CD265 TNFRSF11A (tumor necrosis factor receptor superfamily member 11A), TRANCER, RANK, OFE, ODFR
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Broad
Osteoclast
Dendritic Cell
Ubiquitous
Adrenal Gland
Small intestine
Colon
Liver
Thymus
Skeletal muscle
T Cell
Hematopoietic Cell
97 / 97

Expression
CD265 is expressed on dendritic cells, osteoclasts, broad cells and all hemopoietic cells with the exception of stem cells and erythrocytes.  Expression is ubiquitous with high levels in human tissues, skeletal muscle, thymus, liver, colon, small intestine and adrenal gland.

Structure
MOLECULAR FAMILY NAME: Belongs to the tumor necrosis factor receptor family.

CD265 is a single-pass type-1 587 aa glycoprotein.  It contains a 21 aa N-terminal signal, a 53 aa extracellular domain which contains 4 TNFR cysteine-rich repeats and 2 potential N-glycosylation sites, a 21 aa transmembrane and a 383 aa cytoplasmic domain which contains tumor necrosis factor receptor associated factors (TRAFs 1, 2, 3, 5) which interact with CD265 in the membrane distal region of the cytoplasmic domain and TRAF6 binds to a distinct membrane-proximal Pro-X-Glu-X-X (aromatic acid residue) motif.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD265

CD265 binds CD254 (TRANCE).

Function
CD265 is a functional receptor for CD254 (TRANCE) and together these proteins are required for osteoclast differentiation and activation, for bone homeostastis and lymph node development.  The CD265/CD254 interaction activates the bone resorption function of osteoclasts.  Studies of the mouse counterpart suggests that this receptor directly mediates the osteoprotegerin ligand (OPGL)-induced osteoclastogenesis in osteoclast precursor cells.  Signaling by CD265 is mediated by the TRAFs which are the most important adaptor for signaling which induces the activation of NF-κB and MAPK8/JNK.  CD265 expression is inducible in dendritic cells during maturations and upon ligation by CD254 (TRANCE) activates anti-apoptotic signaling to prolong dendritic survival.  The receptor and its ligand, CD265/CD254 (RANK/RANKL) are important regulators of the interaction between the T cell and dendritic cell communications.  ImmatureCD34+ dendritic cells express both CD265 and are capable of autocrine survival signaling.  CD264/CD254 interaction plays a role in the induction of T cell tolerance.  CD265-/- muce and CD254-/- mice and TRAF6-/- mice are almost phenotypically identical displaying partially defective JNK activation and complete absence of NF-κB activation.  
             
BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD265 IN INTACT ANIMAL

Isoforms of CD265 are responsible for bone remodeling disorders such as familial Paget's disease of bone (PDB2) and familial expansile osteolysis (FEO), which are characterized by increased osteoclast activity.  These mice are severely osteopetrotic, fail to have tooth and hematopoiesis is diverted to the liver and spleen.  Furthermore, they lack all or almost all lymphonodes which indicates a critical role for CD265/CD254 signaling in lymph node development.  CD265-mediated signaling is also critical for mammary gland development during pregnancy as CD254-/- mice produce insufficient milk to feed their pups due to the absence of growth and expansion of ductal and alveolar epithelium within mammary glands.



Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD265: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD265: No information.

ADDITIONAL INSIGHTS

For further information see Anderson, D. M. et al (1997) Nature 390: 175-179.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 8792Q9Y6Q6
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University