Summary: C-terminal tandem repeated domain in type 4 procollagen
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This is the Wikipedia entry entitled "Type IV collagen C4 domain". More...
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Type IV collagen C4 domain Edit Wikipedia article
the 1.9-a crystal structure of the noncollagenous (nc1) domain of human placenta collagen iv shows stabilization via a novel type of covalent met-lys cross-link
In molecular biology, the type IV collagen C4 domain (or collagen IV NC1 domain) is a duplicated domain present at the C-terminus of type IV collagens. Each type IV collagen contains a long triple-helical collagenous domain flanked by a short 7S domain of 25 amino acids and a globular non-collagenous C4 domain of ~230 amino acids at the N and C terminus, respectively. In protomer assembly, the C4 domains of three chains interact, forming an C4 trimer, to select and register chains for triple helix formation. In network assembly, the C4 trimers of two protomers interact, forming a C4 hexamer structure, to select and connect protomers.
The collagen IV C4 domain contains 12 cysteines, and all of them are involved in disulphide bonds. It folds into a tertiary structure with predominantly beta-strands. The collagen IV C4 domain is composed of two similarly folded subdomains stabilised by 3 intrachain dissulphide bonds involving the following pairs: C1-C6, C2-C5, and C3-C4. Each subdomain represents a compact disulphide-stabilised triangular structure, from which a finger-like hairpin loop projects into an incompletely formed six-stranded beta-sheet of an adjacent subdomain of the same or of an adjacent chain clamping the subdomains tightly together.
- Than ME, Henrich S, Huber R, Ries A, Mann K, Kuhn K, Timpl R, Bourenkov GP, Bartunik HD, Bode W (May 2002). "The 1.9-A crystal structure of the noncollagenous (NC1) domain of human placenta collagen IV shows stabilization via a novel type of covalent Met-Lys cross-link". Proc. Natl. Acad. Sci. U.S.A. 99 (10): 6607–12. doi:10.1073/pnas.062183499. PMC . PMID 12011424.
- Sundaramoorthy M, Meiyappan M, Todd P, Hudson BG (August 2002). "Crystal structure of NC1 domains. Structural basis for type IV collagen assembly in basement membranes". J. Biol. Chem. 277 (34): 31142–53. doi:10.1074/jbc.M201740200. PMID 11970952.
- Vanacore RM, Shanmugasundararaj S, Friedman DB, Bondar O, Hudson BG, Sundaramoorthy M (October 2004). "The alpha1.alpha2 network of collagen IV. Reinforced stabilization of the noncollagenous domain-1 by noncovalent forces and the absence of Met-Lys cross-links". J. Biol. Chem. 279 (43): 44723–30. doi:10.1074/jbc.M406344200. PMID 15299013.
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C-terminal tandem repeated domain in type 4 procollagen Provide feedback
Duplicated domain in C-terminus of type 4 collagens. Mutations in alpha-5 collagen IV are associated with X-linked Alport syndrome.
Pihlajaniemi T, Tryggvason K, Myers JC, Kurkinen M, Lebo R, Cheung MC, Prockop DJ, Boyd CD; , J Biol Chem 1985;260:7681-7687.: cDNA clones coding for the pro-alpha1(IV) chain of human type IV procollagen reveal an unusual homology of amino acid sequences in two halves of the carboxyl-terminal domain. PUBMED:2581969 EPMC:2581969
Tverskaya S, Bobrynina V, Tsalykova F, Ignatova M, Krasnopolskaya X, Evgrafov O; , Hum Mutat 1996;7:149-150.: Substitution of A1498D in noncollagen domain of a5(IV) collagen chain associated with adult-onset X-linked Alport syndrome. PUBMED:8829632 EPMC:8829632
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001442
Collagens are major components of the extracellular matrices of all metazoan life and play crucial roles in developmental processes and tissue homeostasis. Collagens are composed of three polypeptide chains (alpha chains) that fold together to form the characteristic triple helical collagenous domain. Some types of triple helical protomers contain genetically identical alpha chains forming homotrimers, whereas others contain two or three different alpha chains forming heterotrimers. The sequences required to form a collagenous domain are Gly-X-Y repeats in which the X and Y positions are frequently proline and hydroxyproline. Glycine is required every third residue as it is the only amino acid small enough to pack into the central core of the triple helix. The triple helix-forming parts are surrounded by non-collagenous (NC) domains of variable sequence, size, and shape. Even if the triple helical parts represent the most striking feature of collagens, tissue specificity as well as defined binding of non-collagens seem to be encoded in the NC domains. The terminal NC domains are excised, modified, or incorporated directly into the final suprastructure, depending on protomer type and function [PUBMED:12539240, PUBMED:1639194].
Type IV collagen is one of the major constituents of basement membranes, a specialised form of extracellular matrix underlying epithelia that compartmentalises tissues and provides molecular signals for influencing cell behaviour. Each type IV chain contains a long triple-helical collagenous domain flanked by a short 7S domain of 25 residues and a globular non-collagenous NC1 domain of ~230 residues at the N and C terminus, respectively. In protomer assembly, the NC1 domains (monomers) of three chains interact, forming an NC1 trimer, to select and register chains for triple helix formation. In network assembly, the NC1 trimers of two protomers interact, forming a NC1 hexamer structure, to select and connect protomers [PUBMED:12011424, PUBMED:11970952, PUBMED:15299013].
The collagen IV NC1 domain contains 12 cysteines, and all of them are involved in disulphide bonds. It folds into a tertiary structure with predominantly beta-strands. The collagen IV NC1 domain is composed of two similarly folded subdomains stabilised by 3 intrachain dissulphide bonds involving the following pairs: C1-C6, C2-C5, and C3-C4. Each subdomain represents a compact disulphide-stabilised triangular structure, from which a finger-like hairpin loop projects into an incompletely formed six-stranded beta-sheet of an adjacent subdomain of the same or of an adjacent chain clamping the subdomains tightly together [PUBMED:12011424, PUBMED:11970952, PUBMED:15299013].
This duplicated domain is present at the C-terminal of type 4 collagen, the major structural component of glomerular basement membranes (GMB) forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. Mutations in alpha-5 collagen IV are associated with X-linked Alport syndrome.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||collagen trimer (GO:0005581)|
|Molecular function||extracellular matrix structural constituent (GO:0005201)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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This clan contains domains that have a C-type lectin fold. Many of these are known or expected to mediate interactions with sugars.
The clan contains the following 12 members:APT C4 Chordopox_A33R DUF1554 DUF5075 Endostatin FGE-sulfatase Intimin_C Lectin_C Ly49 UL45 Xlink
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Author:||Ponting CP , Schultz J, Bork P|
|Number in seed:||151|
|Number in full:||2657|
|Average length of the domain:||105.80 aa|
|Average identity of full alignment:||46 %|
|Average coverage of the sequence by the domain:||14.95 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 45638612 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||19|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
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The tree shows the occurrence of this domain across different species. More...
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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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 C4 domain has been found. There are 60 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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