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141  structures 328  species 2  interactions 41902  sequences 548  architectures

Family: Cadherin (PF00028)

Summary: Cadherin domain

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 "Cadherin". More...

Cadherin Edit Wikipedia article

Principal interactions of structural proteins at cadherin-based adherens junction. Actin filaments are linked to α-actinin and to membrane through vinculin. The head domain of vinculin associates to E-cadherin via α-, β-, and γ-catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.

Cadherins (named for "calcium-dependent adhesion") are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, forming adherens junctions to bind cells within tissues together. They are dependent on calcium (Ca2+) ions to function, hence their name.

The cadherin superfamily includes cadherins, protocadherins, desmogleins, and desmocollins, and more.[1][2] In structure, they share cadherin repeats, which are the extracellular Ca2+-binding domains. There are multiple classes of cadherin molecule, each designated with a prefix (in general, noting the type of tissue with which it is associated). It has been observed that cells containing a specific cadherin subtype tend to cluster together to the exclusion of other types, both in cell culture and during development.[3] For example, cells containing N-cadherin tend to cluster with other N-cadherin-expressing cells. However, it has been noted that the mixing speed in the cell culture experiments can have an effect on the extent of homotypic specificity.[4] In addition, several groups have observed heterotypic binding affinity (i.e., binding of different types of cadherin together) in various assays.[5][6] One current model proposes that cells distinguish cadherin subtypes based on kinetic specificity rather than thermodynamic specificity, as different types of cadherin homotypic bonds have different lifetimes.[7]

Structure and Function[edit]

Cadherins are synthesized as polypeptides and undergo many post-translational modifications to become the proteins which mediate cell-cell adhesion and recognition.[8] These polypeptides are approximately 720–750 amino acids long. Each cadherin has a small cytoplasmic component, a transmembrane component, and the remaining bulk of the protein is extra-cellular (outside the cell). To date, over 80 types of cadherins in humans have been identified and sequenced.[9]

Cadherins behave as both receptors and ligands and other molecules. During development, their behavior assists in properly positioning cells: they are responsible for the separation of the different tissue layers, and for cellular migration.[10] In the very early stages of development, E-cadherin (epithelial cadherin) is most greatly expressed. During the next stage, the development of the neural plate, N-cadherin (neural cadherin) is expressed and there is a decrease in E-cadherin. Finally, during the development of the notochord and the condensation of somites, E- P- and N-cadherin expression increases. After development, cadherins play a role in maintaining cell and tissue structure, and in cellular movement.[9]

Types[edit]

Cadherin domain
Identifiers
Symbol Cadherin
Pfam PF00028
InterPro IPR002126
SMART CA
PROSITE PDOC00205
SCOP 1nci
SUPERFAMILY 1nci
Ribbon representation of a repeating unit in the extracellular E-cadherin ectodomain of the mouse (Mus Musculus) [11]

Cadherins can be classified into four groups: classical, desmosomal, protocadherins, and unconventional.[12]

Classical[edit]

Different members of the cadherin family are found in different locations.

  • CDH1 - E-cadherin (epithelial): E-cadherins are found in epithelial tissue
  • CDH2 - N-cadherin (neural): N-cadherins are found in neurons
  • CDH12 - cadherin 12, type 2 (N-cadherin 2)
  • CDH3 - P-cadherin (placental): P-cadherins are found in the placenta.

Desmosomal[edit]

Protocadherins[edit]

PCDH15; PCDH17; PCDH18; PCDH19; PCDH20; PCDH7; PCDH8; PCDH9; PCDHA1; PCDHA10; PCDHA11; PCDHA12; PCDHA13; PCDHA2; PCDHA3; PCDHA4; PCDHA5; PCDHA6; PCDHA7; PCDHA8; PCDHA9; PCDHAC1; PCDHAC2; PCDHB1; PCDHB10; PCDHB11; PCDHB12; PCDHB13; PCDHB14; PCDHB15; PCDHB16; PCDHB17; PCDHB18; PCDHB2; PCDHB3; PCDHB4; PCDHB5; PCDHB6; PCDHB7; PCDHB8; PCDHB9; PCDHGA1; PCDHGA10; PCDHGA11; PCDHGA12; PCDHGA2; PCDHGA3; PCDHGA4; PCDHGA5; PCDHGA6; PCDHGA7; PCDHGA8; PCDHGA9; PCDHGB1; PCDHGB2; PCDHGB3; PCDHGB4; PCDHGB5; PCDHGB6; PCDHGB7; PCDHGC3; PCDHGC4; PCDHGC5

FAT; FAT2; FAT4;

Unconventional/ungrouped[edit]

  • CDH9 - cadherin 9, type 2 (T1-cadherin)
  • CDH10 - cadherin 10, type 2 (T2-cadherin)
  • CDH4 - R-cadherin (retinal)
  • CDH5 - VE-cadherin (vascular endothelial)
  • CDH6 - K-cadherin (kidney)
  • CDH7 - cadherin 7, type 2
  • CDH8 - cadherin 8, type 2
  • CDH11 - OB-cadherin (osteoblast)
  • CDH13 - T-cadherin - H-cadherin (heart)
  • CDH15 - M-cadherin (myotubule)
  • CDH16 - KSP-cadherin
  • CDH17 - LI cadherin (liver-intestine)
  • CDH18 - cadherin 18, type 2
  • CDH19 - cadherin 19, type 2
  • CDH20 - cadherin 20, type 2
  • CDH23 - cadherin 23, (neurosensory epithelium)

CDH18; CDH19; CDH20; CDH22; CDH23; CDH24; CDH26; CDH28; CDH4; CDH5; CDH6; CDH7; CDH8; CDH9;

CELSR1; CELSR2; CELSR3; CLSTN1; CLSTN2; CLSTN3; DCHS1; DCHS2; LOC389118;

See also[edit]

References[edit]

  1. ^ Hulpiau P, van Roy F (February 2009). "Molecular evolution of the cadherin superfamily". Int. J. Biochem. Cell Biol. 41 (2): 349–69. doi:10.1016/j.biocel.2008.09.027. PMID 18848899. 
  2. ^ Angst B, Marcozzi C, Magee A (February 2001). "The cadherin superfamily: diversity in form and function". J Cell Sci 114 (Pt 4): 629–41. PMID 11171368. 
  3. ^ Bello S.M., Millo H., Rajebhosale M., Price S.R. (2012) Catenin-dependent cadherin function drives divisional segregation of spinal chord motor neurons. J. Neuroscience 32(2):490-505
  4. ^ Duguay, D.; A. Foty R., RA; S. Steinberg M., MS (2003). "Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants". Dev. Biol. 253 (2): 309–323. doi:10.1016/S0012-1606(02)00016-7. PMID 12645933. 
  5. ^ Niessen, Carien M.; Gumbiner, Barry M. (2002). "Cadherin-mediated cell sorting not determined by binding or adhesion specificity". The Journal of Cell Biology 156 (2): 389–399. doi:10.1083/jcb.200108040. PMC 2199232. PMID 11790800. 
  6. ^ Volk, T.; Cohen, O.; Geiger, B. (1987). "Formation of heterotypic adherens-type junctions between L-CAM containing liver cells and A-CAM containing lens cells". Cell 50 (6): 987–994. doi:10.1016/0092-8674(87)90525-3. PMID 3621349. 
  7. ^ Bayas, Marco V.; Leung, Andrew; Evans, Evan; Leckband, Deborah (2005). "Lifetime Measurements Reveal Kinetic Differences between Homophilic Cadherin Bonds". Biophysical Journal 90 (4): 1385–95. doi:10.1529/biophysj.105.069583. PMC 1367289. PMID 16326909. 
  8. ^ Harris, Tony J.C., and Ulrich Tepass. "Adherins Junctions: From Molecules to Morphogenesis" Nature Reviews Molecular Cell Biology. 502-514. July 2010. doi:10.1038/nrm2927.
  9. ^ a b Tepass, Ulrich, et al. "Cadherins in Embryonic and Neural Morphogenisis" Nature Reviews Molecular Cell Biology. November 2000.
  10. ^ Gumbiner, Barry M. "Regulation of Cadherin-Mediated Adhesion in Morphogenesis" Nature Reviews Molecular Cell Biology. 622-634. August 2005.
  11. ^ PDB 3Q2V; Harrison, O.J., Jin, X., Hong, S., Bahna, F., Ahlsen, G., Brasch, J., Wu, Y., Vendome, J., Felsovalyi, K., Hampton, C.M., Troyanovsky, R.B., Ben-Shaul, A., Frank, J., Troyanovsky, S.M., Shapiro, L., Honig, B. (2011). "The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins". Structure 19 (2): 244–56. doi:10.1016/j.str.2010.11.016. PMC 3070544. PMID 21300292. ; rendered with PyMOL
  12. ^ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 306–. ISBN 978-3-540-38916-3. Retrieved 14 December 2010. 

