Q9Y275 (TN13B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor ligand superfamily member 13B

Alternative name(s):
B lymphocyte stimulator
Short name=BLyS
B-cell-activating factor
BAFF
Dendritic cell-derived TNF-like molecule
TNF- and APOL-related leukocyte expressed ligand 1
Short name=TALL-1
CD_antigen=CD257

Cleaved into the following 2 chains:

1. Tumor necrosis factor ligand superfamily member 13b, membrane form
2. Tumor necrosis factor ligand superfamily member 13b, soluble form

Gene names

Name:	TNFSF13B
Synonyms:	BAFF, BLYS, TALL1, TNFSF20, ZTNF4
ORF Names:	UNQ401/PRO738

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	285 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cytokine that binds to TNFRSF13B/TACI and TNFRSF17/BCMA. TNFSF13/APRIL binds to the same 2 receptors. Together, they form a 2 ligands -2 receptors pathway involved in the stimulation of B- and T-cell function and the regulation of humoral immunity. A third B-cell specific BAFF-receptor (BAFFR/BR3) promotes the survival of mature B-cells and the B-cell response. Ref.15 Isoform 2 seems to inhibit isoform 1 secretion and bioactivity By similarity. Ref.15
Subunit structure	Homotrimer. Isoform 2 heteromultimerizes with isoform 1, probably limiting the amount of functional isoform 1 on the cell surface. Ref.4
Subcellular location	Cell membrane; Single-pass type II membrane protein. Tumor necrosis factor ligand superfamily member 13b, soluble form: Secreted.
Tissue specificity	Abundantly expressed in peripheral blood Leukocytes and is specifically expressed in monocytes and macrophages. Also found in the spleen, lymph node, bone marrow, T-cells and dendritic cells. A lower expression seen in placenta, heart, lung, fetal liver, thymus, and pancreas. Isoform 2 is expressed in many myeloid cell lines. Ref.4
Induction	Up-regulated by exposure to IFNG/IFN-gamma. Down-regulated by phorbol myristate acetate/ionomycin treatment.
Post-translational modification	The soluble form derives from the membrane form by proteolytic processing. Isoform 2 is not efficiently shed from the membrane unlike isoform 1 By similarity. N-glycosylated.
Sequence similarities	Belongs to the tumor necrosis factor family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing 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 cell proliferation Traceable author statement PubMed 10908663. Source: ProtInc immune response Inferred from electronic annotation. Source: InterPro immunoglobulin secretion 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 cell proliferation Traceable author statement Ref.2. Source: ProtInc positive regulation of germinal center formation Inferred from electronic annotation. Source: Compara signal transduction Traceable author statement PubMed 10908663. Source: ProtInc
Cellular_component	extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Non-traceable author statement Ref.4. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	receptor binding Traceable author statement PubMed 10908663. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TNFRSF13B	O14836	7	EBI-519169,EBI-519160

Alternative products

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

Isoform 1 (identifier: Q9Y275-1)

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: Q9Y275-2)

Also known as: DeltaBAFF;

The sequence of this isoform differs from the canonical sequence as follows:
     142-160: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 285

285

Tumor necrosis factor ligand superfamily member 13b, membrane form

PRO_0000034528

Chain

134 – 285

152

Tumor necrosis factor ligand superfamily member 13b, soluble form

PRO_0000034529

Regions

Topological domain

1 – 46

46

Cytoplasmic Potential

Transmembrane

47 – 67

21

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

Topological domain

68 – 285

218

Extracellular Potential

Sites

Site

133 – 134

2

Cleavage

Amino acid modifications

Glycosylation

124

1

N-linked (GlcNAc...)

Glycosylation

242

1

N-linked (GlcNAc...) (high mannose)

Disulfide bond

232 ↔ 245

Natural variations

Alternative sequence

142 – 160

19

Missing in isoform 2.

VSP_041183

Natural variant

105

1

A → T. Ref.14

VAR_013483

Secondary structure

1

.

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.

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.

.

.

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.

.

.

.

.

.

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285

Helix Strand Turn

Details...

Beta strand

146 – 151

6

Beta strand

158 – 160

3

Beta strand

163 – 165

3

Beta strand

168 – 181

14

Beta strand

184 – 187

4

Beta strand

191 – 201

11

Beta strand

205 – 215

11

Beta strand

225 – 235

11

Beta strand

238 – 240

3

Beta strand

243 – 253

11

Beta strand

258 – 265

8

Turn

274 – 276

3

Beta strand

277 – 283

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 1. Checksum: 48ED0D7AB38C8867	FASTA	285	31,223
	10 20 30 40 50 60 MDDSTEREQS RLTSCLKKRE EMKLKECVSI LPRKESPSVR SSKDGKLLAA TLLLALLSCC 70 80 90 100 110 120 LTVVSFYQVA ALQGDLASLR AELQGHHAEK LPAGAGAPKA GLEEAPAVTA GLKIFEPPAP 130 140 150 160 170 180 GEGNSSQNSR NKRAVQGPEE TVTQDCLQLI ADSETPTIQK GSYTFVPWLL SFKRGSALEE 190 200 210 220 230 240 KENKILVKET GYFFIYGQVL YTDKTYAMGH LIQRKKVHVF GDELSLVTLF RCIQNMPETL 250 260 270 280 PNNSCYSAGI AKLEEGDELQ LAIPRENAQI SLDGDVTFFG ALKLL
	Isoform 2 (DeltaBAFF) [UniParc]. Checksum: 6BD06F90061152C6	FASTA	266	29,137
	10 20 30 40 50 60 MDDSTEREQS RLTSCLKKRE EMKLKECVSI LPRKESPSVR SSKDGKLLAA TLLLALLSCC 70 80 90 100 110 120 LTVVSFYQVA ALQGDLASLR AELQGHHAEK LPAGAGAPKA GLEEAPAVTA GLKIFEPPAP 130 140 150 160 170 180 GEGNSSQNSR NKRAVQGPEE TGSYTFVPWL LSFKRGSALE EKENKILVKE TGYFFIYGQV 190 200 210 220 230 240 LYTDKTYAMG HLIQRKKVHV FGDELSLVTL FRCIQNMPET LPNNSCYSAG IAKLEEGDEL 250 260 QLAIPRENAQ ISLDGDVTFF GALKLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"TALL-1 is a novel member of the TNF family that is down-regulated by mitogens." Shu H.-B., Hu W.-H., Johnson H. J. Leukoc. Biol. 65:680-683(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth." Schneider P., MacKay F., Steiner V., Hofmann K., Bodmer J.-L., Holler N., Ambrose C., Lawton P., Bixler S., Acha-Orbea H., Valmori D., Romero P., Werner-Favre C., Zubler R.H., Browning J.L., Tschopp J. J. Exp. Med. 189:1747-1756(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 134-148.
[3]	"BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator." Moore P.A., Belvedere O., Orr A., Pieri K., LaFleur D.W., Feng P., Soppet D., Charters M., Gentz R., Parmelee D., Li Y., Galperina O., Giri J., Roschke V., Nardelli B., Carrell J., Sosnovtseva S., Greenfield W. , Ruben S.M., Olsen H.S., Fikes J., Hilbert D.M. Science 285:260-263(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Monocyte and Neutrophil.
[4]	"DeltaBAFF, an alternate splice isoform that regulates receptor binding and biopresentation of the B cell survival cytokine, BAFF." Gavin A.L., Ait-Azzouzene D., Ware C.F., Nemazee D. J. Biol. Chem. 278:38220-38228(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY, SUBUNIT.
[5]	"Homo sapiens homolog of tumor necrosis factor." Farrah T., Gross J., Piddington C., O'Hara P. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"A novel dendritic cell-derived TNF-like molecule." Zhang W., Wan T., Yu Y., Cao X. Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Dendritic cell.
[7]	Gao H., He F., Li R. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[8]	Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[9]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[10]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[11]	"The DNA sequence and analysis of human chromosome 13." Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T. Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta.
[14]	"New polymorphisms of human BLyS gene." Kawasaki A., Tsuchiya N., Fukazawa T., Hashimoto H., Tokunaga K. Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-135, VARIANT THR-105.
[15]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[16]	"Crystal structure of sTALL-1 reveals a virus-like assembly of TNF family ligands." Liu Y., Xu L., Opalka N., Kappler J., Shu H.-B., Zhang G. Cell 108:383-394(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 142-285.
[17]	"Crystal structure of extracellular human BAFF, a TNF family member that stimulates B lymphocytes." Karpusas M., Cachero T.G., Qian F., Boriack-Sjodin A., Mullen C., Strauch K., Hsu Y.-M., Kalled S.L. J. Mol. Biol. 315:1145-1154(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 136-285.
[18]	"Structural basis of BLyS receptor recognition." Oren D.A., Li Y., Volovik Y., Morris T.S., Dharia C., Das K., Galperina O., Gentz R., Arnold E. Nat. Struct. Biol. 9:288-292(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 134-285.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Proteic grace - Issue 77 of December 2006

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF136293 mRNA. Translation: AAD29421.1.
AF116456 mRNA. Translation: AAD25356.1.
AF132600 mRNA. Translation: AAD21092.1.
AY302751 mRNA. Translation: AAP83164.1.
AF186114 mRNA. Translation: AAF01432.1.
AF134715 mRNA. Translation: AAF60219.1.
AY129225 mRNA. Translation: AAN08421.1.
EF064706 Genomic DNA. Translation: ABK41889.1.
AY358881 mRNA. Translation: AAQ89240.1.
CR541818 mRNA. Translation: CAG46617.1.
AL157762 Genomic DNA. Translation: CAH70631.1.
CH471085 Genomic DNA. Translation: EAX09099.1.
BC020674 mRNA. Translation: AAH20674.1.
AB073225 Genomic DNA. Translation: BAB90856.1.

IPI

IPI00031802.
IPI00923520.

RefSeq

NP_001139117.1. NM_001145645.2.
NP_006564.1. NM_006573.4.

UniGene

Hs.525157.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JH5	X-ray	3.00	A/B/C/D/E/F/G/H/I/J	142-285	[»]
1KD7	X-ray	2.80	A/B/C/K/L/M	136-285	[»]
1KXG	X-ray	2.00	A/B/C/D/E/F	134-285	[»]
1OQD	X-ray	2.60	A/B/C/D/E/F/G/H/I/J	142-285	[»]
1OQE	X-ray	2.50	A/B/C/D/E/F/G/H/I/J	142-285	[»]
1OSG	X-ray	3.00	A/B/C/D/E/F	82-285	[»]
1OTZ	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	138-285	[»]
3V56	X-ray	3.00	A/B/C/D/E/F	82-285	[»]

ProteinModelPortal

Q9Y275.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6225N.

IntAct

Q9Y275. 2 interactions.

STRING

9606.ENSP00000365048.

PTM databases

PhosphoSite

Q9Y275.

Polymorphism databases

DMDM

13124573.

Proteomic databases

PaxDb

Q9Y275.

PRIDE

Q9Y275.

Protocols and materials databases

DNASU

10673.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375887; ENSP00000365048; ENSG00000102524.
ENST00000430559; ENSP00000389540; ENSG00000102524.

GeneID

10673.

KEGG

hsa:10673.

UCSC

uc001vqr.3. human.
uc010agj.3. human.

Organism-specific databases

CTD

10673.

GeneCards

GC13P108903.

HGNC

HGNC:11929. TNFSF13B.

HPA

CAB009188.

MIM

603969. gene.

neXtProt

NX_Q9Y275.

PharmGKB

PA434.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG47835.

HOGENOM

HOG000036810.

HOVERGEN

HBG061472.

InParanoid

Q9Y275.

KO

K05476.

OMA

ILPQKES.

OrthoDB

EOG47M206.

PhylomeDB

Q9Y275.

Gene expression databases

ArrayExpress

Q9Y275.

Bgee

Q9Y275.

CleanEx

HS_TNFSF13B.

Genevestigator

Q9Y275.

GermOnline

ENSG00000102524. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.40. 1 hit.

InterPro

IPR006052. TNF.
IPR008983. Tumour_necrosis_fac-like_dom.
[Graphical view]

Pfam

PF00229. TNF. 1 hit.
[Graphical view]

SMART

SM00207. TNF. 1 hit.
[Graphical view]

SUPFAM

SSF49842. TNF_like. 1 hit.

PROSITE

PS00251. TNF_1. False negative.
PS50049. TNF_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q9Y275.

GenomeRNAi

10673.

NextBio

40587.

SOURCE

Search...

Entry information

Entry name

TN13B_HUMAN

Accession

Primary (citable) accession number: Q9Y275
Secondary accession number(s): Q6FHD6, Q7Z5J2

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 142 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.