Mannose-1-phosphate guanyltransferase beta (GMPPB)

The protein contains 360 amino acids for an estimated molecular weight of 39834 Da.

 

Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids. (updated: Jan. 31, 2018)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 0%
Model score: 87

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VariantDescription
MDDGC14
MDDGC14
MDDGB14
dbSNP:rs34345884
dbSNP:rs1466685
MDDGB14
MDDGB14 and MDDGC14
MDDGC14
MDDGA14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14
MDDGC14

The reference OMIM entry for this protein is 615320

Gdp-mannose pyrophosphorylase b; gmppb
Gdp-mannose pyrophosphorylase, beta subunit
Gmpp-beta

DESCRIPTION

The GMPPB gene encodes the beta subunit of an essential enzyme, GDP-mannose pyrophosphorylase (EC 2.7.7.13), that catalyzes the conversion of mannose-1-phosphate and GTP to inorganic diphosphate and GDP-mannose, a major mannosyl donor for mannose-containing polymers (Ning and Elbein, 2000). GDP-mannose is required in 4 glycosylation pathways, including O-mannosylation of membrane and secretory glycoproteins, such as alpha-dystroglycan (DAG1; 128239) (summary by Carss et al., 2013).

CLONING

By searching databases for sequences similar to porcine Gmpp-beta, Ning and Elbein (2000) identified human GMPPB, as well as GMPPB orthologs in several lower species, including nematode, yeast, and plants. The 360-amino acid human protein shares 96% identity with porcine Gmpp-beta. The GMPPB protein contains 2 main functional domains: a nucleotidyl transferase domain and a bacterial transferase hexapeptide domain. Carss et al. (2013) determined that the GMPPB gene is transcribed as 2 isoforms in human tissues. The longer isoform (GenBank GENBANK NM_021971.1) was strongly expressed in all fetal and adult tissues tested, including brain and skeletal muscle, whereas the shorter isoform (GenBank GENBANK NM_013334.2) was weakly expressed in the tissues tested. There appeared to be no developmental difference in the expression of the 2 isoforms. By sequencing clones obtained from a size-fractionated adult brain cDNA library, Nagase et al. (2001) obtained a clone, which they designated KIAA1851, containing 2 coding regions separated by 2.4 kb. They identified the upstream coding region as that of GMPPB and suggested that KIAA1851 may represent a read-through transcript of the GMPPB gene. Hartz (2014) determined that the KIAA1851 sequence (GenBank GENBANK AB058754) includes the sequence of AMIGO3 (615691) (GenBank GENBANK AY237003) in addition to that of GMPPB.

GENE STRUCTURE

The coding DNA sequence of one isoform of the GMPPB gene (GenBank GENBANK NM_021971.1) contains 10 exons, whereas that of another isoform (GenBank GENBANK NM_013334.2) contains 8 exons (Carss et al., 2013).

MAPPING

Hartz (2013) mapped the GMPPB gene to chromosome 3p21.31 based on an alignment of the GMPPB sequence (GenBank GENBANK AB058754) with the genomic sequence (GRCh37).

GENE FUNCTION

Ning and Elbein (2000) found that recombinant porcine Gmpp-beta catalyzed bidirectional conversion of mannose-1-phosphate and GTP to inorganic diphosphate and GDP-mannose. Compared with purified pig liver Gmpp, which was a dimer of alpha and beta subunits, recombinant Gmpp-beta showed much lower activity as a GDP-glucose pyrophosphorylase (EC 2.7.7.34). Divalent cations, particularly Mn(2+), enhanced the Gmpp-beta reaction, whereas Mg(2+) was the preferred cofactor for the endogenous dimeric enzyme.

MOLECULAR GENETICS

By exome sequencing combined with Sanger sequencing of 8 unrelated patients with various forms of congenital muscular dystrophy, Carss et al. (2013) identified 8 different mutations in the GMPPB gene (GenBank GENBANK NM_02197.1) (615320.0001-615320.0008). All mutations occurred in homozygous or compound heterozygous state and segregated with the disorder in the families in whom parental DNA was available. All affected individuals had at least 1 mutation affecting the highly conserved nucleotidyl transferase domain. The phenotype was highly variable. The most severely affected patient had muscle weakness at birth ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 615320 was added.

Feb. 24, 2016: Protein entry updated
Automatic update: model status changed