Reviewed, UniProtKB/Swiss-Prot O14836 (TR13B_HUMAN)

Names and origin

Protein names

Recommended name:
    Tumor necrosis factor receptor superfamily member 13B
Alternative name(s):
    Transmembrane activator and CAML interactor
    CD_antigen=CD267

Gene names

Name:	TNFRSF13B
Synonyms:	TACI

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	293 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for TNFSF13/APRIL and TNFSF13B/TALL1/BAFF/BLYS that binds both ligands with similar high affinity. Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-B and AP-1. Involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. Ref.6 Ref.7
Subunit structure	Binds TRAF2, TRAF5 and TRAF6. Binds the NH2-terminal domain of CAMLG with its C-terminus.
Subcellular location	Membrane; Single-pass type III membrane protein.
Tissue specificity	Highly expressed in spleen, thymus, small intestine and peripheral blood leukocytes. Expressed in resting B-cells and activated T-cells, but not in resting T-cells.
Involvement in disease	Defects in TNFRSF13B are a cause of common variable immunodeficiency (CVID) [MIM:240500]. CVID is characterized by a deficiency in all immunoglobulin (Ig) isotypes. Individuals with CVID suffer from recurrent sinopulmonary and gastrointestinal infections and have an increased incidence of autoimmune disorders and of lymphoid and non-lymphoid malignancies. There is evidence for a global isotype switching defect in some individuals with CVID. But CVID is a complex and heterogeneous disease in which defects in B-cell survival, number of circulating CD27+ memory B-cells (including IgM+CD27+ B-cells), B-cell activation after antigen receptor cross-linking, T-cell signaling and cytokine expression have been observed. Ref.10 Defects in TNFRSF13B are a cause of immunoglobulin A deficiency 2 (IGAD2) [MIM:609529]. Selective deficiency of immunoglobulin A (IGAD) is the most common form of primary immunodeficiency, with an incidence of approximately 1 in 600 individuals in the western world. Individuals with symptomatic IGAD often have deficiency of IgG subclasses or decreased antibody response to carbohydrate antigens such as pneumococcal polysaccharide vaccine. Individuals with IGAD also suffer from recurrent sinopulmonary and gastrointestinal infections and have an increased incidence of autoimmune disorders and of lymphoid and non-lymphoid malignancies. In vitro studies have suggested that some individuals with IGAD have impaired isotype class switching to IgA and others may have a post-switch defect. IGAD and CVID have been known to coexist in families. Some individuals initially present with IGAD1 and then develop CVID. These observations suggest that some cases of IGAD and CVID may have a common etiology.
Sequence similarities	Contains 2 TNFR-Cys repeats.

Ontologies

Keywords
Biological process	Immune response
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Repeat Signal-anchor Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell surface receptor linked signal transduction Ref.1 Traceable author statement. Source: ProtInc immune response Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.6 Inferred from physical interaction. Source: IntAct receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFSF13	O75888	1	EBI-519160,EBI-519208
TNFSF13B	Q9Y275	4	EBI-519160,EBI-519169

Alternative products

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

Isoform 1 (identifier: O14836-1)

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: O14836-2)

The sequence of this isoform differs from the canonical sequence as follows:
     21-67: FPQGLWTGVAMRSCPEEQYWDPLLGTCMSCKTICNHQSQRTCAAFCR → W

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 293

293

Tumor necrosis factor receptor superfamily member 13B

PRO_0000058931

Regions

Topological domain

1 – 165

165

Extracellular Potential

Transmembrane

166 – 186

21

Signal-anchor for type III membrane protein Potential

Topological domain

187 – 293

107

Cytoplasmic Potential

Repeat

33 – 67

35

TNFR-Cys 1

Repeat

70 – 104

35

TNFR-Cys 2

Amino acid modifications

Glycosylation

128

1

N-linked (GlcNAc...) Potential

Disulfide bond

34 ↔ 47

By similarity

Disulfide bond

50 ↔ 62

By similarity

Disulfide bond

54 ↔ 66

By similarity

Disulfide bond

71 ↔ 86

Disulfide bond

89 ↔ 100

Disulfide bond

93 ↔ 104

Natural variations

Alternative sequence

21 – 67

47

FPQGL…AAFCR → W in isoform 2.

VSP_013798

Natural variant

104

1

C → R in CVID and IGAD2. dbSNP rs34557412. Ref.10

VAR_024027

Natural variant

181

1

A → G in CVID. Ref.10

VAR_024028

Natural variant

202

1

R → H in CVID. Ref.10

VAR_024029

Natural variant

251

1

P → L: dbSNP rs34562254. Ref.3

VAR_052353

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

293

Helix Strand Turn

Details...

Helix

73 – 75

3

Beta strand

77 – 80

4

Turn

81 – 84

4

Beta strand

85 – 88

4

Helix

89 – 92

4

Helix

98 – 100

3

Helix

101 – 104

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 411799F3DE17A5EB	FASTA	293	31,816
	10 20 30 40 50 60 MSGLGRSRRG GRSRVDQEER FPQGLWTGVA MRSCPEEQYW DPLLGTCMSC KTICNHQSQR 70 80 90 100 110 120 TCAAFCRSLS CRKEQGKFYD HLLRDCISCA SICGQHPKQC AYFCENKLRS PVNLPPELRR 130 140 150 160 170 180 QRSGEVENNS DNSGRYQGLE HRGSEASPAL PGLKLSADQV ALVYSTLGLC LCAVLCCFLV 190 200 210 220 230 240 AVACFLKKRG DPCSCQPRSR PRQSPAKSSQ DHAMEAGSPV STSPEPVETC SFCFPECRAP 250 260 270 280 290 TQESAVTPGT PDPTCAGRWG CHTRTTVLQP CPHIPDSGLG IVCVPAQEGG PGA
	Isoform 2. Checksum: 850E1F4C2578E8E6	FASTA	247	26,664
	10 20 30 40 50 60 MSGLGRSRRG GRSRVDQEER WSLSCRKEQG KFYDHLLRDC ISCASICGQH PKQCAYFCEN 70 80 90 100 110 120 KLRSPVNLPP ELRRQRSGEV ENNSDNSGRY QGLEHRGSEA SPALPGLKLS ADQVALVYST 130 140 150 160 170 180 LGLCLCAVLC CFLVAVACFL KKRGDPCSCQ PRSRPRQSPA KSSQDHAMEA GSPVSTSPEP 190 200 210 220 230 240 VETCSFCFPE CRAPTQESAV TPGTPDPTCA GRWGCHTRTT VLQPCPHIPD SGLGIVCVPA QEGGPGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NF-AT activation induced by a CAML-interacting member of the tumor necrosis factor receptor superfamily." von Buelow G.-U., Bram R.J. Science 278:138-141(1997) [PubMed: 9311921] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: B-cell.
[2]	Zhou G., Ke R., Li H., Zheng G., Shen C., Lin L., Yang S. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-251. Tissue: Spleen.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[6]	"Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS." Wu Y., Bressette D., Carrell J.A., Kaufman T., Feng P., Taylor K., Gan Y., Cho Y.H., Garcia A.D., Gollatz E., Dimke D., LaFleur D., Migone T.S., Nardelli B., Wei P., Ruben S.M., Ullrich S.J., Olsen H.S. , Kanakaraj P., Moore P.A., Baker K.P. J. Biol. Chem. 275:35478-35485(2000) [PubMed: 10956646] [Abstract] Cited for: FUNCTION.
[7]	"APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity." Yu G., Boone T., Delaney J., Hawkins N., Kelley M.J., Ramakrishnan M., McCabe S., Qiu W.R., Kornuc M., Xia X.-Z., Guo J., Stolina M., Boyle W.J., Sarosi I., Hsu H., Senaldi G., Theill L.E. Nat. Immunol. 1:252-256(2000) [PubMed: 10973284] [Abstract] Cited for: FUNCTION.
[8]	"TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation." Xia X.-Z., Treanor J., Senaldi G., Khare S.D., Boone T., Kelley M., Theill L.E., Colombero A., Solovyev I., Lee F., McCabe S., Elliott R., Miner K., Hawkins N., Guo J., Stolina M., Yu G., Wang J. , Delaney J., Meng S.-Y., Boyle W.J., Hsu H. J. Exp. Med. 192:137-143(2000) [PubMed: 10880535] [Abstract] Cited for: INTERACTION WITH TRAF2 AND TRAF5.
[9]	"Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding." Hymowitz S.G., Patel D.R., Wallweber H.J., Runyon S., Yan M., Yin J., Shriver S.K., Gordon N.C., Pan B., Skelton N.J., Kelley R.F., Starovasnik M.A. J. Biol. Chem. 280:7218-7227(2005) [PubMed: 15542592] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 68-109 IN COMPLEX WITH MOUSE TNFSF13, STRUCTURE BY NMR OF 68-109.
[10]	"TACI is mutant in common variable immunodeficiency and IgA deficiency." Castigli E., Wilson S.A., Garibyan L., Rachid R., Bonilla F., Schneider L., Geha R.S. Nat. Genet. 37:829-834(2005) [PubMed: 16007086] [Abstract] Cited for: VARIANT CVID/IGAD2 ARG-104, VARIANTS CVID GLY-181 AND HIS-202.
+	Additional computationally mapped references.

