations (DMDM)

More...DMDMi		1705499

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000649791 – 726Biotin--protein ligaseAdd BLAST726

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei147PhosphoserineCombined sources1
Modified residuei299PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P50747

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P50747

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P50747

MaxQB - The MaxQuant DataBase

More...MaxQBi		P50747

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P50747

PeptideAtlas

More...PeptideAtlasi		P50747

PRoteomics IDEntifications database

More...PRIDEi		P50747

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		56260

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P50747

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P50747

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely expressed (PubMed:7842009, PubMed:7753853). Mostly expressed in muscle, placenta and to a lower extent in the brain, kidney, pancreas, liver and lung (PubMed:7842009).2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000159267, Expressed in cerebral cortex and 177 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P50747, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P50747, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000159267, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		109386, 25 interactors

Protein interaction database and analysis system

More...IntActi		P50747, 18 interactors

Molecular INTeraction database

More...MINTi		P50747

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000382071

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P50747

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P50747, protein

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini463 – 652BPL/LPL catalyticPROSITE-ProRule annotationAdd BLAST190

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the biotin--protein ligase family.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1536, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00390000002960

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_006150_2_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P50747

Identification of Orthologs from Complete Genome Data

More...OMAi		PDLPYDH

Database of Orthologous Groups

More...OrthoDBi		1392751at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P50747

TreeFam database of animal gene trees

More...TreeFami		TF105860

Family and domain databases

Conserved Domains Database

More...CDDi		cd16442, BPL, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR019197, Biotin-prot_ligase_N
IPR004408, Biotin_CoA_COase_ligase
IPR003142, BPL_C
IPR004143, BPL_LPL_catalytic

Pfam protein domain database

More...Pfami		View protein in Pfam
PF02237, BPL_C, 1 hit
PF03099, BPL_LplA_LipB, 1 hit
PF09825, BPL_N, 1 hit

TIGRFAMs; a protein family database

More...TIGRFAMsi		TIGR00121, birA_ligase, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51733, BPL_LPL_CATALYTIC, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P50747-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEDRLHMDNG LVPQKIVSVH LQDSTLKEVK DQVSNKQAQI LEPKPEPSLE 
        60         70         80         90        100
IKPEQDGMEH VGRDDPKALG EEPKQRRGSA SGSEPAGDSD RGGGPVEHYH 
       110        120        130        140        150
LHLSSCHECL ELENSTIESV KFASAENIPD LPYDYSSSLE SVADETSPER 
       160        170        180        190        200
EGRRVNLTGK APNILLYVGS DSQEALGRFH EVRSVLADCV DIDSYILYHL 
       210        220        230        240        250
LEDSALRDPW TDNCLLLVIA TRESIPEDLY QKFMAYLSQG GKVLGLSSSF 
       260        270        280        290        300
TFGGFQVTSK GALHKTVQNL VFSKADQSEV KLSVLSSGCR YQEGPVRLSP 
       310        320        330        340        350
GRLQGHLENE DKDRMIVHVP FGTRGGEAVL CQVHLELPPS SNIVQTPEDF 
       360        370        380        390        400
NLLKSSNFRR YEVLREILTT LGLSCDMKQV PALTPLYLLS AAEEIRDPLM 
       410        420        430        440        450
QWLGKHVDSE GEIKSGQLSL RFVSSYVSEV EITPSCIPVV TNMEAFSSEH 
       460        470        480        490        500
FNLEIYRQNL QTKQLGKVIL FAEVTPTTMR LLDGLMFQTP QEMGLIVIAA 
       510        520        530        540        550
RQTEGKGRGG NVWLSPVGCA LSTLLISIPL RSQLGQRIPF VQHLMSVAVV 
       560        570        580        590        600
EAVRSIPEYQ DINLRVKWPN DIYYSDLMKI GGVLVNSTLM GETFYILIGC 
       610        620        630        640        650
GFNVTNSNPT ICINDLITEY NKQHKAELKP LRADYLIARV VTVLEKLIKE 
       660        670        680        690        700
FQDKGPNSVL PLYYRYWVHS GQQVHLGSAE GPKVSIVGLD DSGFLQVHQE 
       710        720 
GGEVVTVHPD GNSFDMLRNL ILPKRR
Length:726
Mass (Da):80,760
Last modified:October 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i855B8E52106D675F
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A6Q8PFK4A0A6Q8PFK4_HUMAN
Biotin--protein ligase
HLCS
604Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
C9JCQ9C9JCQ9_HUMAN
Biotin--protein ligase
HLCS
77Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A0C4DG27A0A0C4DG27_HUMAN
Biotin--protein ligase
HLCS
92Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

