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Protein

Glycophorin-A

Gene

GYPA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

Complete GO annotation...

Keywords - Molecular functioni

Blood group antigen, Host cell receptor for virus entry, Receptor

Keywords - Biological processi

Host-virus interaction

Keywords - Ligandi

Sialic acid

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170180-MONOMER.

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

HGNCiHGNC:4702. GYPA.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: ProtInc
  • plasma membrane Source: ProtInc
Complete GO annotation...

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...)2 Publications1
Glycosylationi22O-linked (GalNAc...)2 Publications1
Glycosylationi23O-linked (GalNAc...)2 Publications1
Glycosylationi29O-linked (GalNAc...)2 Publications1
Glycosylationi30O-linked (GalNAc...)2 Publications1
Glycosylationi31O-linked (GalNAc...)2 Publications1
Glycosylationi32O-linked (GalNAc...)2 Publications1
Glycosylationi36O-linked (GalNAc...)1 Publication1
Glycosylationi38O-linked (GalNAc...)1 Publication1
Glycosylationi41O-linked (GalNAc...)2 Publications1
Glycosylationi44O-linked (GalNAc...)2 Publications1
Glycosylationi45N-linked (GlcNAc...)2 Publications1
Glycosylationi52O-linked (GalNAc...)1 Publication1
Glycosylationi56O-linked (GalNAc...)2 Publications1
Glycosylationi63O-linked (GalNAc...)2 Publications1
Glycosylationi66O-linked (GalNAc...)2 Publications1
Glycosylationi69O-linked (GalNAc...)2 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

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

WithEntry#Exp.IntActNotes
itself3EBI-702665,EBI-702665

Protein-protein interaction databases

BioGridi109248. 13 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

InterProiIPR001195. Glycophorin.
IPR018938. Glycophorin_CS.
[Graphical view]
PANTHERiPTHR13813. PTHR13813. 1 hit.
PIRSFiPIRSF002466. Glycophorin. 1 hit.
PROSITEiPS00312. GLYCOPHORIN_A. 1 hit.
[Graphical view]

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 → A.7 PublicationsCorresponds to variant rs4449373dbSNPEnsembl.1
Natural variantiVAR_05997713E → G.Corresponds to variant rs4449373dbSNPEnsembl.1
Natural variantiVAR_00319020S → L in N antigen and M(g) antigen. 3 PublicationsCorresponds to variant rs7682260dbSNPEnsembl.1
Natural variantiVAR_05891223T → N in M(g) antigen. 1 Publication1
Natural variantiVAR_05891324G → D.Corresponds to variant rs7658293dbSNPEnsembl.1
Natural variantiVAR_00319124G → E in N antigen, in M(c) antigen and in M(g) antigen. 4 PublicationsCorresponds to variant rs7687256dbSNPEnsembl.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 rs56077914dbSNPEnsembl.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 rs56172553dbSNPEnsembl.1
Natural variantiVAR_05892278G → R in ERIK antigen. 1 PublicationCorresponds to variant rs1800582dbSNPEnsembl.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]
GeneIDi2993.
KEGGihsa:2993.
UCSCiuc003ijo.5. human. [P02724-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

dbRBC/BGMUT

Blood group antigen gene mutation database

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.

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...

Protein-protein interaction databases

BioGridi109248. 13 interactors.
STRINGi9606.ENSP00000354003.

Chemistry databases

BindingDBiP02724.
ChEMBLiCHEMBL5806.

PTM databases

iPTMnetiP02724.
PhosphoSitePlusiP02724.
UniCarbKBiP02724.

Polymorphism and mutation databases

BioMutaiGYPA.
DMDMi259016238.

Proteomic databases

PaxDbiP02724.
PeptideAtlasiP02724.
PRIDEiP02724.

Protocols and materials databases

DNASUi2993.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2993.
DisGeNETi2993.
GeneCardsiGYPA.
HGNCiHGNC:4702. GYPA.
HPAiCAB002658.
HPA014811.
MalaCardsiGYPA.
MIMi111300. gene+phenotype.
611162. phenotype.
neXtProtiNX_P02724.
OpenTargetsiENSG00000170180.
PharmGKBiPA29080.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JM5B. Eukaryota.
ENOG4111AH6. LUCA.
GeneTreeiENSGT00550000075214.
HOGENOMiHOG000089933.
HOVERGENiHBG005850.
InParanoidiP02724.
KOiK06575.
PhylomeDBiP02724.
TreeFamiTF338555.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000170180-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP02724.
GeneWikiiGYPA.
GenomeRNAii2993.
PROiP02724.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000170180.
CleanExiHS_GYPA.
ExpressionAtlasiP02724. baseline and differential.
GenevisibleiP02724. HS.

Family and domain databases

InterProiIPR001195. Glycophorin.
IPR018938. Glycophorin_CS.
[Graphical view]
PANTHERiPTHR13813. PTHR13813. 1 hit.
PIRSFiPIRSF002466. Glycophorin. 1 hit.
PROSITEiPS00312. GLYCOPHORIN_A. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGLPA_HUMAN
AccessioniPrimary (citable) accession number: P02724
Secondary accession number(s): A8K3E6
, B8Q182, B8Q185, Q9BS51
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: September 22, 2009
Last modified: November 2, 2016
This is version 183 of the entry and version 2 of the sequence. [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

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.

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.