GNPTAB

Protein identityUniProt · HPA

UniProt accession

Q3T906

Gene

GNPTAB

Ensembl

ENSG00000111670

Chromosome

12

Canonical length

1256 aa

Protein class

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

Subcellular location

Golgi apparatus

OverviewNCBI Gene

This gene encodes two of three subunit types of the membrane-bound enzyme N-acetylglucosamine-1-phosphotransferase, a heterohexameric complex composed of two alpha, two beta, and two gamma subunits. The encoded protein is proteolytically cleaved at the Lys928-Asp929 bond to yield mature alpha and beta polypeptides while the gamma subunits are the product of a distinct gene (GeneID 84572). In the Golgi apparatus, the heterohexameric complex catalyzes the first step in the synthesis of mannose 6-phosphate recognition markers on certain oligosaccharides of newly synthesized lysosomal enzymes. These recognition markers are essential for appropriate trafficking of lysosomal enzymes. Mutations in this gene have been associated with both mucolipidosis II and mucolipidosis IIIA.[provided by RefSeq, May 2010]

Canonical amino-acid sequenceUniProt

1256 residues, UniProt reviewed canonical sequence.

>Q3T906|GNPTAB
     1  MLFKLLQRQT YTCLSHRYGL YVCFLGVVVT IVSAFQFGEV VLEWSRDQYH VLFDSYRDNI
    61  AGKSFQNRLC LPMPIDVVYT WVNGTDLELL KELQQVREQM EEEQKAMREI LGKNTTEPTK
   121  KSEKQLECLL THCIKVPMLV LDPALPANIT LKDLPSLYPS FHSASDIFNV AKPKNPSTNV
   181  SVVVFDSTKD VEDAHSGLLK GNSRQTVWRG YLTTDKEVPG LVLMQDLAFL SGFPPTFKET
   241  NQLKTKLPEN LSSKVKLLQL YSEASVALLK LNNPKDFQEL NKQTKKNMTI DGKELTISPA
   301  YLLWDLSAIS QSKQDEDISA SRFEDNEELR YSLRSIERHA PWVRNIFIVT NGQIPSWLNL
   361  DNPRVTIVTH QDVFRNLSHL PTFSSPAIES HIHRIEGLSQ KFIYLNDDVM FGKDVWPDDF
   421  YSHSKGQKVY LTWPVPNCAE GCPGSWIKDG YCDKACNNSA CDWDGGDCSG NSGGSRYIAG
   481  GGGTGSIGVG QPWQFGGGIN SVSYCNQGCA NSWLADKFCD QACNVLSCGF DAGDCGQDHF
   541  HELYKVILLP NQTHYIIPKG ECLPYFSFAE VAKRGVEGAY SDNPIIRHAS IANKWKTIHL
   601  IMHSGMNATT IHFNLTFQNT NDEEFKMQIT VEVDTREGPK LNSTAQKGYE NLVSPITLLP
   661  EAEILFEDIP KEKRFPKFKR HDVNSTRRAQ EEVKIPLVNI SLLPKDAQLS LNTLDLQLEH
   721  GDITLKGYNL SKSALLRSFL MNSQHAKIKN QAIITDETND SLVAPQEKQV HKSILPNSLG
   781  VSERLQRLTF PAVSVKVNGH DQGQNPPLDL ETTARFRVET HTQKTIGGNV TKEKPPSLIV
   841  PLESQMTKEK KITGKEKENS RMEENAENHI GVTEVLLGRK LQHYTDSYLG FLPWEKKKYF
   901  QDLLDEEESL KTQLAYFTDS KNTGRQLKDT FADSLRYVNK ILNSKFGFTS RKVPAHMPHM
   961  IDRIVMQELQ DMFPEEFDKT SFHKVRHSED MQFAFSYFYY LMSAVQPLNI SQVFDEVDTD
  1021  QSGVLSDREI RTLATRIHEL PLSLQDLTGL EHMLINCSKM LPADITQLNN IPPTQESYYD
  1081  PNLPPVTKSL VTNCKPVTDK IHKAYKDKNK YRFEIMGEEE IAFKMIRTNV SHVVGQLDDI
  1141  RKNPRKFVCL NDNIDHNHKD AQTVKAVLRD FYESMFPIPS QFELPREYRN RFLHMHELQE
  1201  WRAYRDKLKF WTHCVLATLI MFTIFSFFAE QLIALKRKIF PRRRIHKEAS PNRIRV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GNPTAB 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

Other membrane

Secreted

No

Transmembrane segments

2

Mean surface accessibility (rSASA)

0.39

Highest tissue expression

51 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GNPTAB.

Disease | AllUniProt

Conditions GNPTAB is implicated in, by any mechanism.

• Mucolipidosis type II (MLII) MIM:252500
• Mucolipidosis type III complementation group A (MLIIIA) MIM:252600

Disease | GeneticClinVar

439 pathogenic / likely-pathogenic of 1,783 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mucolipidosis type II
• Pseudo-Hurler polydystrophy
• GNPTAB-mucolipidosis
• Mucolipidosis
• GNPTAB-Related Disorders

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)

0.82

gnomAD pLI

0

gnomAD missense Z

1.19

DepMap mean gene effect

-0.12

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

• carbohydrate phosphorylation
• lysosome organization
• N-glycan processing to lysosome
• secretion of lysosomal enzymes

Molecular functions

• calcium ion binding
• UDP-N-acetylglucosamine-lysosomal-enzyme N-acetylglucosaminephosphotransferase activity

Cellular components

• Golgi apparatus
• Golgi membrane

Protein domainsUniProt · Pfam · InterPro

• Notch domain
• EF-hand domain
• DMAP1-binding domain
• EF-Hand 1, calcium-binding site
• Notch-like domain superfamily
• LNR domain
• DMAP1-binding Domain
• Stealth protein CR2, conserved region 2
• Stealth protein CR4, conserved region 4
• Stealth protein CR3, conserved region 3
• Stealth protein CR1, conserved region 1
• N-acetylglucosamine-1-phosphotransferase subunit alpha/beta, regulatory domain
• Stealth family
• Stealth protein CR2, conserved region 2
• Stealth protein CR1, conserved region 1
• Stealth protein CR3, conserved region 3
• Stealth protein CR4, conserved region 4
• Putative GlcNAc-1 phosphotransferase regulatory domain

KeywordsUniProt

• Calcium
• Disulfide bond
• Glycoprotein
• Golgi apparatus
• Membrane
• Metal-binding
• Mucolipidosis
• Repeat
• Signal-anchor
• Transferase
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

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

• LYSET