Q9Y5P6 · GMPPB_HUMAN

  • Protein
    Mannose-1-phosphate guanylyltransferase catalytic subunit beta
  • Gene
    GMPPB
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Catalytic subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552).
Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids (PubMed:33986552).
Can catalyze the reverse reaction in vitro (PubMed:33986552).
Together with GMPPA regulates GDP-alpha-D-mannose levels (PubMed:33986552).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

Note: Coordinates binding with substrate and required for enzymatic activity.

Activity regulation

Enzyme activity is reduced by incorporation into the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552).
Allosterically inhibited, when part of the GMPPA-GMPPB complex, by GDP-alpha-D-mannose binding to GMPPA (PubMed:33986552).

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
11.45 μMmannose-1-phosphate37
12.13 μMGTP37
25.22 μMGDP-mannose37
kcat is 23.71 sec-1 with mannose-1-phosphate as substrate (PubMed:33986552).
kcat is 21.48 sec-1 with GTP as substrate (PubMed:33986552).
kcat is 10.53 sec-1 with GDP-mannose as substrate (PubMed:33986552).

Pathway

Nucleotide-sugar biosynthesis; GDP-alpha-D-mannose biosynthesis; GDP-alpha-D-mannose from alpha-D-mannose 1-phosphate (GTP route): step 1/1.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site110GDP-alpha-D-mannose (UniProtKB | ChEBI)
Binding site110Mg2+ (UniProtKB | ChEBI)
Active site162
Binding site218GDP-alpha-D-mannose (UniProtKB | ChEBI)
Binding site218Mg2+ (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular ComponentGDP-mannose pyrophosphorylase complex
Molecular FunctionGTP binding
Molecular Functionmannose-1-phosphate guanylyltransferase (GTP) activity
Biological ProcessGDP-mannose biosynthetic process
Biological ProcessGDP-mannose metabolic process
Biological Processprotein glycosylation

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Mannose-1-phosphate guanylyltransferase catalytic subunit beta
  • EC number
  • Alternative names
    • GDP-mannose pyrophosphorylase B
    • GTP-mannose-1-phosphate guanylyltransferase beta

Gene names

    • Name
      GMPPB

Organism names

  • Taxonomic identifier
  • Organism
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q9Y5P6
  • Secondary accessions
    • A8K6N5
    • Q9H7U3

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Involvement in disease

Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A14 (MDDGA14)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An autosomal recessive disorder characterized by congenital muscular dystrophy associated with brain anomalies, eye malformations, and profound intellectual disability. The disorder includes a severe form designated as Walker-Warburg syndrome and a less severe phenotype known as muscle-eye-brain disease. MDDGA14 features include increased muscle tone, microcephaly, cleft palate, feeding difficulties, severe muscle weakness, sensorineural hearing loss, cerebellar hypoplasia, ataxia, and retinal dysfunction.
  • See also
    MIM:615350
Natural variants in MDDGA14
Variant IDPosition(s)ChangeDescription
VAR_070148334D>Nin MDDGA14; causes protein aggregation; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs397509422

Muscular dystrophy-dystroglycanopathy congenital with impaired intellectual development B14 (MDDGB14)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A congenital muscular dystrophy characterized by severe muscle weakness apparent in infancy and intellectual disability. Some patients may have additional features, such as microcephaly, cardiac dysfunction, seizures, or cerebellar hypoplasia.
  • See also
    MIM:615351
Natural variants in MDDGB14
Variant IDPosition(s)ChangeDescription
VAR_07014432P>Lin MDDGB14; causes protein aggregation; reduces catalytic activity; fails to rescue phenotype when expressed in a zebrafish disease model; dbSNP:rs397509426
VAR_070145185R>Cin MDDGB14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; dbSNP:rs397509425
VAR_070146287R>Qin MDDGB14 and MDDGC14; dbSNP:rs202160208

Muscular dystrophy-dystroglycanopathy limb-girdle C14 (MDDGC14)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An autosomal recessive form of muscular dystrophy characterized by mild proximal muscle weakness with onset in early childhood. Some patients may have additional features, such as mild intellectual disability or seizures.
  • See also
    MIM:615352
Natural variants in MDDGC14
Variant IDPosition(s)ChangeDescription
VAR_07014222P>Sin MDDGC14; causes protein aggregation; reduces catalytic activity; dbSNP:rs397509424
VAR_07014327D>Hin MDDGC14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; reduces catalytic activity; dbSNP:rs142336618
VAR_07976132P>Sin MDDGC14
VAR_079762132S>Cin MDDGC14; dbSNP:rs145535498
VAR_079763219I>Tin MDDGC14; reduces catalytic activity; dbSNP:rs761714818
VAR_079764241P>Sin MDDGC14
VAR_079765254V>Min MDDGC14; dbSNP:rs875989850
VAR_070146287R>Qin MDDGB14 and MDDGC14; dbSNP:rs202160208
VAR_079766287R>Win MDDGC14; dbSNP:rs142908436
VAR_079767293R>Win MDDGC14; slight reduction in protein abundance; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs756682220
VAR_079768318V>Ain MDDGC14; dbSNP:rs559784211
VAR_079769322N>Kin MDDGC14; no change in protein abundance; dbSNP:rs781114909
VAR_070147330V>Iin MDDGC14; causes protein aggregation; dbSNP:rs199922550
VAR_079770340G>Rin MDDGC14; slight reduction in protein abundance; shows an increased propensity to form punctate aggregates; dbSNP:rs1064796834
VAR_079771357R>Hin MDDGC14; no change in protein abundance; shows an increased propensity to form punctate aggregates; reduces interaction with GMPPA but not with GMPPB; dbSNP:rs771861177

Features

Showing features for natural variant, mutagenesis.

TypeIDPosition(s)Description
Natural variantVAR_07014222in MDDGC14; causes protein aggregation; reduces catalytic activity; dbSNP:rs397509424
Natural variantVAR_07014327in MDDGC14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; reduces catalytic activity; dbSNP:rs142336618
Natural variantVAR_07014432in MDDGB14; causes protein aggregation; reduces catalytic activity; fails to rescue phenotype when expressed in a zebrafish disease model; dbSNP:rs397509426
Natural variantVAR_07976132in MDDGC14
Natural variantVAR_035372126in dbSNP:rs34345884
Natural variantVAR_079762132in MDDGC14; dbSNP:rs145535498
Natural variantVAR_035373184in dbSNP:rs1466685
Natural variantVAR_070145185in MDDGB14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; dbSNP:rs397509425
Mutagenesis193Reduces enzymatic activity.
Mutagenesis218Reduces GDP-alpha-D-mannose binding affinity and inhibits catalytic activity but does not affect assembly of GMPPA-GMPPB complex. Does not rescue the knockdown phenotype in a zebrafish disease model.
Mutagenesis218Abrogates enzyme activity.
Natural variantVAR_079763219in MDDGC14; reduces catalytic activity; dbSNP:rs761714818
Natural variantVAR_079764241in MDDGC14
Natural variantVAR_079765254in MDDGC14; dbSNP:rs875989850
Mutagenesis266Reduces interaction with GMPPB but not with GMPPA.
Natural variantVAR_070146287in MDDGB14 and MDDGC14; dbSNP:rs202160208
Natural variantVAR_079766287in MDDGC14; dbSNP:rs142908436
Mutagenesis287Disrupts interaction with other GMPPB molecules but not with GMPPA.
Natural variantVAR_079767293in MDDGC14; slight reduction in protein abundance; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs756682220
Mutagenesis303Reduces interaction with GMPPB but not with GMPPA.
Natural variantVAR_079768318in MDDGC14; dbSNP:rs559784211
Natural variantVAR_079769322in MDDGC14; no change in protein abundance; dbSNP:rs781114909
Natural variantVAR_070147330in MDDGC14; causes protein aggregation; dbSNP:rs199922550
Natural variantVAR_070148334in MDDGA14; causes protein aggregation; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs397509422
Mutagenesis335Disrupted interaction with GMPPA and other GMPPB molecules.
Natural variantVAR_079770340in MDDGC14; slight reduction in protein abundance; shows an increased propensity to form punctate aggregates; dbSNP:rs1064796834
Mutagenesis344-347Does not disrupt the interaction with GMPPA or other GMPPB molecules.
Natural variantVAR_079771357in MDDGC14; no change in protein abundance; shows an increased propensity to form punctate aggregates; reduces interaction with GMPPA but not with GMPPB; dbSNP:rs771861177
Mutagenesis358-360Reduced efficiency of allosteric inhibition by GMPPA but interaction with GMPPA or other GMPPB molecules is not disrupted.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 480 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00003071621-360Mannose-1-phosphate guanylyltransferase catalytic subunit beta

