HEXB

Protein identityUniProt · HPA

UniProt accession

P07686

Gene

HEXB

Ensembl

ENSG00000049860

Chromosome

5

Canonical length

556 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

Hexosaminidase B is the beta subunit of the lysosomal enzyme beta-hexosaminidase that, together with the cofactor GM2 activator protein, catalyzes the degradation of the ganglioside GM2, and other molecules containing terminal N-acetyl hexosamines. Beta-hexosaminidase is composed of two subunits, alpha and beta, which are encoded by separate genes. Both beta-hexosaminidase alpha and beta subunits are members of family 20 of glycosyl hydrolases. Mutations in the alpha or beta subunit genes lead to an accumulation of GM2 ganglioside in neurons and neurodegenerative disorders termed the GM2 gangliosidoses. Beta subunit gene mutations lead to Sandhoff disease (GM2-gangliosidosis type II). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2014]

Canonical amino-acid sequenceUniProt

556 residues, UniProt reviewed canonical sequence.

>P07686|HEXB
     1  MELCGLGLPR PPMLLALLLA TLLAAMLALL TQVALVVQVA EAARAPSVSA KPGPALWPLP
    61  LLVKMTPNLL HLAPENFYIS HSPNSTAGPS CTLLEEAFRR YHGYIFGFYK WHHEPAEFQA
   121  KTQVQQLLVS ITLQSECDAF PNISSDESYT LLVKEPVAVL KANRVWGALR GLETFSQLVY
   181  QDSYGTFTIN ESTIIDSPRF SHRGILIDTS RHYLPVKIIL KTLDAMAFNK FNVLHWHIVD
   241  DQSFPYQSIT FPELSNKGSY SLSHVYTPND VRMVIEYARL RGIRVLPEFD TPGHTLSWGK
   301  GQKDLLTPCY SRQNKLDSFG PINPTLNTTY SFLTTFFKEI SEVFPDQFIH LGGDEVEFKC
   361  WESNPKIQDF MRQKGFGTDF KKLESFYIQK VLDIIATINK GSIVWQEVFD DKAKLAPGTI
   421  VEVWKDSAYP EELSRVTASG FPVILSAPWY LDLISYGQDW RKYYKVEPLD FGGTQKQKQL
   481  FIGGEACLWG EYVDATNLTP RLWPRASAVG ERLWSSKDVR DMDDAYDRLT RHRCRMVERG
   541  IAAQPLYAGY CNHENM

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HEXB 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)

0.25

Highest tissue expression

303 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HEXB.

Disease | AllUniProt

Conditions HEXB is implicated in, by any mechanism.

• GM2-gangliosidosis 2 (GM2G2) MIM:268800

Disease | GeneticClinVar

226 pathogenic / likely-pathogenic of 943 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Sandhoff disease
• Sandhoff disease, infantile form
• Sandhoff disease, adult form
• See cases
• Sandhoff disease, juvenile form

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)

0.92

gnomAD pLI

0

gnomAD missense Z

0.65

DepMap mean gene effect

0.01

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• astrocyte cell migration
• chondroitin sulfate proteoglycan catabolic process
• dermatan sulfate proteoglycan catabolic process
• ganglioside catabolic process
• glycosaminoglycan metabolic process
• hyaluronan catabolic process
• intracellular calcium ion homeostasis
• lipid storage
• locomotory behavior
• lysosome organization
• myelination
• N-acetylglucosamine metabolic process
• N-glycan processing
• neuromuscular process controlling balance
• neuron cellular homeostasis
• oligosaccharide catabolic process
• oogenesis
• penetration of zona pellucida
• phospholipid biosynthetic process
• positive regulation of transcription by RNA polymerase II
• regulation of cell shape
• sensory perception of sound
• single fertilization
• skeletal system development
• male courtship behavior

Molecular functions

• acetylglucosaminyltransferase activity
• beta-N-acetylhexosaminidase activity
• carbohydrate binding
• identical protein binding
• protein-containing complex binding
• beta-N-acetylglucosaminidase activity

Cellular components

• acrosomal vesicle
• azurophil granule
• azurophil granule lumen
• beta-N-acetylhexosaminidase complex
• cortical granule
• extracellular exosome
• extracellular region
• lysosomal lumen
• lysosome
• membrane

Protein domainsUniProt · Pfam · InterPro

• Beta-hexosaminidase, catalytic domain
• Glycoside hydrolase superfamily
• Beta-hexosaminidase
• Beta-hexosaminidase-like, domain 2
• Beta-hexosaminidase, eukaryotic type, N-terminal
• Glycosyl hydrolase family 20, catalytic domain
• beta-acetyl hexosaminidase like

KeywordsUniProt

• Cytoplasmic vesicle
• Disulfide bond
• Gangliosidosis
• Glycoprotein
• Glycosidase
• Hydrolase
• Lipid metabolism
• Lysosome
• Neurodegeneration
• Signal
• Zymogen

InteractionsUniProt · HPA

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

• HEXA