LOCUS NM_003701 2216 bp mRNA linear PRI 11-JUN-2018 DEFINITION Homo sapiens TNF superfamily member 11 (TNFSF11), transcript variant 1, mRNA. ACCESSION NM_003701 VERSION NM_003701.3 KEYWORDS RefSeq. SOURCE Homo sapiens (human) ORGANISM Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. REFERENCE 1 (bases 1 to 2216) AUTHORS Kambayashi Y, Fujimura T, Furudate S, Lyu C, Hidaka T, Kakizaki A, Sato Y, Tanita K and Aiba S. TITLE The Expression of Matrix Metalloproteinases in Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-expressing Cancer of Apocrine Origin JOURNAL Anticancer Res. 38 (1), 113-120 (2018) PUBMED 29277763 REMARK GeneRIF: Our study suggests that the RANKL/RANK pathway contributes to the development and maintenance of the immunosuppressive tumor microenvironment and denosumab may be a promising adjuvant therapy targeting TAMs in cancer of apocrine origin REFERENCE 2 (bases 1 to 2216) AUTHORS Harper E, Rochfort KD, Forde H, Davenport C, Smith D and Cummins PM. TITLE TRAIL attenuates RANKL-mediated osteoblastic signalling in vascular cell mono-culture and co-culture models JOURNAL PLoS ONE 12 (11), e0188192 (2017) PUBMED 29145460 REMARK GeneRIF: present clear evidence that TRAIL can block several key signalling actions of RANKL in vascular cells, providing further evidence of its vasoprotective potential Publication Status: Online-Only REFERENCE 3 (bases 1 to 2216) AUTHORS Meng YH, Zhou WJ, Jin LP, Liu LB, Chang KK, Mei J, Li H, Wang J, Li DJ and Li MQ. TITLE RANKL-mediated harmonious dialogue between fetus and mother guarantees smooth gestation by inducing decidual M2 macrophage polarization JOURNAL Cell Death Dis 8 (10), e3105 (2017) PUBMED 29022922 REMARK GeneRIF: receptor activator for nuclear factor-kappa B ligand (RANKL), secreted by human embryonic trophoblasts and maternal decidual stromal cells, polarizes decidual macrophages toward a M2 phenotype. Publication Status: Online-Only REFERENCE 4 (bases 1 to 2216) AUTHORS Sarink D, Schock H, Johnson T, Overvad K, Holm M, Tjonneland A, Boutron-Ruault MC, His M, Kvaskoff M, Boeing H, Lagiou P, Papatesta EM, Trichopoulou A, Palli D, Pala V, Mattiello A, Tumino R, Sacerdote C, Bueno-de-Mesquita HBA, van Gils CH, Peeters PH, Weiderpass E, Agudo A, Sanchez MJ, Chirlaque MD, Ardanaz E, Amiano P, Khaw KT, Travis R, Dossus L, Gunter M, Rinaldi S, Merritt M, Riboli E, Kaaks R and Fortner RT. TITLE Circulating RANKL and RANKL/OPG and Breast Cancer Risk by ER and PR Subtype: Results from the EPIC Cohort JOURNAL Cancer Prev Res (Phila) 10 (9), 525-534 (2017) PUBMED 28701332 REMARK GeneRIF: Higher concentrations of serum sRANKL were positively associated with risk of estrogen receptor positive breast cancer. REFERENCE 5 (bases 1 to 2216) AUTHORS Balci Yuce H, Gokturk O, Aydemir Turkal H, Inanir A, Benli I and Demir O. TITLE Assessment of local and systemic 25-hydroxy-vitamin D, RANKL, OPG, and TNF levels in patients with rheumatoid arthritis and periodontitis JOURNAL J Oral Sci 59 (3), 397-404 (2017) PUBMED 28904316 REMARK GeneRIF: Vitamin D, tumor necrosis factor (TNF)-alpha, receptor activator of nuclear factor-KB ligand (RANKL), and OPG levels were determined in GCF and serum. Baseline clinical parameters were similar in all periodontitis groups (P > 0.05) but were higher than that in controls REFERENCE 6 (bases 1 to 2216) AUTHORS Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J and Boyle WJ. TITLE Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation JOURNAL Cell 93 (2), 165-176 (1998) PUBMED 9568710 REFERENCE 7 (bases 1 to 2216) AUTHORS 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 and Suda T. TITLE Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL JOURNAL Proc. Natl. Acad. Sci. U.S.A. 95 (7), 3597-3602 (1998) PUBMED 9520411 REFERENCE 8 (bases 1 to 2216) AUTHORS Wong BR, Josien R, Lee SY, Sauter B, Li HL, Steinman RM and Choi Y. TITLE TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine), a new TNF family member predominantly expressed in T cells, is a dendritic cell-specific survival factor JOURNAL J. Exp. Med. 186 (12), 2075-2080 (1997) PUBMED 9396779 REFERENCE 9 (bases 1 to 2216) AUTHORS Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D and Galibert L. TITLE A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function JOURNAL Nature 390 (6656), 175-179 (1997) PUBMED 9367155 REFERENCE 10 (bases 1 to 2216) AUTHORS Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FS 3rd, Frankel WN, Lee SY and Choi Y. TITLE TRANCE is a novel ligand of the tumor necrosis factor receptor family that activates c-Jun N-terminal kinase in T cells JOURNAL J. Biol. Chem. 272 (40), 25190-25194 (1997) PUBMED 9312132 COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The reference sequence was derived from AL139382.12, BC117286.1 and BQ007726.1. On Sep 4, 2008 this sequence version replaced NM_003701.2. Summary: This gene encodes a member of the tumor necrosis factor (TNF) cytokine family which is a ligand for osteoprotegerin and functions as a key factor for osteoclast differentiation and activation. This protein was shown to be a dentritic cell survival factor and is involved in the regulation of T cell-dependent immune response. T cell activation was reported to induce expression of this gene and lead to an increase of osteoclastogenesis and bone loss. This protein was shown to activate antiapoptotic kinase AKT/PKB through a signaling complex involving SRC kinase and tumor necrosis factor receptor-associated factor (TRAF) 6, which indicated this protein may have a role in the regulation of cell apoptosis. Targeted disruption of the related gene in mice led to severe osteopetrosis and a lack of osteoclasts. The deficient mice exhibited defects in early differentiation of T and B lymphocytes, and failed to form lobulo-alveolar mammary structures during pregnancy. Two alternatively spliced transcript variants have been found. [provided by RefSeq, Jul 2008]. Transcript Variant: This variant (1) encodes the longer protein (isoform 1). Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1163657.193210.1, AF019047.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## COMPLETENESS: complete on the 3' end. PRIMARY REFSEQ_SPAN PRIMARY_IDENTIFIER PRIMARY_SPAN COMP 1-117 AL139382.12 125383-125499 c 118-1214 BC117286.1 1-1097 1215-2051 AL139382.12 91788-92624 c 2052-2216 BQ007726.1 1-165 c FEATURES Location/Qualifiers source 1..2216 /organism="Homo sapiens" /mol_type="mRNA" /db_xref="taxon:9606" /chromosome="13" /map="13q14.11" gene 1..2216 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /note="TNF superfamily member 11" /db_xref="GeneID:8600" /db_xref="HGNC:HGNC:11926" /db_xref="MIM:602642" exon 1..368 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /inference="alignment:Splign:2.1.0" STS 118..1214 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /db_xref="UniSTS:490453" STS 120..1122 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /db_xref="UniSTS:482057" CDS 150..1103 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /note="isoform 1 is encoded by transcript variant 1; TNF-related activation-induced cytokine; receptor activator of nuclear factor kappa B ligand; osteoclast differentiation factor; osteoprotegerin ligand; tumor necrosis factor (ligand) superfamily, member 11; tumor necrosis factor ligand 6B; tumor necrosis factor superfamily member 11" /codon_start=1 /product="tumor necrosis factor ligand superfamily member 11 isoform 1" /protein_id="NP_003692.1" /db_xref="CCDS:CCDS9384.1" /db_xref="GeneID:8600" /db_xref="HGNC:HGNC:11926" /db_xref="MIM:602642" /translation="MRRASRDYTKYLRGSEEMGGGPGAPHEGPLHAPPPPAPHQPPAA SRSMFVALLGLGLGQVVCSVALFFYFRAQMDPNRISEDGTHCIYRILRLHENADFQDT TLESQDTKLIPDSCRRIKQAFQGAVQKELQHIVGSQHIRAEKAMVDGSWLDLAKRSKL EAQPFAHLTINATDIPSGSHKVSLSSWYHDRGWAKISNMTFSNGKLIVNQDGFYYLYA NICFRHHETSGDLATEYLQLMVYVTKTSIKIPSSHTLMKGGSTKYWSGNSEFHFYSIN VGGFFKLRSGEEISIEVSNPSLLDPDQDATYFGAFKVRDID" misc_feature 291..353 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /experiment="experimental evidence, no additional details recorded" /note="propagated from UniProtKB/Swiss-Prot (O14788.1); transmembrane region" misc_feature 564..569 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /experiment="experimental evidence, no additional details recorded" /note="Cleavage. {ECO:0000250}; propagated from UniProtKB/Swiss-Prot (O14788.1); cleavage site" exon 369..536 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /inference="alignment:Splign:2.1.0" exon 537..582 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /inference="alignment:Splign:2.1.0" exon 583..681 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /inference="alignment:Splign:2.1.0" exon 682..2198 /gene="TNFSF11" /gene_synonym="CD254; hRANKL2; ODF; OPGL; OPTB2; RANKL; sOdf; TNLG6B; TRANCE" /inference="alignment:Splign:2.1.0" ORIGIN 1 cgctcgcccg cgcgccccag gacccaaagc cgggctccaa gtcggcgccc cacgtcgagg 61 ctccgccgca gcctccggag ttggccgcag acaagaaggg gagggagcgg gagagggagg 121 agagctccga agcgagaggg ccgagcgcca tgcgccgcgc cagcagagac tacaccaagt 181 acctgcgtgg ctcggaggag atgggcggcg gccccggagc cccgcacgag ggccccctgc 241 acgccccgcc gccgcctgcg ccgcaccagc cccctgccgc ctcccgctcc atgttcgtgg 301 ccctcctggg gctggggctg ggccaggttg tctgcagcgt cgccctgttc ttctatttca 361 gagcgcagat ggatcctaat agaatatcag aagatggcac tcactgcatt tatagaattt 421 tgagactcca tgaaaatgca gattttcaag acacaactct ggagagtcaa gatacaaaat 481 taatacctga ttcatgtagg agaattaaac aggcctttca aggagctgtg caaaaggaat 541 tacaacatat cgttggatca cagcacatca gagcagagaa agcgatggtg gatggctcat 601 ggttagatct ggccaagagg agcaagcttg aagctcagcc ttttgctcat ctcactatta 661 atgccaccga catcccatct ggttcccata aagtgagtct gtcctcttgg taccatgatc 721 ggggttgggc caagatctcc aacatgactt ttagcaatgg aaaactaata gttaatcagg 781 atggctttta ttacctgtat gccaacattt gctttcgaca tcatgaaact tcaggagacc 841 tagctacaga gtatcttcaa ctaatggtgt acgtcactaa aaccagcatc aaaatcccaa 901 gttctcatac cctgatgaaa ggaggaagca ccaagtattg gtcagggaat tctgaattcc 961 atttttattc cataaacgtt ggtggatttt ttaagttacg gtctggagag gaaatcagca 1021 tcgaggtctc caacccctcc ttactggatc cggatcagga tgcaacatac tttggggctt 1081 ttaaagttcg agatatagat tgagccccag tttttggagt gttatgtatt tcctggatgt 1141 ttggaaacat tttttaaaac aagccaagaa agatgtatat aggtgtgtga gactactaag 1201 aggcatggcc ccaacggtac acgactcagt atccatgctc ttgaccttgt agagaacacg 1261 cgtatttaca gccagtggga gatgttagac tcatggtgtg ttacacaatg gtttttaaat 1321 tttgtaatga attcctagaa ttaaaccaga ttggagcaat tacggggtga ccttatgaga 1381 aactgcatgt gggctatggg aggggttggt ccctggtcat gtgccccttc gcagctgaag 1441 tggagagggt gtcatctagc gcaattgaag gatcatctga aggggcaaat tcttttgaat 1501 tgttacatca tgctggaacc tgcaaaaaat actttttcta atgaggagag aaaatatatg 1561 tatttttata taatatctaa agttatattt cagatgtaat gttttctttg caaagtattg 1621 taaattatat ttgtgctata gtatttgatt caaaatattt aaaaatgtct tgctgttgac 1681 atatttaatg ttttaaatgt acagacatat ttaactggtg cactttgtaa attccctggg 1741 gaaaacttgc agctaaggag gggaaaaaaa tgttgtttcc taatatcaaa tgcagtatat 1801 ttcttcgttc tttttaagtt aatagatttt ttcagacttg tcaagcctgt gcaaaaaaat 1861 taaaatggat gccttgaata ataagcagga tgttggccac caggtgcctt tcaaatttag 1921 aaactaattg actttagaaa gctgacattg ccaaaaagga tacataatgg gccactgaaa 1981 tctgtcaaga gtagttatat aattgttgaa caggtgtttt tccacaagtg ccgcaaattg 2041 tacctttttt gttttttcaa aatagaaaag ttattagtgg tttatcagca aaaaagtcca 2101 attttaattt agtaaatgtt atcttatact gtacaataaa aacattgcct ttgaatgtta 2161 attttttggt acaaaaataa atttatatga aaacctgcaa aaaaaaaaaa aaaaaa //