Q96RJ3 (TR13C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor receptor superfamily member 13C

Alternative name(s):
B-cell-activating factor receptor
BAFF receptor
Short name=BAFF-R
BLyS receptor 3
CD_antigen=CD268

Gene names

Name:	TNFRSF13C
Synonyms:	BAFFR, BR3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	184 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response. Ref.3 Ref.4
Subcellular location	Membrane; Single-pass type III membrane protein Probable.
Tissue specificity	Highly expressed in spleen and lymph node, and in resting B-cells. Detected at lower levels in activated B-cells, resting CD4+ T-cells, in thymus and peripheral blood leukocytes.
Involvement in disease	Immunodeficiency, common variable, 4 (CVID4) [MIM:613494]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B cells is usually in the normal range, but can be low. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10
Sequence similarities	Contains 1 TNFR-Cys repeat.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell costimulation Inferred from electronic annotation. Source: Compara B cell homeostasis Inferred from electronic annotation. Source: Compara T cell costimulation Inferred from electronic annotation. Source: Compara positive regulation of B cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of T cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of germinal center formation Inferred from electronic annotation. Source: Compara positive regulation of interferon-gamma biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96RJ3-1)

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: Q96RJ3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     143-143: P → PA

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 184

184

Tumor necrosis factor receptor superfamily member 13C

PRO_0000058933

Regions

Topological domain

1 – 78

78

Extracellular Potential

Transmembrane

79 – 99

21

Helical; Signal-anchor for type III membrane protein; Potential

Topological domain

100 – 184

85

Cytoplasmic Potential

Repeat

18 – 35

18

TNFR-Cys; truncated

Region

26 – 31

6

Essential for TNFSF13B/TALL1/BAFF/BLyS binding

Amino acid modifications

Disulfide bond

19 ↔ 32

Ref.4 Ref.5 Ref.6 Ref.7

Disulfide bond

24 ↔ 35

Ref.4 Ref.5 Ref.6 Ref.7

Natural variations

Alternative sequence

143

1

P → PA in isoform 2.

VSP_006505

Natural variant

64

1

G → V. Ref.9

VAR_063888

Natural variant

65 – 72

8

AGAGEAAL → V in CVID4; fails to bind TNFSF13B and fails to induce downstream NF-kappa-B processing.

VAR_063889

Natural variant

159

1

H → Y. Ref.9

VAR_063890

Experimental info

Mutagenesis

24

1

C → Y: Abolishes a disulfide bond and thereby changes the specificity, so that both TNFSF13B and TNFSF13 can be bound. Ref.6

Mutagenesis

26

1

D → A: Strongly reduced affinity for TNFSF13B. Ref.5

Mutagenesis

28

1

L → A: Strongly reduced affinity for TNFSF13B. Ref.5

Mutagenesis

35

1

C → S: Abolishes a disulfide bond and thereby changes the specificity, so that both TNFSF13B and TNFSF13 can be bound. Ref.6

Secondary structure

1

.

.

.

.

.

.

184

Helix Strand Turn

Details...

