P13987 (CD59_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
CD59 glycoprotein

Alternative name(s):
1F5 antigen
20 kDa homologous restriction factor
Short name=HRF-20
Short name=HRF20
MAC-inhibitory protein
Short name=MAC-IP
MEM43 antigen
Membrane attack complex inhibition factor
Short name=MACIF
Membrane inhibitor of reactive lysis
Short name=MIRL
Protectin
CD_antigen=CD59

Gene names

Name:	CD59
Synonyms:	MIC11, MIN1, MIN2, MIN3, MSK21

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	128 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore. This inhibitor appears to be species-specific. Involved in signal transduction for T-cell activation complexed to a protein tyrosine kinase. The soluble form from urine retains its specific complement binding activity, but exhibits greatly reduced ability to inhibit MAC assembly on cell membranes.
Subunit structure	Interacts with T-cell surface antigen CD2. Ref.13
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor. Secreted. Note: Soluble form found in a number of tissues. Ref.12 Ref.16 Ref.20
Post-translational modification	N- and O-glycosylated. The N-glycosylation mainly consists of a family of biantennary complex-type structures with and without lactosamine extensions and outer arm fucose residues. Also significant amounts of triantennary complexes (22%). Variable sialylation also present in the Asn-43 oligosaccharide. The predominant O-glycans are mono-sialylated forms of the disaccharide, Gal-beta-1,3GalNAc, and their sites of attachment are probably on Thr-76 and Thr-77. The GPI-anchor of soluble urinary CD59 has no inositol-associated phospholipid, but is composed of seven different GPI-anchor variants of one or more monosaccharide units. Major variants contain sialic acid, mannose and glucosamine Sialic acid linked to an N-acetylhexosamine-galactose arm is present in two variants. Ref.11 Ref.16 Glycated. Glycation is found in diabetic subjects, but only at minimal levels in nondiabetic subjects. Glycated CD59 lacks MAC-inhibitory function and confers to vascular complications of diabetes.
Involvement in disease	CD59 deficiency (CD59D) [MIM:612300]: A deficiency resulting in chronic complement-mediated intravascular hemolysis, anemia, hemoglobinuria and thrombosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25
Sequence similarities	Contains 1 UPAR/Ly6 domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Disease	Hereditary hemolytic anemia
Domain	Signal
PTM	Disulfide bond GPI-anchor Glycation Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	blood coagulation Traceable author statement Ref.6. Source: ProtInc cell surface receptor signaling pathway Traceable author statement PubMed 7691713. Source: ProtInc negative regulation of activation of membrane attack complex Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	anchored to external side of plasma membrane Inferred from direct assay PubMed 9724629. Source: MGI compact myelin Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara sarcolemma Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TMED10	O35587	5	EBI-297972,EBI-4405327	From a different organism.
TMED2	Q15363	4	EBI-297972,EBI-998485

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 25

25

Ref.16

Chain

26 – 102

77

CD59 glycoprotein

PRO_0000036108

Propeptide

103 – 128

26

Removed in mature form

PRO_0000036109

Regions

Domain

26 – 108

83

UPAR/Ly6

Amino acid modifications

Lipidation

102

1

GPI-anchor amidated asparagine Ref.12 Ref.16 Ref.18 Ref.19 Ref.20

Glycosylation

43

1

N-linked (GlcNAc...) Ref.11 Ref.21

Glycosylation

66

1

N-linked (Glc) (glycation) Ref.17

Glycosylation

69

1

N-linked (Glc) (glycation) Ref.17

Glycosylation

76

1

O-linked (GlcNAc...) Probable

Glycosylation

77

1

O-linked (GlcNAc...) Probable

Disulfide bond

28 ↔ 51

Ref.12

Disulfide bond

31 ↔ 38

Ref.12

Disulfide bond

44 ↔ 64

Ref.12

Disulfide bond

70 ↔ 88

Ref.12

Disulfide bond

89 ↔ 94

Ref.12

Experimental info

Mutagenesis

29

1

Y → R: No loss of function.

Mutagenesis

33

1

N → R or Q: No loss of function.

Mutagenesis

37

1

D → R: No loss of function.

Mutagenesis

48

1

F → R: Some loss of function. Some lysis.

Mutagenesis

49

1

D → R: Loss of function. Lysis.

