HLCS

Protein identityUniProt · HPA

UniProt accession

P50747

Gene

HLCS

Ensembl

ENSG00000159267

Chromosome

21

Canonical length

726 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes an enzyme that catalyzes the binding of biotin to carboxylases and histones. The protein plays an important role in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. Defects in this gene are the cause of holocarboxylase synthetase deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified.[provided by RefSeq, Jun 2011]

Canonical amino-acid sequenceUniProt

726 residues, UniProt reviewed canonical sequence.

>P50747|HLCS
     1  MEDRLHMDNG LVPQKIVSVH LQDSTLKEVK DQVSNKQAQI LEPKPEPSLE IKPEQDGMEH
    61  VGRDDPKALG EEPKQRRGSA SGSEPAGDSD RGGGPVEHYH LHLSSCHECL ELENSTIESV
   121  KFASAENIPD LPYDYSSSLE SVADETSPER EGRRVNLTGK APNILLYVGS DSQEALGRFH
   181  EVRSVLADCV DIDSYILYHL LEDSALRDPW TDNCLLLVIA TRESIPEDLY QKFMAYLSQG
   241  GKVLGLSSSF TFGGFQVTSK GALHKTVQNL VFSKADQSEV KLSVLSSGCR YQEGPVRLSP
   301  GRLQGHLENE DKDRMIVHVP FGTRGGEAVL CQVHLELPPS SNIVQTPEDF NLLKSSNFRR
   361  YEVLREILTT LGLSCDMKQV PALTPLYLLS AAEEIRDPLM QWLGKHVDSE GEIKSGQLSL
   421  RFVSSYVSEV EITPSCIPVV TNMEAFSSEH FNLEIYRQNL QTKQLGKVIL FAEVTPTTMR
   481  LLDGLMFQTP QEMGLIVIAA RQTEGKGRGG NVWLSPVGCA LSTLLISIPL RSQLGQRIPF
   541  VQHLMSVAVV EAVRSIPEYQ DINLRVKWPN DIYYSDLMKI GGVLVNSTLM GETFYILIGC
   601  GFNVTNSNPT ICINDLITEY NKQHKAELKP LRADYLIARV VTVLEKLIKE FQDKGPNSVL
   661  PLYYRYWVHS GQQVHLGSAE GPKVSIVGLD DSGFLQVHQE GGEVVTVHPD GNSFDMLRNL
   721  ILPKRR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HLCS can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.3

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HLCS.

Disease | AllUniProt

Conditions HLCS is implicated in, by any mechanism.

• Holocarboxylase synthetase deficiency (HLCS deficiency) MIM:253270

Disease | GeneticClinVar

194 pathogenic / likely-pathogenic of 1,117 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Holocarboxylase synthetase deficiency
• Inborn genetic diseases
• Ovarian serous cystadenocarcinoma

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.88

gnomAD pLI

0

gnomAD missense Z

0.15

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• biotin metabolic process
• post-translational protein modification
• response to biotin

Molecular functions

• ATP binding
• biotin binding
• enzyme binding
• identical protein binding
• biotin--[biotin carboxyl-carrier protein] ligase activity

Cellular components

• chromatin
• cytoplasm
• cytosol
• mitochondrion
• nuclear lamina
• nuclear matrix

Protein domainsUniProt · Pfam · InterPro

• Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL), catalytic domain
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• Biotin protein ligase, C-terminal
• Biotin--acetyl-CoA-carboxylase ligase
• Biotin protein ligase C terminal domain
• Biotin/lipoate A/B protein ligase family

KeywordsUniProt

• ATP-binding
• Cytoplasm
• Ligase
• Mitochondrion
• Multifunctional enzyme
• Nucleotide-binding
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of HLCS in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ACACB
• SPATA46