P04921 (GLPC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycophorin-C

Alternative name(s):
Glycoconnectin
Glycophorin-D
Short name=GPD
Glycoprotein beta
PAS-2'
Sialoglycoprotein D
CD_antigen=CD236

Gene names

Name:	GYPC
Synonyms:	GLPC, GPC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	128 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This protein is a minor sialoglycoprotein in human erythrocyte membranes. The blood group Gerbich antigens and receptors for Plasmodium falciparum merozoites are most likely located within the extracellular domain. Glycophorin-C plays an important role in regulating the stability of red cells.
Subcellular location	Cell membrane; Single-pass type III membrane protein. Note: Linked to the membrane via band 4.1.
Tissue specificity	Glycophorin-C is expressed in erythrocytes. Glycophorin-D is ubiquitous.
Post-translational modification	O-glycosylated with core 1 or possibly core 8 glycans. Ref.12 Ref.20
Polymorphism	GYPC is responsible for the Gerbich blood group system. Deletion of exon 3 in GYPC changes the serologic phenotype of the Gerbich blood group system, resulting in Ge negativity. Ge negative individuals are protected against severe malaria due to erythrocytes resistance to Plasmodium falciparum invasion [MIM:611162].
Sequence similarities	Belongs to the glycophorin-C family.
Sequence caution	The sequence CAA32093.1 differs from that shown. Reason: Frameshift at position 35.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Sialic acid
Molecular function	Blood group antigen
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular component	cortical cytoskeleton Inferred from direct assay PubMed 16669616. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction PubMed 16669616. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform Glycophorin-C (identifier: P04921-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform Glycophorin-D (identifier: P04921-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 128	128	Glycophorin-C		PRO_0000149050
Regions
	Topological domain	1 – 57	57	Extracellular
	Transmembrane	58 – 81	24	Helical; Signal-anchor for type III membrane protein
	Topological domain	82 – 128	47	Cytoplasmic
Sites
	Site	8	1	Not glycosylated; in variant Webb antigen
Amino acid modifications
	Modified residue	104	1	Phosphoserine Ref.19
	Glycosylation	3	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	4	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	6	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	8	1	N-linked (GlcNAc...) Ref.12
	Glycosylation	9	1	O-linked (GalNAc...) Ref.12
	Glycosylation	10	1	O-linked (GalNAc...) Ref.12
	Glycosylation	15	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	24	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	26	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	27	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	28	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	31	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	32	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	33	1	O-linked (GalNAc...) Ref.9 Ref.12
	Glycosylation	42	1	O-linked (GalNAc...) Ref.9 Ref.12 Ref.20
Natural variations
	Alternative sequence	1 – 21	21	Missing in isoform Glycophorin-D.		VSP_001777
	Natural variant	8	1	N → S in Webb (WB) antigen.		VAR_003193
	Natural variant	14	1	L → F in Duch (DH(a)) antigen.		VAR_003194
	Natural variant	23	1	A → S in Ahonen (AN(a)) antigen.		VAR_003195
	Natural variant	124	1	K → E. Ref.6 Corresponds to variant rs28370000 [ dbSNP | Ensembl ].		VAR_021342

Sequences

	Sequence		Length	Mass (Da)
	Isoform Glycophorin-C [UniParc]. Last modified August 13, 1987. Version 1. Checksum: C9C654009A5642D5	FASTA	128	13,811
	10 20 30 40 50 60 MWSTRSPNST AWPLSLEPDP GMASASTTMH TTTIAEPDPG MSGWPDGRME TSTPTIMDIV 70 80 90 100 110 120 VIAGVIAAVA IVLVSLLFVM LRYMYRHKGT YHTNEAKGTE FAESADAALQ GDPALQDAGD SSRKEYFI
	Isoform Glycophorin-D [UniParc]. Checksum: B7D025DEF0555290	FASTA	107	11,499
	10 20 30 40 50 60 MASASTTMHT TTIAEPDPGM SGWPDGRMET STPTIMDIVV IAGVIAAVAI VLVSLLFVML 70 80 90 100 RYMYRHKGTY HTNEAKGTEF AESADAALQG DPALQDAGDS SRKEYFI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of cDNA clones and complete amino acid sequence of human erythrocyte glycophorin C." Colin Y., Rahuel C., London J., Romeo P.-H., D'Auriol L., Galibert F., Cartron J.-P. J. Biol. Chem. 261:229-233(1986) [PubMed: 2416746] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLYCOPHORIN-C).
[2]	"Human erythrocyte membrane sialoglycoprotein beta. The cDNA sequence suggests the absence of a cleaved N-terminal signal sequence." High S., Tanner M.J.A. Biochem. J. 243:277-280(1987) [PubMed: 3606576] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLYCOPHORIN-C).
[3]	"Structure of human erythrocyte glycophorin C deduced from cDNA analysis." Cartron J.-P., Colin Y., le van Kim C., Rahuel C., Blanchard D., Bloy C., London J. Rev. Fr. Transfus. Immunohematol. 29:267-285(1986) [PubMed: 3544149] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLYCOPHORIN-C).
[4]	"Gerbich blood group deficiency of the Ge:-1,-2,-3 and Ge:-1,-2,3 types. Immunochemical study and genomic analysis with cDNA probes." le van Kim C., Colin Y., Blanchard D., Dahr W., London J., Cartron J.-P. Eur. J. Biochem. 165:571-579(1987) [PubMed: 3595602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GLYCOPHORIN-C). Tissue: Liver.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GLYCOPHORIN-C).
[6]	SeattleSNPs variation discovery resource Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-124.
[7]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GLYCOPHORIN-C).
[9]	"Glycophorins B and C from human erythrocyte membranes. Purification and sequence analysis." Blanchard D., Dahr W., Hummel M., Latron F., Beyreuther K., Cartron J.-P. J. Biol. Chem. 262:5808-5811(1987) [PubMed: 3571235] [Abstract] Cited for: PROTEIN SEQUENCE OF 49-88.
[10]	"Isolation and structural analysis of glycophorin C." Dahr W., Humel M., Blanchard D., Beyreuther K., Cartron J.-P. Biol. Chem. Hoppe-Seyler 366:777-778(1985) Cited for: PROTEIN SEQUENCE OF 1-87. Tissue: Blood.
[11]	"A revision of the N-terminal structure of sialoglycoprotein D (glycophorin C) from human erythrocyte membranes." Dahr W., Beyreuther K. Biol. Chem. Hoppe-Seyler 366:1067-1070(1985) [PubMed: 4074499] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-48. Tissue: Blood.
[12]	"N-terminal amino acid sequence of sialoglycoprotein D (glycophorin C) from human erythrocyte membranes." Dahr W., Beyreuther K., Kordowicz M., Krueger J. Eur. J. Biochem. 125:57-62(1982) [PubMed: 7106126] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 1-48, GLYCOSYLATION AT SER-3; THR-4; SER-6; ASN-8; SER-9; THR-10; SER-15; SER-24; SER-26; THR-27; THR-28; THR-31; THR-32; THR-33 AND SER-42. Tissue: Blood.
[13]	"Structural homology between glycophorins C and D of human erythrocytes." El-Maliki B., Blanchard D., Dahr W., Beyreuther K., Cartron J.-P. Eur. J. Biochem. 183:639-643(1989) [PubMed: 2776757] [Abstract] Cited for: PROTEIN SEQUENCE OF 30-91.
[14]	"An ubiquitous isoform of glycophorin C is produced by alternative splicing." le van Kim C., Mitjavila M.T., Clerget M., Cartron J.-P., Colin Y. Nucleic Acids Res. 18:3076-3076(1990) [PubMed: 2349119] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-22 AND 42-128. Tissue: Spleen.
[15]	"Structure of the promoter region and tissue specificity of the human glycophorin C gene." le van Kim C., Colin Y., Mitjavila M.T., Clerget M., Dubart A., Nakazawa M., Vainchenker W., Cartron J.-P. J. Biol. Chem. 264:20407-20414(1989) [PubMed: 2584223] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
[16]	"Rearrangements of the red-cell membrane glycophorin C (sialoglycoprotein beta) gene. A further study of alterations in the glycophorin C gene." High S., Tanner M.J.A., Macdonald E.N., Anstee D.J. Biochem. J. 262:47-54(1989) [PubMed: 2818576] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 17-128.
[17]	"Human erythrocyte glycophorin C. Gene structure and rearrangement in genetic variants." Colin Y., le van Kim C., Tsapis A., Clerget M., D'Auriol L., London J., Galibert F., Cartron J.-P. J. Biol. Chem. 264:3773-3780(1989) [PubMed: 2917976] [Abstract] Cited for: GENE STRUCTURE.
[18]	"Plasmodium falciparum erythrocyte invasion through glycophorin C and selection for Gerbich negativity in human populations." Maier A.G., Duraisingh M.T., Reeder J.C., Patel S.S., Kazura J.W., Zimmerman P.A., Cowman A.F. Nat. Med. 9:87-92(2003) [PubMed: 12469115] [Abstract] Cited for: POLYMORPHISM, INVOLVEMENT IN PROTECTION AGAINST MALARIA.
[19]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed: 22171320] [Abstract] Cited for: GLYCOSYLATION AT SER-42, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[21]	"Molecular characterization of erythrocyte glycophorin C variants." Chang S., Reid M.E., Conboy J., Kan Y.W., Mohandas N. Blood 77:644-648(1991) [PubMed: 1991173] [Abstract] Cited for: VARIANT BLOOD GROUP ANTIGEN WB.
[22]	"Point mutation in the glycophorin C gene results in the expression of the blood group antigen Dha." King M.J., Avent N.D., Mallinson G., Reid M.E. Vox Sang. 63:56-58(1992) [PubMed: 1413665] [Abstract] Cited for: VARIANT BLOOD GROUP ANTIGEN DH(A).
[23]	"A point mutation in the GYPC gene results in the expression of the blood group Ana antigen on glycophorin D but not on glycophorin C: further evidence that glycophorin D is a product of the GYPC gene." Daniels G., King M.J., Avent N.D., Khalid G., Reid M.E., Mallinson G., Symthe J., Cedergren B. Blood 82:3198-3203(1993) [PubMed: 8219208] [Abstract] Cited for: VARIANT BLOOD GROUP ANTIGEN AN(A).
+	Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

