Summary: Putative GlcNAc-1 phosphotransferase regulatory domain
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This is the Wikipedia entry entitled "N-acetylglucosamine-1-phosphate transferase". More...
N-acetylglucosamine-1-phosphate transferase Edit Wikipedia article
N-acetylglucosamine-1-phosphate transferase, alpha and beta subunits | |
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Identifiers | |
Symbol | GNPTAB |
Alt. symbols | GNPTA |
NCBI gene | 79158 |
HGNC | 29670 |
OMIM | 607840 |
RefSeq | NM_024312 |
UniProt | Q3T906 |
Other data | |
Locus | Chr. 12 q23.3 |
N-acetylglucosamine-1-phosphate transferase, gamma subunit | |
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Identifiers | |
Symbol | GNPTG |
Alt. symbols | GNPTAG |
NCBI gene | 84572 |
HGNC | 23026 |
OMIM | 607838 |
RefSeq | NM_032520 |
UniProt | Q9UJJ9 |
Other data | |
Locus | Chr. 16 p13.3 |
N-acetylglucosamine-1-phosphate transferase is a transferase enzyme.
Function
It is made up of two alpha (α), two betas (β), and two gammas (γ) subunits. GNPTAB produces the alpha and beta subunits, GNPTG produces the gamma subunit. GlcNAc-1-phosphotransferase functions to prepare newly made enzymes for lysosome transportation (lysosomal hydrolases to the lysosome). Lysosomes, a part of an animal cell, helps break down large molecules into smaller ones that can be reused. GlcNAc-1-phosphotransferase catalyzes the N-linked glycosylation of asparagine residues with a molecule called mannose-6-phosphate (M6P). M6P acts as an indicator of whether a hydrolase should be transported to the lysosome or not. Once a hydrolase indicates an M6P, it can be transported to a lysosome. Surprisingly some lysosomal enzymes are only tagged at a rate of 5% or lower.
Clinical significance
It is associated with the following conditions:[1][2]
- mucolipidosis II alpha/beta (I-cell disease) - GNPTAB
- mucolipidosis III alpha/beta (pseudo-Hurler polydystrophy) - GNPTAB
- mucolipidosis III gamma - GNPTG
- stuttering (Kang et al., 2010)
In melanocytic cells, GNPTG gene expression may be regulated by MITF.[3]
References
- ^ Online Mendelian Inheritance in Man (OMIM) MUCOLIPIDOSIS II ALPHA/BETA -252500
- ^ Online Mendelian Inheritance in Man (OMIM) MUCOLIPIDOSIS III GAMMA -252605
- ^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
Kang, C., Riazuddin, S., Mundorff, J., Krasnewich, D., Friedman, P., Mullikin, J.C., and Drayna, D. (2010). Mutations in the Lysosomal Enzyme–Targeting Pathway and Persistent Stuttering. New England Journal of Medicine 362, 677-685.
External links
- GeneReviews/NCBI/NIH/UW entry on Mucolipidosis III Alpha/Beta
- GeneReviews/NIH/NCBI/UW entry on Mucolipidosis II
- GeneReviews/NIH/NCBI/UW entry on Mucolipidosis III Gamma
- N-acetylglucosamine-1-phosphate+transferase at the US National Library of Medicine Medical Subject Headings (MeSH)
- EC 2.7.8.15
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Putative GlcNAc-1 phosphotransferase regulatory domain Provide feedback
The Golgi enzyme UDP-GlcNAc-lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase), an alpha2beta2gamma2 hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes [1]. GNPTAB encodes the alpha and beta subunits of GlcNAc-1-phosphotransferase, and mutations in this gene cause the lysosomal storage disorders mucolipidosis II and III alpha-beta The alpha-beta subunits contain three identifiable domains separated by so-called spacer regions. This domain is part of the first spacer region, Spacer-1 [2]. Studies indicate that GlcNAc-1 lacking spacer-1 exhibits enhanced phosphorylation of several non-lysosomal glycoproteins, while the phosphorylation of lysosomal acid hydrolases is not altered. In view of these effects on the maturation and function of GlcNAc-1, it is suggested to rename 'spacer-1' the 'regulatory-1' domain [1].
Literature references
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Liu L, Lee WS, Doray B, Kornfeld S;, FEBS Lett. 2017;591:47-55.: Role of spacer-1 in the maturation and function of GlcNAc-1-phosphotransferase. PUBMED:27981560 EPMC:27981560
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Qian Y, van Meel E, Flanagan-Steet H, Yox A, Steet R, Kornfeld S;, J Biol Chem. 2015;290:3045-3056.: Analysis of mucolipidosis II/III GNPTAB missense mutations identifies domains of UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase involved in catalytic function and lysosomal enzyme recognition. PUBMED:25505245 EPMC:25505245
This tab holds annotation information from the InterPro database.
InterPro entry IPR041536
The Golgi enzyme UDP-GlcNAc-lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase), an alpha2beta2gamma2 hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes [PUBMED:27981560]. GNPTAB encodes the alpha and beta subunits of GlcNAc-1-phosphotransferase, and mutations in this gene cause the lysosomal storage disorders mucolipidosis II and III alpha-beta The alpha-beta subunits contain three identifiable domains separated by so-called spacer regions. This domain is part of the first spacer region, Spacer-1 [PUBMED:25505245]. Studies indicate that GlcNAc-1 lacking spacer-1 exhibits enhanced phosphorylation of several non-lysosomal glycoproteins, while the phosphorylation of lysosomal acid hydrolases is not altered. In view of these effects on the maturation and function of GlcNAc-1, it is suggested to rename 'spacer-1' the 'regulatory-1' domain [PUBMED:27981560].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan RRM (CL0221), which has the following description:
This clan contains families that are related to the RNA recognition motif domains. However, not all these families are RNA binding.
The clan contains the following 31 members:
BRAP2 Calcipressin DbpA DUF1743 DUF1866 DUF4523 GlcNAc-1_reg GUCT Limkain-b1 Nup35_RRM Nup35_RRM_2 PHM7_cyt RL RNA_bind RRM_1 RRM_2 RRM_3 RRM_5 RRM_7 RRM_8 RRM_9 RRM_occluded RRM_Rrp7 SET_assoc Smg4_UPF3 Spo7_2_N Tap-RNA_bind Transposase_22 U1snRNP70_N XS YlmH_RBDAlignments
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Seed (2) |
Full (242) |
Representative proteomes | UniProt (385) |
NCBI (697) |
Meta (0) |
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RP15 (20) |
RP35 (59) |
RP55 (173) |
RP75 (266) |
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PP/heatmap | 1 |
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Seed (2) |
Full (242) |
Representative proteomes | UniProt (385) |
NCBI (697) |
Meta (0) |
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RP15 (20) |
RP35 (59) |
RP55 (173) |
RP75 (266) |
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Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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Curation and family details
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Curation
Seed source: | ECOD:EUF06676 |
Previous IDs: | none |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
El-Gebali S |
Number in seed: | 2 |
Number in full: | 242 |
Average length of the domain: | 85.60 aa |
Average identity of full alignment: | 73 % |
Average coverage of the sequence by the domain: | 7.37 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 88 | ||||||||||||
Family (HMM) version: | 2 | ||||||||||||
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Species distribution
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Structures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the GlcNAc-1_reg domain has been found. There are 1 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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