Proteomic databases

PTM databases

Expression

Tissue specificity

Isoform 1

Ubiquitously expressed, including in brain and skeletal muscle.

Isoform 2

Weakly expressed with highest expression in skeletal muscle, brain and gonads.

Developmental stage

Isoform 2

Higher expression levels in fetal skeletal muscle and brain than in adult.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Component of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex composed of 4 GMPPA subunits and 8 GMPPB subunits; the complex is organized into three layers, a central layer made up of 2 GMPPA dimers sandwiched between two layers each made up of 2 GMPPB dimers (PubMed:33986552).
GMPPB catalytic activity is reduced when part of the complex and binding of GDP-alpha-D-Mannose by GMPPA induces allosteric feedback inhibition of GMPPB (PubMed:33986552).

Binary interactions

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region2-222Substrate-binding domain
Region245-360Hexapeptide repeat domain

Domain

The N-terminal substrate-binding domain adopts a Rossman-like fold and has a binding pocket for GTP or GDP-alpha-D-mannose (PubMed:33986552).
Substrate binding is coordinated by an Mg2+ ion (PubMed:33986552).
The C-terminal domain consists of a series of tandem hexapeptide repeats that adopt a beta-helix conformation (PubMed:33986552).
The beta-helix forms several protein interaction surfaces involved in assembly of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex (PubMed:33986552).

Sequence similarities

Belongs to the transferase hexapeptide repeat family.

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q9Y5P6-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    360
  • Mass (Da)
    39,834
  • Last updated
    2007-10-23 v2
  • Checksum
    8212C77BBB2EF960
MKALILVGGYGTRLRPLTLSTPKPLVDFCNKPILLHQVEALAAAGVDHVILAVSYMSQVLEKEMKAQEQRLGIRISMSHEEEPLGTAGPLALARDLLSETADPFFVLNSDVICDFPFQAMVQFHRHHGQEGSILVTKVEEPSKYGVVVCEADTGRIHRFVEKPQVFVSNKINAGMYILSPAVLQRIQLQPTSIEKEVFPIMAKEGQLYAMELQGFWMDIGQPKDFLTGMCLFLQSLRQKQPERLCSGPGIVGNVLVDPSARIGQNCSIGPNVSLGPGVVVEDGVCIRRCTVLRDARIRSHSWLESCIVGWRCRVGQWVRMENVTVLGEDVIVNDELYLNGASVLPHKSIGESVPEPRIIM

Q9Y5P6-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 317-317: W → WVSLWAGLGGERGGECACLPDKAYPLLE

Computationally mapped potential isoform sequences

There are 4 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A7I2YQI5A0A7I2YQI5_HUMANGMPPB396
A0A7I2V2Y5A0A7I2V2Y5_HUMANGMPPB238
A0A7I2V4B5A0A7I2V4B5_HUMANGMPPB255
A0A7I2V691A0A7I2V691_HUMANGMPPB156

Features

Showing features for alternative sequence.

TypeIDPosition(s)Description
Alternative sequenceVSP_028619317in isoform 2

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF135421
EMBL· GenBank· DDBJ
AAD38516.1
EMBL· GenBank· DDBJ
mRNA
AK024319
EMBL· GenBank· DDBJ
BAB14882.1
EMBL· GenBank· DDBJ
mRNA
AK291700
EMBL· GenBank· DDBJ
BAF84389.1
EMBL· GenBank· DDBJ
mRNA
AC099668
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC001141
EMBL· GenBank· DDBJ
AAH01141.1
EMBL· GenBank· DDBJ
mRNA
BC008033
EMBL· GenBank· DDBJ
AAH08033.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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