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1  structure 113  species 0  interactions 136  sequences 21  architectures

Family: GlcNAc-1_reg (PF18440)

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
Identifiers
Symbol GNPTAB
Alt. symbols GNPTA
Entrez 79158
HUGO 29670
OMIM 607840
RefSeq NM_024312
UniProt Q3T906
Other data
Locus Chr. 12 q23.3
N-acetylglucosamine-1-phosphate transferase, gamma subunit
Identifiers
Symbol GNPTG
Alt. symbols GNPTAG
Entrez 84572
HUGO 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 beta (β), and two gamma (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 cells, 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 indicator whether a hydrolase should be transported to the lysosome or not. Once a hydrolase has the indication from an M6P, it can be transported to a lysosome. Surprisingly some lyosomal enzyme are only tagged at a rate of 5% or lower.

Clinical significance

It is associated with the following conditions:[1][2]

In melanocytic cells GNPTG gene expression may be regulated by MITF.[3]

References

  1. ^ Online Mendelian Inheritance in Man (OMIM) MUCOLIPIDOSIS II ALPHA/BETA -252500
  2. ^ Online Mendelian Inheritance in Man (OMIM) MUCOLIPIDOSIS III GAMMA -252605
  3. ^ 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


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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

  1. 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

  2. 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.

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Domain organisation

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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_RBD

Alignments

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(2)
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(201)
NCBI
(521)
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RP15
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RP35
(46)
RP55
(105)
RP75
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  Seed
(2)
Full
(136)
Representative proteomes UniProt
(201)
NCBI
(521)
Meta
(0)
RP15
(21)
RP35
(46)
RP55
(105)
RP75
(126)
Alignment:
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  Seed
(2)
Full
(136)
Representative proteomes UniProt
(201)
NCBI
(521)
Meta
(0)
RP15
(21)
RP35
(46)
RP55
(105)
RP75
(126)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

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HMM logo

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

This family is new in this Pfam release.

Seed source: ECOD:EUF06676
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: El-Gebali S
Number in seed: 2
Number in full: 136
Average length of the domain: 85.70 aa
Average identity of full alignment: 74 %
Average coverage of the sequence by the domain: 7.55 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.4 26.4
Trusted cut-off 27.3 29.9
Noise cut-off 25.7 25.6
Model length: 88
Family (HMM) version: 1
Download: download the raw HMM for this family

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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