Reviewed, UniProtKB/Swiss-Prot Q9Y6Q6 (TNR11_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 11A
Alternative name(s):
    Receptor activator of NF-KB
    Osteoclast differentiation factor receptor
      Short name(s)=ODFR
    CD_antigen=CD265

Gene names

Name:	TNFRSF11A
Synonyms:	RANK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	616 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis. Involved in the regulation of interactions between T-cells and dendritic cells.
Subunit structure	Interacts with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6.
Subcellular location	Membrane; Single-pass type I membrane proteinPotential.
Tissue specificity	Ubiquitous expression with high levels in skeletal muscle, thymus, liver, colon, small intestine and adrenal gland.
Involvement in disease	Defects in TNFRSF11A are the cause of familial expansile osteolysis (FEO) [MIM:174810]. FEO is a 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. Defects in TNFRSF11A are a cause of Paget disease of bone 2 (PDB2) [MIM:602080]; also known as familial Paget disease of bone. PDB2 is a 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.
Sequence similarities	Contains 4 TNFR-Cys repeats.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Deafness Disease mutation
Domain	Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	cell-cell signaling Ref.1 Traceable author statement. Source: ProtInc positive regulation of cell proliferation Ref.1 Traceable author statement. Source: ProtInc signal transduction Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Inferred from physical interaction. Source: IntAct receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRAF2	Q12933	1	EBI-525675,EBI-355744
TRAF5	O00463	1	EBI-525675,EBI-523498
TRAF6	Q9Y4K3	1	EBI-525675,EBI-359276

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Signal peptide	1 – 29	29	Potential
	Chain	30 – 616	587	Tumor necrosis factor receptor superfamily member 11A
Regions
	Topological domain	30 – 212	183	Extracellular Potential
	Transmembrane	213 – 233	21	Potential
	Topological domain	234 – 616	383	Cytoplasmic Potential
	Repeat	34 – 68	35	TNFR-Cys 1
	Repeat	71 – 112	42	TNFR-Cys 2
	Repeat	114 – 151	38	TNFR-Cys 3
	Repeat	154 – 194	41	TNFR-Cys 4
Amino acid modifications
	Glycosylation	105	1	N-linked (GlcNAc...) Potential
	Glycosylation	174	1	N-linked (GlcNAc...) Potential
	Disulfide bond	34 ↔ 46		By similarity
	Disulfide bond	47 ↔ 60		By similarity
	Disulfide bond	50 ↔ 68		By similarity
	Disulfide bond	71 ↔ 86		By similarity
	Disulfide bond	92 ↔ 112		By similarity
	Disulfide bond	114 ↔ 127		By similarity
	Disulfide bond	133 ↔ 151		By similarity
Natural variations
	Natural variant	21	1	L → LALLLLCALL in PDB2.
	Natural variant	21	1	L → LLLCALL in FEO.
	Natural variant	192	1	A → V: dbSNP rs1805034.

Sequences

	Sequence		Length	Mass (Da)
	Q9Y6Q6-1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: E3DE9A7A08196F81	FASTA	616	66,034
	10 20 30 40 50 60 MAPRARRRRP LFALLLLCAL LARLQVALQI APPCTSEKHY EHLGRCCNKC EPGKYMSSKC 70 80 90 100 110 120 TTTSDSVCLP CGPDEYLDSW NEEDKCLLHK VCDTGKALVA VVAGNSTTPR RCACTAGYHW 130 140 150 160 170 180 SQDCECCRRN TECAPGLGAQ HPLQLNKDTV CKPCLAGYFS DAFSSTDKCR PWTNCTFLGK 190 200 210 220 230 240 RVEHHGTEKS DAVCSSSLPA RKPPNEPHVY LPGLIILLLF ASVALVAAII FGVCYRKKGK 250 260 270 280 290 300 ALTANLWHWI NEACGRLSGD KESSGDSCVS THTANFGQQG ACEGVLLLTL EEKTFPEDMC 310 320 330 340 350 360 YPDQGGVCQG TCVGGGPYAQ GEDARMLSLV SKTEIEEDSF RQMPTEDEYM DRPSQPTDQL 370 380 390 400 410 420 LFLTEPGSKS TPPFSEPLEV GENDSLSQCF TGTQSTVGSE SCNCTEPLCR TDWTPMSSEN 430 440 450 460 470 480 YLQKEVDSGH CPHWAASPSP NWADVCTGCR NPPGEDCEPL VGSPKRGPLP QCAYGMGLPP 490 500 510 520 530 540 EEEASRTEAR DQPEDGADGR LPSSARAGAG SGSSPGGQSP ASGNVTGNSN STFISSGQVM 550 560 570 580 590 600 NFKGDIIVVY VSQTSQEGAA AAAEPMGRPV QEETLARRDS FAGNGPRFPD PCGGPEGLRE 610 PEKASRPVQE QGGAKA

References

[1]	"A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function." Anderson D.M., Maraskovsky E., Billingsley W.L., Dougall W.C., Tometsko M.E., Roux E.R., Teepe M.C., DuBose R.F., Cosman D., Galibert L. Nature 390:175-179(1997) [PubMed: 9367155] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Dendritic cell.
[2]	"RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis." Nakagawa N., Kinosaki M., Yamaguchi K., Shima N., Yasuda H., Yano K., Morinaga T., Higashio K. Biochem. Biophys. Res. Commun. 253:395-400(1998) [PubMed: 9878548] [Abstract] Cited for: FUNCTION.
[3]	"The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor." Wong B.R., Josien R., Lee S.Y., Vologodskaia M., Steinman R.M., Choi Y. J. Biol. Chem. 273:28355-28359(1998) [PubMed: 9774460] [Abstract] Cited for: INTERACTION WITH TRAF1; TRAF2; TRAF3; TRAF5 AND TRAF6.
[4]	"Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis." Hughes A.E., Ralston S.H., Marken J., Bell C., MacPherson H., Wallace R.G.H., van Hul W., Whyte M.P., Nakatsuka K., Hovy L., Anderson D.M. Nat. Genet. 24:45-48(2000) [PubMed: 10615125] [Abstract] Cited for: VARIANT FEO LEU-LEU-CYS-ALA-LEU-LEU-21 INS, VARIANT PDB2 ALA-LEU-LEU-LEU-LEU-CYS-ALA-LEU-LEU-21 INS, VARIANT VAL-192.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF018253 mRNA. Translation: AAB86809.1.
RefSeq	NP_003830.1.
UniGene	Hs.204044
3D structure databases
HSSP	HSSP built from PDB template 1JMA based on UniProtKB Q92956.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6Q6.
Genome annotation databases
Ensembl	ENSG00000141655. Homo sapiens. [Contig view]
GeneID	8792.
KEGG	hsa:8792.
Organism-specific databases
H-InvDB	HIX0039706.
HGNC	HGNC:11908. TNFRSF11A.
HPA	CAB010391.
MIM	174810. phenotype. 602080. phenotype. 603499. gene.
Orphanet	85195. Expansile osteolysis, familial form.
PharmGKB	PA36601.
GenAtlas	Search...
GeneCards	Search...
GeneLynx	Search...
Phylogenomic databases
HOGENOM	Q9Y6Q6.
HOVERGEN	Q9Y6Q6.
Gene expression databases
ArrayExpress	Q9Y6Q6.
CleanEx	HS_TNFRSF11A.
GermOnline	ENSG00000141655. Homo sapiens.
Family and domain databases
InterPro	IPR001368. TNFR_c6. [Graphical view]
Pfam	PF00020. TNFR_c6. 1 hit. [Graphical view]
SMART	SM00208. TNFR. 4 hits. [Graphical view]
PROSITE	PS00652. TNFR_NGFR_1. 1 hit. PS50050. TNFR_NGFR_2. 1 hit. [Graphical view]
ProDom	Q9Y6Q6. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

TNR11_HUMAN

Accession

Primary (citable) accession number: Q9Y6Q6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	November 1, 1999
Last modified:	July 22, 2008
This is version 66 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)