ID TNR11_HUMAN Reviewed; 616 AA. AC Q9Y6Q6; DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 25-NOV-2008, entry version 69. DE RecName: Full=Tumor necrosis factor receptor superfamily member 11A; DE AltName: Full=Receptor activator of NF-KB; DE AltName: Full=Osteoclast differentiation factor receptor; DE Short=ODFR; DE AltName: CD_antigen=CD265; DE Flags: Precursor; GN Name=TNFRSF11A; Synonyms=RANK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Dendritic cell; RX MEDLINE=98032977; PubMed=9367155; DOI=10.1038/36593; RA Anderson D.M., Maraskovsky E., Billingsley W.L., Dougall W.C., RA Tometsko M.E., Roux E.R., Teepe M.C., DuBose R.F., Cosman D., RA Galibert L.; RT "A homologue of the TNF receptor and its ligand enhance T-cell growth RT and dendritic-cell function."; RL Nature 390:175-179(1997). RN [2] RP FUNCTION. RX MEDLINE=99097247; PubMed=9878548; DOI=10.1006/bbrc.1998.9788; RA Nakagawa N., Kinosaki M., Yamaguchi K., Shima N., Yasuda H., Yano K., RA Morinaga T., Higashio K.; RT "RANK is the essential signaling receptor for osteoclast RT differentiation factor in osteoclastogenesis."; RL Biochem. Biophys. Res. Commun. 253:395-400(1998). RN [3] RP INTERACTION WITH TRAF1; TRAF2; TRAF3; TRAF5 AND TRAF6. RX MEDLINE=98447691; PubMed=9774460; DOI=10.1074/jbc.273.43.28355; RA Wong B.R., Josien R., Lee S.Y., Vologodskaia M., Steinman R.M., RA Choi Y.; RT "The TRAF family of signal transducers mediates NF-kappaB activation RT by the TRANCE receptor."; RL J. Biol. Chem. 273:28355-28359(1998). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463, AND MASS RP SPECTROMETRY. RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [5] RP VARIANT FEO LEU-LEU-CYS-ALA-LEU-LEU-21 INS, VARIANT PDB2 RP ALA-LEU-LEU-LEU-LEU-CYS-ALA-LEU-LEU-21 INS, AND VARIANT VAL-192. RX MEDLINE=20082806; PubMed=10615125; DOI=10.1038/71667; RA Hughes A.E., Ralston S.H., Marken J., Bell C., MacPherson H., RA Wallace R.G.H., van Hul W., Whyte M.P., Nakatsuka K., Hovy L., RA Anderson D.M.; RT "Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause RT familial expansile osteolysis."; RL Nat. Genet. 24:45-48(2000). RN [6] RP VARIANTS ARG-53; CYS-129; GLY-170; ARG-175 AND SER-244, AND RP INVOLVEMENT IN OSTEOCLAST-POOR OSTEOPETROSIS. RX PubMed=18606301; DOI=10.1016/j.ajhg.2008.06.015; RA Guerrini M.M., Sobacchi C., Cassani B., Abinun M., Kilic S.S., RA Pangrazio A., Moratto D., Mazzolari E., Clayton-Smith J., Orchard P., RA Coxon F.P., Helfrich M.H., Crockett J.C., Mellis D., Vellodi A., RA Tezcan I., Notarangelo L.D., Rogers M.J., Vezzoni P., Villa A., RA Frattini A.; RT "Human osteoclast-poor osteopetrosis with hypogammaglobulinemia due to RT TNFRSF11A (RANK) mutations."; RL Am. J. Hum. Genet. 83:64-76(2008). CC -!- FUNCTION: Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for CC RANKL-mediated osteoclastogenesis. Involved in the regulation of CC interactions between T-cells and dendritic cells. CC -!- SUBUNIT: Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6. CC -!- INTERACTION: CC Q12933:TRAF2; NbExp=1; IntAct=EBI-525675, EBI-355744; CC O00463:TRAF5; NbExp=1; IntAct=EBI-525675, EBI-523498; CC Q9Y4K3:TRAF6; NbExp=1; IntAct=EBI-525675, EBI-359276; CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein (Potential). CC -!- TISSUE SPECIFICITY: Ubiquitous expression with high levels in CC skeletal muscle, thymus, liver, colon, small intestine and adrenal CC gland. CC -!- DISEASE: Defects in TNFRSF11A are the cause of familial expansile CC osteolysis (FEO) [MIM:174810]. FEO is a rare autosomal dominant CC bone disorder characterized by focal areas of increased bone CC remodeling. The osteolytic lesions develop usually in the long CC bones during early adulthood. FEO is often associated with early CC onset deafness and loss of dentition. CC -!