Beta strand

23 – 26

4

Turn

27 – 30

4

Beta strand

31 – 34

4

Helix

35 – 37

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: F2BFB98099A27138	FASTA	184	18,864
	10 20 30 40 50 60 MRRGPRSLRG RDAPAPTPCV PAECFDLLVR HCVACGLLRT PRPKPAGASS PAPRTALQPQ 70 80 90 100 110 120 ESVGAGAGEA ALPLPGLLFG APALLGLALV LALVLVGLVS WRRRQRRLRG ASSAEAPDGD 130 140 150 160 170 180 KDAPEPLDKV IILSPGISDA TAPAWPPPGE DPGTTPPGHS VPVPATELGS TELVTTKTAG PEQQ
	Isoform 2 [UniParc]. Checksum: 2E64C16E672A6C64	FASTA	185	18,935
	10 20 30 40 50 60 MRRGPRSLRG RDAPAPTPCV PAECFDLLVR HCVACGLLRT PRPKPAGASS PAPRTALQPQ 70 80 90 100 110 120 ESVGAGAGEA ALPLPGLLFG APALLGLALV LALVLVGLVS WRRRQRRLRG ASSAEAPDGD 130 140 150 160 170 180 KDAPEPLDKV IILSPGISDA TAPAAWPPPG EDPGTTPPGH SVPVPATELG STELVTTKTA GPEQQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BAFF-R, a newly identified TNF receptor that specifically interacts with BAFF." Thompson J.S., Bixler S.A., Qian F., Vora K., Scott M.L., Cachero T.G., Hession C., Schneider P., Sizing I.D., Mullen C., Strauch K., Zafari M., Benjamin C.D., Tschopp J., Browning J.L., Ambrose C. Science 293:2108-2111(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). Tissue: B-cell lymphoma.
[2]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Identification of a novel receptor for B lymphocyte stimulator that is mutated in a mouse strain with severe B cell deficiency." Yan M., Brady J.R., Chan B., Lee W.P., Hsu B., Harless S.M., Cancro M.P., Grewal I.S., Dixit V.M. Curr. Biol. 11:1547-1552(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"BAFF/BLyS receptor 3 binds the B cell survival factor BAFF ligand through a discrete surface loop and promotes processing of NF-kappaB2." Kayagaki N., Yan M., Seshasayee D., Wang H., Lee W., French D.M., Grewal I.S., Cochran A.G., Gordon N.C., Yin J., Starovasnik M.A., Dixit V.M. Immunity 17:515-524(2002) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 26-33, FUNCTION, DISULFIDE BONDS.
[5]	"BAFF/BLyS receptor 3 comprises a minimal TNF receptor-like module that encodes a highly focused ligand-binding site." Gordon N.C., Pan B., Hymowitz S.G., Yin J., Kelley R.F., Cochran A.G., Yan M., Dixit V.M., Fairbrother W.J., Starovasnik M.A. Biochemistry 42:5977-5983(2003) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-61, X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 26-31 IN COMPLEX WITH TNFSF13B/TALL1/BAFF/BLYS, DISULFIDE BONDS, MUTAGENESIS OF ASP-26 AND LEU-28.
[6]	"Ligand-receptor binding revealed by the TNF family member TALL-1." Liu Y., Hong X., Kappler J., Jiang L., Zhang R., Xu L., Pan C.-H., Martin W.E., Murphy R.C., Shu H.-B., Dai S., Zhang G. Nature 423:49-56(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 16-46 IN COMPLEX WITH TNFSF13B/TALL1/BAFF/BLYS, DISULFIDE BONDS, MUTAGENESIS OF CYS-24 AND CYS-35.
[7]	"Crystal structure of the BAFF-BAFF-R complex and its implications for receptor activation." Kim H.M., Yu K.S., Lee M.E., Shin D.R., Kim Y.S., Paik S.-G., Yoo O.J., Lee H., Lee J.-O. Nat. Struct. Biol. 10:342-348(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 1-63 IN COMPLEX WITH TNFSF13B/TALL1/BAFF/BLYS, DISULFIDE BONDS.
[8]	"Synthetic anti-BR3 antibodies that mimic BAFF binding and target both human and murine B cells." Lee C.V., Hymowitz S.G., Wallweber H.J., Gordon N.C., Billeci K.L., Tsai S.-P., Compaan D.M., Yin J., Gong Q., Kelley R.F., DeForge L.E., Martin F., Starovasnik M.A., Fuh G. Blood 108:3103-3111(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 7-54, INTERACTION WITH TNFSF13B/TALL1/BAFF/BLYS.
[9]	"Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency." Losi C.G., Silini A., Fiorini C., Soresina A., Meini A., Ferrari S., Notarangelo L.D., Lougaris V., Plebani A. J. Clin. Immunol. 25:496-502(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS VAL-64 AND TYR-159.
[10]	"B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans." Warnatz K., Salzer U., Rizzi M., Fischer B., Gutenberger S., Boehm J., Kienzler A.-K., Pan-Hammarstroem Q., Hammarstroem L., Rakhmanov M., Schlesier M., Grimbacher B., Peter H.-H., Eibel H. Proc. Natl. Acad. Sci. U.S.A. 106:13945-13950(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CVID4 65-ALA--LEU-72 DELINS VAL, CHARACTERIZATION OF VARIANT CVID4 65-ALA--LEU-72 DELINS VAL.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF373846 mRNA. Translation: AAK91826.1.
Z99716 Genomic DNA. No translation available.

IPI

IPI00045337.
IPI00218927.

RefSeq

NP_443177.1. NM_052945.3.

UniGene

Hs.344088.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MPV	NMR	-	A	26-33	[»]
1OQE	X-ray	2.50	K/L/M/N/O/P/Q/R	16-46	[»]
1OSX	NMR	-	A	1-61	[»]
1P0T	X-ray	3.30	0/1/2/3/4/5/6/7/8/9/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d/e/f/g/h/i/j/k/l/m/n/o/p/q/r/s/t/u/v/w/x	1-63	[»]
2HFG	X-ray	2.61	R	7-54	[»]

ProteinModelPortal

Q96RJ3.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000291232.

PTM databases

PhosphoSite

Q96RJ3.

Polymorphism databases

DMDM

21264093.

Proteomic databases

PRIDE

Q96RJ3.

Protocols and materials databases

DNASU

115650.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000291232; ENSP00000291232; ENSG00000159958.

GeneID

115650.

KEGG

hsa:115650.

UCSC

uc003bbl.2. human.

Organism-specific databases

CTD

115650.

GeneCards

GC22M042321.

HGNC

HGNC:17755. TNFRSF13C.

HPA

CAB008380.
HPA003246.

MIM

606269. gene.
613494. phenotype.

neXtProt

NX_Q96RJ3.

Orphanet

183672. Common variable immunodeficiency due to TNFR deficiency.

PharmGKB

PA38466.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG43121.

HOGENOM

HOG000132919.

HOVERGEN

HBG055867.

InParanoid

Q96RJ3.

KO

K05151.

OMA

ACKLFRT.

OrthoDB

EOG4D26RC.

PhylomeDB

Q96RJ3.

Gene expression databases

ArrayExpress

Q96RJ3.

Bgee

Q96RJ3.

CleanEx

HS_TNFRSF13C.

Genevestigator

Q96RJ3.

GermOnline

ENSG00000159958. Homo sapiens.

Family and domain databases

InterPro

IPR022338. TNFR_13C.
IPR015336. TNFR_13C_TALL-1-bd.
[Graphical view]

Pfam

PF09256. BaffR-Tall_bind. 1 hit.
[Graphical view]

PRINTS

PR01964. TNFACTORR13C.

PROSITE

PS00652. TNFR_NGFR_1. False negative.
PS50050. TNFR_NGFR_2. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q96RJ3.

GenomeRNAi

115650.

NextBio

79628.

SOURCE

Search...

Entry information

Entry name

TR13C_HUMAN

Accession

Primary (citable) accession number: Q96RJ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 103 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.