Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
0  structures 9  species 0  interactions 10  sequences 1  architecture

Family: FDC-SP (PF15215)

Summary: Follicular dendritic cell secreted peptide

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "FDC-SP". More...

FDC-SP Edit Wikipedia article

FDC-SP or follicular dendritic cell-secreted protein, is a small, secreted protein, located on chromosome 4 in humans. It is thought to play an immune role in the junctional epithelium at the gingival crevice in the human mouth. It is very similar in structure to statherin, a protein contained in saliva.[1] [2]

Contents

[edit] Structure and genetics

FDC-SP is an 68-amino acid protein containing a signal peptide at its N terminus, which is used for directing the transport of the protein. Adjacent to the signal peptide, the protein contains a highly-charged N-terminal sequence.[2] The C-terminal half of FDC-SP is proline-rich and not highly conserved between species, but the alignment of proline residues within this region is highly conserved. FDC-SP homologues are only easily located within the human, rat, mouse and chimpanzee genome. There is a 70% sequence homology between mouse and rat[3] and a 45% homology between human and mouse. The N-terminal, however, is highly conserved between all three species and is thought to contain potential casein kinase 2 (CK2) phosphorylation sites. CK2 is a constitutively and widely expressed serine/threonine kinase that has many substrates related to signal transduction and cell growth regulation. Several casein genes have also been found nearby to the FDC-SP gene. Numerous genes that are expressed in oral tissues, including statherin, mucin, ameloblastin, histatin, enamelin and proline-rich protein are also located in close proximity to the FDC-SP gene. This indicates that the aforementioned genes may be expressed through the same mechanism. The recent evolutionary development of FDC-SP correlates with the development of certain aspects of the mammalian immune system and with the emergence of the follicular germinal centre (GC) reaction in secondary lymphoid tissues.[4]

Chromosome 4

[edit] Expression

In humans, FDC-SP was first found within follicular dendritic cell isolates from the tonsil, and later was found to be specifically expressed within the periodontal ligament. FDC-SP expression can be induced in human FDC-like cell lines by exposure to tumour necrosis factor (TNF). Exposure of human peripheral blood cells to LPS can also result in FDC-SP expression, but TNF exposure does not cause FDC-SP expression and similarly LPS exposure does not cause expression within FDC-like cell lines. Expression in mouse splenocytes can be induced by LPS in a similar manner to that of human peripheral blood cells.[4]

In mice, as in humans, FDC-SP is not expressed in B cells, but FDC-SP expression in FDCs can be dependent on B cells after their stimulation by CD40. After stimulation with CD40, B cells have been shown to be able to induce phenotypic changes in FDCs through the B cell's surface TNF expression. It has therefore been suggested that the expression of TNF cytokines by B cells causes FDC-SP expression within FDCs upon contact. This reaction is said to be typical during GC formation.[4]

FDC-SP is highly expressed in the junctional epithelium and well as in the tonsils, prostate, lymph nodes and trachea. The proline rich region in the C-terminal half bears some resemblance to the antimicrobial peptide Bac5. FDC-SP may therefore have a role in microbial defense in the oral cavity. [2]

[edit] Function

In transgenic mice engineered to constitutively express FDC-SP, the number and size of GCs formed after immunization with a T-dependent antigen significantly decreased. The position of these GCs is normal, but they do not form centres of highly-proliferating B cells, which us thought be due to FDC-SP affecting the development of GCs. The mechanism by which FDC-SP exerts its effects upon GC development is not currently known. The formation of FDC networks appears to be normal in transgenic mice, as does T cell response.[4]

FDC-SP is an amphipathic molecule, similar to surfactant proteins A and D, which are thought to be involved in the innate immune system of the lung. These proteins allow for the phagocytosis of bacteria by binding to them. Stathrin has been proposed to have similar properties, which itself possesses similar properties to FDC-SP. Stathrin can bind oral bacteria, so it has been proposed that FDC-SP acts as part of a host defence mechanism against oral pathogens.[3]

FDC-SP is thought to bind target cells through a specific receptor in a similar manner to cytokines and chemokines. Although it shares no sequence homology with chemokines or cytokines, FDC-SP has several properties in common with several inflammatory mediators, including molecular mass and amino acid composition. The FDC-SP gene is also located next to a group of proline-rich salivary peptide genes, which themselves are next several to CXC chemokine genes. FDC-SP has an effect on B cell migration when used in conjunction with L cells, and migration is significantly increased when the B cells are stimulated with anti-CD40 plus IL-4. The addition of anti-CD40 causes the B cells to resemble those found in the GC. Pertussis toxin is known to inhbibit the action of G proteins and B cells treated with the toxin were observed to migrate poorly in response to FDC-SP.[4]

FDC-SP has been found to have an unusually high level of expression in a number of tumours, including breast carcinoma, epithelial ovarian carcinoma and endometrial carcinoma. It is hypothesised that FDC-SP can influence cell motility by specific receptor binding in a similar manner to chemokines. It is also thought that FDC-SP can regulate the assembly of the actin cytoskeleton, which may have an effect on cell motility. [5]

[edit] References

  1. ^ Tamayuki Shinomura et al. (November 28, 2008). "Adsorption of Follicular Dendritic Cell-secreted Protein (FDC-SP) onto Mineral Deposits". J. Biol. Chem. 283 (48): 33658–33664. doi:10.1074/jbc.M800719200. PMC 2662279. PMID 18806264. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2662279/.
  2. ^ a b c Aaron J. Marshall et al. (September 1, 2002). "FDC-SP, a Novel Secreted Protein Expressed by Follicular Dendritic Cells". The Journal of Immunology 169 (5): 2381–2389.
  3. ^ a b Sayaka Nakamura et al. (2005). "Identification of genes preferentially expressed in periodontal ligament: Specific expression of a novel secreted protein, FDC-SP". Biochemical and Biophysical Research Communications 338: 1197–1203. doi:10.1016/j.bbrc.2005.10.076.
  4. ^ a b c d e Monther Al-Alwan (2007). "Follicular Dendritic Cell Secreted Protein (FDC-SP) Regulates Germinal Center and Antibody Responses". The Journal of Immunology 178: 7859–7867.
  5. ^ Changyu Wang (2010). "C4orf7 contributes to ovarian cancer metastasis by promoting cancer cell migration and invasion". Oncology Reports 24: 933–936. doi:10.3892/or_00000939.

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.

Follicular dendritic cell secreted peptide Provide feedback

No Pfam abstract.

External database links

This tab holds annotation information from the InterPro database.

No InterPro data for this Pfam family.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(2)
Full
(10)
Representative proteomes NCBI
(10)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(1)
RP75
(1)
Jalview View  View  View  View  View  View  View   
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(2)
Full
(10)
Representative proteomes NCBI
(10)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(1)
RP75
(1)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(2)
Full
(10)
Representative proteomes NCBI
(10)
Meta
(0)
RP15
(1)
RP35
(1)
RP55
(1)
RP75
(1)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download    

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

This family is new in this Pfam release.

Seed source: Jackhmmer:Q8NFU4
Previous IDs: none
Type: Family
Author: Eberhardt RY, Coggill P, Hetherington K
Number in seed: 2
Number in full: 10
Average length of the domain: 65.10 aa
Average identity of full alignment: 68 %
Average coverage of the sequence by the domain: 77.32 %

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 27.0 27.0
Trusted cut-off 75.2 75.0
Noise cut-off 24.2 24.0
Model length: 67
Family (HMM) version: 1
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.