- DISEASE: Defects in TNFRSF11A are a cause of Paget disease of bone CC 2 (PDB2) [MIM:602080]; also known as familial Paget disease of CC bone. PDB2 is a bone-remodeling disorder with clinical CC similarities to FEO. Unlike FEO, however, affected individuals CC have involvement of the axial skeleton with lesions in the spine, CC pelvis and skull. CC -!- DISEASE: Defects in TNFRSF11A may be the cause of osteoclast-poor CC osteopetrosis. CC -!- SIMILARITY: Contains 4 TNFR-Cys repeats. CC -!- WEB RESOURCE: Name=GeneReviews; CC URL="http://www.genetests.org/query?gene=PDB2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF018253; AAB86809.1; -; mRNA. DR RefSeq; NP_003830.1; -. DR UniGene; Hs.204044; -. DR HSSP; Q92956; 1JMA. DR IntAct; Q9Y6Q6; -. DR PhosphoSite; Q9Y6Q6; -. DR Ensembl; ENSG00000141655; Homo sapiens. DR GeneID; 8792; -. DR KEGG; hsa:8792; -. DR H-InvDB; HIX0039706; -. DR HGNC; HGNC:11908; TNFRSF11A. DR HPA; CAB010391; -. DR MIM; 174810; phenotype. DR MIM; 602080; phenotype. DR MIM; 603499; gene. DR Orphanet; 85195; Expansile osteolysis, familial form. DR PharmGKB; PA36601; -. DR HOGENOM; Q9Y6Q6; -. DR HOVERGEN; Q9Y6Q6; -. DR NextBio; 32972; -. DR ArrayExpress; Q9Y6Q6; -. DR CleanEx; HS_TNFRSF11A; -. DR GermOnline; ENSG00000141655; Homo sapiens. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0004872; F:receptor activity; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:ProtInc. DR GO; GO:0007605; P:sensory perception of sound; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR InterPro; IPR001368; TNFR_c6. DR Pfam; PF00020; TNFR_c6; 1. DR SMART; SM00208; TNFR; 4. DR PROSITE; PS00652; TNFR_NGFR_1; 1. DR PROSITE; PS50050; TNFR_NGFR_2; 1. PE 1: Evidence at protein level; KW Deafness; Disease mutation; Glycoprotein; Membrane; Osteopetrosis; KW Phosphoprotein; Polymorphism; Receptor; Repeat; Signal; Transmembrane. FT SIGNAL 1 29 Potential. FT CHAIN 30 616 Tumor necrosis factor receptor FT superfamily member 11A. FT /FTId=PRO_0000034585. FT TOPO_DOM 30 212 Extracellular (Potential). FT TRANSMEM 213 233 Potential. FT TOPO_DOM 234 616 Cytoplasmic (Potential). FT REPEAT 34 68 TNFR-Cys 1. FT REPEAT 71 112 TNFR-Cys 2. FT REPEAT 114 151 TNFR-Cys 3. FT REPEAT 154 194 TNFR-Cys 4. FT MOD_RES 463 463 Phosphoserine. FT CARBOHYD 105 105 N-linked (GlcNAc...) (Potential). FT CARBOHYD 174 174 N-linked (GlcNAc...) (Potential). FT DISULFID 34 46 By similarity. FT DISULFID 47 60 By similarity. FT DISULFID 50 68 By similarity. FT DISULFID 71 86 By similarity. FT DISULFID 92 112 By similarity. FT DISULFID 114 127 By similarity. FT DISULFID 133 151 By similarity. FT VARIANT 21 21 L -> LALLLLCALL (in PDB2). FT /FTId=VAR_011516. FT VARIANT 21 21 L -> LLLCALL (in FEO). FT /FTId=VAR_011517. FT VARIANT 53 53 G -> R (in two patients with osteoclast- FT poor osteopetrosis). FT /FTId=VAR_046788. FT VARIANT 129 129 R -> C (in a patient with osteoclast-poor FT osteopetrosis). FT /FTId=VAR_046789. FT VARIANT 141 141 H -> Y (in dbSNP:rs35211496). FT /FTId=VAR_046790. FT VARIANT 170 170 R -> G (in two siblings with osteoclast- FT poor osteopetrosis). FT /FTId=VAR_046791. FT VARIANT 175 175 C -> R (in two patients with osteoclast- FT poor osteopetrosis). FT /FTId=VAR_046792. FT VARIANT 192 192 A -> V (in dbSNP:rs1805034). FT /FTId=VAR_011518. FT VARIANT 244 244 A -> S (in a patient with osteoclast-poor FT osteopetrosis). FT /FTId=VAR_046793. SQ SEQUENCE 616 AA; 66034 MW; E3DE9A7A08196F81 CRC64; MAPRARRRRP LFALLLLCAL LARLQVALQI APPCTSEKHY EHLGRCCNKC EPGKYMSSKC TTTSDSVCLP CGPDEYLDSW NEEDKCLLHK VCDTGKALVA VVAGNSTTPR RCACTAGYHW SQDCECCRRN TECAPGLGAQ HPLQLNKDTV CKPCLAGYFS DAFSSTDKCR PWTNCTFLGK RVEHHGTEKS DAVCSSSLPA RKPPNEPHVY LPGLIILLLF ASVALVAAII FGVCYRKKGK ALTANLWHWI NEACGRLSGD KESSGDSCVS THTANFGQQG ACEGVLLLTL EEKTFPEDMC YPDQGGVCQG TCVGGGPYAQ GEDARMLSLV SKTEIEEDSF RQMPTEDEYM DRPSQPTDQL LFLTEPGSKS TPPFSEPLEV GENDSLSQCF TGTQSTVGSE SCNCTEPLCR TDWTPMSSEN YLQKEVDSGH CPHWAASPSP NWADVCTGCR NPPGEDCEPL VGSPKRGPLP QCAYGMGLPP EEEASRTEAR DQPEDGADGR LPSSARAGAG SGSSPGGQSP ASGNVTGNSN STFISSGQVM NFKGDIIVVY VSQTSQEGAA AAAEPMGRPV QEETLARRDS FAGNGPRFPD PCGGPEGLRE PEKASRPVQE QGGAKA //