ID TR13C_HUMAN Reviewed; 184 AA. AC Q96RJ3; DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 27-MAR-2024, entry version 174. DE RecName: Full=Tumor necrosis factor receptor superfamily member 13C; DE AltName: Full=B-cell-activating factor receptor; DE AltName: Full=BAFF receptor; DE Short=BAFF-R; DE AltName: Full=BLyS receptor 3; DE AltName: CD_antigen=CD268; GN Name=TNFRSF13C; Synonyms=BAFFR, BR3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=B-cell lymphoma; RX PubMed=11509692; DOI=10.1126/science.1061965; RA Thompson J.S., Bixler S.A., Qian F., Vora K., Scott M.L., Cachero T.G., RA Hession C., Schneider P., Sizing I.D., Mullen C., Strauch K., Zafari M., RA Benjamin C.D., Tschopp J., Browning J.L., Ambrose C.; RT "BAFF-R, a newly identified TNF receptor that specifically interacts with RT BAFF."; RL Science 293:2108-2111(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [3] RP FUNCTION. RX PubMed=11591325; DOI=10.1016/s0960-9822(01)00481-x; RA Yan M., Brady J.R., Chan B., Lee W.P., Hsu B., Harless S.M., Cancro M.P., RA Grewal I.S., Dixit V.M.; RT "Identification of a novel receptor for B lymphocyte stimulator that is RT mutated in a mouse strain with severe B cell deficiency."; RL Curr. Biol. 11:1547-1552(2001). RN [4] RP STRUCTURE BY NMR OF 26-33, FUNCTION, AND DISULFIDE BONDS. RX PubMed=12387744; DOI=10.1016/s1074-7613(02)00425-9; RA Kayagaki N., Yan M., Seshasayee D., Wang H., Lee W., French D.M., RA Grewal I.S., Cochran A.G., Gordon N.C., Yin J., Starovasnik M.A., RA Dixit V.M.; RT "BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through RT a discrete surface loop and promotes processing of NF-kappaB2."; RL Immunity 17:515-524(2002). RN [5] RP STRUCTURE BY NMR OF 1-61, X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 26-31 IN RP COMPLEX WITH TNFSF13B/TALL1/BAFF/BLYS, DISULFIDE BONDS, AND MUTAGENESIS OF RP ASP-26 AND LEU-28. RX PubMed=12755599; DOI=10.1021/bi034017g; RA Gordon N.C., Pan B., Hymowitz S.G., Yin J., Kelley R.F., Cochran A.G., RA Yan M., Dixit V.M., Fairbrother W.J., Starovasnik M.A.; RT "BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that RT encodes a highly focused ligand-binding site."; RL Biochemistry 42:5977-5983(2003). RN [6] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 16-46 IN COMPLEX WITH RP TNFSF13B/TALL1/BAFF/BLYS, DISULFIDE BONDS, AND MUTAGENESIS OF CYS-24 AND RP CYS-35. RX PubMed=12721620; DOI=10.1038/nature01543; RA Liu Y., Hong X., Kappler J., Jiang L., Zhang R., Xu L., Pan C.-H., RA Martin W.E., Murphy R.C., Shu H.-B., Dai S., Zhang G.; RT "Ligand-receptor binding revealed by the TNF family member TALL-1."; RL Nature 423:49-56(2003). RN [7] RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 1-63 IN COMPLEX WITH RP TNFSF13B/TALL1/BAFF/BLYS, AND DISULFIDE BONDS. RX PubMed=12715002; DOI=10.1038/nsb925; RA Kim H.M., Yu K.S., Lee M.E., Shin D.R., Kim Y.S., Paik S.-G., Yoo O.J., RA Lee H., Lee J.