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Protein

Mannose-1-phosphate guanyltransferase alpha

Gene

GMPPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

May serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose.1 Publication

Caution

GMPPA is a close homolog of GMPPB, that has been shown to catalyze the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids. However, lymphocytes from AAMR patients, that exhibit very low GMPPA protein levels, have unchanged GDP-mannose pyrophosphorylase activity and higher GDP-mannose levels than those from healthy controls. Affected individuals and control subjects show similar N-glycosylation profiles, both for transferrin glycosylation and for N-glycans derived from either total serum protein or immunoglobulin G. These observations led to the hypothesis that GMPPA might serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose. Alignment of GMPPAs and GMPPBs from various species shows that GMPPAs are characterized by a 2 amino acid-insertion (residues 11-12) in a highly conserved motif that borders the catalytic pocket and binds the nucleotide substrate in homologous enzymes. This insertion might inactivate the ancestral catalytic site, converting it to an allosteric site (PubMed:24035193).1 Publication

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-446205 Synthesis of GDP-mannose

Names & Taxonomyi

Protein namesi
Recommended name:
Mannose-1-phosphate guanyltransferase alpha
Alternative name(s):
GDP-mannose pyrophosphorylase A
Short name:
GMPP-alpha
GTP-mannose-1-phosphate guanylyltransferase alpha
Gene namesi
Name:GMPPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000144591.18
HGNCiHGNC:22923 GMPPA
MIMi615495 gene
neXtProtiNX_Q96IJ6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Alacrima, achalasia, and mental retardation syndrome (AAMR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by onset of alacrima, achalasia, and mental retardation at birth or in early infancy. More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency.
See also OMIM:615510
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070203182G → D in AAMR; drastically reduced protein expression. 1 PublicationCorresponds to variant dbSNP:rs397518462EnsemblClinVar.1
Natural variantiVAR_070204334T → M in AAMR. 1 PublicationCorresponds to variant dbSNP:rs774778439Ensembl.1
Natural variantiVAR_070205334T → P in AAMR; drastically reduced protein expression. 1 PublicationCorresponds to variant dbSNP:rs397518461EnsemblClinVar.1
Natural variantiVAR_070206390R → P in AAMR; drastically reduced protein expression. 1 Publication1
Natural variantiVAR_070207401N → T in AAMR; drastically reduced protein expression. 1 Publication1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi29926
MalaCardsiGMPPA
MIMi615510 phenotype
OpenTargetsiENSG00000144591
Orphaneti869 Triple A syndrome
PharmGKBiPA134925506

Polymorphism and mutation databases

BioMutaiGMPPA
DMDMi74732065

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003278721 – 420Mannose-1-phosphate guanyltransferase alphaAdd BLAST420

Proteomic databases

EPDiQ96IJ6
MaxQBiQ96IJ6
PaxDbiQ96IJ6
PeptideAtlasiQ96IJ6
PRIDEiQ96IJ6
ProteomicsDBi76833
76834 [Q96IJ6-2]

PTM databases

iPTMnetiQ96IJ6
PhosphoSitePlusiQ96IJ6

Expressioni

Tissue specificityi

Expressed in fibroblasts (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000144591
CleanExiHS_GMPPA
ExpressionAtlasiQ96IJ6 baseline and differential
GenevisibleiQ96IJ6 HS

Organism-specific databases

HPAiHPA035512
HPA035513

Interactioni

Subunit structurei

Associates with GMPPB.By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi118967, 14 interactors
IntActiQ96IJ6, 9 interactors
MINTiQ96IJ6
STRINGi9606.ENSP00000315925

Structurei

3D structure databases

ProteinModelPortaliQ96IJ6
SMRiQ96IJ6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1460 Eukaryota
COG1208 LUCA
GeneTreeiENSGT00530000063581
HOVERGENiHBG059531
InParanoidiQ96IJ6
KOiK00966
OMAiANRHYLA
OrthoDBiEOG091G07X0
PhylomeDBiQ96IJ6
TreeFamiTF300832