Wikipedia

Glycophorin C entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M11802 mRNA. Translation: AAA60023.1.
M36284 mRNA. Translation: AAA52625.1.
X12496 mRNA. Translation: CAA31016.1.
X51973 mRNA. Translation: CAA36235.1.
M28335 mRNA. Translation: AAA52574.1.
AK312032 mRNA. Translation: BAG34969.1.
AY838876 Genomic DNA. Translation: AAV80423.1.
AC013474 Genomic DNA. Translation: AAY14660.1.
BC106051 mRNA. Translation: AAI06052.1.
BC104246 mRNA. Translation: AAI04247.1.
BC104247 mRNA. Translation: AAI04248.1.
X14242 Genomic DNA. Translation: CAA32458.1.
M29662 Genomic DNA. Translation: AAA52626.1.
X13890, X13892, X13893 Genomic DNA. Translation: CAA32093.1. Frameshift.

IPI

IPI00026299.
IPI00218128.

PIR

GFHUC. A92573.

RefSeq

NP_001243513.1. NM_001256584.1.
NP_002092.1. NM_002101.4.
NP_058131.1. NM_016815.3.

UniGene

Hs.59138.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EJY	NMR	-	B	117-128	[»]

ProteinModelPortal

P04921.

ModBase

Search...

Protein-protein interaction databases

STRING

P04921.

PTM databases

PhosphoSite

P04921.

Polymorphism databases

DMDM

121407.

Proteomic databases

PRIDE

P04921.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000259254; ENSP00000259254; ENSG00000136732.

GeneID

2995.

KEGG

hsa:2995.

UCSC

uc002tnq.3. human.

Organism-specific databases

CTD

2995.

GeneCards

GC02P127413.

HGNC

HGNC:4704. GYPC.

HPA

CAB009445.
HPA008965.

MIM

110750. gene+phenotype.
611162. phenotype.

neXtProt

NX_P04921.

PharmGKB

PA29082.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG146330.

GeneTree

ENSGT00510000049102.

HOGENOM

HOG000112742.

HOVERGEN

HBG094619.

InParanoid

P04921.

KO

K06576.

OrthoDB

EOG49GKJC.

PhylomeDB

P04921.

Gene expression databases

ArrayExpress

P04921.

Bgee

P04921.

CleanEx

HS_GYPC.

Genevestigator

P04921.

GermOnline

ENSG00000136732. Homo sapiens.

Family and domain databases

InterPro

IPR024834. Glycophorin-C.
IPR003585. Neurexin-like.
[Graphical view]

PANTHER

PTHR26398:SF9. PTHR26398:SF9. 1 hit.

SMART

SM00294. 4.1m. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P04921.

NextBio

11870.

SOURCE

Search...

Entry information

Entry name

GLPC_HUMAN

Accession

Primary (citable) accession number: P04921
Secondary accession number(s): B2R522, Q53SV9, Q92642

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	May 16, 2012
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.