Tumor necrosis factor ligand superfamily member 11

Contribute

Send feedback

Read comments (1) or add your own

Reviewed, UniProtKB/Swiss-Prot O14788 (TNF11_HUMAN)

Last modified June 16, 2009. Version 89. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data |

Customize display

text xml rdf/xml gff fasta

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor ligand superfamily member 11
Alternative name(s):
    Receptor activator of nuclear factor kappa B ligand
      Short name=RANKL
    TNF-related activation-induced cytokine
      Short name=TRANCE
    Osteoprotegerin ligand
      Short name=OPGL
    Osteoclast differentiation factor
      Short name=ODF
    CD_antigen=CD254
Cleaved into the following 2 chains:
    1- Recommended name:
            Tumor necrosis factor ligand superfamily member 11, membrane form
    2- Recommended name:
            Tumor necrosis factor ligand superfamily member 11, soluble form

Gene names

Name:	TNFSF11
Synonyms:	OPGL, RANKL, TRANCE

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Hide | Top

Protein attributes

Sequence length	317 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
Subunit structure	Homotrimer By similarity.
Subcellular location	Isoform 1: Cell membrane; Single-pass type II membrane protein. Isoform 3: Cell membrane; Single-pass type II membrane protein. Isoform 2: Cytoplasm By similarity. Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted By similarity.
Tissue specificity	Highest in the peripheral lymph nodes, weak in spleen, peripheral blood Leukocytes, bone marrow, heart, placenta, skeletal muscle, stomach and thyroid.
Induction	Up-regulated by T-cell receptor stimulation.
Post-translational modification	The soluble form of isoform 1 derives from the membrane form by proteolytic processing By similarity. The cleavage may be catalyzed by ADAM17.
Involvement in disease	Defects in TNFSF11 are the cause of osteopetrosis autosomal recessive type 2 (OPTB2) [MIM:259710]; also known as osteoclast-poor osteopetrosis. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder 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. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB2 is characterized by paucity of osteoclasts, suggesting a molecular defect in osteoclast development. Ref.7
Sequence similarities	Belongs to the tumor necrosis factor family.

Hide | Top

Ontologies

Keywords
Biological process	Differentiation
Cellular component	Cell membrane Cytoplasm Membrane Secreted
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Osteopetrosis
Domain	Signal-anchor Transmembrane
Molecular function	Cytokine Developmental protein Receptor
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	immune response Ref.6 Non-traceable author statement. Source: UniProtKB osteoclast differentiation Ref.2 Non-traceable author statement. Source: UniProtKB positive regulation of bone resorption Inferred from direct assay. Source: UniProtKB positive regulation of osteoclast differentiation Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Ref.6 Non-traceable author statement. Source: UniProtKB
Molecular function	cytokine activity Ref.2 Non-traceable author statement. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Ref.1 Ref.6 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Hide | Top

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O14788-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O14788-2) Also known as: SODF; The sequence of this isoform differs from the canonical sequence as follows: 1-73: Missing.

Isoform 3 (identifier: O14788-3) The sequence of this isoform differs from the canonical sequence as follows: 1-47: Missing.

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 317

317

Tumor necrosis factor ligand superfamily member 11, membrane form

PRO_0000034514

Chain

140 – 317

178

Tumor necrosis factor ligand superfamily member 11, soluble form By similarity

PRO_0000034515

Regions

Topological domain

1 – 47

Cytoplasmic Potential

Transmembrane

48 – 68

Signal-anchor for type II membrane protein Potential

Topological domain

69 – 317

249

Extracellular Potential

Sites

Site

139 – 140

Cleavage By similarity

Amino acid modifications

Glycosylation

171

N-linked (GlcNAc...) Potential

Glycosylation

198

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 73

Missing in isoform 2.

VSP_006447

Alternative sequence

1 – 47

Missing in isoform 3.

VSP_006446

Natural variant

199

M → K in OPTB2. Ref.7

VAR_037424

Experimental info

Sequence conflict

194

A → G in AAC51762. Ref.6

Hide | Top

Sequences

Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 766176446348097F Show »	FASTA	317	35,478
10 20 30 40 50 60 MRRASRDYTK YLRGSEEMGG GPGAPHEGPL HAPPPPAPHQ PPAASRSMFV ALLGLGLGQV 70 80 90 100 110 120 VCSVALFFYF RAQMDPNRIS EDGTHCIYRI LRLHENADFQ DTTLESQDTK LIPDSCRRIK 130 140 150 160 170 180 QAFQGAVQKE LQHIVGSQHI RAEKAMVDGS WLDLAKRSKL EAQPFAHLTI NATDIPSGSH 190 200 210 220 230 240 KVSLSSWYHD RGWAKISNMT FSNGKLIVNQ DGFYYLYANI CFRHHETSGD LATEYLQLMV 250 260 270 280 290 300 YVTKTSIKIP SSHTLMKGGS TKYWSGNSEF HFYSINVGGF FKLRSGEEIS IEVSNPSLLD 310 PDQDATYFGA FKVRDID « Hide
Isoform 2 (SODF). Checksum: C827590684B6B83C Show »	FASTA	244	27,690
10 20 30 40 50 60 MDPNRISEDG THCIYRILRL HENADFQDTT LESQDTKLIP DSCRRIKQAF QGAVQKELQH 70 80 90 100 110 120 IVGSQHIRAE KAMVDGSWLD LAKRSKLEAQ PFAHLTINAT DIPSGSHKVS LSSWYHDRGW 130 140 150 160 170 180 AKISNMTFSN GKLIVNQDGF YYLYANICFR HHETSGDLAT EYLQLMVYVT KTSIKIPSSH 190 200 210 220 230 240 TLMKGGSTKY WSGNSEFHFY SINVGGFFKL RSGEEISIEV SNPSLLDPDQ DATYFGAFKV RDID « Hide
Isoform 3. Checksum: 5C7754CE32E6F368 Show »	FASTA	270	30,523
10 20 30 40 50 60 MFVALLGLGL GQVVCSVALF FYFRAQMDPN RISEDGTHCI YRILRLHENA DFQDTTLESQ 70 80 90 100 110 120 DTKLIPDSCR RIKQAFQGAV QKELQHIVGS QHIRAEKAMV DGSWLDLAKR SKLEAQPFAH 130 140 150 160 170 180 LTINATDIPS GSHKVSLSSW YHDRGWAKIS NMTFSNGKLI VNQDGFYYLY ANICFRHHET 190 200 210 220 230 240 SGDLATEYLQ LMVYVTKTSI KIPSSHTLMK GGSTKYWSGN SEFHFYSINV GGFFKLRSGE 250 260 270 EISIEVSNPS LLDPDQDATY FGAFKVRDID « Hide

Hide | Top

References

	« Hide 'large scale' referencesShow 'large scale' 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] (ISOFORM 1). Tissue: Bone marrow and Peripheral blood.
[2]	"Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation." Lacey D.L., Timms E., Tan H.-L., Kelley M.J., Dunstan C.R., Burgess T., Elliott R., Colombero A., Elliott G., Scully S., Hsu H., Sullivan J., Hawkins N., Davy E., Capparelli C., Eli A., Qian Y.-X., Kaufman S. Boyle W.J. Cell 93:165-176(1998) [PubMed: 9568710] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Lymph node.
[3]	"Determination of human RANKL isoforms." Ikeda T., Kuroyama H., Hirokawa K. Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[4]	"Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation." Nagai M., Kyakumoto S., Sato N. Biochem. Biophys. Res. Commun. 269:532-536(2000) [PubMed: 10708588] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Tongue.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[6]	"TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells." Wong B.R., Rho J., Arron J., Robinson E., Orlinick J., Chao M., Kalachikov S., Cayani E., Bartlett F.S. III, Frankel W.N., Lee S.Y., Choi Y. J. Biol. Chem. 272:25190-25194(1997) [PubMed: 9312132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 73-317. Tissue: Thymocyte.
[7]	"Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL." Sobacchi C., Frattini A., Guerrini M.M., Abinun M., Pangrazio A., Susani L., Bredius R., Mancini G., Cant A., Bishop N., Grabowski P., Del Fattore A., Messina C., Errigo G., Coxon F.P., Scott D.I., Teti A., Rogers M.J. , Vezzoni P., Villa A., Helfrich M.H. Nat. Genet. 39:960-962(2007) [PubMed: 17632511] [Abstract] Cited for: VARIANT OPTB2 LYS-199.
+	Additional computationally mapped references.

Hide | Top

Cross-references

Sequence databases
	AF019047 mRNA. Translation: AAB86811.1. AF053712 mRNA. Translation: AAC39731.1. AB064269 mRNA. Translation: BAB79694.1. AB061227 mRNA. Translation: BAB71768.1. AB064270 mRNA. Translation: BAB79695.1. AB037599 mRNA. Translation: BAA90488.1. BC074823 mRNA. Translation: AAH74823.1. BC074890 mRNA. Translation: AAH74890.1. AF013171 mRNA. Translation: AAC51762.1.
IPI	IPI00023732. IPI00219810. IPI00219811.
RefSeq	NP_003692.1.
UniGene	Hs.333791
3D structure databases
HSSP	HSSP built from PDB template 1JTZ based on UniProtKB O35235.
SMR	O14788. Positions 162-317.
ModBase	Search...
Proteomic databases
PRIDE	O14788.
Genome annotation databases
Ensembl	ENSG00000120659. Homo sapiens. [Contig view]
GeneID	8600.
KEGG	hsa:8600.
Organism-specific databases
GeneCards	GC13P042034.
H-InvDB	HIX0037293.
HGNC	HGNC:11926. TNFSF11.
HPA	CAB009193.
MIM	259710. phenotype. 602642. gene.
Orphanet	2781. Osteopetrosis.
PharmGKB	PA36619.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O14788.
HOVERGEN	O14788.
OMA	O14788. QHIRAEK.
Enzyme and pathway databases
Pathway_Interaction_DB	il6_7pathway. IL6-mediated signaling events.
Gene expression databases
ArrayExpress	O14788.
Bgee	O14788.
CleanEx	HS_TNFSF11.
GermOnline	ENSG00000120659. Homo sapiens.
Family and domain databases
InterPro	IPR017355. TNF10_TNF11. IPR006052. TNF_family. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
Pfam	PF00229. TNF. 1 hit. [Graphical view]
PIRSF	PIRSF038013. TNF10_TNF11. 1 hit.
ProDom	PD002012. TNF_subf. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00207. TNF. 1 hit. [Graphical view]
PROSITE	PS00251. TNF_1. False negative. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	32221.
PMAP-CutDB	O14788.
SOURCE	Search...

Hide | Top

Entry information

Entry name

TNF11_HUMAN

Accession

Primary (citable) accession number: O14788
Secondary accession number(s): O14723, Q96Q17, Q9P2Q3

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	January 1, 1998
Last modified:	June 16, 2009
This is version 89 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top

Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents