APRIL (protein)

Last updated
TNFSF13
Available structures
PDB Ortholog search: PDBe RCSB
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
Orthologs
SpeciesHumanMouse
Entrez

8741

69583

Ensembl

ENSG00000161955

ENSMUSG00000089669

UniProt

O75888

Q9D777

RefSeq (mRNA)

NM_001159505
NM_023517

RefSeq (protein)

NP_001152977
NP_076006

Location (UCSC) Chr 17: 7.56 – 7.56 Mb Chr 11: 69.57 – 69.58 Mb
PubMed search [3] [4]
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]

Contents

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]

Related Research Articles

<span class="mw-page-title-main">TNF receptor superfamily</span> Protein superfamily of cytokine receptors

The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth factor (NGF), all TNFs are homologous to the archetypal TNF-alpha. In their active form, the majority of TNF receptors form trimeric complexes in the plasma membrane. Accordingly, most TNF receptors contain transmembrane domains (TMDs), although some can be cleaved into soluble forms, and some lack a TMD entirely. In addition, most TNF receptors require specific adaptor protein such as TRADD, TRAF, RIP and FADD for downstream signalling. TNF receptors are primarily involved in apoptosis and inflammation, but they can also take part in other signal transduction pathways, such as proliferation, survival, and differentiation. TNF receptors are expressed in a wide variety of tissues in mammals, especially in leukocytes.

<span class="mw-page-title-main">B-cell activating factor</span> Mammalian protein found in Homo sapiens

B-cell activating factor (BAFF) also known as tumor necrosis factor ligand superfamily member 13B and CD257 among other names, is a protein that in humans is encoded by the TNFSF13B gene. BAFF is also known as B Lymphocyte Stimulator (BLyS) and TNF- and APOL-related leukocyte expressed ligand (TALL-1) and the Dendritic cell-derived TNF-like molecule.

<span class="mw-page-title-main">TRAF1</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor 1 is a protein that in humans is encoded by the TRAF1 gene.

<span class="mw-page-title-main">Lymphotoxin alpha</span> Protein found in humans

Lymphotoxin-alpha (LT-α) formerly known as tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene. Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. As a cytotoxic protein, LT-α performs a variety of important roles in immune regulation depending on the form that it is secreted as. Unlike other members of the TNF superfamily, LT-α is only found as a soluble homotrimer, when found at the cell surface it is found only as a heterotrimer with LTβ.

<span class="mw-page-title-main">TRAF3</span> Protein-coding gene in the species Homo sapiens

TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene.

<span class="mw-page-title-main">LIGHT (protein)</span> Secreted protein of the TNF superfamily

LIGHT, also known as tumor necrosis factor superfamily member 14 (TNFSF14), is a secreted protein of the TNF superfamily. It is recognized by herpesvirus entry mediator (HVEM), as well as decoy receptor 3.

<span class="mw-page-title-main">TNFSF12</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor ligand superfamily member 12 also known as TNF-related weak inducer of apoptosis (TWEAK) is a protein that in humans is encoded by the TNFSF12 gene.

<span class="mw-page-title-main">Decoy receptor 3</span> Protein found in humans

Decoy receptor 3 (Dcr3), also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), TR6 and M68, is a soluble protein of the tumor necrosis factor receptor superfamily which inhibits Fas ligand-induced apoptosis.

<span class="mw-page-title-main">Transmembrane activator and CAML interactor</span> Protein-coding gene in the species Homo sapiens

Transmembrane activator and CAML interactor (TACI), also known as tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) is a protein that in humans is encoded by the TNFRSF13B gene.

<span class="mw-page-title-main">BAFF receptor</span> Mammalian protein found in Homo sapiens

BAFF receptor, also known as tumor necrosis factor receptor superfamily member 13C (TNFRSF13C) and BLyS receptor 3 (BR3), is a membrane protein of the TNF receptor superfamily which recognizes BAFF, an essential factor for B cell maturation and survival. In humans it is encoded by the TNFRSF13C gene.

<span class="mw-page-title-main">Death receptor 3</span> Protein found in humans

Death receptor 3 (DR3), also known as tumor necrosis factor receptor superfamily member 25 (TNFRSF25), is a cell surface receptor of the tumor necrosis factor receptor superfamily which mediates apoptotic signalling and differentiation. Its only known TNFSF ligand is TNF-like protein 1A (TL1A).

<span class="mw-page-title-main">TNFRSF12A</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily member 12A also known as the TWEAK receptor (TWEAKR) is a protein that in humans is encoded by the TNFRSF12A gene.

<span class="mw-page-title-main">Vascular endothelial growth inhibitor</span> Protein-coding gene in the species Homo sapiens

Vascular endothelial growth inhibitor (VEGI), also known as TNF-like ligand 1A (TL1A) and TNF superfamily member 15 (TNFSF15), is protein that in humans is encoded by the TNFSF15 gene. VEGI is an anti-angiogenic protein. It belongs to tumor necrosis factor (ligand) superfamily, where it is member 15. It is the sole known ligand for death receptor 3, and it can also be recognized by decoy receptor 3.

<span class="mw-page-title-main">B-cell maturation antigen</span> Protein-coding gene in the species Homo sapiens

B-cell maturation antigen, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), is a protein that in humans is encoded by the TNFRSF17 gene.

<span class="mw-page-title-main">Calcium modulating ligand</span> Protein-coding gene in humans

Calcium modulating ligand, also known as calcium-modulating cyclophilin ligand, is a signalling protein recognized by the TNF receptor TACI.

<span class="mw-page-title-main">TNFRSF18</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor receptor superfamily member 18 (TNFRSF18), also known as glucocorticoid-induced TNFR-related protein (GITR) or CD357. GITR is encoded and tnfrsf18 gene at chromosome 4 in mice. GITR is type I transmembrane protein and is described in 4 different isoforms. GITR human orthologue, also called activation-inducible TNFR family receptor (AITR), is encoded by the TNFRSF18 gene at chromosome 1.

<span class="mw-page-title-main">TNFSF18</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor ligand superfamily member 18 is a protein that in humans is encoded by the TNFSF18 gene.

<span class="mw-page-title-main">TNFSF12-TNFSF13</span> Protein-coding gene in the species Homo sapiens

Tumor necrosis factor (ligand) superfamily, member 12-member 13, also known as TNFSF12-TNFSF13, is a human gene.

<span class="mw-page-title-main">Tumor necrosis factor receptor 2</span> Membrane receptor protein found in humans

Tumor necrosis factor receptor 2 (TNFR2), also known as tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) and CD120b, is one of two membrane receptors that binds tumor necrosis factor-alpha (TNFα). Like its counterpart, tumor necrosis factor receptor 1 (TNFR1), the extracellular region of TNFR2 consists of four cysteine-rich domains which allow for binding to TNFα. TNFR1 and TNFR2 possess different functions when bound to TNFα due to differences in their intracellular structures, such as TNFR2 lacking a death domain (DD).

<span class="mw-page-title-main">TACI-CRD2 protein domain</span>

In molecular biology, TACI-CRD2 represents the second cysteine-rich protein domain found in the TACI family of proteins. Members of this family are predominantly found in tumour necrosis factor receptor superfamily, member 13b (TACI), and are required for binding to the ligands APRIL and BAFF. TACI-CRD2 stands for Transmembrane Activator and CAML Interactor- Cysteine Rich Domain 2.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000161955 - Ensembl, May 2017
  2. 1 2 3 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.
  5. ↑ Hahne M, Kataoka T, Schröter M, Hofmann K, Irmler M, Bodmer JL, Schneider P, Bornand T, Holler N, French LE, Sordat B, Rimoldi D, Tschopp J (September 1998). "APRIL, a new ligand of the tumor necrosis factor family, stimulates tumor cell growth". The Journal of Experimental Medicine. 188 (6): 1185–90. doi:10.1084/jem.188.6.1185. PMC   2212534 . PMID   9743536.
  6. 1 2 "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, Olsson C, Tom L, Erickson S, French D, Schow P, Grewal IS, Ashkenazi A (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.
  8. ↑ Belnoue E, Pihlgren M, McGaha TL, Tougne C, Rochat AF, Bossen C, Schneider P, Huard B, Lambert PH, Siegrist CA (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): 2755–64. doi: 10.1182/blood-2007-09-110858 . PMID   18180376.
  9. ↑ Roth W, Wagenknecht B, Klumpp A, Naumann U, Hahne M, Tschopp J, Weller M (April 2001). "APRIL, a new member of the tumor necrosis factor family, modulates death ligand-induced apoptosis". Cell Death and Differentiation. 8 (4): 403–10. doi: 10.1038/sj.cdd.4400827 . PMID   11550092.
  10. ↑ Wu Y, Bressette D, Carrell JA, Kaufman T, Feng P, Taylor K, Gan Y, Cho YH, Garcia AD, Gollatz E, Dimke D, LaFleur D, Migone TS, Nardelli B, Wei P, Ruben SM, Ullrich SJ, Olsen HS, Kanakaraj P, Moore PA, Baker KP (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): 35478–85. doi: 10.1074/jbc.M005224200 . PMID   10956646.
  11. ↑ Roschke V, Sosnovtseva S, Ward CD, Hong JS, Smith R, Albert V, Stohl W, Baker KP, Ullrich S, Nardelli B, Hilbert DM, Migone TS (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): 4314–21. 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.

Further reading

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