Tumor necrosis factor ligand superfamily member 11

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O14788 (TNF11_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 111. History...

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

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Tumor necrosis factor ligand superfamily member 11

Alternative name(s):
Osteoclast differentiation factor
Short name=ODF
Osteoprotegerin ligand
Short name=OPGL
Receptor activator of nuclear factor kappa-B ligand
Short name=RANKL
TNF-related activation-induced cytokine
Short name=TRANCE
CD_antigen=CD254

Cleaved into the following 2 chains:

Tumor necrosis factor ligand superfamily member 11, membrane form
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

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

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.

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 Transmembrane helix
Molecular function	Cytokine Developmental protein Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	immune response Non-traceable author statement Ref.6. Source: UniProtKB monocyte chemotaxis Inferred from direct assay. Source: BHF-UCL osteoclast differentiation Non-traceable author statement Ref.2. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling Inferred from direct assay. Source: BHF-UCL positive regulation of NF-kappaB transcription factor activity Inferred from direct assay Ref.1. Source: BHF-UCL positive regulation of T cell activation Inferred from direct assay Ref.1. Source: BHF-UCL positive regulation of bone resorption Inferred from direct assay. Source: UniProtKB positive regulation of corticotropin-releasing hormone secretion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of fever generation by positive regulation of prostaglandin secretion Inferred from sequence or structural similarity. Source: BHF-UCL positive regulation of homotypic cell-cell adhesion Inferred from direct assay Ref.1. Source: BHF-UCL 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 Non-traceable author statement Ref.6. Source: UniProtKB
Molecular function	cytokine activity Non-traceable author statement Ref.2. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Non-traceable author statement Ref.6 Ref.1. Source: UniProtKB
Complete GO annotation...

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.

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

Helical; 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

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) [UniParc]. 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 [UniParc]. 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

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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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. NM_003701.3. NP_143026.1. NM_033012.3.
UniGene	Hs.333791.
3D structure databases
ProteinModelPortal	O14788.
SMR	O14788. Positions 162-317.
ModBase	Search...
Protein-protein interaction databases
STRING	O14788.
Proteomic databases
PRIDE	O14788.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000239849; ENSP00000239849; ENSG00000120659.
GeneID	8600.
KEGG	hsa:8600.
UCSC	uc001uyu.1. human.
Organism-specific databases
CTD	8600.
GeneCards	GC13P043136.
HGNC	HGNC:11926. TNFSF11.
HPA	CAB009193.
MIM	259710. phenotype. 602642. gene.
neXtProt	NX_O14788.
Orphanet	667. Autosomal recessive malignant osteopetrosis.
PharmGKB	PA36619.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG19778.
HOGENOM	HBG278561.
HOVERGEN	HBG054257.
InParanoid	O14788.
OMA	GKLIVNQ.
PhylomeDB	O14788.
Enzyme and pathway databases
Pathway_Interaction_DB	il6_7pathway. IL6-mediated signaling events.
Gene expression databases
ArrayExpress	O14788.
Bgee	O14788.
CleanEx	HS_TNFSF11.
Genevestigator	O14788.
GermOnline	ENSG00000120659. Homo sapiens.
Family and domain databases
InterPro	IPR006052. TNF. IPR017355. TNF_ligand_10/11. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
KO	K05473.
Pfam	PF00229. TNF. 1 hit. [Graphical view]
PIRSF	PIRSF038013. TNF10_TNF11. 1 hit.
SMART	SM00207. TNF. 1 hit. [Graphical view]
SUPFAM	SSF49842. TNF_like. 1 hit.
PROSITE	PS00251. TNF_1. False negative. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	32221.
PMAP-CutDB	O14788.
SOURCE	Search...

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:	January 25, 2012
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

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

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents