TR13C_HUMAN
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 03-AUG-2022, entry version 165.
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.
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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 AlphaFoldDB; Q96RJ3; -.
DR BMRB; Q96RJ3; -.
DR SMR; Q96RJ3; -.
DR BioGRID; 125443; 15.
DR STRING; 9606.ENSP00000291232; -.
DR ChEMBL; CHEMBL4630882; -.
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; 675 antibodies from 41 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 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; 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 SignaLink; Q96RJ3; -.
DR SIGNOR; Q96RJ3; -.
DR BioGRID-ORCS; 115650; 49 hits in 1068 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 109 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: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; 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 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
