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Database: UniProt
Entry: Q96RJ3
LinkDB: Q96RJ3
Original site: Q96RJ3 
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   02-DEC-2020, entry version 158.
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 mutations affecting the gene represented in this
CC       entry.
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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   BMRB; Q96RJ3; -.
DR   SMR; Q96RJ3; -.
DR   BioGRID; 125443; 5.
DR   STRING; 9606.ENSP00000291232; -.
DR   GuidetoPHARMACOLOGY; 1886; -.
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; Q96RJ3; -.
DR   PeptideAtlas; Q96RJ3; -.
DR   PRIDE; Q96RJ3; -.
DR   ProteomicsDB; 77970; -. [Q96RJ3-1]
DR   ProteomicsDB; 77971; -. [Q96RJ3-2]
DR   ABCD; Q96RJ3; 3 sequenced antibodies.
DR   Antibodypedia; 307; 673 antibodies.
DR   DNASU; 115650; -.
DR   Ensembl; ENST00000291232; ENSP00000291232; ENSG00000159958. [Q96RJ3-1]
DR   GeneID; 115650; -.
DR   KEGG; hsa:115650; -.
DR   UCSC; uc003bbl.3; human. [Q96RJ3-1]
DR   CTD; 115650; -.
DR   DisGeNET; 115650; -.
DR   EuPathDB; HostDB:ENSG00000159958.4; -.
DR   GeneCards; TNFRSF13C; -.
DR   HGNC; HGNC:17755; TNFRSF13C.
DR   HPA; ENSG00000159958; Tissue enhanced (blood, 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   eggNOG; ENOG502T201; Eukaryota.
DR   GeneTree; ENSGT00940000154485; -.
DR   HOGENOM; CLU_131020_0_0_1; -.
DR   InParanoid; Q96RJ3; -.
DR   OMA; AQCFDPL; -.
DR   OrthoDB; 702827at2759; -.
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   SIGNOR; Q96RJ3; -.
DR   BioGRID-ORCS; 115650; 37 hits in 842 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 tonsil and 162 other tissues.
DR   ExpressionAtlas; Q96RJ3; baseline and differential.
DR   Genevisible; Q96RJ3; HS.
DR   GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0001782; P:B cell homeostasis; IEA:Ensembl.
DR   GO; GO:0030890; P:positive regulation of B cell proliferation; IBA:GO_Central.
DR   GO; GO:0002636; P:positive regulation of germinal center formation; IEA:Ensembl.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl.
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; TAS:Reactome.
DR   InterPro; IPR022338; TNFR_13C.
DR   InterPro; IPR043521; TNFR_13C/17.
DR   InterPro; IPR015336; TNFR_13C_TALL-1-bd.
DR   PANTHER; PTHR20437; PTHR20437; 1.
DR   PANTHER; PTHR20437:SF2; PTHR20437:SF2; 1.
DR   Pfam; PF09256; BaffR-Tall_bind; 1.
DR   PRINTS; PR01964; TNFACTORR13C.
PE   1: Evidence at protein level;
KW   3D-structure; Adaptive immunity; Alternative splicing; Disease mutation;
KW   Disulfide bond; Immunity; Membrane; Polymorphism; Receptor;
KW   Reference proteome; 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   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:0000244|PDB:1OQE"
FT   TURN            27..30
FT                   /evidence="ECO:0000244|PDB:1OQE"
FT   STRAND          31..34
FT                   /evidence="ECO:0000244|PDB:1OQE"
FT   HELIX           35..37
FT                   /evidence="ECO:0000244|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
//
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