Family and domain databases

Gene3Di3.90.550.10, 1 hit
InterProiView protein in InterPro
IPR001451 Hexapep
IPR018357 Hexapep_transf_CS
IPR005835 NTP_transferase_dom
IPR029044 Nucleotide-diphossugar_trans
PfamiView protein in Pfam
PF00132 Hexapep, 1 hit
PF00483 NTP_transferase, 1 hit
SUPFAMiSSF53448 SSF53448, 1 hit
PROSITEiView protein in PROSITE
PS00101 HEXAPEP_TRANSFERASES, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96IJ6-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLKAVILIGG PQKGTRFRPL SFEVPKPLFP VAGVPMIQHH IEACAQVPGM
60 70 80 90 100
QEILLIGFYQ PDEPLTQFLE AAQQEFNLPV RYLQEFAPLG TGGGLYHFRD
110 120 130 140 150
QILAGSPEAF FVLNADVCSD FPLSAMLEAH RRQRHPFLLL GTTANRTQSL
160 170 180 190 200
NYGCIVENPQ THEVLHYVEK PSTFISDIIN CGIYLFSPEA LKPLRDVFQR
210 220 230 240 250
NQQDGQLEDS PGLWPGAGTI RLEQDVFSAL AGQGQIYVHL TDGIWSQIKS
260 270 280 290 300
AGSALYASRL YLSRYQDTHP ERLAKHTPGG PWIRGNVYIH PTAKVAPSAV
310 320 330 340 350
LGPNVSIGKG VTVGEGVRLR ESIVLHGATL QEHTCVLHSI VGWGSTVGRW
360 370 380 390 400
ARVEGTPSDP NPNDPRARMD SESLFKDGKL LPAITILGCR VRIPAEVLIL
410 420
NSIVLPHKEL SRSFTNQIIL
Length:420
Mass (Da):46,291
Last modified:December 1, 2001 - v1
Checksum:i741B77ABA198D4BC
GO
Isoform 2 (identifier: Q96IJ6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     285-285: G → GTQPAPIPNLWLPPQPSEPGFLTSSPELKPQSLPLPDQIRFGIFAPRASLLLLG

Show »
Length:473
Mass (Da):52,018
Checksum:i0F283DF3FEA4C6E9
GO

Sequence cautioni

The sequence AAD38517 differs from that shown. Reason: Frameshift at position 355.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti57G → C in BAD96671 (Ref. 3) Curated1
Sequence conflicti67Q → H in BAF83360 (PubMed:14702039).Curated1
Sequence conflicti118C → Y in BAA91460 (PubMed:14702039).Curated1
Sequence conflicti339S → C in AAD38517 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04243421S → F. Corresponds to variant dbSNP:rs34218609Ensembl.1
Natural variantiVAR_042435156V → A. Corresponds to variant dbSNP:rs13396066Ensembl.1
Natural variantiVAR_070203182G → D in AAMR; drastically reduced protein expression. 1 PublicationCorresponds to variant dbSNP:rs397518462EnsemblClinVar.1
Natural variantiVAR_070204334T → M in AAMR. 1 PublicationCorresponds to variant dbSNP:rs774778439Ensembl.1
Natural variantiVAR_070205334T → P in AAMR; drastically reduced protein expression. 1 PublicationCorresponds to variant dbSNP:rs397518461EnsemblClinVar.1
Natural variantiVAR_070206390R → P in AAMR; drastically reduced protein expression. 1 Publication1
Natural variantiVAR_070207401N → T in AAMR; drastically reduced protein expression. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_032741285G → GTQPAPIPNLWLPPQPSEPG FLTSSPELKPQSLPLPDQIR FGIFAPRASLLLLG in isoform 2. Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF135422 mRNA Translation: AAD38517.1 Frameshift.
AK000999 mRNA Translation: BAA91460.1
AK022578 mRNA Translation: BAG51096.1
AK290671 mRNA Translation: BAF83360.1
AK222951 mRNA Translation: BAD96671.1
AC053503 Genomic DNA Translation: AAY15053.1
CH471063 Genomic DNA Translation: EAW70755.1
CH471063 Genomic DNA Translation: EAW70759.1
BC007456 mRNA Translation: AAH07456.1
CCDSiCCDS2441.1 [Q96IJ6-1]
RefSeqiNP_037467.2, NM_013335.3 [Q96IJ6-1]
NP_995319.1, NM_205847.2 [Q96IJ6-1]
XP_005246543.1, XM_005246486.3 [Q96IJ6-1]
XP_016859398.1, XM_017003909.1 [Q96IJ6-2]
XP_016859399.1, XM_017003910.1 [Q96IJ6-2]
XP_016859400.1, XM_017003911.1 [Q96IJ6-2]
UniGeneiHs.27059

Genome annotation databases

EnsembliENST00000313597; ENSP00000315925; ENSG00000144591 [Q96IJ6-1]
ENST00000341142; ENSP00000340760; ENSG00000144591 [Q96IJ6-1]
ENST00000358215; ENSP00000350949; ENSG00000144591 [Q96IJ6-1]
ENST00000373908; ENSP00000363016; ENSG00000144591 [Q96IJ6-1]
ENST00000373917; ENSP00000363027; ENSG00000144591 [Q96IJ6-2]
GeneIDi29926
KEGGihsa:29926
UCSCiuc002vlr.4 human [Q96IJ6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGMPPA_HUMAN
AccessioniPrimary (citable) accession number: Q96IJ6
Secondary accession number(s): A6NJ74
, A8K3Q6, B3KMT4, Q53GI0, Q9NWC3, Q9Y5P5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: December 1, 2001
Last modified: July 18, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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