<p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AK307940 differs from that shown. Reason: Frameshift.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti209P → T in AK307940 (PubMed:14702039).Curated1
Sequence conflicti463K → R in BAG36868 (PubMed:14702039).Curated1
Sequence conflicti558E → K in BAA13332 (PubMed:9037601).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03580042E → D in HLCS deficiency; benign variant; conserves enzymatic wild-type activity. 2 PublicationsCorresponds to variant dbSNP:rs61732504Ensembl.1
Natural variantiVAR_046507183R → P in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant). 1 Publication1
Natural variantiVAR_021218216L → R in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant); growth of patients' fibroblasts is compromised compared with normal fibroblasts; patients cells are not sensitive to biotin-depletion from the media; growth rates cannot be restored by re-administration of biotin; enzyme activity is severely compromised and cannot be increased by additional biotin; turn-over rate for the mutant protein is double that of wild-type enzyme. 4 PublicationsCorresponds to variant dbSNP:rs28934602Ensembl.1
Natural variantiVAR_005084237L → P in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant). 5 PublicationsCorresponds to variant dbSNP:rs119103227Ensembl.1
Natural variantiVAR_073074241G → W in HLCS deficiency. 1 Publication1
Natural variantiVAR_009196333V → E in HLCS deficiency; <10% activity; has normal or low KM values for biotin (non-KM mutant). 3 PublicationsCorresponds to variant dbSNP:rs1198548955Ensembl.1
Natural variantiVAR_046508360R → S in HLCS deficiency; 22% activity; shows elevated KM values for biotin (KM mutant) compared with that of the wild-type form. 1 PublicationCorresponds to variant dbSNP:rs1230666123Ensembl.1
Natural variantiVAR_046509363V → D in HLCS deficiency; has normal or low KM values for biotin (non-KM mutant). 2 PublicationsCorresponds to variant dbSNP:rs769499327Ensembl.1
Natural variantiVAR_046510456Y → C in HLCS deficiency; 0.2% activity. 1 PublicationCorresponds to variant dbSNP:rs781603756Ensembl.1
Natural variantiVAR_009197462T → I in HLCS deficiency; <10% activity. 1 PublicationCorresponds to variant dbSNP:rs1256356959Ensembl.1
Natural variantiVAR_046511470L → S in HLCS deficiency; 4.3% activity. 1 PublicationCorresponds to variant dbSNP:rs1261821166Ensembl.1
Natural variantiVAR_073075505G → R in HLCS deficiency. 1 PublicationCorresponds to variant dbSNP:rs1555885056Ensembl.1
Natural variantiVAR_013009508R → W in HLCS deficiency. 4 PublicationsCorresponds to variant dbSNP:rs119103229Ensembl.1
Natural variantiVAR_021219511N → K in HLCS deficiency. 1 Publication1
Natural variantiVAR_046512518G → E in HLCS deficiency. 1 Publication1
Natural variantiVAR_046513547V → G in HLCS deficiency; 3.4% activity. 1 Publication1
Natural variantiVAR_009198550V → M in HLCS deficiency. 4 PublicationsCorresponds to variant dbSNP:rs119103231Ensembl.1
Natural variantiVAR_009199571D → N in HLCS deficiency; almost no activity. 2 PublicationsCorresponds to variant dbSNP:rs119103228Ensembl.1
Natural variantiVAR_009200581G → S in HLCS deficiency; <10% activity. 4 PublicationsCorresponds to variant dbSNP:rs119103230Ensembl.1
Natural variantiVAR_021220582G → R in HLCS deficiency. 1 PublicationCorresponds to variant dbSNP:rs376899782Ensembl.1
Natural variantiVAR_009201610Missing in HLCS deficiency; 14% of activity; shows elevated KM values for biotin (KM mutant) compared with that of the wild-type form. 3 Publications1
Natural variantiVAR_046514615D → Y in HLCS deficiency. 1 Publication1
Natural variantiVAR_046515634D → N in HLCS deficiency. 1 PublicationCorresponds to variant dbSNP:rs149399432Ensembl.1
Natural variantiVAR_046516634D → Y in HLCS deficiency; 12% activity. 1 Publication1
Natural variantiVAR_046517715D → G in HLCS deficiency. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
D23672 mRNA Translation: BAA04902.1
D87328 mRNA Translation: BAA13332.1
AP000697 AP000698 Genomic DNA Translation: BAA89434.1
AB063285 Genomic DNA Translation: BAB68550.1
AK307940 mRNA No translation available.
AK314189 mRNA Translation: BAG36868.1
AP001726 Genomic DNA Translation: BAA95510.1
AP001727 Genomic DNA Translation: BAA95511.1
CH471079 Genomic DNA Translation: EAX09731.1
CH471079 Genomic DNA Translation: EAX09732.1
BC060787 mRNA Translation: AAH60787.1
AJ001864 mRNA Translation: CAA05056.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS13647.1

Protein sequence database of the Protein Information Resource

More...PIRi		S50833

NCBI Reference Sequences

More...RefSeqi		NP_000402.3, NM_000411.6
NP_001229713.1, NM_001242784.1
NP_001229714.1, NM_001242785.1
XP_005261012.1, XM_005260955.3
XP_005261013.1, XM_005260956.3
XP_006724057.1, XM_006723994.2
XP_006724058.1, XM_006723995.1
XP_011527840.1, XM_011529538.1
XP_011527841.1, XM_011529539.2
XP_011527843.1, XM_011529541.2
XP_016883819.1, XM_017028330.1

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000336648; ENSP00000338387; ENSG00000159267
ENST00000399120; ENSP00000382071; ENSG00000159267
ENST00000612277; ENSP00000479939; ENSG00000159267
ENST00000674895; ENSP00000502087; ENSG00000159267
ENST00000675307; ENSP00000501750; ENSG00000159267

Database of genes from NCBI RefSeq genomes

More...GeneIDi		3141

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:3141

UCSC genome browser

More...UCSCi		uc002yvs.4, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D23672 mRNA Translation: BAA04902.1
D87328 mRNA Translation: BAA13332.1
AP000697 AP000698 Genomic DNA Translation: BAA89434.1
AB063285 Genomic DNA Translation: BAB68550.1
AK307940 mRNA No translation available.
AK314189 mRNA Translation: BAG36868.1
AP001726 Genomic DNA Translation: BAA95510.1
AP001727 Genomic DNA Translation: BAA95511.1
CH471079 Genomic DNA Translation: EAX09731.1
CH471079 Genomic DNA Translation: EAX09732.1
BC060787 mRNA Translation: AAH60787.1
AJ001864 mRNA Translation: CAA05056.1
CCDSiCCDS13647.1
PIRiS50833
RefSeqiNP_000402.3, NM_000411.6
NP_001229713.1, NM_001242784.1
NP_001229714.1, NM_001242785.1
XP_005261012.1, XM_005260955.3
XP_005261013.1, XM_005260956.3
XP_006724057.1, XM_006723994.2
XP_006724058.1, XM_006723995.1
XP_011527840.1, XM_011529538.1
XP_011527841.1, XM_011529539.2
XP_011527843.1, XM_011529541.2
XP_016883819.1, XM_017028330.1

3D structure databases

Database of comparative protein structure models

More...ModBasei		Search...

SWISS-MODEL Interactive Workspace

More...SWISS-MODEL-Workspacei		Submit a new modelling project...

Protein-protein interaction databases

BioGRIDi109386, 25 interactors
IntActiP50747, 18 interactors
MINTiP50747
STRINGi9606.ENSP00000382071

Chemistry databases

BindingDBiP50747
ChEMBLiCHEMBL2062354
DrugBankiDB00121, Biotin

PTM databases

iPTMnetiP50747
PhosphoSitePlusiP50747

Genetic variation databases

BioMutaiHLCS
DMDMi1705499

Proteomic databases

EPDiP50747
jPOSTiP50747
MassIVEiP50747
MaxQBiP50747
PaxDbiP50747
PeptideAtlasiP50747
PRIDEiP50747
ProteomicsDBi56260

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		8381, 153 antibodies

Genome annotation databases

EnsembliENST00000336648; ENSP00000338387; ENSG00000159267
ENST00000399120; ENSP00000382071; ENSG00000159267
ENST00000612277; ENSP00000479939; ENSG00000159267
ENST00000674895; ENSP00000502087; ENSG00000159267
ENST00000675307; ENSP00000501750; ENSG00000159267
GeneIDi3141
KEGGihsa:3141
UCSCiuc002yvs.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		3141
DisGeNETi3141

GeneCards: human genes, protein and diseases

More...GeneCardsi		HLCS
HGNCiHGNC:4976, HLCS
HPAiENSG00000159267, Low tissue specificity
MalaCardsiHLCS
MIMi253270, phenotype
609018, gene
neXtProtiNX_P50747
OpenTargetsiENSG00000159267
Orphaneti79242, Holocarboxylase synthetase deficiency
PharmGKBiPA29310
VEuPathDBiHostDB:ENSG00000159267.14

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1536, Eukaryota
GeneTreeiENSGT00390000002960
HOGENOMiCLU_006150_2_0_1
InParanoidiP50747
OMAiPDLPYDH
OrthoDBi1392751at2759
PhylomeDBiP50747
TreeFamiTF105860

Enzyme and pathway databases

PathwayCommonsiP50747
ReactomeiR-HSA-196780, Biotin transport and metabolism
R-HSA-3371599, Defective HLCS causes multiple carboxylase deficiency
SABIO-RKiP50747

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		3141, 16 hits in 998 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		HLCS, human

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		3141
PharosiP50747, Tchem

Protein Ontology

More...PROi		PR:P50747
RNActiP50747, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000159267, Expressed in cerebral cortex and 177 other tissues
ExpressionAtlasiP50747, baseline and differential
GenevisibleiP50747, HS

Family and domain databases

CDDicd16442, BPL, 1 hit
InterProiView protein in InterPro
IPR019197, Biotin-prot_ligase_N
IPR004408, Biotin_CoA_COase_ligase
IPR003142, BPL_C
IPR004143, BPL_LPL_catalytic
PfamiView protein in Pfam
PF02237, BPL_C, 1 hit
PF03099, BPL_LplA_LipB, 1 hit
PF09825, BPL_N, 1 hit
TIGRFAMsiTIGR00121, birA_ligase, 1 hit
PROSITEiView protein in PROSITE
PS51733, BPL_LPL_CATALYTIC, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiBPL1_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P50747
Secondary accession number(s): B2RAH1, D3DSG6, Q99451
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 7, 2021
This is version 196 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families
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