Mutagenesis

58

1

L → E: No loss of function.

Mutagenesis

63

1

K → E: No loss of function.

Mutagenesis

65

1

W → E: Complete loss of function. Lysis.

Mutagenesis

66

1

K → D: No loss of function. Ref.17

Mutagenesis

66

1

K → Q: Loss of glycation mediated inactivation. Ref.17

Mutagenesis

67

1

F → K: No loss of function.

Mutagenesis

69

1

H → Q: Loss of glycation mediated inactivation. Ref.17

Mutagenesis

72

1

F → E: Almost complete loss of function. Lysis.

Mutagenesis

78

1

R → E: Loss of function. Lysis.

Mutagenesis

79

1

L → D: No loss of function.

Mutagenesis

81

1

E → R: Almost complete loss of function. Lysis.

Mutagenesis

82

1

N → K: No loss of function.

Mutagenesis

87

1

Y → R: No loss of function.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

128

Helix Strand Turn

Details...

Beta strand

27 – 29

3

Beta strand

32 – 34

3

Beta strand

41 – 43

3

Beta strand

50 – 56

7

Beta strand

59 – 65

7

Helix

67 – 69

3

Helix

72 – 79

8

Beta strand

85 – 89

5

Beta strand

91 – 93

3

Helix

97 – 99

3

Sequences

	Sequence		Length	Mass (Da)
	P13987 [UniParc]. Last modified January 1, 1990. Version 1. Checksum: 2F0D29CBE3C28505	FASTA	128	14,177
	10 20 30 40 50 60 MGIQGGSVLF GLLLVLAVFC HSGHSLQCYN CPNPTADCKT AVNCSSDFDA CLITKAGLQV 70 80 90 100 110 120 YNKCWKFEHC NFNDVTTRLR ENELTYYCCK KDLCNFNEQL ENGGTSLSEK TVLLLVTPFL AAAWSLHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CD59, an LY-6-like protein expressed in human lymphoid cells, regulates the action of the complement membrane attack complex on homologous cells." Davies A., Simmons D.L., Hale G., Harrison R.A., Tighe H., Lachmann P.J., Waldmann H. J. Exp. Med. 170:637-654(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: T-cell.
[2]	"The CD59 antigen is a structural homologue of murine Ly-6 antigens but lacks interferon inducibility." Philbrick W.M., Palfree R.G.E., Roger G.E., Maher S.E., Bridgett M.M., Sirlin S., Bothwell A.L.M. Eur. J. Immunol. 20:87-92(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"20 KDa homologous restriction factor of complement resembles T cell activating protein." Okada H., Nagami Y., Takahashi K., Okada N., Hideshima T., Takizawa H., Kondo J. Biochem. Biophys. Res. Commun. 162:1553-1559(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Molecular cloning and characterization of MACIF, an inhibitor of membrane channel formation of complement." Sugita Y., Tobe T., Oda E., Tomita M., Yasukawa K., Yamaji N., Takemoto T., Furuichi K., Takayama M., Yano S. J. Biochem. 106:555-557(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Isolation and expression of the full-length cDNA encoding CD59 antigen of human lymphocytes." Sawada R., Ohashi K., Anaguchi H., Okazaki H., Hattori M., Minato N., Naruto M. DNA Cell Biol. 9:213-220(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"Structure of the CD59-encoding gene: further evidence of a relationship to murine lymphocyte antigen Ly-6 protein." Petranka J.G., Fleenor D.E., Sykes K., Kaufman R.E., Rosse W.F. Proc. Natl. Acad. Sci. U.S.A. 89:7876-7879(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]	"Gene structure of human CD59 and demonstration that discrete mRNAs are generated by alternative polyadenylation." Tone M., Walsh L.A., Waldmann H. J. Mol. Biol. 227:971-976(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[8]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[10]	"Complementary DNA sequence and deduced peptide sequence for CD59/MEM-43 antigen, the human homologue of murine lymphocyte antigen Ly-6C." Sawada R., Ohashi K., Okano K., Hattori M., Minato N., Naruto M. Nucleic Acids Res. 17:6728-6728(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-128.
[11]	"Structural composition and functional characterization of soluble CD59: heterogeneity of the oligosaccharide and glycophosphoinositol (GPI) anchor revealed by laser-desorption mass spectrometric analysis." Meri S., Lehto T., Sutton C.W., Tyynelaa J., Baumann M. Biochem. J. 316:923-935(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, MASS SPECTROMETRY, GLYCOSYLATION AT ASN-43, STRUCTURE OF CARBOHYDRATES.