Web resources

TNFRSF13Bbase

TNFRSF13B mutation db

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF023614 mRNA. Translation: AAC51790.1.
AY302137 mRNA. Translation: AAP57629.1.
AK313302 mRNA. Translation: BAG36107.1.
CH471196 Genomic DNA. Translation: EAW55729.1.
BC109392 mRNA. Translation: AAI09393.1.

IPI

IPI00018362.
IPI00385403.

RefSeq

NP_036584.1.

UniGene

Hs.158341

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XU1	X-ray	1.90	R/S/T	68-109	[»]
1XUT	NMR	-	A	68-109	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6224N.

IntAct

O14836. 3 interactions.

STRING

O14836.

Proteomic databases

PRIDE

O14836.

Genome annotation databases

Ensembl

ENST00000261652; ENSP00000261652; ENSG00000240505; Homo sapiens. [Genome view]

GeneID

23495.

KEGG

hsa:23495.

UCSC

uc002gqs.1. human.

Organism-specific databases

CTD

23495.

GeneCards

GC17M016783.

H-InvDB

HIX0013576.

HGNC

HGNC:18153. TNFRSF13B.

MIM

240500. phenotype.
604907. gene.
609529. phenotype.

Orphanet

1572. Common variable immunodeficiency.
69127. Immunoglobulin A deficiency.

PharmGKB

PA38509.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19158.

HOGENOM

HBG278162.

HOVERGEN

O14836.

InParanoid

O14836.

OMA

CHTRTTV.

PhylomeDB

O14836.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_2_pathway. Syndecan-2-mediated signaling events.
syndecan_4_pathway. Syndecan-4-mediated signaling events.

Gene expression databases

ArrayExpress

O14836.

Bgee

O14836.

CleanEx

HS_TNFRSF13B.

Genevestigator

O14836.

GermOnline

ENSG00000108516. Homo sapiens.

Family and domain databases

InterPro

IPR015384. TACI_Cys-rich-dom.
[Graphical view]

Pfam

PF09305. TACI-CRD2. 2 hits.
[Graphical view]

PROSITE

PS00652. TNFR_NGFR_1. 1 hit.
PS50050. TNFR_NGFR_2. False negative.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

45863.

SOURCE

Search...

Entry information

Entry name

TR13B_HUMAN

Accession

Primary (citable) accession number: O14836
Secondary accession number(s): B2R8B0, Q32LX4, Q7Z6F5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 27, 2002
Last sequence update:	January 1, 1998
Last modified:	January 19, 2010
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.