RANK Receptor, Soluble (RANK RECEPTOR) Human Active Protein

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptors can interact with various TRAF family proteins, through which this receptor induces the activation of NF-kappa B and MAPK8/JNK. This receptor and its ligand are important regulators of the interaction between T cells and dendritic cells. This receptor is also an essential mediator for osteoclast and lymph node development. Mutations at this locus have been associated with familial expansile osteolysis, autosomal recessive osteopetrosis, and Paget disease of bone. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Aug 2012]

Function: Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells. Ref.3

Subunit structure: Binds to the clefts between the subunits of the TNFSF11 ligand trimer to form a heterohexamer

By similarity. Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. Interacts (via cytoplasmic domain) with GAB2. Ref.4 Ref.5

Subcellular location: Membrane; Single-pass type I membrane protein

Potential.

Tissue specificity: Ubiquitous expression with high levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland.

Involvement in disease: Familial expansile osteolysis (FEO) [MIM:174810]: Rare autosomal dominant bone disorder characterized by focal areas of increased bone remodeling. The osteolytic lesions develop usually in the long bones during early adulthood. FEO is often associated with early-onset deafness and loss of dentition.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7Paget disease of bone 2 (PDB2) [MIM:602080]: Bone-remodeling disorder with clinical similarities to FEO. Unlike FEO, however, affected individuals have involvement of the axial skeleton with lesions in the spine, pelvis and skull.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7Osteopetrosis, autosomal recessive 7 (OPTB7) [MIM:612301]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB7 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. OPTB7 is associated with hypogammaglobulinemia.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities: Contains 4 TNFR-Cys repeats.