APRIL (protein)

TNFSF13
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4ZCH
Identifiers
Aliases	TNFSF13, APRIL, CD256, TALL-2, TALL2, TRDL-1, ZTNF2, UNQ383/PRO715, TNLG7B, tumor necrosis factor superfamily member 13, TNF superfamily member 13
External IDs	OMIM: 604472; MGI: 1916833; HomoloGene: 56971; GeneCards: TNFSF13; OMA:TNFSF13 - orthologs
Gene location (Human)
Chr.	Chromosome 17 (human)
End	7,561,608 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	69,576,610 bp
RNA expression pattern
	Top expressed in
	monocyte; ; granulocyte; ; duodenum; ; mucosa of transverse colon; ; gallbladder; ; blood; ; right lung; ; upper lobe of left lung; ; human kidney; ; rectum;
	Top expressed in
	layer of retina; ; neural layer of retina; ; colon; ; ileum; ; jejunum; ; duodenum; ; granulocyte; ; lung; ; esophagus; ; bone marrow;
	More reference expression data
	n/a
Gene ontology
Molecular function	signaling receptor binding; tumor necrosis factor receptor binding; cytokine activity;
Cellular component	cytosol; membrane; nucleoplasm; cytoplasm; extracellular exosome; extracellular region; extracellular space;
Biological process	tumor necrosis factor-mediated signaling pathway; regulation of mRNA stability; positive regulation of cell population proliferation; immune system process; signal transduction; positive regulation of isotype switching to IgA isotypes; immune response; regulation of signaling receptor activity;
	Sources:Amigo / QuickGO
Orthologs
	8741
	69583
	ENSG00000161955
	ENSMUSG00000089669
	O75888
	Q9D777
NM_001198622; NM_001198623; NM_001198624; NM_003808; NM_172087;
	NM_172088
	NM_001159505; NM_023517
NP_001185551; NP_001185552; NP_001185553; NP_003799; NP_742084;
	NP_742085
	NP_001152977; NP_076006
	Wikidata
View/Edit Human	View/Edit Mouse

A proliferation-inducing ligand (APRIL), also known as tumor necrosis factor ligand superfamily member 13 (TNFSF13), is a protein of the TNF superfamily recognized by the cell surface receptor TACI.^[5]^[6] It is encoded by the TNFSF13 gene.^[6]

Nomenclature

In the cluster of differentiation terminology, APRIL is designated CD256.

Function

The protein encoded by this gene is a member of the tumor necrosis factor ligand (TNF) ligand family. This protein is a ligand for TNFRSF17/BCMA, a member of the TNF receptor family. This protein and its receptor are both found to be important for B cell development. In vivo experiments suggest an important role for APRIL in the long-term survival of plasma cells in the bone marrow. Mice deficient in APRIL have normal immune system development.^[7] However, APRIL-deficient mice have also been reported to possess a reduced ability to support plasma cell survival.^[8] In vitro experiments suggested that this protein may be able to induce apoptosis through its interaction with other TNF receptor family proteins such as TNFRSF6/FAS and TNFRSF14/HVEM.^[9] Three alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.

Interactions

TNFSF13 has been shown to interact with TNFRSF13B^[10] and B-cell activating factor.^[11]

Clinical significance

APRIL is being explored as a target for autoimmune diseases and B cell malignancies.^[12] At least one anti-APRIL monoclonal antibody has been announced to enter phase I clinical trials for multiple myeloma.^[13]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000161955 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000089669 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, et al. (September 1998). "APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth". The Journal of Experimental Medicine. 188 (6): 1185–1190. doi:10.1084/jem.188.6.1185. PMC 2212534. PMID 9743536.
^ ^a ^b "Entrez Gene: TNFSF13 tumor necrosis factor (ligand) superfamily, member 13". National Library of Medicine. 10 October 2023. Retrieved 13 October 2023.
^ Varfolomeev E, Kischkel F, Martin F, Seshasayee D, Wang H, Lawrence D, et al. (February 2004). "APRIL-deficient mice have normal immune system development". Molecular and Cellular Biology. 24 (3): 997–1006. doi:10.1128/MCB.24.3.997-1006.2004. PMC 321448. PMID 14729948.
^ Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, et al. (March 2008). "APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells". Blood. 111 (5): 2755–2764. doi:10.1182/blood-2007-09-110858. PMID 18180376.
^ Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, et al. (April 2001). "APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis". Cell Death and Differentiation. 8 (4): 403–410. doi:10.1038/sj.cdd.4400827. PMID 11550092.
^ Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, et al. (November 2000). "Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS". The Journal of Biological Chemistry. 275 (45): 35478–35485. doi:10.1074/jbc.M005224200. PMID 10956646.
^ Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, et al. (October 2002). "BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases". Journal of Immunology. 169 (8): 4314–4321. doi:10.4049/jimmunol.169.8.4314. PMID 12370363.
^ Ryan MC, Grewal IS (2009-01-01). "Targeting of BAFF and APRIL for Autoimmunity and Oncology". In Grewal IS (ed.). Therapeutic Targets of the TNF Superfamily. Advances in Experimental Medicine and Biology. Vol. 647. New York: Springer. pp. 52–63. doi:10.1007/978-0-387-89520-8_4. ISBN 978-0-387-89519-2. PMID 19760066.
^ "Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma". AACR 2017 Proceedings. April 2017.

External links

TNFSF13+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Human TNFSF13 genome location and TNFSF13 gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000161955 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000089669 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9743536-5] Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, et al. (September 1998). "APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth". The Journal of Experimental Medicine. 188 (6): 1185–1190. doi:10.1084/jem.188.6.1185. PMC 2212534. PMID 9743536.

[entrez-6] "Entrez Gene: TNFSF13 tumor necrosis factor (ligand) superfamily, member 13". National Library of Medicine. 10 October 2023. Retrieved 13 October 2023.

[7] Varfolomeev E, Kischkel F, Martin F, Seshasayee D, Wang H, Lawrence D, et al. (February 2004). "APRIL-deficient mice have normal immune system development". Molecular and Cellular Biology. 24 (3): 997–1006. doi:10.1128/MCB.24.3.997-1006.2004. PMC 321448. PMID 14729948.

[entrez2-8] Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, et al. (March 2008). "APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells". Blood. 111 (5): 2755–2764. doi:10.1182/blood-2007-09-110858. PMID 18180376.

[9] Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, et al. (April 2001). "APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis". Cell Death and Differentiation. 8 (4): 403–410. doi:10.1038/sj.cdd.4400827. PMID 11550092.

[pmid10956646-10] Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, et al. (November 2000). "Tumor necrosis factor (TNF) receptor superfamily member TACI is a high affinity receptor for TNF family members APRIL and BLyS". The Journal of Biological Chemistry. 275 (45): 35478–35485. doi:10.1074/jbc.M005224200. PMID 10956646.

[pmid12370363-11] Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, et al. (October 2002). "BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases". Journal of Immunology. 169 (8): 4314–4321. doi:10.4049/jimmunol.169.8.4314. PMID 12370363.

[12] Ryan MC, Grewal IS (2009-01-01). "Targeting of BAFF and APRIL for Autoimmunity and Oncology". In Grewal IS (ed.). Therapeutic Targets of the TNF Superfamily. Advances in Experimental Medicine and Biology. Vol. 647. New York: Springer. pp. 52–63. doi:10.1007/978-0-387-89520-8_4. ISBN 978-0-387-89519-2. PMID 19760066.

[13] "Development of a first in class APRIL fully blocking antibody BION-1301 for the treatment of multiple myeloma". AACR 2017 Proceedings. April 2017.

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