-O.; RT "Crystal structure of the BAFF-BAFF-R complex and its implications for RT receptor activation."; RL Nat. Struct. Biol. 10:342-348(2003). RN [8] RP X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 7-54, AND INTERACTION WITH RP TNFSF13B/TALL1/BAFF/BLYS. RX PubMed=16840730; DOI=10.1182/blood-2006-03-011031; RA Lee C.V., Hymowitz S.G., Wallweber H.J., Gordon N.C., Billeci K.L., RA Tsai S.-P., Compaan D.M., Yin J., Gong Q., Kelley R.F., DeForge L.E., RA Martin F., Starovasnik M.A., Fuh G.; RT "Synthetic anti-BR3 antibodies that mimic BAFF binding and target both RT human and murine B cells."; RL Blood 108:3103-3111(2006). RN [9] RP VARIANTS VAL-64 AND TYR-159. RX PubMed=16160919; DOI=10.1007/s10875-005-5637-2; RA Losi C.G., Silini A., Fiorini C., Soresina A., Meini A., Ferrari S., RA Notarangelo L.D., Lougaris V., Plebani A.; RT "Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients RT with common variable immunodeficiency."; RL J. Clin. Immunol. 25:496-502(2005). RN [10] RP VARIANT CVID4 89-LEU--VAL-96 DEL, AND CHARACTERIZATION OF VARIANT CVID4 RP 89-LEU--VAL-96 DEL. RX PubMed=19666484; DOI=10.1073/pnas.0903543106; RA Warnatz K., Salzer U., Rizzi M., Fischer B., Gutenberger S., Boehm J., RA Kienzler A.-K., Pan-Hammarstroem Q., Hammarstroem L., Rakhmanov M., RA Schlesier M., Grimbacher B., Peter H.-H., Eibel H.; RT "B-cell activating factor receptor deficiency is associated with an adult- RT onset antibody deficiency syndrome in humans."; RL Proc. Natl. Acad. Sci. U.S.A. 106:13945-13950(2009). CC -!- FUNCTION: B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. CC Promotes the survival of mature B-cells and the B-cell response. CC {ECO:0000269|PubMed:11591325, ECO:0000269|PubMed:12387744}. CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type III CC membrane protein {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96RJ3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96RJ3-2; Sequence=VSP_006505; CC -!- TISSUE SPECIFICITY: Highly expressed in spleen and lymph node, and in CC resting B-cells. Detected at lower levels in activated B-cells, resting CC CD4+ T-cells, in thymus and peripheral blood leukocytes. CC -!- DISEASE: Immunodeficiency, common variable, 4 (CVID4) [MIM:613494]: A CC primary immunodeficiency characterized by antibody deficiency, CC hypogammaglobulinemia, recurrent bacterial infections and an inability CC to mount an antibody response to antigen. The defect results from a CC failure of B-cell differentiation and impaired secretion of CC immunoglobulins; the numbers of circulating B-cells is usually in the CC normal range, but can be low. {ECO:0000269|PubMed:19666484}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF373846; AAK91826.1; -; mRNA. DR EMBL; Z99716; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS14024.1; -. [Q96RJ3-1] DR RefSeq; NP_443177.1; NM_052945.3. [Q96RJ3-1] DR PDB; 1MPV; NMR; -; A=26-31. DR PDB; 1OQE; X-ray; 2.50 A; K/L/M/N/O/P/Q/R=16-46. DR PDB; 1OSX; NMR; -; A=1-61. DR PDB; 2HFG; X-ray; 2.61 A; R=7-54. DR PDB; 3V56; X-ray; 3.00 A; G/H/I/J/K/L/Z=23-35. DR PDB; 4V46; X-ray; 3.30 A; B0/B1/B2/B3/B4/B5/B6/B7/B8/B9/BA/BB/BC/BD/BE/BF/BG/BH/BI/BJ/BK/BL/BM/BN/BO/BP/BQ/BR/BS/BT/BU/BV/BW/BX/BY/BZ/Ba/Bb/Bc/Bd/Be/Bf/Bg/Bh/Bi/Bj/Bk/Bl/Bm/Bn/Bo/Bp/Bq/Br/Bs/Bt/Bu/Bv/Bw/Bx=1-63. DR PDBsum; 1MPV; -. DR PDBsum; 1OQE; -. DR PDBsum; 1OSX; -. DR PDBsum; 2HFG; -. DR PDBsum; 3V56; -. DR PDBsum; 4V46; -. DR AlphaFoldDB; Q96RJ3; -. DR BMRB; Q96RJ3; -. DR SMR; Q96RJ3; -. DR BioGRID; 125443; 15. DR STRING; 9606.ENSP00000291232; -. DR ChEMBL; CHEMBL4630882; -. DR GuidetoPHARMACOLOGY; 1886; -. DR GlyCosmos; Q96RJ3; 1 site, 1 glycan. DR GlyGen; Q96RJ3; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96RJ3; -. DR PhosphoSitePlus; Q96RJ3; -. DR BioMuta; TNFRSF13C; -. DR DMDM; 21264093; -. DR jPOST; Q96RJ3; -. DR MassIVE; Q96RJ3; -. DR PaxDb; 9606-ENSP00000291232; -. DR PeptideAtlas; Q96RJ3; -. DR ProteomicsDB; 77970; -. [Q96RJ3-1] DR ProteomicsDB; 77971; -. [Q96RJ3-2] DR ABCD; Q96RJ3; 3 sequenced antibodies. DR Antibodypedia; 307; 756 antibodies from 42 providers. DR DNASU; 115650; -. DR Ensembl; ENST00000291232.5; ENSP00000291232.3; ENSG00000159958.7. [Q96RJ3-1] DR GeneID; 115650; -. DR KEGG; hsa:115650; -. DR MANE-Select; ENST00000291232.5; ENSP00000291232.3; NM_052945.4; NP_443177.1. DR UCSC; uc003bbl.3; human. [Q96RJ3-1] DR AGR; HGNC:17755; -. DR CTD; 115650; -. DR DisGeNET; 115650; -. DR GeneCards; TNFRSF13C; -. DR HGNC; HGNC:17755; TNFRSF13C. DR HPA; ENSG00000159958; Group enriched (intestine, lymphoid tissue). DR MalaCards; TNFRSF13C; -. DR MIM; 606269; gene. DR MIM; 613494; phenotype. DR neXtProt; NX_Q96RJ3; -. DR OpenTargets; ENSG00000159958; -. DR Orphanet; 1572; Common variable immunodeficiency. DR PharmGKB; PA38466; -. DR VEuPathDB; HostDB:ENSG00000159958; -. DR eggNOG; ENOG502T201; Eukaryota. DR GeneTree; ENSGT00940000154485; -. DR HOGENOM; CLU_131020_0_0_1; -. DR InParanoid; Q96RJ3; -. DR OMA; RPCCQGD; -. DR OrthoDB; 4642470at2759; -. DR PhylomeDB; Q96RJ3; -. DR TreeFam; TF336877; -. DR PathwayCommons; Q96RJ3; -. DR Reactome; R-HSA-5668541; TNFR2 non-canonical NF-kB pathway. DR Reactome; R-HSA-5676594; TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway. DR SignaLink; Q96RJ3; -. DR SIGNOR; Q96RJ3; -. DR BioGRID-ORCS; 115650; 49 hits in 1144 CRISPR screens. DR ChiTaRS; TNFRSF13C; human. DR EvolutionaryTrace; Q96RJ3; -. DR GeneWiki; TNFRSF13C; -. DR GenomeRNAi; 115650; -. DR Pharos; Q96RJ3; Tbio. DR PRO; PR:Q96RJ3; -. DR Proteomes; UP000005640; Chromosome 22. DR RNAct; Q96RJ3; Protein. DR Bgee; ENSG00000159958; Expressed in spleen and 110 other cell types or tissues. DR ExpressionAtlas; Q96RJ3; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0038023; F:signaling receptor activity; IEA:InterPro. DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0031296; P:B cell costimulation; IBA:GO_Central. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IBA:GO_Central. DR GO; GO:0042102; P:positive regulation of T cell proliferation; IBA:GO_Central. DR GO; GO:0031295; P:T cell costimulation; IBA:GO_Central. DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:InterPro. DR InterPro; IPR022338; TNFR_13C. DR InterPro; IPR043521; TNFR_13C/17. DR InterPro; IPR015336; TNFR_13C_TALL-1-bd. DR PANTHER; PTHR20437; TUMOR NECROSIS FACTOR RECEPTOR SUBFAMILY MEMBER 13/17; 1. DR PANTHER; PTHR20437:SF2; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 13C; 1. DR Pfam; PF09256; BaffR-Tall_bind; 1. DR PRINTS; PR01964; TNFACTORR13C. DR SUPFAM; SSF57586; TNF receptor-like; 1. DR Genevisible; Q96RJ3; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Disease variant; KW Disulfide bond; Immunity; Membrane; Receptor; Reference proteome; KW Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1..184 FT /note="Tumor necrosis factor receptor superfamily member FT 13C" FT /id="PRO_0000058933" FT TOPO_DOM 1..78 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 79..99 FT /note="Helical; Signal-anchor for type III membrane FT protein" FT /evidence="ECO:0000255" FT TOPO_DOM 100..184 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 18..35 FT /note="TNFR-Cys; truncated" FT REGION 26..31 FT /note="Essential for TNFSF13B/TALL1/BAFF/BLyS binding" FT REGION 43..62 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 107..184 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 108..127 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 141..159 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 169..184 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT DISULFID 19..32 FT DISULFID 24..35 FT VAR_SEQ 143 FT /note="P -> PA (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11509692" FT /id="VSP_006505" FT VARIANT 64 FT /note="G -> V (in dbSNP:rs547352394)" FT /evidence="ECO:0000269|PubMed:16160919" FT /id="VAR_063888" FT VARIANT 89..96 FT /note="Missing (in CVID4; fails to bind TNFSF13B and fails FT to induce downstream NF-kappa-B processing)" FT /evidence="ECO:0000269|PubMed:19666484" FT /id="VAR_063889" FT VARIANT 159 FT /note="H -> Y (in dbSNP:rs61756766)" FT /evidence="ECO:0000269|PubMed:16160919" FT /id="VAR_063890" FT MUTAGEN 24 FT /note="C->Y: Abolishes a disulfide bond and thereby changes FT the specificity, so that both TNFSF13B and TNFSF13 can be FT bound." FT /evidence="ECO:0000269|PubMed:12721620" FT MUTAGEN 26 FT /note="D->A: Strongly reduced affinity for TNFSF13B." FT /evidence="ECO:0000269|PubMed:12755599" FT MUTAGEN 28 FT /note="L->A: Strongly reduced affinity for TNFSF13B." FT /evidence="ECO:0000269|PubMed:12755599" FT MUTAGEN 35 FT /note="C->S: Abolishes a disulfide bond and thereby changes FT the specificity, so that both TNFSF13B and TNFSF13 can be FT bound." FT /evidence="ECO:0000269|PubMed:12721620" FT STRAND 23..26 FT /evidence="ECO:0007829|PDB:1OQE" FT TURN 27..30 FT /evidence="ECO:0007829|PDB:1OQE" FT STRAND 31..34 FT /evidence="ECO:0007829|PDB:1OQE" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:1OQE" SQ SEQUENCE 184 AA; 18864 MW; F2BFB98099A27138 CRC64; MRRGPRSLRG RDAPAPTPCV PAECFDLLVR HCVACGLLRT PRPKPAGASS PAPRTALQPQ ESVGAGAGEA ALPLPGLLFG APALLGLALV LALVLVGLVS WRRRQRRLRG ASSAEAPDGD KDAPEPLDKV IILSPGISDA TAPAWPPPGE DPGTTPPGHS VPVPATELGS TELVTTKTAG PEQQ //