CD59

Protein identityUniProt · HPA

UniProt accession

P13987

Gene

CD59

Ensembl

ENSG00000085063

Chromosome

11

Canonical length

128 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Golgi apparatus,Vesicles

Secretome location

Intracellular and membrane

OverviewNCBI Gene

This gene encodes a cell surface glycoprotein that regulates complement-mediated cell lysis, and it is involved in lymphocyte signal transduction. This protein is a potent inhibitor of the complement membrane attack complex, whereby it binds complement C8 and/or C9 during the assembly of this complex, thereby inhibiting the incorporation of multiple copies of C9 into the complex, which is necessary for osmolytic pore formation. This protein also plays a role in signal transduction pathways in the activation of T cells. Mutations in this gene cause CD59 deficiency, a disease resulting in hemolytic anemia and thrombosis, and which causes cerebral infarction. Multiple alternatively spliced transcript variants, which encode the same protein, have been identified for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

128 residues, UniProt reviewed canonical sequence.

>P13987|CD59
     1  MGIQGGSVLF GLLLVLAVFC HSGHSLQCYN CPNPTADCKT AVNCSSDFDA CLITKAGLQV
    61  YNKCWKFEHC NFNDVTTRLR ENELTYYCCK KDLCNFNEQL ENGGTSLSEK TVLLLVTPFL
   121  AAAWSLHP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CD59 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

1,376 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CD59.

Disease | AllUniProt

Conditions CD59 is implicated in, by any mechanism.

• Hemolytic anemia, CD59-mediated, with or without polyneuropathy (HACD59) MIM:612300

Disease | GeneticClinVar

11 pathogenic / likely-pathogenic of 122 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Primary CD59 deficiency

ReferencesPubMed · IEDB

Publications for CD59 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1

gnomAD pLI

0.61

gnomAD missense Z

-0.05

DepMap mean gene effect

0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• blood coagulation
• cell surface receptor signaling pathway
• negative regulation of activation of membrane attack complex
• negative regulation of complement activation
• negative regulation of complement-dependent cytotoxicity
• regulation of complement activation
• regulation of complement-dependent cytotoxicity

Molecular functions

• complement binding
• protein sequestering activity

Cellular components

• cell surface
• endoplasmic reticulum membrane
• endoplasmic reticulum-Golgi intermediate compartment membrane
• ER to Golgi transport vesicle membrane
• external side of plasma membrane
• extracellular exosome
• extracellular space
• focal adhesion
• Golgi membrane
• membrane
• plasma membrane
• specific granule membrane
• tertiary granule membrane
• transport vesicle
• vesicle

Protein domainsUniProt · Pfam · InterPro

• Ly-6 antigen/uPA receptor-like
• CD59 antigen, conserved site
• Snake toxin-like superfamily
• CD59 glycoprotein
• CD59 glycoprotein

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycation
• Glycoprotein
• GPI-anchor
• Hereditary hemolytic anemia
• Lipoprotein
• Membrane
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of CD59 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TMED2
• TMED10