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Protein

Glycophorin-A

Gene

GYPA

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

Functioni

Glycophorin A is the major intrinsic membrane protein of the erythrocyte. The N-terminal glycosylated segment, which lies outside the erythrocyte membrane, has MN blood group receptors. Appears to be important for the function of SLC4A1 and is required for high activity of SLC4A1. May be involved in translocation of SLC4A1 to the plasma membrane. Is a receptor for influenza virus. Is a receptor for Plasmodium falciparum erythrocyte-binding antigen 175 (EBA-175); binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans. Appears to be a receptor for Hepatitis A virus (HAV).6 Publications

Miscellaneous

Involved in several unequal homologous recombinations or gene conversion events, predominantly with GYPB and more rarely with GYPE. The resulting fusion proteins are observed in different phenotypes and encode low incidence bloodgroup antigens.

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionBlood group antigen, Host cell receptor for virus entry, Receptor
Biological processHost-virus interaction
LigandSialic acid

Enzyme and pathway databases

ReactomeiR-HSA-202733 Cell surface interactions at the vascular wall

Names & Taxonomyi

Protein namesi
Recommended name:
Glycophorin-A
Alternative name(s):
MN sialoglycoprotein
PAS-2
Sialoglycoprotein alpha
CD_antigen: CD235a
Gene namesi
Name:GYPA
Synonyms:GPA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000170180.19
HGNCiHGNC:4702 GYPA
MIMi111300 gene+phenotype
neXtProtiNX_P02724

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 91ExtracellularAdd BLAST72
Transmembranei92 – 114HelicalAdd BLAST23
Topological domaini115 – 150CytoplasmicAdd BLAST36

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi87F → C: Diminishes dimerization. 1 Publication1
Mutagenesisi88S → C: Diminishes dimerization. 1 Publication1
Mutagenesisi90P → C: Diminishes dimerization. 1 Publication1
Mutagenesisi91E → C: Diminishes dimerization. 1 Publication1
Mutagenesisi94L → I: Diminishes dimerization. 1 Publication1
Mutagenesisi95I → A: Diminishes dimerization. 1 Publication1
Mutagenesisi98G → L: Diminishes dimerization. 1 Publication1
Mutagenesisi102G → L: Abolishes dimerization. 1 Publication1

Organism-specific databases

DisGeNETi2993
MalaCardsiGYPA
MIMi111300 gene+phenotype
611162 phenotype
OpenTargetsiENSG00000170180
PharmGKBiPA29080

Chemistry databases

ChEMBLiCHEMBL5806

Polymorphism and mutation databases

BioMutaiGYPA
DMDMi259016238

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 191 PublicationAdd BLAST19
ChainiPRO_000001213420 – 150Glycophorin-AAdd BLAST131

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi21O-linked (GalNAc...) serine2 Publications1
Glycosylationi22O-linked (GalNAc...) threonine2 Publications1
Glycosylationi23O-linked (GalNAc...) threonine2 Publications1
Glycosylationi29O-linked (GalNAc...) threonine2 Publications1
Glycosylationi30O-linked (GalNAc...) serine2 Publications1
Glycosylationi31O-linked (GalNAc...) threonine2 Publications1
Glycosylationi32O-linked (GalNAc...) serine2 Publications1
Glycosylationi36O-linked (GalNAc...) threonine1 Publication1
Glycosylationi38O-linked (GalNAc...) serine1 Publication1
Glycosylationi41O-linked (GalNAc...) serine2 Publications1
Glycosylationi44O-linked (GalNAc...) threonine2 Publications1
Glycosylationi45N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi52O-linked (GalNAc...) threonine1 Publication1
Glycosylationi56O-linked (GalNAc...) threonine2 Publications1
Glycosylationi63O-linked (GalNAc...) serine2 Publications1
Glycosylationi66O-linked (GalNAc...) serine2 Publications1
Glycosylationi69O-linked (GalNAc...) threonine2 Publications1
Modified residuei133PhosphothreonineCombined sources1
Modified residuei138PhosphoserineCombined sources1
Modified residuei148PhosphoserineCombined sources1

Post-translational modificationi

The major O-linked glycan are NeuAc-alpha-2-3-Gal-beta-1-3-[NeuAc-alpha-2-6]-GalNAcOH (about 78 %) and NeuAc-alpha-2-3-Gal-beta-1-3-GalNAcOH (17 %). Minor O-glycans (5 %) include NeuAc-alpha-2-3-Gal-beta-1-3-[NeuAc-alpha-2-6]-GalNAcOH NeuAc-alpha-2-8-NeuAc-alpha-2-3-Gal-beta-1-3-GalNAcOH. About 1% of all O-linked glycans carry blood group A, B and H determinants. They derive from a type-2 precursor core structure, Gal-beta-(1,3)-GlcNAc-beta-1-R, and the antigens are synthesized by addition of fucose (H antigen-specific) and then N-acetylgalactosamine (A antigen-specific) or galactose (B antigen-specific). Specifically O-linked-glycans are NeuAc-alpha-2-3-Gal-beta-1-3-GalNAcOH-6-1-GlcNAc-beta-4-1-[Fuc-alpha-1-2]-Gal-beta-3-1-GalNAc-alpha (about 1%, B antigen-specific) and NeuAc-alpha-2-3-Gal-beta-1-3-GalNAcOH-6-1-GlcNAc-beta-4-1-[Fuc-alpha-1-2]-Gal-beta (1 %, O antigen-, A antigen- and B antigen-specific).5 Publications

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP02724
PeptideAtlasiP02724
PRIDEiP02724

PTM databases

GlyConnecti187
188
189
iPTMnetiP02724
PhosphoSitePlusiP02724
UniCarbKBiP02724

Expressioni

Gene expression databases

BgeeiENSG00000170180
CleanExiHS_GYPA
ExpressionAtlasiP02724 baseline and differential
GenevisibleiP02724 HS

Organism-specific databases

HPAiCAB002658
HPA014811

Interactioni

Subunit structurei

Homodimer. Interacts with Streptococcus gordonii hsa protein.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi109248, 13 interactors
IntActiP02724, 8 interactors
STRINGi9606.ENSP00000354003

Chemistry databases

BindingDBiP02724

Structurei

Secondary structure

1150
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi84 – 86Combined sources3
Helixi92 – 115Combined sources24

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AFONMR-A/B81-120[»]
1MSRmodel-A/B93-110[»]
2KPENMR-A/B89-117[»]
2KPFNMR-A/B80-117[»]
5EH4X-ray2.81A/B/C/D89-117[»]
5EH6X-ray1.92A89-117[»]
ProteinModelPortaliP02724
SMRiP02724
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02724

Family & Domainsi

Sequence similaritiesi

Belongs to the glycophorin A family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410JM5B Eukaryota
ENOG4111AH6 LUCA
GeneTreeiENSGT00550000075214
HOGENOMiHOG000089933
HOVERGENiHBG005850
InParanoidiP02724
KOiK06575
PhylomeDBiP02724
TreeFamiTF338555

Family and domain databases

InterProiView protein in InterPro
IPR001195 Glycophorin
IPR018938 Glycophorin_CS
PANTHERiPTHR13813 PTHR13813, 1 hit
PIRSFiPIRSF002466 Glycophorin, 1 hit
PROSITEiView protein in PROSITE
PS00312 GLYCOPHORIN_A, 1 hit

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P02724-1) [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
MYGKIIFVLL LSEIVSISAS STTGVAMHTS TSSSVTKSYI SSQTNDTHKR
60 70 80 90 100
DTYAATPRAH EVSEISVRTV YPPEEETGER VQLAHHFSEP EITLIIFGVM
110 120 130 140 150
AGVIGTILLI SYGIRRLIKK SPSDVKPLPS PDTDVPLSSV EIENPETSDQ
Length:150
Mass (Da):16,331
Last modified:September 22, 2009 - v2
Checksum:i48A5450E22FA99C9
GO
Isoform 2 (identifier: P02724-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-26: Missing.

Show »
Length:124
Mass (Da):13,649
Checksum:iD257CA020BB42AFD
GO
Isoform 3 (identifier: P02724-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     13-45: Missing.

Show »
Length:117
Mass (Da):13,000
Checksum:i3F1878ED9D7ADB29
GO

Sequence cautioni

The sequence AAA52624 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti30S → T AA sequence (PubMed:1059087).Curated1
Sequence conflicti36T → S AA sequence (PubMed:1059087).Curated1
Sequence conflicti133T → R in AAA88044 (PubMed:3456608).Curated1

Polymorphismi

Along with GYPB, GYPA is responsible for the MNS blood group system. The molecular basis of the GPA M/N bloodgroup antigen is a variation at positions 20 and 24. Ser-20 and Gly-24 correspond to M (shown); 'Leu-20' and 'Glu-24' correspond to N.
GYPA polymorphisms are involved in resistance to malaria [MIMi:611162].

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05891113E → A7 PublicationsCorresponds to variant dbSNP:rs4449373Ensembl.1
Natural variantiVAR_05997713E → G. Corresponds to variant dbSNP:rs4449373Ensembl.1
Natural variantiVAR_00319020S → L in N antigen and M(g) antigen. 3 PublicationsCorresponds to variant dbSNP:rs7682260Ensembl.1
Natural variantiVAR_05891223T → N in M(g) antigen. 1 Publication1
Natural variantiVAR_05891324G → D. Corresponds to variant dbSNP:rs7658293Ensembl.1
Natural variantiVAR_00319124G → E in N antigen, M(c) antigen and M(g) antigen. 4 PublicationsCorresponds to variant dbSNP:rs7687256Ensembl.1
Natural variantiVAR_05891446D → E in Ny(a) antigen. 1 Publication1
Natural variantiVAR_05891547T → K in ENEH/Hut antigen. 1 Publication1
Natural variantiVAR_05891647T → M in ENEH/Vw antigen. 1 Publication1
Natural variantiVAR_05891750R → W in Or antigen. 1
Natural variantiVAR_05891866S → Y in Vr antigen. 1 PublicationCorresponds to variant dbSNP:rs56077914Ensembl.1
Natural variantiVAR_05891973P → S in Os(a) antigen. 1 Publication1
Natural variantiVAR_05892076E → K in Ri(a) antigen. 1
Natural variantiVAR_05892177T → I in Mt(a) antigen. 1 PublicationCorresponds to variant dbSNP:rs56172553Ensembl.1
Natural variantiVAR_05892278G → R in ERIK antigen. 1 PublicationCorresponds to variant dbSNP:rs1800582EnsemblClinVar.1
Natural variantiVAR_05892382Q → K in ENAV/MARS antigen. 1
Natural variantiVAR_05892484A → P in ENEP/HAG antigen. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0478221 – 26Missing in isoform 2. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_04782313 – 45Missing in isoform 3. CuratedAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12857 mRNA Translation: AAA88044.1
X08054 mRNA Translation: CAA30843.1
M24128
, M24123, M24134, M24124, M24126, M24127 Genomic DNA Translation: AAA52768.1
X51798 mRNA Translation: CAA36095.1
L31860 mRNA Translation: AAA88051.1
EU338231 mRNA Translation: ACA96789.1
EU338233 mRNA Translation: ACA96791.1
EU338234 mRNA Translation: ACA96792.1
GU347002 mRNA Translation: ADU25340.1
GU347003 mRNA Translation: ADU25341.1
AK290561 mRNA Translation: BAF83250.1
AC107223 Genomic DNA No translation available.
BC005319 mRNA Translation: AAH05319.1
BC013328 mRNA Translation: AAH13328.1
M36281 mRNA Translation: AAA52624.1 Different initiation.
CCDSiCCDS34069.1 [P02724-1]
CCDS82959.1 [P02724-3]
PIRiA33931 A25131
RefSeqiNP_001295119.1, NM_001308190.1 [P02724-3]
NP_002090.4, NM_002099.7
XP_016863624.1, XM_017008135.1 [P02724-2]
UniGeneiHs.434973

Genome annotation databases

EnsembliENST00000324022; ENSP00000324483; ENSG00000170180 [P02724-3]
ENST00000641688; ENSP00000493142; ENSG00000170180 [P02724-2]
GeneIDi2993
KEGGihsa:2993
UCSCiuc003ijo.5 human [P02724-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiGLPA_HUMAN
AccessioniPrimary (citable) accession number: P02724
Secondary accession number(s): A8K3E6
, B8Q182, B8Q185, Q9BS51
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: September 22, 2009
Last modified: May 23, 2018
This is version 195 of the entry and version 2 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Blood group antigen proteins
    Nomenclature of blood group antigens and list of entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  8. SIMILARITY comments
    Index of protein domains and families

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