[12]	"Determination of carboxyl-terminal residue and disulfide bonds of MACIF (CD59), a glycosyl-phosphatidylinositol-anchored membrane protein." Sugita Y., Nakano Y., Oda E., Noda K., Tobe T., Miura N.H., Tomita M. J. Biochem. 114:473-477(1993) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR AT ASN-102, DISULFIDE BONDS.
[13]	"The human complement regulatory protein CD59 binds to the alpha-chain of C8 and to the ''b'' domain of C9." Ninomiya H., Sims P.J. J. Biol. Chem. 267:13675-13680(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH C8 AND C9.
[14]	"Mapping the regions of the complement inhibitor CD59 responsible for its species selective activity." Yu J., Dong S., Rushmere N.K., Morgan B.P., Abagyan R., Tomlinson S. Biochemistry 36:9423-9428(1997) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION OF COMPLEMENT INHIBITORY DOMAIN.
[15]	"Mutational analysis of the active site and antibody epitopes of the complement-inhibitory glycoprotein, CD59." Bodian D.L., Davis S.J., Morgan B.P., Rushmere N.K. J. Exp. Med. 185:507-516(1997) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[16]	"The glycosylation of the complement regulatory protein, human erythrocyte CD59." Rudd P.M., Morgan B.P., Wormald M.R., Harvey D.J., van den Berg C.W., Davis S.J., Ferguson M.A., Dwek R.A. J. Biol. Chem. 272:7229-7244(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE OF CARBOHYDRATES, STRUCTURE OF THE GPI-ANCHOR, PROTEIN SEQUENCE OF N-TERMINUS.
[17]	"Molecular basis for a link between complement and the vascular complications of diabetes." Acosta J., Hettinga J., Flueckiger R., Krumrei N., Goldfine A., Angarita L., Halperin J. Proc. Natl. Acad. Sci. U.S.A. 97:5450-5455(2000) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY GLYCATION, GLYCATION AT LYS-66 AND HIS-69, MUTAGENESIS OF LYS-66 AND HIS-69.
[18]	"Proteomic analysis of glycosylphosphatidylinositol-anchored membrane proteins." Elortza F., Nuehse T.S., Foster L.J., Stensballe A., Peck S.C., Jensen O.N. Mol. Cell. Proteomics 2:1261-1270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment." Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N. J. Proteome Res. 5:935-943(2006) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"Computational approach for identification and characterization of GPI-anchored peptides in proteomics experiments." Omaetxebarria M.J., Elortza F., Rodriguez-Suarez E., Aloria K., Arizmendi J.M., Jensen O.N., Matthiesen R. Proteomics 7:1951-1960(2007) [PubMed] [Europe PMC] [Abstract] Cited for: GPI-ANCHOR AT ASN-102, MASS SPECTROMETRY.
[21]	"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry." Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F. Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-43, MASS SPECTROMETRY. Tissue: Milk.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"Three-dimensional solution structure of the extracellular region of the complement regulatory protein CD59, a new cell-surface protein domain related to snake venom neurotoxins." Kieffer B., Driscoll P.C., Campbell I.D., Willis A.C., van der Merwe P.A., Davis S.J. Biochemistry 33:4471-4482(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 26-95.
[24]	"Structure of a soluble, glycosylated form of the human complement regulatory protein CD59." Fletcher C.M., Harrison R.A., Lachmann P.J., Neuhaus D. Structure 2:185-199(1994) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 26-102. Tissue: Urine.
[25]	"Paroxysmal nocturnal hemoglobinuria due to hereditary nucleotide deletion in the HRF20 (CD59) gene." Motoyama N., Okada N., Yamashina M., Okada H. Eur. J. Immunol. 22:2669-2673(1992) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN CD59D.
+	Additional computationally mapped references.

Web resources

CD59base

CD59 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M27909 mRNA. Translation: AAA60543.1.
M95708 mRNA. Translation: AAA60957.1.
X16447 mRNA. Translation: CAA34467.1.
X17198 mRNA. Translation: CAA35059.1.
M34671 mRNA. Translation: AAA51952.1.
M84345 Genomic DNA. No translation available.
M84349, M84346, M84348 Genomic DNA. Translation: AAA88793.1.
Z14113, Z14114, Z14115 Genomic DNA. Translation: CAA78486.1.
BT007104 mRNA. Translation: AAP35768.1.
BC001506 mRNA. Translation: AAH01506.1.

IPI

IPI00011302.

PIR

RWHU59. A46252.

RefSeq

NP_000602.1. NM_000611.5.
NP_001120695.1. NM_001127223.1.
NP_001120697.1. NM_001127225.1.
NP_001120698.1. NM_001127226.1.
NP_001120699.1. NM_001127227.1.
NP_976074.1. NM_203329.2.
NP_976075.1. NM_203330.2.
NP_976076.1. NM_203331.2.

UniGene

Hs.278573.
Hs.709466.
Hs.710641.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CDQ	NMR	-	A	26-102	[»]
1CDR	NMR	-	A	26-102	[»]
1CDS	NMR	-	A	26-102	[»]
1ERG	NMR	-	A	26-95	[»]
1ERH	NMR	-	A	26-95	[»]
2J8B	X-ray	1.15	A	26-103	[»]
2OFS	X-ray	2.12	A	26-99	[»]
2UWR	X-ray	1.34	A	26-102	[»]
2UX2	X-ray	1.80	A/B/C	26-102	[»]

ProteinModelPortal

P13987.

ModBase

Search...

Protein-protein interaction databases

IntAct

P13987. 8 interactions.

MINT

MINT-5000502.

STRING

9606.ENSP00000340210.

PTM databases

GlycoSuiteDB

P13987.

PhosphoSite

P13987.

Polymorphism databases

DMDM

116021.

Proteomic databases

PaxDb

P13987.

PeptideAtlas

P13987.

PRIDE

P13987.

Protocols and materials databases

DNASU

966.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000351554; ENSP00000340210; ENSG00000085063.
ENST00000395850; ENSP00000379191; ENSG00000085063.
ENST00000415002; ENSP00000404822; ENSG00000085063.
ENST00000426650; ENSP00000402425; ENSG00000085063.
ENST00000437761; ENSP00000410182; ENSG00000085063.
ENST00000445143; ENSP00000403511; ENSG00000085063.
ENST00000525763; ENSP00000435179; ENSG00000085063.
ENST00000527577; ENSP00000432942; ENSG00000085063.
ENST00000528700; ENSP00000434617; ENSG00000085063.

GeneID

966.

KEGG

hsa:966.

UCSC

uc001mus.4. human.

Organism-specific databases

CTD

966.

GeneCards

GC11M033721.

H-InvDB

HIX0171358.

HGNC

HGNC:1689. CD59.

HPA

CAB001448.
HPA026494.

MIM

107271. gene.
612300. phenotype.

neXtProt

NX_P13987.

Orphanet

169464. CD59 deficiency.

PharmGKB

PA26228.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG83475.

HOGENOM

HOG000232180.

HOVERGEN

HBG005284.

InParanoid

P13987.

KO

K04008.

OMA

AAWSLHP.

OrthoDB

EOG451DSB.

PhylomeDB

P13987.

Enzyme and pathway databases

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.

Gene expression databases

ArrayExpress

P13987.

Bgee

P13987.

CleanEx

HS_CD59.

Genevestigator

P13987.

GermOnline

ENSG00000085063. Homo sapiens.

Family and domain databases

InterPro

IPR018363. CD59_antigen_CS.
IPR027101. CD59_glyco.
IPR016054. LY6_UPA_recep-like.
IPR001526. LY6_UPAR.
[Graphical view]

PANTHER

PTHR10036:SF0. PTHR10036:SF0. 1 hit.

Pfam

PF00021. UPAR_LY6. 1 hit.
[Graphical view]

SMART

SM00134. LU. 1 hit.
[Graphical view]

PROSITE

PS00983. LY6_UPAR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

CD59. human.

EvolutionaryTrace

P13987.

GenomeRNAi

966.

NextBio

4034.

SOURCE

Search...

Entry information

Entry name

CD59_HUMAN

Accession

Primary (citable) accession number: P13987

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 1, 1990
Last modified:	May 1, 2013
This is version 152 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.