Q9Y5P6 · GMPPB_HUMAN
- ProteinMannose-1-phosphate guanylyltransferase catalytic subunit beta
- GeneGMPPB
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids360 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
- alpha-D-mannose 1-phosphate + GTP + H+ = diphosphate + GDP-alpha-D-mannoseThis reaction proceeds in the forward and the backward directions.
Cofactor
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).
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 μM | mannose-1-phosphate | 37 | ||||
12.13 μM | GTP | 37 | ||||
25.22 μM | GDP-mannose | 37 |
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).
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.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | GDP-mannose pyrophosphorylase complex | |
Molecular Function | GTP binding | |
Molecular Function | mannose-1-phosphate guanylyltransferase (GTP) activity | |
Biological Process | GDP-mannose biosynthetic process | |
Biological Process | GDP-mannose metabolic process | |
Biological Process | protein glycosylation |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMannose-1-phosphate guanylyltransferase catalytic subunit beta
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9Y5P6
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A14 (MDDGA14)
- Note
- DescriptionAn 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 alsoMIM:615350
Natural variants in MDDGA14
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070148 | 334 | D>N | in 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
- DescriptionA 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 alsoMIM:615351
Natural variants in MDDGB14
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070144 | 32 | P>L | in MDDGB14; causes protein aggregation; reduces catalytic activity; fails to rescue phenotype when expressed in a zebrafish disease model; dbSNP:rs397509426 | |
VAR_070145 | 185 | R>C | in MDDGB14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; dbSNP:rs397509425 | |
VAR_070146 | 287 | R>Q | in MDDGB14 and MDDGC14; dbSNP:rs202160208 |
Muscular dystrophy-dystroglycanopathy limb-girdle C14 (MDDGC14)
- Note
- DescriptionAn 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 alsoMIM:615352
Natural variants in MDDGC14
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070142 | 22 | P>S | in MDDGC14; causes protein aggregation; reduces catalytic activity; dbSNP:rs397509424 | |
VAR_070143 | 27 | D>H | in MDDGC14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; reduces catalytic activity; dbSNP:rs142336618 | |
VAR_079761 | 32 | P>S | in MDDGC14 | |
VAR_079762 | 132 | S>C | in MDDGC14; dbSNP:rs145535498 | |
VAR_079763 | 219 | I>T | in MDDGC14; reduces catalytic activity; dbSNP:rs761714818 | |
VAR_079764 | 241 | P>S | in MDDGC14 | |
VAR_079765 | 254 | V>M | in MDDGC14; dbSNP:rs875989850 | |
VAR_070146 | 287 | R>Q | in MDDGB14 and MDDGC14; dbSNP:rs202160208 | |
VAR_079766 | 287 | R>W | in MDDGC14; dbSNP:rs142908436 | |
VAR_079767 | 293 | R>W | in MDDGC14; slight reduction in protein abundance; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs756682220 | |
VAR_079768 | 318 | V>A | in MDDGC14; dbSNP:rs559784211 | |
VAR_079769 | 322 | N>K | in MDDGC14; no change in protein abundance; dbSNP:rs781114909 | |
VAR_070147 | 330 | V>I | in MDDGC14; causes protein aggregation; dbSNP:rs199922550 | |
VAR_079770 | 340 | G>R | in MDDGC14; slight reduction in protein abundance; shows an increased propensity to form punctate aggregates; dbSNP:rs1064796834 | |
VAR_079771 | 357 | R>H | in 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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_070142 | 22 | in MDDGC14; causes protein aggregation; reduces catalytic activity; dbSNP:rs397509424 | |||
Sequence: P → S | ||||||
Natural variant | VAR_070143 | 27 | in MDDGC14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; reduces catalytic activity; dbSNP:rs142336618 | |||
Sequence: D → H | ||||||
Natural variant | VAR_070144 | 32 | in MDDGB14; causes protein aggregation; reduces catalytic activity; fails to rescue phenotype when expressed in a zebrafish disease model; dbSNP:rs397509426 | |||
Sequence: P → L | ||||||
Natural variant | VAR_079761 | 32 | in MDDGC14 | |||
Sequence: P → S | ||||||
Natural variant | VAR_035372 | 126 | in dbSNP:rs34345884 | |||
Sequence: H → D | ||||||
Natural variant | VAR_079762 | 132 | in MDDGC14; dbSNP:rs145535498 | |||
Sequence: S → C | ||||||
Natural variant | VAR_035373 | 184 | in dbSNP:rs1466685 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_070145 | 185 | in MDDGB14; the protein remains distributed in the cytoplasm and has no discernable changes compared to wild-type; dbSNP:rs397509425 | |||
Sequence: R → C | ||||||
Mutagenesis | 193 | Reduces enzymatic activity. | ||||
Sequence: I → T | ||||||
Mutagenesis | 218 | Reduces 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. | ||||
