CD133  PROML1(prominin 1), AC133
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 3 glycoprotein, 5 span
Hematopoietic Cell
Stem Cell
Progenitor Cell
Endothelial Cell
Epithelial Cell
Pancreas
Prostate
Kidney
Liver
Lung
Brain
Heart
Blood Cell
Placenta
120 / 120

Expression
CD133 is selectively expressed on CD34 hematopoietic stem and progenitor cells in adult fetal bone marrow, fetal liver, cord blood and adult peripheral blood but is not detected on other blood cells.  It is expressed on a number of nonlymphoid tissues including retina, pancreas, placenta, kidney, liver, lung, brain and heart.  The CD133 positive cells are CD90 Thy-1 positive, most of the CD117 c-kit positive, and most of the HLA-DR positive population of progenitors.  CD34 bright CD133 positive cells are predominantly negative for other erythroid progenitor markers such as CD36 and glycophorin A and are negative/dim for the activation marker CD71.  CD133 expression has been demonstrated in developing the epithelium, neuroepithelium, kidney and gut in 5 week old human embryos, in the colon carcinoma cell line Caco 2, in the teratocarcinoma cell line NT-2, in retina and retinoblastoma cell lines which express the CD133 antigen, and in endothelial cell precursors hemangioblasts.  Of the known antibodies 5 of the 6 show cross-blocking and hence recognize the same or a related epitope, whereas AC141 is the 1 exception.  AC141 submitted as antibody #70382 to HLDA 7 recognizes an epitope of the CD133 molecule which is spatially distinct from that recognized by all other known antibodies. 

CD133 is concentrated in microvilli and other plasma membrane protrusions of stem/progenitor cells, and in the apical but not the baso-lateral membrane surface of some epithelial cells.  Expression patterns generally mimic those of the murine prominin molecule, although the CD133 antigen has not yet been demonstrated on adult epithelial tissue.


Structure
MOLECULAR FAMILY NAME: Belongs to the prominin family.

CD133 is a multi-pass type-3, 5-span, 865 aa transmembrane glycoprotein.  It contains a short 85 aa extracellular domain which contains a N-terminus outside the cell, 2 closely spaced short intracellular loops, 2 long extracellular loops (the first has 255 aa and the second has 290 aa), 1 intracellular C-terminus inside the cell and 8 potential N-glycosylation sites, a transmembrane domain and a 50 aa C-terminal cytoplasmic domain.  CD133 belongs to a new molecular family of 5-TM proteins.  CD133 and prominin in the mouse were the 1st descriptions of a 5-TM glycoprotein structure.  This "family" includes members from several different species, which may be homologs, including human, mouse, rat, fly and worm. 

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
purified CD34+ cells from peripheral blood and fetal liver and retinoblastoma 120 kDa 120 kDa Deglycosylated MW is 97 kDa
Caco2 cells 120 kDa 120 kDa Deglycosylated MW is 97 kDa

POST-TRANSCRIPTIONAL MODIFICATION

There is no known alternate splicing of the CD133 transcript.  The message stability has not been determined.

POST-TRANSLATIONAL MODIFICATION

The CD133 sequence contains 8 potential N-linked glycosylation sites.  All epitopes combining sites so far identified are thought to be sugar or sugar dependent epitopes, which are trypsin, neuraminidase and chymopapain resistant.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD133: No information.

Function
No natural ligand has been demonstrated for CD133 and its function in hematopoietic tissue is unknown. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD133 IN INTACT ANIMAL

CD133 is a stem cell marker and its application has identified and isolated hematopoietic stem cells, including isolation for stem cell transplantation and has been used as an alternative to the widely used CD34.  The CD133 positive fraction of human bone marrow, cord blood and peripheral blood have been shown to efficiently engraft in xenotransplantation models, and have been shown to contain the majority of the granulocyte/macrophage precursors, NOD/SCID repopulating cells and CD34+ dendritic cell precursors.  Phenotypically, CD133 positive cells in blood and marrow are CD34 bright, with CD34 dim CD71 bright cells being negative for CD133.  Many leukemias express CD133 as well as CD34 but some invesigators have noted leukemic blasts which are CD133+ and CD34-.  Defects in CD133 is responsible for retinal degeneration in an Indian pedigree. 


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD133: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD133: No information.

ADDITONAL INSIGHTS

There are 2 epitopes which are distinguished with mAbs AC133 and AC141.  CD133 has been noted in some acute myelogenous leukemias (AML) and in myelodysplastic syndrome (MDS).  It has been seen in the human fetal spinal cord and brain.   AC133 antibody routinely stains the blood vessel endothelium, whereas AC141 staining is routinely absent.  The biological significance of this differential epitope expression is not known.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8842O43490
Antibodies

Revised June 25, 2008


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