Further reading[edit]

  • Beavon IR (2000). "The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation". Eur. J. Cancer 36 (13 Spec No): 1607–20. doi:10.1016/S0959-8049(00)00158-1. PMID 10959047. 
  • Berx G, Becker KF, Höfler H, van Roy F (1998). "Mutations of the human E-cadherin (CDH1) gene". Hum. Mutat. 12 (4): 226–37. doi:10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D. PMID 9744472. 
  • Bryant DM, Stow JL (2005). "The ins and outs of E-cadherin trafficking". Trends Cell Biol. 14 (8): 427–34. doi:10.1016/j.tcb.2004.07.007. PMID 15308209. 
  • Chun YS, Lindor NM, Smyrk TC, et al. (2001). "Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?". Cancer 92 (1): 181–7. doi:10.1002/1097-0142(20010701)92:1<181::AID-CNCR1307>3.0.CO;2-J. PMID 11443625. 
  • Georgolios A, Batistatou A, Manolopoulos L, Charalabopoulos K (2006). "Role and expression patterns of E-cadherin in head and neck squamous cell carcinoma (HNSCC)". J. Exp. Clin. Cancer Res. 25 (1): 5–14. PMID 16761612. 
  • Hazan RB, Qiao R, Keren R, et al. (2004). "Cadherin switch in tumor progression". Ann. N. Y. Acad. Sci. 1014: 155–63. doi:10.1196/annals.1294.016. PMID 15153430. 
  • Moran CJ, Joyce M, McAnena OJ (2005). "CDH1 associated gastric cancer: a report of a family and review of the literature". Eur J Surg Oncol 31 (3): 259–64. doi:10.1016/j.ejso.2004.12.010. PMID 15780560. 
  • Reynolds AB, Carnahan RH (2005). "Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer". Semin. Cell Dev. Biol. 15 (6): 657–63. doi:10.1016/j.semcdb.2004.09.003. PMID 15561585. 
  • Wang HD, Ren J, Zhang L (2004). "CDH1 germline mutation in hereditary gastric carcinoma". World J. Gastroenterol. 10 (21): 3088–93. PMID 15457549. 
  • Wijnhoven BP, Dinjens WN, Pignatelli M (2000). "E-cadherin-catenin cell-cell adhesion complex and human cancer". The British journal of surgery 87 (8): 992–1005. doi:10.1046/j.1365-2168.2000.01513.x. PMID 10931041. 
  • Wilson PD (2001). "Polycystin: new aspects of structure, function, and regulation". J. Am. Soc. Nephrol. 12 (4): 834–45. PMID 11274246. 
  • Renaud-Young M, Gallin WJ (2002). "In the first extracellular domain of E-cadherin, heterophilic interactions, but not the conserved His-Ala-Val motif, are required for adhesion". Journal of Biological Chemistry 277 (42): 39609–39616. doi:10.1074/jbc.M201256200. PMID 12154084. 

External links[edit]

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

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Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002126

Cadherins are a family of adhesion molecules that mediate Ca2+-dependent cell-cell adhesion in all solid tissues of the organism which modulate a wide variety of processes including cell polarisation and migration [PUBMED:2197976, PUBMED:,PUBMED:14570569]. Cadherin-mediated cell-cell junctions are formed as a result of interaction between extracellular domains of identical cadherins, which are located on the membranes of the neighbouring cells. The stability of these adhesive junctions is ensured by binding of the intracellular cadherin domain with the actin cytoskeleton. There are a number of different isoforms distributed in a tissue-specific manner in a wide variety of organisms. Cells containing different cadherins tend to segregate in vitro, while those that contain the same cadherins tend to preferentially aggregate together. This observation is linked to the finding that cadherin expression causes morphological changes involving the positional segregation of cells into layers, suggesting they may play an important role in the sorting of different cell types during morphogenesis, histogenesis and regeneration. They may also be involved in the regulation of tight and gap junctions, and in the control of intercellular spacing. Cadherins are evolutionary related to the desmogleins which are component of intercellular desmosome junctions involved in the interaction of plaque proteins.

Structurally, cadherins comprise a number of domains: classically, these include a signal sequence; a propeptide of around 130 residues; a single transmembrane domain and five tandemly repeated extracellular cadherin domains, 4 of which are cadherin repeats, and the fifth contains 4 conserved cysteines and a N-terminal cytoplasmic domain [PUBMED:11736639]. However, proteins are designated as members of the broadly defined cadherin family if they have one or more cadherin repeats. A cadherin repeat is an independently folding sequence of approximately 110 amino acids that contains motifs with the conserved sequences DRE, DXNDNAPXF, and DXD. Crystal structures have revealed that multiple cadherin domains form Ca2+-dependent rod-like structures with a conserved Ca2+-binding pocket at the domain-domain interface. Cadherins depend on calcium for their function: calcium ions bind to specific residues in each cadherin repeat to ensure its proper folding, to confer rigidity upon the extracellular domain and is essential for cadherin adhesive function and for protection against protease digestion.

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 E-set (CL0159), which has the following description:

This clan includes a diverse range of domains that have an Ig-like fold and appear to be distantly related to each other. The clan includes: PKD domains, cadherins and several families of bacterial Ig-like domains as well as viral tail fibre proteins. it also includes several Fibronectin type III domain-containing families.

The clan contains the following 63 members:

A2M_N Alpha_adaptinC2 Big_1 Big_2 Big_3 Big_3_2 Big_3_3 Big_3_4 Big_4 Big_5 BiPBP_C BsuPI Cadherin Cadherin-like Cadherin_2 Cadherin_pro CARDB CHB_HEX_C CHB_HEX_C_1 ChitinaseA_N CHU_C Coatamer_beta_C COP-gamma_platf CopC DUF1034 DUF11 DUF1973 DUF2271 DUF4165 DUF4625 DUF916 EpoR_lig-bind Filamin FixG_C FlgD_ig fn3 Fn3_assoc He_PIG HYR IFNGR1 IL6Ra-bind Integrin_alpha2 Interfer-bind Invasin_D3 MG1 Mo-co_dimer Neurexophilin NPCBM_assoc PapD_N PKD PPC Qn_am_d_aIII REJ Rib SoxZ SprB SWM_repeat T2SS-T3SS_pil_N TIG Tissue_fac Transglut_C TRAP_beta Y_Y_Y

Alignments

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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
(57)
Full
(41902)
Representative proteomes NCBI
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Meta
(1579)
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(4217)
RP35
(6276)
RP55
(12981)
RP75
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  Seed
(57)
Full
(41902)
Representative proteomes NCBI
(37651)
Meta
(1579)
RP15
(4217)
RP35
(6276)
RP55
(12981)
RP75
(21785)
Alignment:
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  Seed
(57)
Full
(41902)
Representative proteomes NCBI
(37651)
Meta
(1579)
RP15
(4217)
RP35
(6276)
RP55
(12981)
RP75
(21785)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
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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

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.

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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 View help on the curation process

Seed source: Swissprot_feature_table
Previous IDs: cadherin;
Type: Family
Author: Sonnhammer ELL
Number in seed: 57
Number in full: 41902
Average length of the domain: 93.10 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 44.86 %

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 28.8 28.8
Trusted cut-off 28.8 28.8
Noise cut-off 28.7 28.7
Model length: 93
Family (HMM) version: 12
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 2 interactions for this family. More...

Cadherin LRR_1

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 Cadherin domain has been found. There are 141 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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