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O35235 (TNF11_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
Gene names
Name:Tnfsf11
Synonyms:Opgl, Rankl, Trance
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length316 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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. Interacts with TNFRSF11A and TNFRSF11B. Ref.9 Ref.10 Ref.11

Subcellular location

Isoform 1: Cell membrane; Single-pass type II membrane protein.

Isoform 2: Cell membrane; Single-pass type II membrane protein.

Isoform 3: Cytoplasm.

Tumor necrosis factor ligand superfamily member 11, soluble form: Secreted.

Tissue specificity

Highly expressed in thymus and lymph nodes, but not in non-lymphoid tissues and is abundantly expressed in T-cells but not in B-cells. A high level expression is also seen in the trabecular bone and lung.

Post-translational modification

N-glycosylated. Ref.8

The soluble form of isoform 1 derives from the membrane form by proteolytic processing. The cleavage may be catalyzed by ADAM17. A further shorter soluble form was observed.

Involvement in disease

Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.

Sequence similarities

Belongs to the tumor necrosis factor family.

Ontologies

Keywords
   Biological processDifferentiation
   Cellular componentCell membrane
Cytoplasm
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   Molecular functionCytokine
Developmental protein
Receptor
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processERK1 and ERK2 cascade

Inferred from direct assay PubMed 19252502. Source: DFLAT

activation of JUN kinase activity

Inferred from direct assay PubMed 19252502. Source: DFLAT

bone resorption

Inferred from direct assay PubMed 12490655. Source: MGI

calcium ion homeostasis

Inferred from genetic interaction PubMed 21982707. Source: MGI

immune response

Inferred from electronic annotation. Source: InterPro

lymph node development

Traceable author statement PubMed 10687308. Source: MGI

mammary gland alveolus development

Inferred from mutant phenotype PubMed 11051546. Source: MGI

mammary gland epithelial cell proliferation

Inferred from mutant phenotype PubMed 11051546. Source: MGI

monocyte chemotaxis

Inferred from electronic annotation. Source: Ensembl

organ morphogenesis

Inferred from mutant phenotype PubMed 9950424. Source: MGI

ossification

Inferred from mutant phenotype PubMed 9950424. Source: MGI

osteoclast differentiation

Inferred from mutant phenotype PubMed 15750601. Source: UniProtKB

osteoclast proliferation

Inferred from direct assay PubMed 22451653. Source: MGI

positive regulation of ERK1 and ERK2 cascade via TNFSF11-mediated signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay PubMed 19298785. Source: MGI

positive regulation of JNK cascade

Inferred from genetic interaction PubMed 22073305. Source: MGI

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone resorption

Inferred from electronic annotation. Source: Ensembl

positive regulation of corticotropin-releasing hormone secretion

Inferred from direct assay PubMed 19940926. Source: BHF-UCL

positive regulation of fever generation by positive regulation of prostaglandin secretion

Inferred from direct assay PubMed 19940926. Source: BHF-UCL

positive regulation of homotypic cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

positive regulation of osteoclast differentiation

Inferred from direct assay PubMed 15657444PubMed 15724149. Source: MGI

positive regulation of phosphorylation

Inferred from direct assay PubMed 19252502. Source: DFLAT

positive regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 11051546. Source: MGI

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 19940926. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

protein homooligomerization

Inferred from direct assay PubMed 11859102. Source: MGI

regulation of osteoclast differentiation

Inferred from direct assay PubMed 12490655PubMed 23395171. Source: MGI

tumor necrosis factor-mediated signaling pathway

Inferred from genetic interaction PubMed 19940926. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular

Inferred from direct assay PubMed 19723499. Source: MGI

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functiontumor necrosis factor receptor superfamily binding

Inferred from physical interaction Ref.2. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O35235-1)

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: O35235-2)

The sequence of this isoform differs from the canonical sequence as follows:
     14-44: SSEEMGSGPGVPHEGPLHPAPSAPAPAPPPA → TP
Isoform 3 (identifier: O35235-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 316316Tumor necrosis factor ligand superfamily member 11, membrane form
PRO_0000034516
Chain139 – 316178Tumor necrosis factor ligand superfamily member 11, soluble form
PRO_0000034517

Regions

Topological domain1 – 4848Cytoplasmic Potential
Transmembrane49 – 6921Helical; Signal-anchor for type II membrane protein; Potential
Topological domain70 – 316247Extracellular Potential

Sites

Site138 – 1392Cleavage

Amino acid modifications

Glycosylation1971N-linked (GlcNAc...) Potential
Glycosylation2621N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 117117Missing in isoform 3.
VSP_006448
Alternative sequence14 – 4431SSEEM…APPPA → TP in isoform 2.
VSP_006449

Experimental info

Sequence conflict991D → G in AAC71061. Ref.1
Sequence conflict991D → G in AAC40113. Ref.3
Sequence conflict991D → G in BAA25425. Ref.4
Sequence conflict991D → G in BAA36970. Ref.5
Sequence conflict991D → G in BAA97257. Ref.6
Sequence conflict991D → G in BAA97259. Ref.6
Sequence conflict141 – 1433Missing in BAA36970. Ref.5

Secondary structure

............................... 316
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 8AF3825F92E0A786

FASTA31635,003
        10         20         30         40         50         60 
MRRASRDYGK YLRSSEEMGS GPGVPHEGPL HPAPSAPAPA PPPAASRSMF LALLGLGLGQ 

        70         80         90        100        110        120 
VVCSIALFLY FRAQMDPNRI SEDSTHCFYR ILRLHENADL QDSTLESEDT LPDSCRRMKQ 

       130        140        150        160        170        180 
AFQGAVQKEL QHIVGPQRFS GAPAMMEGSW LDVAQRGKPE AQPFAHLTIN AASIPSGSHK 

       190        200        210        220        230        240 
VTLSSWYHDR GWAKISNMTL SNGKLRVNQD GFYYLYANIC FRHHETSGSV PTDYLQLMVY 

       250        260        270        280        290        300 
VVKTSIKIPS SHNLMKGGST KNWSGNSEFH FYSINVGGFF KLRAGEEISI QVSNPSLLDP 

       310 
DQDATYFGAF KVQDID 

« Hide

Isoform 2 [UniParc].

Checksum: 09000919EB550530
Show »

FASTA28732,293
Isoform 3 [UniParc].

Checksum: 401C13EB5E8CE166
Show »

