Full text data of GYPB
GYPB
(GPB)
[Confidence: high (a blood group or CD marker)]
Glycophorin-B (PAS-3; SS-active sialoglycoprotein; Sialoglycoprotein delta; CD235b; Flags: Precursor)
Glycophorin-B (PAS-3; SS-active sialoglycoprotein; Sialoglycoprotein delta; CD235b; Flags: Precursor)
BGMUT
mns
335 mns GYPB and GYPA GYP Dantu GYP B-A hybrid A and B intron 4; breakpoint site in intron4 not defined B(1-58) A(59-118) gDNA Dantu rare 2462250 Huang and Blumenfeld Unequal homologous recombination; B-A hybrid; GYPB pseudoexon is not expressed Blumenfeld OO, curator 2008-04-09 18:44:31.220 NA
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356 mns GYPA and GYPB GYP Mi IX(1) GYP MiIX(1) (Dane,A-B-A hybrid) gene conversion breakpoint in A and B exon III; in GYPA 160-178; in GYPA nt. 160G>C; 165-167delCAC; 170C>A; 173G>C; 174A>T; 178C>A;194T>A A54P; T56del; P57H; R58T; H60N; I65N cDNA; gDNA Dane, MiIX rare 1421409 M87285 Huang et al. Blood 1992 80 2379-2387 Gene conversion; an A-B-A hybrid identical to Mi IX(2) but bearing an additional change 194T>A; an internal segment (minimum size 19 nt) of exon III of GYPA was replaced by a silent segment of GYPB; 194T>A is the accompanying variation. Blumenfeld OO, curator 2008-09-10 18:50:44.240 NA
356 mns GYPA and GYPB GYP Mi IX(1) GYP MiIX(1) (Dane,A-B-A hybrid) gene conversion breakpoint in A and B exon III; in GYPA 160-178; in GYPA nt. 160G>C; 165-167delCAC; 170C>A; 173G>C; 174A>T; 178C>A;194T>A A54P; T56del; P57H; R58T; H60N; I65N cDNA; gDNA Dane, MiIX rare 1421409 M87285 Huang et al. Blood 1992 80 2379-2387 Gene conversion; an A-B-A hybrid identical to Mi IX(2) but bearing an additional change 194T>A; an internal segment (minimum size 19 nt) of exon III of GYPA was replaced by a silent segment of GYPB; 194T>A is the accompanying variation. Blumenfeld OO, curator 2008-09-10 18:50:44.240 NA
372 mns GYPA and GYPE GYP Sta(ERIK/TF) GYPSta(ERIK/TF) (A-E-A hybrid) A and E intron 2+intron 3: minimal sequence transferred from GYPE to GYPA: from 240nt downstrem from 3'end of intron2 + pseudoexon 3 + intron 3 1-25; in GYPA intron 2 -240A>G; -97delG; -84A>G; 79G>A; 76C>T -48A>T; -47C>T: exon III 140C>A; 160 G>C; 165 -167delCAC; 170C>A; 174A>T; 176C>T 178C>A; 194T>A 204G>C; 230C>A; 231C>T; intron 3 1G>A; 55A>G DKHKRDTYPVHSVNEVSEISVTTVSPPEEEN46-78del (sequence encoded by GYPE pseudoexon III is not expressed) cDNA; gDNA Sta/ERIK rare 10862083 AF239850 Huang et al. Gene conversion; A-E-A hybrid;transferred sequence is not expressed because it includes transfer of an inactive splicing signal; similar to Sta proteins and it bears the Sta epitope. Blumenfeld OO, curator 2008-04-09 20:51:37.983 NA
335 mns GYPB and GYPA GYP Dantu GYP B-A hybrid A and B intron 4; breakpoint site in intron4 not defined B(1-58) A(59-118) gDNA Dantu rare 2462250 Huang and Blumenfeld Unequal homologous recombination; B-A hybrid; GYPB pseudoexon is not expressed Blumenfeld OO, curator 2008-04-09 18:44:31.220 NA
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356 mns GYPA and GYPB GYP Mi IX(1) GYP MiIX(1) (Dane,A-B-A hybrid) gene conversion breakpoint in A and B exon III; in GYPA 160-178; in GYPA nt. 160G>C; 165-167delCAC; 170C>A; 173G>C; 174A>T; 178C>A;194T>A A54P; T56del; P57H; R58T; H60N; I65N cDNA; gDNA Dane, MiIX rare 1421409 M87285 Huang et al. Blood 1992 80 2379-2387 Gene conversion; an A-B-A hybrid identical to Mi IX(2) but bearing an additional change 194T>A; an internal segment (minimum size 19 nt) of exon III of GYPA was replaced by a silent segment of GYPB; 194T>A is the accompanying variation. Blumenfeld OO, curator 2008-09-10 18:50:44.240 NA
356 mns GYPA and GYPB GYP Mi IX(1) GYP MiIX(1) (Dane,A-B-A hybrid) gene conversion breakpoint in A and B exon III; in GYPA 160-178; in GYPA nt. 160G>C; 165-167delCAC; 170C>A; 173G>C; 174A>T; 178C>A;194T>A A54P; T56del; P57H; R58T; H60N; I65N cDNA; gDNA Dane, MiIX rare 1421409 M87285 Huang et al. Blood 1992 80 2379-2387 Gene conversion; an A-B-A hybrid identical to Mi IX(2) but bearing an additional change 194T>A; an internal segment (minimum size 19 nt) of exon III of GYPA was replaced by a silent segment of GYPB; 194T>A is the accompanying variation. Blumenfeld OO, curator 2008-09-10 18:50:44.240 NA
372 mns GYPA and GYPE GYP Sta(ERIK/TF) GYPSta(ERIK/TF) (A-E-A hybrid) A and E intron 2+intron 3: minimal sequence transferred from GYPE to GYPA: from 240nt downstrem from 3'end of intron2 + pseudoexon 3 + intron 3 1-25; in GYPA intron 2 -240A>G; -97delG; -84A>G; 79G>A; 76C>T -48A>T; -47C>T: exon III 140C>A; 160 G>C; 165 -167delCAC; 170C>A; 174A>T; 176C>T 178C>A; 194T>A 204G>C; 230C>A; 231C>T; intron 3 1G>A; 55A>G DKHKRDTYPVHSVNEVSEISVTTVSPPEEEN46-78del (sequence encoded by GYPE pseudoexon III is not expressed) cDNA; gDNA Sta/ERIK rare 10862083 AF239850 Huang et al. Gene conversion; A-E-A hybrid;transferred sequence is not expressed because it includes transfer of an inactive splicing signal; similar to Sta proteins and it bears the Sta epitope. Blumenfeld OO, curator 2008-04-09 20:51:37.983 NA
UniProt
P06028
ID GLPB_HUMAN Reviewed; 91 AA.
AC P06028; B8Q174; E2QBW7; Q0VAF4; Q58HE9; Q58HF0; Q58HF1; Q9UCH7;
read moreDT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 3.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Glycophorin-B;
DE AltName: Full=PAS-3;
DE AltName: Full=SS-active sialoglycoprotein;
DE AltName: Full=Sialoglycoprotein delta;
DE AltName: CD_antigen=CD235b;
DE Flags: Precursor;
GN Name=GYPB; Synonyms=GPB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-84.
RX PubMed=3477806; DOI=10.1073/pnas.84.19.6735;
RA Siebert P.D., Fukuda M.;
RT "Molecular cloning of a human glycophorin B cDNA: nucleotide sequence
RT and genomic relationship to glycophorin A.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6735-6739(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3196288;
RA Tate C.G., Tanner M.J.A.;
RT "Isolation of cDNA clones for human erythrocyte membrane
RT sialoglycoproteins alpha and delta.";
RL Biochem. J. 254:743-750(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-84.
RX PubMed=2734312; DOI=10.1073/pnas.86.12.4619;
RA Kudo S., Fukuda M.;
RT "Structural organization of glycophorin A and B genes: glycophorin B
RT gene evolved by homologous recombination at Alu repeat sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4619-4623(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Blood;
RA Hsu K., Chi N., Lin M.;
RT "Extensive alternative splicing of glycophorins in Southeast Asian
RT populations.";
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT M(V) SER-22, VARIANTS
RP MIT MET-48 AND HIS-54, VARIANT S(D) ARG-58, AND VARIANT THR-84.
RC TISSUE=Blood;
RX PubMed=11239234; DOI=10.1046/j.1537-2995.2001.41020269.x;
RA Storry J.R., Reid M.E., MacLennan S., Lubenko A., Nortman P.;
RT "The low-incidence MNS antigens M(v), s(D), and Mit arise from single
RT amino acid substitutions on GPB.";
RL Transfusion 41:269-275(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 13-58.
RC TISSUE=Blood;
RX PubMed=2016325;
RA Huang C.-H., Blumenfeld O.O.;
RT "Molecular genetics of human erythrocyte MiIII and MiVI glycophorins.
RT Use of a pseudoexon in construction of two delta-alpha-delta hybrid
RT genes resulting in antigenic diversification.";
RL J. Biol. Chem. 266:7248-7255(1991).
RN [10]
RP PROTEIN SEQUENCE OF 20-90.
RX PubMed=3595615; DOI=10.1111/j.1432-1033.1987.tb13479.x;
RA Dahr W., Beyreuther K., Moulds J., Unger P.;
RT "Hybrid glycophorins from human erythrocyte membranes. I. Isolation
RT and complete structural analysis of the hybrid sialoglycoprotein from
RT Dantu-positive red cells of the N.E. variety.";
RL Eur. J. Biochem. 166:31-36(1987).
RN [11]
RP PROTEIN SEQUENCE OF 20-90.
RX PubMed=3571235;
RA Blanchard D., Dahr W., Hummel M., Latron F., Beyreuther K.,
RA Cartron J.-P.;
RT "Glycophorins B and C from human erythrocyte membranes. Purification
RT and sequence analysis.";
RL J. Biol. Chem. 262:5808-5811(1987).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-45.
RX PubMed=1611092;
RA Huang C.-H., Spruell P., Moulds J.J., Blumenfeld O.O.;
RT "Molecular basis for the human erythrocyte glycophorin specifying the
RT Miltenberger class I (MiI) phenotype.";
RL Blood 80:257-263(1992).
RN [13]
RP PROTEIN SEQUENCE OF 20-40, AND GLYCOSYLATION AT THR-36 AND SER-38.
RX PubMed=7681597; DOI=10.1073/pnas.90.6.2495;
RA Nakada H., Inoue M., Numata Y., Tanaka N., Funakoshi I., Fukui S.,
RA Mellors A., Yamashina I.;
RT "Epitopic structure of Tn glycophorin A for an anti-Tn antibody (MLS
RT 128).";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2495-2499(1993).
CC -!- FUNCTION: This protein is a minor sialoglycoprotein in erythrocyte
CC membranes.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06028-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06028-2; Sequence=VSP_047824;
CC -!- PTM: The N-terminal extracellular domain is heavily glycosylated
CC on serine and threonine residues.
CC -!- POLYMORPHISM: Along with GYPA, GYPB is responsible for the MNS
CC blood group system. The molecular basis of the S/s blood group
CC antigen is a single variation in position 48; Thr-48 corresponds
CC to s=MSN4 and Met-48 to S=MNS3.
CC -!- SIMILARITY: Belongs to the glycophorin-A family.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=mns";
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DR EMBL; J02982; AAA52573.1; -; mRNA.
DR EMBL; X08055; CAB42645.1; -; mRNA.
DR EMBL; M24137; AAA58626.1; -; Genomic_DNA.
DR EMBL; M24130; AAA58626.1; JOINED; Genomic_DNA.
DR EMBL; M24131; AAA58626.1; JOINED; Genomic_DNA.
DR EMBL; M24135; AAA58626.1; JOINED; Genomic_DNA.
DR EMBL; AY950609; AAX53130.1; -; mRNA.
DR EMBL; AY950610; AAX53131.1; -; mRNA.
DR EMBL; AY950611; AAX53132.1; -; mRNA.
DR EMBL; EU338223; ACA96781.1; -; mRNA.
DR EMBL; EU338235; ACA96793.1; -; mRNA.
DR EMBL; AC093890; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX05058.1; -; Genomic_DNA.
DR EMBL; BC069310; AAH69310.1; -; mRNA.
DR EMBL; BC121077; AAI21078.1; -; mRNA.
DR EMBL; BC121078; AAI21079.1; -; mRNA.
DR EMBL; M60708; AAC63048.1; -; Genomic_DNA.
DR PIR; B33931; B33931.
DR RefSeq; NP_002091.3; NM_002100.4.
DR UniGene; Hs.654368; -.
DR ProteinModelPortal; P06028; -.
DR SMR; P06028; 49-91.
DR UniCarbKB; P06028; -.
DR DMDM; 121405; -.
DR DNASU; 2994; -.
DR Ensembl; ENST00000283126; ENSP00000283126; ENSG00000250361.
DR Ensembl; ENST00000502664; ENSP00000427690; ENSG00000250361.
DR Ensembl; ENST00000513128; ENSP00000425244; ENSG00000250361.
DR GeneID; 2994; -.
DR KEGG; hsa:2994; -.
DR CTD; 2994; -.
DR GeneCards; GC04M144918; -.
DR HGNC; HGNC:4703; GYPB.
DR MIM; 111740; gene+phenotype.
DR neXtProt; NX_P06028; -.
DR PharmGKB; PA29081; -.
DR HOGENOM; HOG000089933; -.
DR HOVERGEN; HBG005850; -.
DR KO; K06575; -.
DR OMA; YISSETN; -.
DR GeneWiki; GYPB; -.
DR GenomeRNAi; 2994; -.
DR NextBio; 11866; -.
DR PRO; PR:P06028; -.
DR ArrayExpress; P06028; -.
DR Bgee; P06028; -.
DR CleanEx; HS_GYPB; -.
DR Genevestigator; P06028; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR InterPro; IPR001195; Glycophorin.
DR InterPro; IPR018938; Glycophorin_CS.
DR PANTHER; PTHR13813; PTHR13813; 1.
DR Pfam; PF01102; Glycophorin_A; 1.
DR PROSITE; PS00312; GLYCOPHORIN_A; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Blood group antigen; Cell membrane;
KW Complete proteome; Direct protein sequencing; Glycoprotein; Membrane;
KW Polymorphism; Reference proteome; Sialic acid; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 19
FT CHAIN 20 91 Glycophorin-B.
FT /FTId=PRO_0000012136.
FT TOPO_DOM 20 59 Extracellular (Potential).
FT TRANSMEM 60 81 Helical; (Potential).
FT TOPO_DOM 82 91 Cytoplasmic (Potential).
FT SITE 33 33 Not glycosylated.
FT SITE 34 34 Not glycosylated.
FT CARBOHYD 36 36 O-linked (GalNAc...).
FT CARBOHYD 38 38 O-linked (GalNAc...).
FT VAR_SEQ 13 45 Missing (in isoform 2).
FT /FTId=VSP_047824.
FT VARIANT 22 22 T -> S (in M(v) antigen).
FT /FTId=VAR_047948.
FT VARIANT 48 48 T -> M (in S antigen and Mit antigen;
FT dbSNP:rs7683365).
FT /FTId=VAR_003192.
FT VARIANT 54 54 R -> H (in Mit antigen).
FT /FTId=VAR_047949.
FT VARIANT 58 58 P -> R (in s(D) antigen).
FT /FTId=VAR_047950.
FT VARIANT 84 84 S -> T (in dbSNP:rs1132783).
FT /FTId=VAR_030785.
FT CONFLICT 69 69 C -> S (in Ref. 10; AA sequence and 11;
FT AA sequence).
SQ SEQUENCE 91 AA; 9782 MW; EF15A64BAA929B7B CRC64;
MYGKIIFVLL LSEIVSISAL STTEVAMHTS TSSSVTKSYI SSQTNGETGQ LVHRFTVPAP
VVIILIILCV MAGIIGTILL ISYSIRRLIK A
//
ID GLPB_HUMAN Reviewed; 91 AA.
AC P06028; B8Q174; E2QBW7; Q0VAF4; Q58HE9; Q58HF0; Q58HF1; Q9UCH7;
read moreDT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2012, sequence version 3.
DT 22-JAN-2014, entry version 126.
DE RecName: Full=Glycophorin-B;
DE AltName: Full=PAS-3;
DE AltName: Full=SS-active sialoglycoprotein;
DE AltName: Full=Sialoglycoprotein delta;
DE AltName: CD_antigen=CD235b;
DE Flags: Precursor;
GN Name=GYPB; Synonyms=GPB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT THR-84.
RX PubMed=3477806; DOI=10.1073/pnas.84.19.6735;
RA Siebert P.D., Fukuda M.;
RT "Molecular cloning of a human glycophorin B cDNA: nucleotide sequence
RT and genomic relationship to glycophorin A.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:6735-6739(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3196288;
RA Tate C.G., Tanner M.J.A.;
RT "Isolation of cDNA clones for human erythrocyte membrane
RT sialoglycoproteins alpha and delta.";
RL Biochem. J. 254:743-750(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-84.
RX PubMed=2734312; DOI=10.1073/pnas.86.12.4619;
RA Kudo S., Fukuda M.;
RT "Structural organization of glycophorin A and B genes: glycophorin B
RT gene evolved by homologous recombination at Alu repeat sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:4619-4623(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RC TISSUE=Blood;
RA Hsu K., Chi N., Lin M.;
RT "Extensive alternative splicing of glycophorins in Southeast Asian
RT populations.";
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT M(V) SER-22, VARIANTS
RP MIT MET-48 AND HIS-54, VARIANT S(D) ARG-58, AND VARIANT THR-84.
RC TISSUE=Blood;
RX PubMed=11239234; DOI=10.1046/j.1537-2995.2001.41020269.x;
RA Storry J.R., Reid M.E., MacLennan S., Lubenko A., Nortman P.;
RT "The low-incidence MNS antigens M(v), s(D), and Mit arise from single
RT amino acid substitutions on GPB.";
RL Transfusion 41:269-275(2001).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 13-58.
RC TISSUE=Blood;
RX PubMed=2016325;
RA Huang C.-H., Blumenfeld O.O.;
RT "Molecular genetics of human erythrocyte MiIII and MiVI glycophorins.
RT Use of a pseudoexon in construction of two delta-alpha-delta hybrid
RT genes resulting in antigenic diversification.";
RL J. Biol. Chem. 266:7248-7255(1991).
RN [10]
RP PROTEIN SEQUENCE OF 20-90.
RX PubMed=3595615; DOI=10.1111/j.1432-1033.1987.tb13479.x;
RA Dahr W., Beyreuther K., Moulds J., Unger P.;
RT "Hybrid glycophorins from human erythrocyte membranes. I. Isolation
RT and complete structural analysis of the hybrid sialoglycoprotein from
RT Dantu-positive red cells of the N.E. variety.";
RL Eur. J. Biochem. 166:31-36(1987).
RN [11]
RP PROTEIN SEQUENCE OF 20-90.
RX PubMed=3571235;
RA Blanchard D., Dahr W., Hummel M., Latron F., Beyreuther K.,
RA Cartron J.-P.;
RT "Glycophorins B and C from human erythrocyte membranes. Purification
RT and sequence analysis.";
RL J. Biol. Chem. 262:5808-5811(1987).
RN [12]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 20-45.
RX PubMed=1611092;
RA Huang C.-H., Spruell P., Moulds J.J., Blumenfeld O.O.;
RT "Molecular basis for the human erythrocyte glycophorin specifying the
RT Miltenberger class I (MiI) phenotype.";
RL Blood 80:257-263(1992).
RN [13]
RP PROTEIN SEQUENCE OF 20-40, AND GLYCOSYLATION AT THR-36 AND SER-38.
RX PubMed=7681597; DOI=10.1073/pnas.90.6.2495;
RA Nakada H., Inoue M., Numata Y., Tanaka N., Funakoshi I., Fukui S.,
RA Mellors A., Yamashina I.;
RT "Epitopic structure of Tn glycophorin A for an anti-Tn antibody (MLS
RT 128).";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2495-2499(1993).
CC -!- FUNCTION: This protein is a minor sialoglycoprotein in erythrocyte
CC membranes.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06028-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06028-2; Sequence=VSP_047824;
CC -!- PTM: The N-terminal extracellular domain is heavily glycosylated
CC on serine and threonine residues.
CC -!- POLYMORPHISM: Along with GYPA, GYPB is responsible for the MNS
CC blood group system. The molecular basis of the S/s blood group
CC antigen is a single variation in position 48; Thr-48 corresponds
CC to s=MSN4 and Met-48 to S=MNS3.
CC -!- SIMILARITY: Belongs to the glycophorin-A family.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=mns";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; J02982; AAA52573.1; -; mRNA.
DR EMBL; X08055; CAB42645.1; -; mRNA.
DR EMBL; M24137; AAA58626.1; -; Genomic_DNA.
DR EMBL; M24130; AAA58626.1; JOINED; Genomic_DNA.
DR EMBL; M24131; AAA58626.1; JOINED; Genomic_DNA.
DR EMBL; M24135; AAA58626.1; JOINED; Genomic_DNA.
DR EMBL; AY950609; AAX53130.1; -; mRNA.
DR EMBL; AY950610; AAX53131.1; -; mRNA.
DR EMBL; AY950611; AAX53132.1; -; mRNA.
DR EMBL; EU338223; ACA96781.1; -; mRNA.
DR EMBL; EU338235; ACA96793.1; -; mRNA.
DR EMBL; AC093890; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107223; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110762; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX05058.1; -; Genomic_DNA.
DR EMBL; BC069310; AAH69310.1; -; mRNA.
DR EMBL; BC121077; AAI21078.1; -; mRNA.
DR EMBL; BC121078; AAI21079.1; -; mRNA.
DR EMBL; M60708; AAC63048.1; -; Genomic_DNA.
DR PIR; B33931; B33931.
DR RefSeq; NP_002091.3; NM_002100.4.
DR UniGene; Hs.654368; -.
DR ProteinModelPortal; P06028; -.
DR SMR; P06028; 49-91.
DR UniCarbKB; P06028; -.
DR DMDM; 121405; -.
DR DNASU; 2994; -.
DR Ensembl; ENST00000283126; ENSP00000283126; ENSG00000250361.
DR Ensembl; ENST00000502664; ENSP00000427690; ENSG00000250361.
DR Ensembl; ENST00000513128; ENSP00000425244; ENSG00000250361.
DR GeneID; 2994; -.
DR KEGG; hsa:2994; -.
DR CTD; 2994; -.
DR GeneCards; GC04M144918; -.
DR HGNC; HGNC:4703; GYPB.
DR MIM; 111740; gene+phenotype.
DR neXtProt; NX_P06028; -.
DR PharmGKB; PA29081; -.
DR HOGENOM; HOG000089933; -.
DR HOVERGEN; HBG005850; -.
DR KO; K06575; -.
DR OMA; YISSETN; -.
DR GeneWiki; GYPB; -.
DR GenomeRNAi; 2994; -.
DR NextBio; 11866; -.
DR PRO; PR:P06028; -.
DR ArrayExpress; P06028; -.
DR Bgee; P06028; -.
DR CleanEx; HS_GYPB; -.
DR Genevestigator; P06028; -.
DR GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR InterPro; IPR001195; Glycophorin.
DR InterPro; IPR018938; Glycophorin_CS.
DR PANTHER; PTHR13813; PTHR13813; 1.
DR Pfam; PF01102; Glycophorin_A; 1.
DR PROSITE; PS00312; GLYCOPHORIN_A; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Blood group antigen; Cell membrane;
KW Complete proteome; Direct protein sequencing; Glycoprotein; Membrane;
KW Polymorphism; Reference proteome; Sialic acid; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 19
FT CHAIN 20 91 Glycophorin-B.
FT /FTId=PRO_0000012136.
FT TOPO_DOM 20 59 Extracellular (Potential).
FT TRANSMEM 60 81 Helical; (Potential).
FT TOPO_DOM 82 91 Cytoplasmic (Potential).
FT SITE 33 33 Not glycosylated.
FT SITE 34 34 Not glycosylated.
FT CARBOHYD 36 36 O-linked (GalNAc...).
FT CARBOHYD 38 38 O-linked (GalNAc...).
FT VAR_SEQ 13 45 Missing (in isoform 2).
FT /FTId=VSP_047824.
FT VARIANT 22 22 T -> S (in M(v) antigen).
FT /FTId=VAR_047948.
FT VARIANT 48 48 T -> M (in S antigen and Mit antigen;
FT dbSNP:rs7683365).
FT /FTId=VAR_003192.
FT VARIANT 54 54 R -> H (in Mit antigen).
FT /FTId=VAR_047949.
FT VARIANT 58 58 P -> R (in s(D) antigen).
FT /FTId=VAR_047950.
FT VARIANT 84 84 S -> T (in dbSNP:rs1132783).
FT /FTId=VAR_030785.
FT CONFLICT 69 69 C -> S (in Ref. 10; AA sequence and 11;
FT AA sequence).
SQ SEQUENCE 91 AA; 9782 MW; EF15A64BAA929B7B CRC64;
MYGKIIFVLL LSEIVSISAL STTEVAMHTS TSSSVTKSYI SSQTNGETGQ LVHRFTVPAP
VVIILIILCV MAGIIGTILL ISYSIRRLIK A
//
MIM
111740
*RECORD*
*FIELD* NO
111740
*FIELD* TI
+111740 BLOOD GROUP--Ss LOCUS; Ss
GLYCOPHORIN B, INCLUDED; GPB, INCLUDED;;
GYPB, INCLUDED
read more*FIELD* TX
Ss and MN (GYPA; 111300) are closely linked but separate gene loci on
chromosome 4 (4q28-q31). Several instances of recombination between the
loci have been observed (see review by Race and Sanger, 1975). Close
linkage of the genes for the two sialoglycoproteins that carry the MN
and Ss specificities, respectively, is also indicated by the
identification of hybrid molecules that appear to have arisen by a
Lepore-type mechanism (Mawby et al., 1981). The erythrocyte
glycophorins, which lie partly within the cell membrane and partly
exposed to the exterior, contain 203 amino acids. The amino-terminal
half is exposed and is the one that bears the oligosaccharide complexes
that determine blood-group antigen specificities and serve as receptors
for viruses and plant agglutinins. As indicated in 111300, the Ss blood
group antigens are located on glycophorin B. The structural difference
between SS and ss specificities is a methionine-to-threonine
polymorphism at position 29. Ferrari and Pavia (1986) synthesized 2
peptides, each 8 amino acids long, carrying the Ss specificities: SS,
asn-gly-glu-met-gly-gln-leu-val; ss, asn-gly-glu-thr-gly-gln-leu-val.
Glycophorin C is the site of the Gerbich blood group antigen specificity
(110750). Siebert and Fukuda (1987) isolated a cDNA for human
glycophorin B and determined its nucleotide sequence. They used RNA blot
hybridization with both cDNA and synthetic oligonucleotide probes to
prove that glycophorins A and B are negatively and coordinately
regulated by a tumor-promoting phorbol ester. They established,
furthermore, the intron/exon structure of the glycophorin A and B genes
by oligonucleotide mapping. The results suggested a complex evolution of
the glycophorin genes. Huang et al. (1987) presented evidence derived
from protein and genomic DNA analyses that erythrocytes of 2 unrelated
persons homozygous for the S--s--U-- blood group phenotype lack
delta-glycophorin as a result of a delta-glycophorin gene deletion.
Dantu and Stones are 2 variant antigens carried by hybrid glycoproteins
that appear to be products of delta and alpha glycophorin fusion genes.
In Stones, symbolized St(a), the junction is from amino acid residue 26
or 28 of delta to residue 59 or 61 of alpha, whereas in Dantu, residue
38 or 39 of delta is joined to residue 71 or 72 of alpha.
Huang and Blumenfeld (1988) delineated the structure of the alpha and
delta glycophorins at the genomic level in the DNA from a 3-generation
black family in which both the presence of Dantu and Mi-III (another
rare MNs antigen) and the absence of delta-glycophorin were seen. Kudo
and Fukuda (1989) compared the genomic structures of GPA and GPB; they
consist of 7 and 5 exons, respectively, and both genes have more than
95% identical sequence from the 5-prime flanking region to the region
about 1 kb downstream from the exon encoding the transmembrane region.
In this homologous part of the genes, GPB lacks 1 exon due to a point
mutation at the 5-prime splicing site of the third intron, which
inactivates the 5-prime cleavage event of splicing and leads to ligation
of the second to the fourth exon. No homology could be detected in the
3-prime ends of the 2 genes. The transition from homologous to
nonhomologous sequences is located within Alu repeat sequences. An
ancestral genomic structure appears to have been maintained in the GPA
gene, whereas the GPB gene acquired 3-prime sequences different from
those of the GPA gene by homologous recombination at the Alu repeats
during or after gene duplication. Onda et al. (1993) identified the
putative precursor genomic segment located downstream from the GPA gene.
The isolated genomic clones contained an Alu sequence that appeared to
be involved in the recombination. Downstream from the Alu sequence, the
nucleotide sequence of the precursor genomic segment was almost
identical to that of the GPB or GPE gene (138590). In contrast, the
upstream sequence of the genomic segment differed entirely from that of
the GPA, GPB, and GPE genes. They interpreted the results as indicating
that one of the duplicated ancestral glycophorin genes acquired a unique
3-prime sequence by unequal crossing-over through its Alu sequence and
the further downstream Alu sequence present in the duplicated gene.
Further duplication and divergence of this gene yielded the GPB and GPE
genes. Onda et al. (1993) mapped the precursor genomic sequence to
4q28-q31 by in situ hybridization.
Red cells with the rare En(a-) variant are resistant to falciparum
malaria (see 611162) (Pasvol et al., 1982). Such cells lack glycophorin
A (Siebert and Fukuda, 1986). The rare U(-) variant of the Ss system,
which lacks the other major sialoglycoprotein, glycophorin B, is
relatively resistant to invasion. Wr(b)-negative cells are also
resistant to invasion by P. falciparum despite the fact that they have
normal amounts of glycophorins A and B on their surface. All of these
observations, as well as experiments using antibodies to glycophorins
and certain sugars, particularly N-acetylglucosamine, have led to a
tentative model of the role of glycophorin in the red cell invasion of
P. falciparum (Pasvol and Wilson, 1982).
Onda and Fukuda (1995) isolated several P1 plasmid clones with which
they characterized the organization of the glycophorin A (GPA), B, and E
gene cluster which spans about 330 kb of chromosome 4q31. For each gene,
the first intron varies in size from 25 to 29 kb, while the intergenic
interval is approximately 80 kb. The authors proposed that the
GPA-GPB-GPE cluster arose by 2 successive duplications and a number of
subsequent events, including a gene conversion between the exon 2 region
of GPA and GPE.
EVOLUTION
Glycophorin A (GYPA; 111300) and B, which determine the MN and Ss blood
types, respectively, are 2 major receptors that are expressed on
erythrocyte surfaces and interact with Plasmodium falciparum ligands. Ko
et al. (2011) analyzed nucleotide diversity of the glycophorin gene
family in 15 African populations with different levels of malaria
exposure. High levels of nucleotide diversity and gene conversion were
found at these genes. Ko et al. (2011) identified a haplotype causing 3
amino acid changes in the extracellular domain of glycophorin B. This
haplotype might have evolved adaptively in 5 populations with high
exposure to malaria. Ko et al. (2011) observed divergent patterns of
genetic variation between these duplicated genes and between different
extracellular domains of GYPA. By contrast, Ko et al. (2011) observed an
allele frequency spectrum skewed toward a significant excess of
intermediate-frequency alleles at GYPA exon 2 in many populations; the
degree of spectrum distortion was correlated with malaria exposure,
possibly because of the joint effects of gene conversion and balancing
selection.
*FIELD* SA
Marchesi et al. (1972)
*FIELD* RF
1. Ferrari, B.; Pavia, A. A.: Blood group antigens: synthesis of
Ss antigenic peptides related to human glycophorin B. Int. J. Peptide
Protein Res. 28: 456-461, 1986.
2. Huang, C.-H.; Blumenfeld, O. O.: Characterization of a genomic
hybrid specifying the human erythrocyte antigen Dantu: Dantu gene
is duplicated and linked to a delta glycophorin gene deletion. Proc.
Nat. Acad. Sci. 85: 9640-9644, 1988.
3. Huang, C.-H.; Johe, K.; Moulds, J. J.; Siebert, P. D.; Fukuda,
M.; Blumenfeld, O. O.: Delta-glycophorin (glycophorin B) gene deletion
in two individuals homozygous for the S--s--U-- blood group phenotype. Blood 70:
1830-1835, 1987.
4. Ko, W.-Y.; Kaercher, K. A.; Giombini, E.; Marcatili, P.; Froment,
A.; Ibrahim, M.; Lema, G.; Nyambo, T. B.; Omar, S. A.; Wambebe, C.;
Ranciaro, A.; Hirbo, J. B.; Tishkoff, S. A.: Effects of natural selection
and gene conversion on the evolution of human glycophorins coding
for MNS blood polymorphisms in malaria-endemic African populations. Am.
J. Hum. Genet. 88: 741-754, 2011.
5. Kudo, S.; Fukuda, M.: Structural organization of glycophorin A
and B genes: glycophorin B gene evolved by homologous recombination
at Alu repeat sequences. Proc. Nat. Acad. Sci. 86: 4619-4623, 1989.
6. Marchesi, V. T.; Tillack, T. M.; Jackson, R. L.; Segrest, J. P.;
Scott, R. E.: Chemical characterization and surface orientation of
the major glycoprotein of the human erythrocyte membrane. Proc. Nat.
Acad. Sci. 69: 1445-1449, 1972.
7. Mawby, W. J.; Anstee, D. J.; Tanner, M. J. A.: Immunochemical
evidence for hybrid sialoglycoproteins of human erythrocytes. Nature 291:
161-162, 1981.
8. Onda, M.; Fukuda, M.: Detailed physical mapping of the genes encoding
glycophorins A, B, and E, as revealed by P1 plasmids containing human
genomic DNA. Gene 159: 225-230, 1995.
9. Onda, M.; Kudo, S.; Rearden, A.; Mattei, M.-G.; Fukuda, M.: Identification
of a precursor genomic segment that provided a sequence unique to
glycophorin B and E genes. Proc. Nat. Acad. Sci. 90: 7220-7224,
1993.
10. Pasvol, G.; Wainscoat, J. S.; Weatherall, D. J.: Erythrocytes
deficient in glycophorin resist invasion by the malarial parasite
Plasmodium falciparum. Nature 297: 64-66, 1982.
11. Pasvol, G.; Wilson, R. J. M.: The interaction of malaria parasites
with red blood cells. Brit. Med. Bull. 38: 133-140, 1982.
12. Race, R. R.; Sanger, R.: Blood Groups in Man. Oxford: Blackwell
(pub.) (6th ed.): 1975. Pp. 92-138.
13. Siebert, P. D.; Fukuda, M.: Isolation and characterization of
human glycophorin A cDNA clones by a synthetic oligonucleotide approach:
nucleotide sequence and mRNA structure. Proc. Nat. Acad. Sci. 83:
1665-1669, 1986.
14. Siebert, P. D.; Fukuda, M.: Molecular cloning of a human glycophorin
B cDNA: nucleotide sequence and genomic relationship to glycophorin
A. Proc. Nat. Acad. Sci. 84: 6735-6739, 1987. Note: Erratum: Proc.
Nat. Acad. Sci. 85: 421 only, 1988.
*FIELD* CN
Ada Hamosh - updated: 4/24/2012
Alan F. Scott - updated: 8/9/1995
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 11/13/2012
alopez: 4/24/2012
terry: 4/24/2012
mgross: 7/9/2007
carol: 3/17/2004
carol: 9/10/1999
terry: 7/24/1998
terry: 4/17/1996
mark: 3/7/1996
davew: 8/18/1994
terry: 5/13/1994
carol: 10/4/1993
supermim: 3/16/1992
carol: 3/20/1991
*RECORD*
*FIELD* NO
111740
*FIELD* TI
+111740 BLOOD GROUP--Ss LOCUS; Ss
GLYCOPHORIN B, INCLUDED; GPB, INCLUDED;;
GYPB, INCLUDED
read more*FIELD* TX
Ss and MN (GYPA; 111300) are closely linked but separate gene loci on
chromosome 4 (4q28-q31). Several instances of recombination between the
loci have been observed (see review by Race and Sanger, 1975). Close
linkage of the genes for the two sialoglycoproteins that carry the MN
and Ss specificities, respectively, is also indicated by the
identification of hybrid molecules that appear to have arisen by a
Lepore-type mechanism (Mawby et al., 1981). The erythrocyte
glycophorins, which lie partly within the cell membrane and partly
exposed to the exterior, contain 203 amino acids. The amino-terminal
half is exposed and is the one that bears the oligosaccharide complexes
that determine blood-group antigen specificities and serve as receptors
for viruses and plant agglutinins. As indicated in 111300, the Ss blood
group antigens are located on glycophorin B. The structural difference
between SS and ss specificities is a methionine-to-threonine
polymorphism at position 29. Ferrari and Pavia (1986) synthesized 2
peptides, each 8 amino acids long, carrying the Ss specificities: SS,
asn-gly-glu-met-gly-gln-leu-val; ss, asn-gly-glu-thr-gly-gln-leu-val.
Glycophorin C is the site of the Gerbich blood group antigen specificity
(110750). Siebert and Fukuda (1987) isolated a cDNA for human
glycophorin B and determined its nucleotide sequence. They used RNA blot
hybridization with both cDNA and synthetic oligonucleotide probes to
prove that glycophorins A and B are negatively and coordinately
regulated by a tumor-promoting phorbol ester. They established,
furthermore, the intron/exon structure of the glycophorin A and B genes
by oligonucleotide mapping. The results suggested a complex evolution of
the glycophorin genes. Huang et al. (1987) presented evidence derived
from protein and genomic DNA analyses that erythrocytes of 2 unrelated
persons homozygous for the S--s--U-- blood group phenotype lack
delta-glycophorin as a result of a delta-glycophorin gene deletion.
Dantu and Stones are 2 variant antigens carried by hybrid glycoproteins
that appear to be products of delta and alpha glycophorin fusion genes.
In Stones, symbolized St(a), the junction is from amino acid residue 26
or 28 of delta to residue 59 or 61 of alpha, whereas in Dantu, residue
38 or 39 of delta is joined to residue 71 or 72 of alpha.
Huang and Blumenfeld (1988) delineated the structure of the alpha and
delta glycophorins at the genomic level in the DNA from a 3-generation
black family in which both the presence of Dantu and Mi-III (another
rare MNs antigen) and the absence of delta-glycophorin were seen. Kudo
and Fukuda (1989) compared the genomic structures of GPA and GPB; they
consist of 7 and 5 exons, respectively, and both genes have more than
95% identical sequence from the 5-prime flanking region to the region
about 1 kb downstream from the exon encoding the transmembrane region.
In this homologous part of the genes, GPB lacks 1 exon due to a point
mutation at the 5-prime splicing site of the third intron, which
inactivates the 5-prime cleavage event of splicing and leads to ligation
of the second to the fourth exon. No homology could be detected in the
3-prime ends of the 2 genes. The transition from homologous to
nonhomologous sequences is located within Alu repeat sequences. An
ancestral genomic structure appears to have been maintained in the GPA
gene, whereas the GPB gene acquired 3-prime sequences different from
those of the GPA gene by homologous recombination at the Alu repeats
during or after gene duplication. Onda et al. (1993) identified the
putative precursor genomic segment located downstream from the GPA gene.
The isolated genomic clones contained an Alu sequence that appeared to
be involved in the recombination. Downstream from the Alu sequence, the
nucleotide sequence of the precursor genomic segment was almost
identical to that of the GPB or GPE gene (138590). In contrast, the
upstream sequence of the genomic segment differed entirely from that of
the GPA, GPB, and GPE genes. They interpreted the results as indicating
that one of the duplicated ancestral glycophorin genes acquired a unique
3-prime sequence by unequal crossing-over through its Alu sequence and
the further downstream Alu sequence present in the duplicated gene.
Further duplication and divergence of this gene yielded the GPB and GPE
genes. Onda et al. (1993) mapped the precursor genomic sequence to
4q28-q31 by in situ hybridization.
Red cells with the rare En(a-) variant are resistant to falciparum
malaria (see 611162) (Pasvol et al., 1982). Such cells lack glycophorin
A (Siebert and Fukuda, 1986). The rare U(-) variant of the Ss system,
which lacks the other major sialoglycoprotein, glycophorin B, is
relatively resistant to invasion. Wr(b)-negative cells are also
resistant to invasion by P. falciparum despite the fact that they have
normal amounts of glycophorins A and B on their surface. All of these
observations, as well as experiments using antibodies to glycophorins
and certain sugars, particularly N-acetylglucosamine, have led to a
tentative model of the role of glycophorin in the red cell invasion of
P. falciparum (Pasvol and Wilson, 1982).
Onda and Fukuda (1995) isolated several P1 plasmid clones with which
they characterized the organization of the glycophorin A (GPA), B, and E
gene cluster which spans about 330 kb of chromosome 4q31. For each gene,
the first intron varies in size from 25 to 29 kb, while the intergenic
interval is approximately 80 kb. The authors proposed that the
GPA-GPB-GPE cluster arose by 2 successive duplications and a number of
subsequent events, including a gene conversion between the exon 2 region
of GPA and GPE.
EVOLUTION
Glycophorin A (GYPA; 111300) and B, which determine the MN and Ss blood
types, respectively, are 2 major receptors that are expressed on
erythrocyte surfaces and interact with Plasmodium falciparum ligands. Ko
et al. (2011) analyzed nucleotide diversity of the glycophorin gene
family in 15 African populations with different levels of malaria
exposure. High levels of nucleotide diversity and gene conversion were
found at these genes. Ko et al. (2011) identified a haplotype causing 3
amino acid changes in the extracellular domain of glycophorin B. This
haplotype might have evolved adaptively in 5 populations with high
exposure to malaria. Ko et al. (2011) observed divergent patterns of
genetic variation between these duplicated genes and between different
extracellular domains of GYPA. By contrast, Ko et al. (2011) observed an
allele frequency spectrum skewed toward a significant excess of
intermediate-frequency alleles at GYPA exon 2 in many populations; the
degree of spectrum distortion was correlated with malaria exposure,
possibly because of the joint effects of gene conversion and balancing
selection.
*FIELD* SA
Marchesi et al. (1972)
*FIELD* RF
1. Ferrari, B.; Pavia, A. A.: Blood group antigens: synthesis of
Ss antigenic peptides related to human glycophorin B. Int. J. Peptide
Protein Res. 28: 456-461, 1986.
2. Huang, C.-H.; Blumenfeld, O. O.: Characterization of a genomic
hybrid specifying the human erythrocyte antigen Dantu: Dantu gene
is duplicated and linked to a delta glycophorin gene deletion. Proc.
Nat. Acad. Sci. 85: 9640-9644, 1988.
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*FIELD* CN
Ada Hamosh - updated: 4/24/2012
Alan F. Scott - updated: 8/9/1995
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
terry: 11/13/2012
alopez: 4/24/2012
terry: 4/24/2012
mgross: 7/9/2007
carol: 3/17/2004
carol: 9/10/1999
terry: 7/24/1998
terry: 4/17/1996
mark: 3/7/1996
davew: 8/18/1994
terry: 5/13/1994
carol: 10/4/1993
supermim: 3/16/1992
carol: 3/20/1991