NAGLU

Protein identityUniProt · HPA

UniProt accession

P54802

Gene

NAGLU

Ensembl

ENSG00000108784

Chromosome

17

Canonical length

743 aa

Protein class

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

Secretome location

Intracellular and membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes an enzyme that degrades heparan sulfate by hydrolysis of terminal N-acetyl-D-glucosamine residues in N-acetyl-alpha-D-glucosaminides. Defects in this gene are the cause of mucopolysaccharidosis type IIIB (MPS-IIIB), also known as Sanfilippo syndrome B. This disease is characterized by the lysosomal accumulation and urinary excretion of heparan sulfate. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

743 residues, UniProt reviewed canonical sequence.

>P54802|NAGLU
     1  MEAVAVAAAV GVLLLAGAGG AAGDEAREAA AVRALVARLL GPGPAADFSV SVERALAAKP
    61  GLDTYSLGGG GAARVRVRGS TGVAAAAGLH RYLRDFCGCH VAWSGSQLRL PRPLPAVPGE
   121  LTEATPNRYR YYQNVCTQSY SFVWWDWARW EREIDWMALN GINLALAWSG QEAIWQRVYL
   181  ALGLTQAEIN EFFTGPAFLA WGRMGNLHTW DGPLPPSWHI KQLYLQHRVL DQMRSFGMTP
   241  VLPAFAGHVP EAVTRVFPQV NVTKMGSWGH FNCSYSCSFL LAPEDPIFPI IGSLFLRELI
   301  KEFGTDHIYG ADTFNEMQPP SSEPSYLAAA TTAVYEAMTA VDTEAVWLLQ GWLFQHQPQF
   361  WGPAQIRAVL GAVPRGRLLV LDLFAESQPV YTRTASFQGQ PFIWCMLHNF GGNHGLFGAL
   421  EAVNGGPEAA RLFPNSTMVG TGMAPEGISQ NEVVYSLMAE LGWRKDPVPD LAAWVTSFAA
   481  RRYGVSHPDA GAAWRLLLRS VYNCSGEACR GHNRSPLVRR PSLQMNTSIW YNRSDVFEAW
   541  RLLLTSAPSL ATSPAFRYDL LDLTRQAVQE LVSLYYEEAR SAYLSKELAS LLRAGGVLAY
   601  ELLPALDEVL ASDSRFLLGS WLEQARAAAV SEAEADFYEQ NSRYQLTLWG PEGNILDYAN
   661  KQLAGLVANY YTPRWRLFLE ALVDSVAQGI PFQQHQFDKN VFQLEQAFVL SKQRYPSQPR
   721  GDTVDLAKKI FLKYYPRWVA GSW

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NAGLU 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)

0.21

Highest tissue expression

60 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NAGLU.

Disease | AllUniProt

Conditions NAGLU is implicated in, by any mechanism.

• Mucopolysaccharidosis 3B (MPS3B) MIM:252920
• Charcot-Marie-Tooth disease, axonal, type 2V (CMT2V) MIM:616491

Disease | GeneticClinVar

297 pathogenic / likely-pathogenic of 1,441 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mucopolysaccharidosis, MPS-III-B
• Charcot-Marie-Tooth disease axonal type 2V
• Mucopolysaccharidosis
• NAGLU-related disorder
• Inborn genetic diseases

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)

0.9

gnomAD pLI

0

gnomAD missense Z

0.99

DepMap mean gene effect

-0.2

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult behavior
• amyloid precursor protein metabolic process
• aorta morphogenesis
• astrocyte activation
• autophagy
• cardiac muscle cell development
• cell surface receptor signaling pathway via STAT
• cellular response to oxidative stress
• cerebellar Purkinje cell layer development
• collagen metabolic process
• cone retinal bipolar cell differentiation
• cytoplasm organization
• determination of adult lifespan
• endothelium development
• energy homeostasis
• exploration behavior
• ganglioside metabolic process
• glycosaminoglycan metabolic process
• Golgi organization
• hair follicle morphogenesis
• heparan sulfate proteoglycan catabolic process
• heparin proteoglycan metabolic process
• hormone metabolic process
• inner ear receptor cell development
• left ventricular cardiac muscle tissue morphogenesis
• limb development
• lipid catabolic process
• liver development
• locomotor rhythm
• lysosome organization
• maintenance of blood-brain barrier
• microglia differentiation
• microglial cell activation
• middle ear morphogenesis
• mitral valve morphogenesis
• motor behavior
• multicellular organismal-level iron ion homeostasis
• nerve development
• nervous system development
• proteasome-mediated ubiquitin-dependent protein catabolic process
• protein processing
• response to lipopolysaccharide
• response to wounding
• retinal rod cell development
• rod bipolar cell differentiation
• superoxide metabolic process
• toll-like receptor 4 signaling pathway
• vesicle tethering
• response to disaccharide

Molecular functions

• iron ion sequestering activity
• alpha-N-acetylglucosaminidase activity

Cellular components

• extracellular exosome
• lysosomal lumen
• lysosome
• membrane

Protein domainsUniProt · Pfam · InterPro

• Glycoside hydrolase superfamily
• Beta-hexosaminidase-like, domain 2
• Alpha-N-acetylglucosaminidase
• Alpha-N-acetylglucosaminidase, N-terminal
• Alpha-N-acetylglucosaminidase, C-terminal
• Alpha-N-acetylglucosaminidase, tim-barrel domain
• Alpha-N-acetylglucosaminidase (NAGLU) tim-barrel domain
• Alpha-N-acetylglucosaminidase (NAGLU) N-terminal domain
• Alpha-N-acetylglucosaminidase (NAGLU) C-terminal domain

KeywordsUniProt

• Charcot-Marie-Tooth disease
• Glycoprotein
• Glycosidase
• Hydrolase
• Lysosome
• Mucopolysaccharidosis
• Neurodegeneration
• Neuropathy
• Signal

InteractionsUniProt · HPA

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

• CANX
• FBXO6