O75888 (TNF13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tumor necrosis factor ligand superfamily member 13

Alternative name(s):
A proliferation-inducing ligand
Short name=APRIL
TNF- and APOL-related leukocyte expressed ligand 2
Short name=TALL-2
TNF-related death ligand 1
Short name=TRDL-1
CD_antigen=CD256

Gene names

Name:	TNFSF13
Synonyms:	APRIL, TALL2, ZTNF2
ORF Names:	UNQ383/PRO715

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	250 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 to TNFRSF17/BCMA. May be implicated in the regulation of tumor cell growth. May be involved in monocyte/macrophage-mediated immunological processes. Ref.8
Subunit structure	Homotrimer Potential.
Subcellular location	Secreted Ref.9.
Tissue specificity	Expressed at high levels in transformed cell lines, cancers of colon, thyroid, lymphoid tissues and specifically expressed in monocytes and macrophages.
Induction	Down-regulated by phorbol myristate acetate/ionomycin treatment.
Post-translational modification	The precursor is cleaved by furin. Ref.9
Sequence similarities	Belongs to the tumor necrosis factor family.

Ontologies

Keywords
Biological process	Immunity
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Cytokine
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	mRNA metabolic process Traceable author statement. Source: Reactome positive regulation of cell proliferation Traceable author statement. Source: ProtInc positive regulation of isotype switching to IgA isotypes Inferred from direct assay. Source: MGI signal transduction Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: Reactome extracellular space Inferred from electronic annotation. Source: UniProtKB-KW nucleoplasm Traceable author statement. Source: Reactome
Molecular function	cytokine activity Inferred from electronic annotation. Source: UniProtKB-KW tumor necrosis factor receptor binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform Alpha (identifier: O75888-1)

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 Beta (identifier: O75888-2)

The sequence of this isoform differs from the canonical sequence as follows:
     113-129: KQHSVLHLVPINATSKD → N

Isoform Gamma (identifier: O75888-3)

The sequence of this isoform differs from the canonical sequence as follows:
     247-249: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 104	104			PRO_0000034524
	Chain	105 – 250	146	Tumor necrosis factor ligand superfamily member 13		PRO_0000034525
Sites
	Site	104 – 105	2	Cleavage; by furin
Amino acid modifications
	Glycosylation	124	1	N-linked (GlcNAc...) Potential
	Disulfide bond	196 ↔ 211		Potential
Natural variations
	Alternative sequence	113 – 129	17	KQHSV…ATSKD → N in isoform Beta.		VSP_006450
	Alternative sequence	247 – 249	3	Missing in isoform Gamma.		VSP_006451
	Natural variant	67	1	G → R. Ref.6 Corresponds to variant rs11552708 [ dbSNP | Ensembl ].		VAR_052586
	Natural variant	96	1	N → S. Ref.7 Corresponds to variant rs3803800 [ dbSNP | Ensembl ].		VAR_052587
Experimental info
	Mutagenesis	101 – 104	4	RKRR → AKRA: Abolishes proteolytic processing. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform Alpha [UniParc]. Last modified November 1, 1998. Version 1. Checksum: AE1A6B9457F6E298	FASTA	250	27,433
	10 20 30 40 50 60 MPASSPFLLA PKGPPGNMGG PVREPALSVA LWLSWGAALG AVACAMALLT QQTELQSLRR 70 80 90 100 110 120 EVSRLQGTGG PSQNGEGYPW QSLPEQSSDA LEAWENGERS RKRRAVLTQK QKKQHSVLHL 130 140 150 160 170 180 VPINATSKDD SDVTEVMWQP ALRRGRGLQA QGYGVRIQDA GVYLLYSQVL FQDVTFTMGQ 190 200 210 220 230 240 VVSREGQGRQ ETLFRCIRSM PSHPDRAYNS CYSAGVFHLH QGDILSVIIP RARAKLNLSP 250 HGTFLGFVKL
	Isoform Beta [UniParc]. Checksum: 9F0012E23EBC0780	FASTA	234	25,678
	10 20 30 40 50 60 MPASSPFLLA PKGPPGNMGG PVREPALSVA LWLSWGAALG AVACAMALLT QQTELQSLRR 70 80 90 100 110 120 EVSRLQGTGG PSQNGEGYPW QSLPEQSSDA LEAWENGERS RKRRAVLTQK QKNDSDVTEV 130 140 150 160 170 180 MWQPALRRGR GLQAQGYGVR IQDAGVYLLY SQVLFQDVTF TMGQVVSREG QGRQETLFRC 190 200 210 220 230 IRSMPSHPDR AYNSCYSAGV FHLHQGDILS VIIPRARAKL NLSPHGTFLG FVKL
	Isoform Gamma [UniParc]. Checksum: BAB7F6E2989D9DC8	FASTA	247	27,059
	10 20 30 40 50 60 MPASSPFLLA PKGPPGNMGG PVREPALSVA LWLSWGAALG AVACAMALLT QQTELQSLRR 70 80 90 100 110 120 EVSRLQGTGG PSQNGEGYPW QSLPEQSSDA LEAWENGERS RKRRAVLTQK QKKQHSVLHL 130 140 150 160 170 180 VPINATSKDD SDVTEVMWQP ALRRGRGLQA QGYGVRIQDA GVYLLYSQVL FQDVTFTMGQ 190 200 210 220 230 240 VVSREGQGRQ ETLFRCIRSM PSHPDRAYNS CYSAGVFHLH QGDILSVIIP RARAKLNLSP HGTFLGL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth." Hahne M., Kataoka T., Schroeter M., Hofmann K., Irmler M., Bodmer J.-L., Schneider P., Bornand T., Holler N., French L.E., Sordat B., Rimoldi D., Tschopp J. J. Exp. Med. 188:1185-1190(1998) [PubMed: 9743536] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Uterus.
[2]	"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: 10331498] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Homo sapiens tumor necrosis factor homolog." Farrah T., Grant F., Haldeman B., Whitmore T., Gross J., O'Hara P. Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death." Kelly K.A., Manos E.J., Jensen G.T., Nadauld L., Jones D.A. Cancer Res. 60:1021-1027(2000) [PubMed: 10706119] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA; BETA AND GAMMA).
[5]	"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: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA), VARIANT ARG-67.
[7]	"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 GAMMA), VARIANT SER-96. Tissue: Ovary.
[8]	"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.
[9]	"Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase." Lopez-Fraga M., Fernandez R., Albar J.P., Hahne M. EMBO Rep. 2:945-951(2001) [PubMed: 11571266] [Abstract] Cited for: PROTEOLYTIC PROCESSING BY FURIN, MUTAGENESIS OF 101-ARG--ARG-104, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF046888 mRNA. Translation: AAC61312.1. AF136294 mRNA. Translation: AAD29422.1. AF184972 mRNA. Translation: AAF01321.1. AF114011 mRNA. Translation: AAF59828.1. AF114012 mRNA. Translation: AAF59829.1. AF114013 mRNA. Translation: AAF59830.1. AY358880 mRNA. Translation: AAQ89239.1. BT019561 mRNA. Translation: AAV38368.1. BT019562 mRNA. Translation: AAV38369.1. BC008042 mRNA. Translation: AAH08042.1.
IPI	IPI00027239. IPI00218935. IPI00218937.
RefSeq	NP_003799.1. NM_003808.3. NP_742084.1. NM_172087.2. NP_742085.1. NM_172088.2.
UniGene	Hs.54673.
3D structure databases
ProteinModelPortal	O75888.
SMR	O75888. Positions 114-250.
ModBase	Search...
Protein-protein interaction databases
IntAct	O75888. 2 interactions.
STRING	O75888.
PTM databases
PhosphoSite	O75888.
Proteomic databases
PRIDE	O75888.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338784; ENSP00000343505; ENSG00000161955.
GeneID	8741.
KEGG	hsa:8741.
UCSC	uc002ghj.1. human. uc002ghk.1. human. uc002ghl.1. human.
Organism-specific databases
CTD	8741.
GeneCards	GC17P007461.
HGNC	HGNC:11928. TNFSF13.
HPA	HPA004863.
MIM	604472. gene.
neXtProt	NX_O75888.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	HBG104367.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	O75888.
Bgee	O75888.
CleanEx	HS_TNFSF13.
Genevestigator	O75888.
GermOnline	ENSG00000161955. Homo sapiens.
Family and domain databases
InterPro	IPR006052. TNF. IPR021184. TNF_CS. IPR008983. Tumour_necrosis_fac-like. [Graphical view]
Gene3D	G3DSA:2.60.120.40. Tumour_necrosis_fac-like. 1 hit.
KO	K05475.
Pfam	PF00229. TNF. 1 hit. [Graphical view]
SMART	SM00207. TNF. 1 hit. [Graphical view]
SUPFAM	SSF49842. TNF_like. 1 hit.
PROSITE	PS00251. TNF_1. 1 hit. PS50049. TNF_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	32793.
SOURCE	Search...

Entry information

Entry name

TNF13_HUMAN

Accession

Primary (citable) accession number: O75888
Secondary accession number(s): Q5U0G8 , Q96HV6, Q9P1M8, Q9P1M9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 112 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.