Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q96IJ6 (GMPPA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Mannose-1-phosphate guanyltransferase alpha
Alternative name(s):
GDP-mannose pyrophosphorylase A
Short name=GMPP-alpha
GTP-mannose-1-phosphate guanylyltransferase alpha
Gene names
Name:GMPPA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length420 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose. Ref.8

Subunit structure

Associates with GMPPB By similarity.

Subcellular location

Cytoplasm. Note: Myc-tagged GMPPA shows a diffuse cytoplasmic and nuclear pattern in transfected COS-7 cells. Ref.8

Tissue specificity

Expressed in fibroblasts (at protein level). Ref.8

Involvement in disease

Alacrima, achalasia, and mental retardation syndrome (AAMR) [MIM:615510]: An 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the transferase hexapeptide repeat family.

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 (Ref.8).

Sequence caution

The sequence AAD38517.1 differs from that shown. Reason: Frameshift at position 355.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96IJ6-1)

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.
Isoform 2 (identifier: Q96IJ6-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 420420Mannose-1-phosphate guanyltransferase alpha
PRO_0000327872

Natural variations

Alternative sequence2851G → GTQPAPIPNLWLPPQPSEPG FLTSSPELKPQSLPLPDQIR FGIFAPRASLLLLG in isoform 2.
VSP_032741
Natural variant211S → F.
Corresponds to variant rs34218609 [ dbSNP | Ensembl ].
VAR_042434
Natural variant1561V → A.
Corresponds to variant rs13396066 [ dbSNP | Ensembl ].
VAR_042435
Natural variant1821G → D in AAMR; drastically reduced protein expression in fibroblasts and altered subcellular location; no effect on transferrin N-glycosylation profile. Ref.8
VAR_070203
Natural variant3341T → M in AAMR; no effect on transferrin N-glycosylation profile. Ref.8
VAR_070204
Natural variant3341T → P in AAMR; drastically reduced protein expression in fibroblasts, altered subcellular location and drastically increased GDP-mannose levels in lymphoblast; no effect on GDP-mannose pyrophosphorylase activity in lymphoblasts, nor on transferrin N-glycosylation profile. Ref.8
VAR_070205
Natural variant3901R → P in AAMR; drastically reduced protein expression in fibroblasts; no effect on transferrin N-glycosylation profile. Ref.8
VAR_070206
Natural variant4011N → T in AAMR; drastically reduced protein expression in fibroblasts and drastically increased GDP-mannose levels in lymphoblast; no effect on GDP-mannose pyrophosphorylase activity in lymphoblasts, nor on transferrin, IgG and total serum protein N-glycosylation profiles. Ref.8
VAR_070207

Experimental info

Sequence conflict571G → C in BAD96671. Ref.3
Sequence conflict671Q → H in BAF83360. Ref.2
Sequence conflict1181C → Y in BAA91460. Ref.2
Sequence conflict3391S → C in AAD38517. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: 741B77ABA198D4BC

FASTA42046,291
        10         20         30         40         50         60 
MLKAVILIGG PQKGTRFRPL SFEVPKPLFP VAGVPMIQHH IEACAQVPGM QEILLIGFYQ 

        70         80         90        100        110        120 
PDEPLTQFLE AAQQEFNLPV RYLQEFAPLG TGGGLYHFRD QILAGSPEAF FVLNADVCSD 

       130        140        150        160        170        180 
FPLSAMLEAH RRQRHPFLLL GTTANRTQSL NYGCIVENPQ THEVLHYVEK PSTFISDIIN 

       190        200        210        220        230        240 
CGIYLFSPEA LKPLRDVFQR NQQDGQLEDS PGLWPGAGTI RLEQDVFSAL AGQGQIYVHL 

       250        260        270        280        290        300 
TDGIWSQIKS AGSALYASRL YLSRYQDTHP ERLAKHTPGG PWIRGNVYIH PTAKVAPSAV 

       310        320        330        340        350        360 
LGPNVSIGKG VTVGEGVRLR ESIVLHGATL QEHTCVLHSI VGWGSTVGRW ARVEGTPSDP 

       370        380        390        400        410        420 
NPNDPRARMD SESLFKDGKL LPAITILGCR VRIPAEVLIL NSIVLPHKEL SRSFTNQIIL 

« Hide

Isoform 2 [UniParc].

