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5  structures 27  species 1  interaction 66  sequences 3  architectures

Family: TACI-CRD2 (PF09305)

Summary: TACI, cysteine-rich domain

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This is the Wikipedia entry entitled "TACI-CRD2 protein domain". More...

TACI-CRD2 protein domain Edit Wikipedia article

TACI-CRD2
PDB 1xu1 EBI.jpg
the crystal structure of april bound to taci
Identifiers
Symbol TACI-CRD2
Pfam PF09305
InterPro IPR015384

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.[1] TACI-CRD2 stands for Transmembrane Activator and CAML Interactor- Cysteine Rich Domain 2.

Function[edit]

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.[2][3][4]

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.[5][6] The protein is synthesised as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine.[7] A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers.[8] Both the mature protein and a partially processed form of the hormone are secreted after cleavage of the propeptide.[8]

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.

Formation[edit]

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.

Ligands[edit]

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.


References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ Farrah T, Smith CA (July 1992). "Emerging cytokine family". Nature 358 (6381): 26. doi:10.1038/358026b0. PMID 1377364. 
  4. ^ 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. 
  5. ^ Fransen L, Müller 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ a b 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. 

This article incorporates text from the public domain Pfam and InterPro IPR015384

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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 [1].

Literature references

  1. 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].

Domain organisation

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Alignments

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  Seed
(2)
Full
(66)
Representative proteomes NCBI
(55)
Meta
(0)
RP15
(2)
RP35
(2)
RP55
(6)
RP75
(27)
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  Seed
(2)
Full
(66)
Representative proteomes NCBI
(55)
Meta
(0)
RP15
(2)
RP35
(2)
RP55
(6)
RP75
(27)
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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

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Curation and family details

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Seed source: pdb_1xut
Previous IDs: none
Type: Domain
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.3 21.3
Trusted cut-off 21.4 21.5
Noise cut-off 19.0 20.0
Model length: 41
Family (HMM) version: 5
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Species distribution

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Interactions

There is 1 interaction for this family. More...

TNF

Structures

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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