Summary: Thrombospondin type 1 domain
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This is the Wikipedia entry entitled "Thrombospondin". More...
Thrombospondin Edit Wikipedia article
Thrombospondins are secreted proteins with the ability to inhibit angiogenesis. Overexpression of TSPs in tumor cells results in reduced angiogenesis. Inhibitory peptides and fragments of TSP1 bind to CD36, leading to the expression of FasL, which activates the expression of Fas. This leads to the activation of caspases and apoptosis of the cell.
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Thrombospondin type 1 domain Provide feedback
No Pfam abstract.
Literature references
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Bork P; , FEBS Lett 1993;327:125-130.: The modular architecture of a new family of growth regulators related to connective tissue growth factor. PUBMED:7687569 EPMC:7687569
Internal database links
SCOOP: | ADAMTS_CR_3 TSP1_ADAMTS TSP1_CCN TSP1_spondin |
Similarity to PfamA using HHSearch: | TSP1_spondin TSP1_ADAMTS TSP1_CCN |
External database links
SCOP: | 1lsl |
This tab holds annotation information from the InterPro database.
InterPro entry IPR000884
Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organisation. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain, three TSP1 repeats, three EGF-like domains, TSP3 repeats and a C-terminal domain. They are assembled as trimer. The subgroup B thrombospondins, designated TSP-3, -4, and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers [ PUBMED:11687483 ]. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.
This repeat was first described in 1986 by Lawler and Hynes [ PUBMED:2430973 ]. It was found in the thrombospondin protein where it is repeated 3 times. Now a number of proteins involved in the complement pathway (properdin, C6, C7, C8A, C8B, C9) [ PUBMED:2459396 ] as well as extracellular matrix protein like mindin, F-spondin [ PUBMED:10409509 ], SCO-spondin and even the circumsporozoite surface protein 2 and TRAP proteins of Plasmodium [ PUBMED:10508153 , PUBMED:1501644 ] contain one or more instance of this repeat. It has been involved in cell-cell interaction, inhibition of angiogenesis [ PUBMED:10500044 ] and apoptosis [ PUBMED:9135017 ].
The intron-exon organisation of the properdin gene confirms the hypothesis that the repeat might have evolved by a process involving exon shuffling [ PUBMED:1417780 ]. A study of properdin structure provides some information about the structure of the thrombospondin type I repeat [ PUBMED:1868073 ].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan TSP1 (CL0692), which has the following description:
This superfamiy includes the TSP1 domain and its variants.
The clan contains the following 4 members:
TSP1_ADAMTS TSP1_CCN TSP1_spondin TSP_1Alignments
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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
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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 (24) |
Full (63967) |
Representative proteomes | UniProt (104636) |
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RP15 (14309) |
RP35 (24279) |
RP55 (51747) |
RP75 (66704) |
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PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
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Seed (24) |
Full (63967) |
Representative proteomes | UniProt (104636) |
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RP15 (14309) |
RP35 (24279) |
RP55 (51747) |
RP75 (66704) |
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Raw Stockholm | |||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
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.
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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
Seed source: | Published_alignment |
Previous IDs: | tsp_1; |
Type: | Domain |
Sequence Ontology: | SO:0000417 |
Author: |
Sonnhammer ELL |
Number in seed: | 24 |
Number in full: | 63967 |
Average length of the domain: | 49.5 aa |
Average identity of full alignment: | 34 % |
Average coverage of the sequence by the domain: | 10.76 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
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Model details: |
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Model length: | 49 | ||||||||||||
Family (HMM) version: | 22 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
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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 TSP_1 domain has been found. There are 219 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 sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.