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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

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

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 9172ExtracellularAdd
BLAST
Transmembranei92 – 11423HelicalAdd
BLAST
Topological domaini115 – 15036CytoplasmicAdd
BLAST

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi87 – 871F → C: Diminishes dimerization. 1 Publication
Mutagenesisi88 – 881S → C: Diminishes dimerization. 1 Publication
Mutagenesisi90 – 901P → C: Diminishes dimerization. 1 Publication
Mutagenesisi91 – 911E → C: Diminishes dimerization. 1 Publication
Mutagenesisi94 – 941L → I: Diminishes dimerization. 1 Publication
Mutagenesisi95 – 951I → A: Diminishes dimerization. 1 Publication
Mutagenesisi98 – 981G → L: Diminishes dimerization. 1 Publication
Mutagenesisi102 – 1021G → L: Abolishes dimerization. 1 Publication

Organism-specific databases

MalaCardsiGYPA.
MIMi111300. gene+phenotype.
611162. phenotype.
PharmGKBiPA29080.

Chemistry

ChEMBLiCHEMBL5806.

Polymorphism and mutation databases

BioMutaiGYPA.
DMDMi259016238.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 19191 PublicationAdd
BLAST
Chaini20 – 150131Glycophorin-APRO_0000012134Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi21 – 211O-linked (GalNAc...)2 Publications
Glycosylationi22 – 221O-linked (GalNAc...)2 Publications
Glycosylationi23 – 231O-linked (GalNAc...)2 Publications
Glycosylationi29 – 291O-linked (GalNAc...)2 Publications
Glycosylationi30 – 301O-linked (GalNAc...)2 Publications
Glycosylationi31 – 311O-linked (GalNAc...)2 Publications
Glycosylationi32 – 321O-linked (GalNAc...)2 Publications
Glycosylationi36 – 361O-linked (GalNAc...)1 Publication
Glycosylationi38 – 381O-linked (GalNAc...)1 Publication
Glycosylationi41 – 411O-linked (GalNAc...)2 Publications
Glycosylationi44 – 441O-linked (GalNAc...)2 Publications
Glycosylationi45 – 451N-linked (GlcNAc...)2 Publications
Glycosylationi52 – 521O-linked (GalNAc...)1 Publication
Glycosylationi56 – 561O-linked (GalNAc...)2 Publications
Glycosylationi63 – 631O-linked (GalNAc...)2 Publications
Glycosylationi66 – 661O-linked (GalNAc...)2 Publications
Glycosylationi69 – 691O-linked (GalNAc...)2 Publications
Modified residuei133 – 1331PhosphothreonineCombined sources
Modified residuei138 – 1381PhosphoserineCombined sources
Modified residuei148 – 1481PhosphoserineCombined sources

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.
PhosphoSiteiP02724.
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

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi109248. 13 interactions.
STRINGi9606.ENSP00000354003.

Chemistry

BindingDBiP02724.

Structurei

Secondary structure

1
150
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi84 – 863Combined sources
Helixi92 – 11524Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 81-120.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti30 – 301S → T AA sequence (PubMed:1059087).Curated
Sequence conflicti36 – 361T → S AA sequence (PubMed:1059087).Curated
Sequence conflicti133 – 1331T → R in AAA88044 (PubMed:3456608).Curated

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti13 – 131E → A.7 Publications
Corresponds to variant rs4449373 [ dbSNP | Ensembl ].
VAR_058911
Natural varianti13 – 131E → G.
Corresponds to variant rs4449373 [ dbSNP | Ensembl ].
VAR_059977
Natural varianti20 – 201S → L in N antigen and M(g) antigen. 3 Publications
Corresponds to variant rs7682260 [ dbSNP | Ensembl ].
VAR_003190
Natural varianti23 – 231T → N in M(g) antigen. 1 Publication
VAR_058912
Natural varianti24 – 241G → D.
Corresponds to variant rs7658293 [ dbSNP | Ensembl ].
VAR_058913
Natural varianti24 – 241G → E in N antigen, in M(c) antigen and in M(g) antigen. 4 Publications
Corresponds to variant rs7687256 [ dbSNP | Ensembl ].
VAR_003191
Natural varianti46 – 461D → E in Ny(a) antigen. 1 Publication
VAR_058914
Natural varianti47 – 471T → K in ENEH/Hut antigen. 1 Publication
VAR_058915
Natural varianti47 – 471T → M in ENEH/Vw antigen. 1 Publication
VAR_058916
Natural varianti50 – 501R → W in Or antigen.
VAR_058917
Natural varianti66 – 661S → Y in Vr antigen. 1 Publication
Corresponds to variant rs56077914 [ dbSNP | Ensembl ].
VAR_058918
Natural varianti73 – 731P → S in Os(a) antigen. 1 Publication
VAR_058919
Natural varianti76 – 761E → K in Ri(a) antigen.
VAR_058920
Natural varianti77 – 771T → I in Mt(a) antigen. 1 Publication
Corresponds to variant rs56172553 [ dbSNP | Ensembl ].
VAR_058921
Natural varianti78 – 781G → R in ERIK antigen. 1 Publication
Corresponds to variant rs1800582 [ dbSNP | Ensembl ].
VAR_058922
Natural varianti82 – 821Q → K in ENAV/MARS antigen.
VAR_058923
Natural varianti84 – 841A → P in ENEP/HAG antigen. 1 Publication
VAR_058924

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2626Missing in isoform 2. 1 PublicationVSP_047822Add
BLAST
Alternative sequencei13 – 4533Missing in isoform 3. CuratedVSP_047823Add
BLAST

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]
PIRiA33931. A25131.
RefSeqiNP_001295119.1. NM_001308190.1. [P02724-3]
NP_002090.4. NM_002099.7.
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]
PIRiA33931. A25131.
RefSeqiNP_001295119.1. NM_001308190.1. [P02724-3]
NP_002090.4. NM_002099.7.
UniGeneiHs.434973.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 81-120.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109248. 13 interactions.
STRINGi9606.ENSP00000354003.

Chemistry

BindingDBiP02724.
ChEMBLiCHEMBL5806.

PTM databases

iPTMnetiP02724.
PhosphoSiteiP02724.
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.
GeneCardsiGYPA.
HGNCiHGNC:4702. GYPA.
HPAiCAB002658.
HPA014811.
MalaCardsiGYPA.
MIMi111300. gene+phenotype.
611162. phenotype.
neXtProtiNX_P02724.
PharmGKBiPA29080.
GenAtlasiSearch...

Phylogenomic databases

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

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: September 7, 2016
This is version 181 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.