CD105 ENG (Endoglin)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Endothelial Cell
Cytotrophoblast
Leukemia cell
Bone Marrow
Stromal Cell
Syncytiotrophoblast
Mesenchymal Cell
Endothelium
90 / 90
180 / 180

Expression
CD105 is expressed in vascular endothelial cells, particularly microvascular endothelium, in normal and neoplastic tissues undergoing angiogenesis, small and large vessels, stromal cells of certain tissues including bone marrow and erythroid precursors in fetal and adult bone marrow.  There is also expression on syncytiotrophoblasts throughout pregnancy and cytotrophoblasts transiently during the first trimester.  It is absent from most normal B and T cells, but is present on some leukemic cells of B lymphoid and myeloid origin and on a subset of bone marrow cells.  CD105 expression is weaker in activated monocytes and tissue macrophages but can be induced on the surface of in vitro.  Weaker expression is in follicular dendritic cells, pre-B cells in fetal marrow, erythroid precursors, fibroblasts, melanocytes, heart mesenchymal cells and vascular smooth muscle and mesangial cells. 


Structure
MOLECULAR FAMILY NAME:  Belongs to the transforming growth factor-b type III receptor family.

CD105 is a disulfide-linked homodimeric single-pass type-1 633 aa glycoprotein.  It contains a 25 aa leader sequence, a 561aa extracellular domain which contains 5 potential N-linked glycosylation sites, a region of potential O-linked glycosylation sites between 311 aa and 551 aa and a RGD motif in the exposed region, a 25 aa transmembrane domain and a 47 aa cytoplasmic domain.  The presence of the RGD sequence suggests the protein may interact with integrins or integrun-like molecules although none have been as yet identified as ligands of CD105.  There is no known structural motif but there is a homology with b-glycan and it is a homodimeric protein .  O-glycosylation of CD105 has been demonstrated by digestion with O-glycanase.  The O-glycosylation is likely to be on the membrane-proximal region that contains a high proportion of Thr, Ser and Pro residues.  The N-terminus sequence shows some patches of similarity with another receptor for TGFb namely TGFb receptor type 3, b- glycan.  TGF-β RI complexes with CD105 when its kinase domain is active and binds a different region of the CD105 extracellular domain to TGF-β RII.  TGF-β remains associated with CD105 whether it is active or inactive.

  The highest similarity between the cytoplasmic domains at 70% with an overall sequence identity of 30%.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
HUVEC 180 kDa 90 kDa
Endoglin transfectants 180 kDa 90 kDa
Macrophages 180 kDa 90 kDa
Pre-B leukemia 180 kDa 90 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  A short form of CD105, designated as S-Endoglin, contains a 14 aa cytoplasmic domain is detected by RT-PCR but it appears to be only weakly expressed on the cell surface in endothelial cells, myelomonocytic cell lines and placenta.  It corresponds to a retention of an intron of 125bp has been cloned from the HL60 cell line. 

POST-TRANSLATIONAL MODIFICATION

There are 4 potential N-linked glycosylation sites at residues 63, 96, 109, 282 and a region of potential O-linked glycosylation rich in serine/threonine between residues 311-551.  CD105 is constitutively phosphorylated in endothelial cells and fibroblast transfectants.

Ligands
CD105 is a receptor for transforming growth factor b, TGFb.  CD105 binds with a high affinity at the b1 isoform of kDa=50 pM and b3 isoform but not the b2 isoform of TGFb.  CD105 exists in 2 forms, L and S isoforms, derived from alternative splicing in the cytoplasmic domain and both of these isoforms bind TGFb.

LIGANDS FOR CD105 AND MOLECULES ASSOCIATED WITH CD105
Molecule Comment
TGFb1 Bound by CD105 in association with TGFb receptor II and I, both serine kinases
TGFb3 Bound by CD105 in association with TGFb receptor II and I, both serine kinases

  

Function
CD105 may act as a modulator of cellular responses to TGF-b1 which is essential for angiogenesis in vascular development, and in maintaining vessel wall integrity.  It is one of several receptors for the various isoforms of TGF-b, but only a small proportion of surface expressed CD105 molecules bind TGF-β and it appears to modulate the negative effects of TGF-β1 on cell proliferation, migration and microvessel formation.  Expression of CD105 is elevelated in proliferating endothelial cells in vitro.  CD105 expression is induced by hypoxia and in the absence of TGF-β1, CD105 displays anti-apoptotic effect in endothelial cells under hypoxic strees.  Expression of different extracellular matrix components such as fibronectin and collagen are regulated by CD105 levels suggesting a role in cellular transmission. 


BIOCHEMICAL ACTIVITY

CD105 is a regulatory component of the TGFb receptor complex.

DISEASE RELEVANCE AND FUNCTION OF CD105 IN INTACT ANIMAL

Evidence for a role in angiogenesis comes from the observation that CD105 gene mutations are associated with hereditary hemorrhagic telangiectasia which is characterized by multisystemic vascular dysplasia and recurrent hemorrhage disorders in humans and mice.  CD105 is the target for hereditary hemorrhagic telangiectasia type 1.  Each of the affected families to date has a different endoglin mutation.  CD105 null mice have several vascular and cardiac defects resulting in death at an early embryonic stage.  CD105 is a marker of angiogenesis and a target for tumor imaging and in the treatment of breast cancer.  CD105 can be used as a prognostic marker for several types of cancer where increased intra-tumor expression of CD105 on microvasculature correlates with disease progression and metastasis.  Serum levels may also be a prognostic indicator.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD105: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD105: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 2022P17813
MouseS42844X77952
Antibodies

Revised June 25, 2008


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