FASTA19922,150

References

« Hide 'large scale' references
[1]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Hybridoma.
[2]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Thymic lymphoma.
[3]"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. expand/collapse author list , Sarosi I., Shalhoub V., Senaldi G., Guo J., Delaney J., Boyle W.J.
Cell 93:165-176(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Bone marrow.
[4]"Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL."
Yasuda H., Shima N., Nakagawa N., Yamaguchi K., Kinosaki M., Mochizuki S., Tomoyasu A., Yano K., Goto M., Murakami A., Tsuda E., Morinaga T., Higashio K., Udagawa N., Takahashi N., Suda T.
Proc. Natl. Acad. Sci. U.S.A. 95:3597-3602(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Bone marrow stroma.
[5]"Cloning and characterization of the gene encoding mouse osteoclast differentiation factor."
Kodaira K., Kodaira K., Mizuno A., Yasuda H., Shima N., Murakami A., Ueda M., Higashio K.
Gene 230:121-127(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
Strain: 129.
[6]"Determination of three isoforms of the receptor activator of nuclear factor-kappaB ligand and their differential expression in bone and thymus."
Ikeda T., Kasai M., Utsuyama M., Hirokawa K.
Endocrinology 142:1419-1426(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
[7]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6J.
[8]"Evidence for a role of a tumor necrosis factor-alpha (TNF-alpha)-converting enzyme-like protease in shedding of TRANCE, a TNF family member involved in osteoclastogenesis and dendritic cell survival."
Lum L., Wong B.R., Josien R., Becherer J.D., Erdjument-Bromage H., Schloendorff J., Tempst P., Choi Y., Blobel C.P.
J. Biol. Chem. 274:13613-13618(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 139-147, PROTEOLYTIC PROCESSING, GLYCOSYLATION.
[9]"Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity."
Lam J., Nelson C.A., Ross F.P., Teitelbaum S.L., Fremont D.H.
J. Clin. Invest. 108:971-979(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 158-316, SUBUNIT.
[10]"Crystal structure of the extracellular domain of mouse RANK ligand at 2.2-A resolution."
Ito S., Wakabayashi K., Ubukata O., Hayashi S., Okada F., Hata T.
J. Biol. Chem. 277:6631-6636(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 137-316, SUBUNIT.
[11]"Structural and functional insights of RANKL-RANK interaction and signaling."
Liu C., Walter T.S., Huang P., Zhang S., Zhu X., Wu Y., Wedderburn L.R., Tang P., Owens R.J., Stuart D.I., Ren J., Gao B.
J. Immunol. 184:6910-6919(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 158-316 IN COMPLEX WITH TNFRSF11A, INTERACTION WITH TNFRSF11A, SUBUNIT.
[12]"RANKL employs distinct binding modes to engage RANK and the osteoprotegerin decoy receptor."
Nelson C.A., Warren J.T., Wang M.W., Teitelbaum S.L., Fremont D.H.
Structure 20:1971-1982(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 162-316 IN COMPLEX WITH TNFRSF11B.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF013170 mRNA. Translation: AAC71061.1.
AF019048 mRNA. Translation: AAB86812.1.
AF053713 mRNA. Translation: AAC40113.1.
AB008426 mRNA. Translation: BAA25425.1.
AB022039 Genomic DNA. Translation: BAA36970.1.
AB032771 mRNA. Translation: BAA97257.1.
AB032772 mRNA. Translation: BAA97258.1.
AB036798 mRNA. Translation: BAA97259.1.
AK159498 mRNA. Translation: BAE35131.1.
RefSeqNP_035743.2. NM_011613.3.
UniGeneMm.249221.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IQAX-ray2.20A/B/C157-316[»]
1JTZX-ray2.60X/Y/Z156-316[»]
1S55X-ray1.90A/B/C161-316[»]
3ME2X-ray2.80A158-316[»]
3QBQX-ray2.50A/C157-316[»]
4E4DX-ray2.70X162-316[»]
4GIQX-ray2.70A158-316[»]
ProteinModelPortalO35235.
SMRO35235. Positions 161-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59480N.
IntActO35235. 1 interaction.

PTM databases

PhosphoSiteO35235.

Proteomic databases

PRIDEO35235.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022592; ENSMUSP00000022592; ENSMUSG00000022015. [O35235-1]
GeneID21943.
KEGGmmu:21943.
UCSCuc007ush.1. mouse. [O35235-1]

Organism-specific databases

CTD8600.
MGIMGI:1100089. Tnfsf11.

Phylogenomic databases

eggNOGNOG40842.
GeneTreeENSGT00530000063443.
HOGENOMHOG000132981.
HOVERGENHBG054257.
InParanoidQ3TWY5.
KOK05473.
OMADIPSGSH.
OrthoDBEOG7V4B0Q.
TreeFamTF332169.

Gene expression databases

BgeeO35235.
GenevestigatorO35235.

Family and domain databases

Gene3D2.60.120.40. 1 hit.
InterProIPR006052. TNF_dom.
IPR017355. TNF_ligand_10/11.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]
PfamPF00229. TNF. 1 hit.
[Graphical view]
PIRSFPIRSF038013. TNF10_TNF11. 1 hit.
SMARTSM00207. TNF. 1 hit.
[Graphical view]
SUPFAMSSF49842. SSF49842. 1 hit.
PROSITEPS50049. TNF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTNFSF11. mouse.
EvolutionaryTraceO35235.
NextBio301584.
PMAP-CutDBQ3TWY5.
PROO35235.
SOURCESearch...

Entry information

Entry nameTNF11_MOUSE
AccessionPrimary (citable) accession number: O35235
Secondary accession number(s): O35306 expand/collapse secondary AC list , Q3TWY5, Q9JJK8, Q9JJK9, Q9R1Y0
Entry history
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 140 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot