Summary: TACI, cysteine-rich domain
This is the Wikipedia entry entitled "TACI-CRD2 protein domain". More...
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TACI-CRD2 protein domain Edit Wikipedia article
the crystal structure of april bound to taci
In molecular biology, this protein domain, 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.
TACI functions as a negative regulator of BAFF function given that loss of TACI expression results in the overproduction of B lymphocytes, a type of white blood cell that guards against infection.Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities.
Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a cytotoxin which is derived from a form of white blood cell called monocytes. It is thought to cause tumour regression, septic shock and cachexia. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers. Both the mature protein and a partially processed form of the hormone are secreted after cleavage of the propeptide.
There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors. TACI is a member of the tumor necrosis factor receptor superfamily and has an important role as regulator of B cell function. TACI binds two ligands, APRIL and BAFF, which it binds to with high affinity and contains two cysteine-rich domains (CRDs) in its extracellular region.
TACI-CRD1 forms TACI-CRD2 by removing the N-terminal cysteine rich domain by alternative splicing. This shorter form is capable of ligand-induced cell signaling and that the second CRD alone (TACI-CRD2) contains full affinity for both ligands.
The ligands are type II transmembrane protein cytokines that have various effects on immune cells, including acting as a:
- costimulatory molecules,
- apoptotic agents,
- growth factors
APRIL (also known as TNSF13A, TALL-2, and TRDL-1) is a TNF ligand that is overexpressed by some tumours.
- Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA (February 2005). "Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding". J. Biol. Chem. 280 (8): 7218–27. doi:10.1074/jbc.M411714200. PMID 15542592.
- Peitsch MC, Jongeneel CV (February 1993). "A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors". Int. Immunol. 5 (2): 233–8. doi:10.1093/intimm/5.2.233. PMID 8095800.
- Farrah T, Smith CA (July 1992). "Emerging cytokine family". Nature 358 (6381): 26. doi:10.1038/358026b0. PMID 1377364.
- Bazan JF (September 1993). "Emerging families of cytokines and receptors". Curr. Biol. 3 (9): 603–6. doi:10.1016/0960-9822(93)90009-D. PMID 15335677.
- Fransen L, MÃ¼ller R, Marmenout A, Tavernier J, Van der Heyden J, Kawashima E, Chollet A, Tizard R, Van Heuverswyn H, Van Vliet A (June 1985). "Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression". Nucleic Acids Res. 13 (12): 4417–29. doi:10.1093/nar/13.12.4417. PMC 321797. PMID 2989794.
- Kriegler M, Perez C, DeFay K, Albert I, Lu SD (April 1988). "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF". Cell 53 (1): 45–53. doi:10.1016/0092-8674(88)90486-2. PMID 3349526.
- Sherry B, Jue DM, Zentella A, Cerami A (December 1990). "Characterization of high molecular weight glycosylated forms of murine tumor necrosis factor". Biochem. Biophys. Res. Commun. 173 (3): 1072–8. doi:10.1016/S0006-291X(05)80895-2. PMID 2268312.
- Cseh K, Beutler B (September 1989). "Alternative cleavage of the cachectin/tumor necrosis factor propeptide results in a larger, inactive form of secreted protein". J. Biol. Chem. 264 (27): 16256–60. PMID 2777790.
TACI, cysteine-rich domain Provide feedback
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 .
Hymowitz SG, Patel DR, Wallweber HJ, Runyon S, Yan M, Yin J, Shriver SK, Gordon NC, Pan B, Skelton NJ, Kelley RF, Starovasnik MA; , J Biol Chem. 2005;280:7218-7227.: Structures of APRIL-receptor complexes: like BCMA, TACI employs only a single cysteine-rich domain for high affinity ligand binding. PUBMED:15542592 EPMC:15542592
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR015384
Cytokines can be grouped into a family on the basis of sequence, functional and structural similarities [PUBMED:8095800, PUBMED:1377364, PUBMED:15335677]. Tumor necrosis factor (TNF) (also known as TNF-alpha or cachectin) is a monocyte-derived cytotoxin that has been implicated in tumour regression, septic shock and cachexia [PUBMED:2989794, PUBMED:3349526]. The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine [PUBMED:2268312]. A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers [PUBMED:2777790]. Both the mature protein and a partially-processed form of the hormone are secreted after cleavage of the propeptide [PUBMED:2777790].
There are a number of different families of TNF, but all these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognised by their specific receptors.
This entry represents a cysteine-rich 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 [PUBMED:15542592].
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This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
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Curation and family details
|Author:||Mistry J, Sammut SJ|
|Number in seed:||2|
|Number in full:||66|
|Average length of the domain:||39.30 aa|
|Average identity of full alignment:||55 %|
|Average coverage of the sequence by the domain:||22.37 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||5|
|Download:||download the raw HMM for this family|
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There is 1 interaction for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the TACI-CRD2 domain has been found. There are 5 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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