Checksum: 0F283DF3FEA4C6E9
Show »

FASTA47352,018

References

« Hide 'large scale' references
[1]"Human homolog of GDP-mannose pyrophosphorylase."
Matthijs G., Schollen E., Dierickx D.
Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Embryo.
[3]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Kidney.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph.
[7]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"Mutations in GMPPA cause a glycosylation disorder characterized by intellectual disability and autonomic dysfunction."
Koehler K., Malik M., Mahmood S., Giesselmann S., Beetz C., Hennings J.C., Huebner A.K., Grahn A., Reunert J., Nurnberg G., Thiele H., Altmuller J., Nurnberg P., Mumtaz R., Babovic-Vuksanovic D., Basel-Vanagaite L., Borck G., Bramswig J. expand/collapse author list , Muhlenberg R., Sarda P., Sikiric A., Anyane-Yeboa K., Zeharia A., Ahmad A., Coubes C., Wada Y., Marquardt T., Vanderschaeghe D., Van Schaftingen E., Kurth I., Huebner A., Hubner C.A.
Am. J. Hum. Genet. 93:727-734(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AAMR ASP-182; MET-334; PRO-334; PRO-390 AND THR-401, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_037467.2. NM_013335.3.
NP_995319.1. NM_205847.2.
XP_005246543.1. XM_005246486.1.
UniGeneHs.27059.

3D structure databases

ProteinModelPortalQ96IJ6.
SMRQ96IJ6. Positions 4-416.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118967. 7 interactions.
IntActQ96IJ6. 3 interactions.
MINTMINT-3053969.
STRING9606.ENSP00000315925.

PTM databases

PhosphoSiteQ96IJ6.

Polymorphism databases

DMDM74732065.

Proteomic databases

PaxDbQ96IJ6.
PRIDEQ96IJ6.

Protocols and materials databases

DNASU29926.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000313597; ENSP00000315925; ENSG00000144591. [Q96IJ6-1]
ENST00000341142; ENSP00000340760; ENSG00000144591. [Q96IJ6-1]
ENST00000358215; ENSP00000350949; ENSG00000144591. [Q96IJ6-1]
ENST00000373908; ENSP00000363016; ENSG00000144591. [Q96IJ6-1]
ENST00000373917; ENSP00000363027; ENSG00000144591. [Q96IJ6-2]
GeneID29926.
KEGGhsa:29926.
UCSCuc002vlr.3. human. [Q96IJ6-1]

Organism-specific databases

CTD29926.
GeneCardsGC02P220327.
HGNCHGNC:22923. GMPPA.
HPAHPA035513.
MIM615495. gene.
615510. phenotype.
neXtProtNX_Q96IJ6.
Orphanet869. Triple A syndrome.
PharmGKBPA134925506.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1208.
HOVERGENHBG059531.
KOK00966.
OMAGPRIRGN.
OrthoDBEOG7WHH9C.
PhylomeDBQ96IJ6.
TreeFamTF300832.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.

Gene expression databases

ArrayExpressQ96IJ6.
BgeeQ96IJ6.
CleanExHS_GMPPA.
GenevestigatorQ96IJ6.

Family and domain databases

InterProIPR001451. Hexapep_transf.
IPR018357. Hexapep_transf_CS.
IPR005835. NTP_transferase.
[Graphical view]
PfamPF00132. Hexapep. 1 hit.
PF00483. NTP_transferase. 1 hit.
[Graphical view]
PROSITEPS00101. HEXAPEP_TRANSFERASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi29926.
NextBio52545.
PROQ96IJ6.
SOURCESearch...

Entry information

Entry nameGMPPA_HUMAN
AccessionPrimary (citable) accession number: Q96IJ6
Secondary accession number(s): A6NJ74 expand/collapse secondary AC list , A8K3Q6, B3KMT4, Q53GI0, Q9NWC3, Q9Y5P5
Entry history
Integrated into UniProtKB/Swiss-Prot: April 8, 2008
Last sequence update: December 1, 2001
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM