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FLASH GENE

Symbol

CD59

contributors: mct - updated : 31-10-2012

HGNC name	CD59 molecule, complement regulatory protein
HGNC id	1689

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	33.47 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

Map	pter - HVBS1 - BDNF - FSHB - D11S158 - MPPED2 - D11S16 - D11S315 - D11S914 - D11S1322 - AN (PAX6 ) - WT1 WT1 - CD59 - LMO2 - CAT CAT - CD44 - RAG1 /RAG2 - cen
Authors	Hanson (92), Heckl-Östreicher (93), Bickmore (93), Schwartz (94), Gawin (95)
Text	seeWAGR

RNA

TRANSCRIPTS	type	messenger

text	encoding the same protein

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000611 4 - 7635 NP_000602 - 128 - 2006 16844690 NM_203329 5 - 7751 NP_976074 - 128 - 2006 16844690 NM_203330 6 - 7796 NP_976075 14.2 128 - 2006 16844690 NM_203331 5 - 7680 NP_976076 - 128 - 2006 16844690 NM_001127227 4 - 7573 NP_001120699 - 128 - 2006 16844690 NM_001127226 4 - 7629 NP_001120698 - 128 - 2006 16844690 NM_001127225 5 - 7694 NP_001120697 - 128 - 2006 16844690 NM_001127223 3 - 7801 NP_001120695 - 128 - 2006 16844690

EXPRESSION

Type

expressed in	(based on citations)
organ(s)

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic erthrocyte Lymphoid/Immune lymphocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	glycosyl-phosphatidylinositol (GPI) anchored membrane glycoprotein
	ten conserved cysteine residues
	a W40 AA of CD59 important to its anti-complement activity, and prohibition of this site may be a potential way to increase complement activity and to treat tumors
	one UPAR/Ly6 domain

conjugated

GlycoP

isoforms

Precursor

HOMOLOGY

interspecies

ortholog to murine lymphocyte antigen Ly-6L

Homologene

FAMILY

CATEGORY

antigen

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane

basic FUNCTION	homologous restriction factor (18 kD) binding through C8G to the membrane attack complex of complement as a membrane inhibitor of cell lysis
	functions as a co-receptor in natural killer cell activation
	inhibits assembly of the lytic membrane attack complex of complement by incorporation into the forming complex
	may inhibit the cytolytic activity of complement by binding to C8/C9 and protect host cell membranes against homologous membrane attack complex (MAC)
	broadly expressed GPI-anchored molecule, regulates formation of the membrane attack complex of the complement cascade
	CD55 inhibits the formation of C3 convertases, and CD59 prevents the terminal polymerisation of the membrane attack complex
	CD55 and CD59 restrict complement activation by inhibiting C3/C5 convertases activities and membrane attack complex formation, respectively (
	GPI-anchored membrane regulator of complement expressed on blood cells as well as peripheral tissues

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	membrane attack complex of complement
	physically associated with NKP46 and NCR3
	CD59 (complement defense 59) mRNA is a novel cleavage target of ERN1

cell & other

T cell activation

REGULATION

activated by

HBXIP, that upregulates CD46, CD55 and CD59 through p-ERK1/2/NFKB signaling to protect breast cancer from complement-dependent cytotoxicity

Other	regulated by EHD1 (role for EHD1 in regulating the trafficking of CD59, an endogenous GPI-AP, at early stages of trafficking through the endocytic pathway)

ASSOCIATED DISORDERS

corresponding disease(s)

CD59D

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in cardiac hypertrophy constitutional     --low   on peripheral blood leucocytes in T2DM patients with macrovascular diseases

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast may be a promising target in the gene therapy of breast cancer cancer     blockade of CD59 significantly enhanced the CD4(+) T cell response to two different tumor Ags

ANIMAL & CELL MODELS

	Cd59a inhibits systemic autoimmunity in MRL/lpr mice through a complement-independent mechanism
	Cd59 protects against angiotensin II-induced abdominal aortic aneurysms in mice
	number of endoneurial macrophages was significantly higher in Cd59a deficient mice compared to wildtypes at 1 day post-injury