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40  structures 94  species 1  interaction 1172  sequences 49  architectures

Family: C4 (PF01413)

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...

Type IV collagen C4 domain Edit Wikipedia article

C4
PDB 1li1 EBI.jpg
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
Identifiers
Symbol C4
Pfam PF01413
Pfam clan CL0056
InterPro IPR001442
SMART C4
PROSITE PDOC00031
MEROPS C47
SCOP 1hra
SUPERFAMILY 1hra
TCDB 2.A.16

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.[1][2][3]

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.[1][2][3]

References[edit]

  1. ^ a b 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 124450. PMID 12011424. 
  2. ^ a b 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. 
  3. ^ a b 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. 

This article incorporates text from the public domain Pfam and InterPro IPR001442

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.

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.

Literature references

  1. Matsukura H, Butkowski RJ, Fish AJ; , Nephron 1993;64:532-539.: The Goodpasture antigen: common epitopes in the globular domains of collagen IV. PUBMED:7690113 EPMC:7690113

  2. 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

  3. 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.

Gene Ontology

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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 C_Lectin (CL0056), which has the following description:

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 7 members:

APT C4 Chordopox_A33R Herpes_UL45 Intimin_C Lectin_C Xlink

Alignments

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(26)
Full
(1172)
Representative proteomes NCBI
(965)
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(0)
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(125)
RP35
(159)
RP55
(312)
RP75
(532)
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  Seed
(26)
Full
(1172)
Representative proteomes NCBI
(965)
Meta
(0)
RP15
(125)
RP35
(159)
RP55
(312)
RP75
(532)
Alignment:
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  Seed
(26)
Full
(1172)
Representative proteomes NCBI
(965)
Meta
(0)
RP15
(125)
RP35
(159)
RP55
(312)
RP75
(532)
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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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Pfam alignments:

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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 View help on the curation process

Seed source: SMART
Previous IDs: none
Type: Domain
Author: Ponting CP, Schultz J, Bork P
Number in seed: 26
Number in full: 1172
Average length of the domain: 108.20 aa
Average identity of full alignment: 49 %
Average coverage of the sequence by the domain: 15.42 %

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 19.7 19.7
Trusted cut-off 32.6 20.3
Noise cut-off 16.5 19.5
Model length: 114
Family (HMM) version: 14
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Species distribution

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Interactions

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

C4

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 C4 domain has been found. There are 40 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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