Sequence: D → A | ||||||
Mutagenesis | 218 | Abrogates enzyme activity. | ||||
Sequence: D → Q | ||||||
Natural variant | VAR_079763 | 219 | in MDDGC14; reduces catalytic activity; dbSNP:rs761714818 | |||
Sequence: I → T | ||||||
Natural variant | VAR_079764 | 241 | in MDDGC14 | |||
Sequence: P → S | ||||||
Natural variant | VAR_079765 | 254 | in MDDGC14; dbSNP:rs875989850 | |||
Sequence: V → M | ||||||
Mutagenesis | 266 | Reduces interaction with GMPPB but not with GMPPA. | ||||
Sequence: C → Y | ||||||
Natural variant | VAR_070146 | 287 | in MDDGB14 and MDDGC14; dbSNP:rs202160208 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_079766 | 287 | in MDDGC14; dbSNP:rs142908436 | |||
Sequence: R → W | ||||||
Mutagenesis | 287 | Disrupts interaction with other GMPPB molecules but not with GMPPA. | ||||
Sequence: R → E | ||||||
Natural variant | VAR_079767 | 293 | in MDDGC14; slight reduction in protein abundance; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs756682220 | |||
Sequence: R → W | ||||||
Mutagenesis | 303 | Reduces interaction with GMPPB but not with GMPPA. | ||||
Sequence: L → F | ||||||
Natural variant | VAR_079768 | 318 | in MDDGC14; dbSNP:rs559784211 | |||
Sequence: V → A | ||||||
Natural variant | VAR_079769 | 322 | in MDDGC14; no change in protein abundance; dbSNP:rs781114909 | |||
Sequence: N → K | ||||||
Natural variant | VAR_070147 | 330 | in MDDGC14; causes protein aggregation; dbSNP:rs199922550 | |||
Sequence: V → I | ||||||
Natural variant | VAR_070148 | 334 | in MDDGA14; causes protein aggregation; reduces interaction with GMPPB but not with GMPPA; dbSNP:rs397509422 | |||
Sequence: D → N | ||||||
Mutagenesis | 335 | Disrupted interaction with GMPPA and other GMPPB molecules. | ||||
Sequence: E → R | ||||||
Natural variant | VAR_079770 | 340 | in MDDGC14; slight reduction in protein abundance; shows an increased propensity to form punctate aggregates; dbSNP:rs1064796834 | |||
Sequence: G → R | ||||||
Mutagenesis | 344-347 | Does not disrupt the interaction with GMPPA or other GMPPB molecules. | ||||
Sequence: LPHK → AAAA | ||||||
Natural variant | VAR_079771 | 357 | in MDDGC14; no change in protein abundance; shows an increased propensity to form punctate aggregates; reduces interaction with GMPPA but not with GMPPB; dbSNP:rs771861177 | |||
Sequence: R → H | ||||||
Mutagenesis | 358-360 | Reduced efficiency of allosteric inhibition by GMPPA but interaction with GMPPA or other GMPPB molecules is not disrupted. | ||||
Sequence: Missing |
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.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000307162 | 1-360 | Mannose-1-phosphate guanylyltransferase catalytic subunit beta | |||
Sequence: MKALILVGGYGTRLRPLTLSTPKPLVDFCNKPILLHQVEALAAAGVDHVILAVSYMSQVLEKEMKAQEQRLGIRISMSHEEEPLGTAGPLALARDLLSETADPFFVLNSDVICDFPFQAMVQFHRHHGQEGSILVTKVEEPSKYGVVVCEADTGRIHRFVEKPQVFVSNKINAGMYILSPAVLQRIQLQPTSIEKEVFPIMAKEGQLYAMELQGFWMDIGQPKDFLTGMCLFLQSLRQKQPERLCSGPGIVGNVLVDPSARIGQNCSIGPNVSLGPGVVVEDGVCIRRCTVLRDARIRSHSWLESCIVGWRCRVGQWVRMENVTVLGEDVIVNDELYLNGASVLPHKSIGESVPEPRIIM |
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).
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
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9Y5P6 | DPPA4 Q7L190 | 3 | EBI-750945, EBI-710457 | |
BINARY | Q9Y5P6 | GLYCTK Q8IVS8 | 5 | EBI-750945, EBI-748515 | |
BINARY | Q9Y5P6 | GMPPA Q96IJ6 | 10 | EBI-750945, EBI-750953 | |
BINARY | Q9Y5P6 | POLR1C O15160 | 3 | EBI-750945, EBI-1055079 | |
BINARY | Q9Y5P6 | TXNDC5 Q86UY0 | 3 | EBI-750945, EBI-2825190 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 2-222 | Substrate-binding domain | ||||
Sequence: KALILVGGYGTRLRPLTLSTPKPLVDFCNKPILLHQVEALAAAGVDHVILAVSYMSQVLEKEMKAQEQRLGIRISMSHEEEPLGTAGPLALARDLLSETADPFFVLNSDVICDFPFQAMVQFHRHHGQEGSILVTKVEEPSKYGVVVCEADTGRIHRFVEKPQVFVSNKINAGMYILSPAVLQRIQLQPTSIEKEVFPIMAKEGQLYAMELQGFWMDIGQP | ||||||
Region | 245-360 | Hexapeptide repeat domain | ||||
Sequence: CSGPGIVGNVLVDPSARIGQNCSIGPNVSLGPGVVVEDGVCIRRCTVLRDARIRSHSWLESCIVGWRCRVGQWVRMENVTVLGEDVIVNDELYLNGASVLPHKSIGESVPEPRIIM |
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).
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).
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
- Sequence statusComplete
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.
- Name1
- Length360
- Mass (Da)39,834
- Last updated2007-10-23 v2
- Checksum8212C77BBB2EF960
Q9Y5P6-2
- Name2
- Differences from canonical
- 317-317: W → WVSLWAGLGGERGGECACLPDKAYPLLE
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7I2YQI5 | A0A7I2YQI5_HUMAN | GMPPB | 396 | ||
A0A7I2V2Y5 | A0A7I2V2Y5_HUMAN | GMPPB | 238 | ||
A0A7I2V4B5 | A0A7I2V4B5_HUMAN | GMPPB | 255 | ||
A0A7I2V691 | A0A7I2V691_HUMAN | GMPPB | 156 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_028619 | 317 | in isoform 2 | |||
Sequence: W → WVSLWAGLGGERGGECACLPDKAYPLLE |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |