This is the Wikipedia entry entitled "Ephrin". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
Ephrin Edit Wikipedia article
structural and biophysical characterization of the ephb4-ephrinb2 protein protein interaction and receptor specificity.
Ephrins also known as ephrin ligands or Eph family receptor interacting proteins are a family of proteins that serve as the ligands of the ephrin receptor. Ephrin receptors in turn compose the largest known subfamily of receptor protein-tyrosine kinases (RTKs).
Since ephrin ligands (ephrins) and Eph receptors (Ephs) are both membrane-bound proteins, binding and activation of Eph/epherin intracellular signaling pathways can only occur via direct cell-cell interaction. Eph/epherin signaling regulates a variety of biological processes during embryonic development including the guidance of axon growth cones, formation of tissue boundaries, cell migration, and segmentation. Additionally, Eph/epherin signaling has recently been identified to play a critical role in the maintenance of several processes during adulthood including long-term potentiation, angiogenesis, and stem cell differentiation.
Ephrin ligands are divided into two subclasses of ephrin-A and ephrin-B based on their structure and linkage to the cell membrane. Ephrin-As are anchored to the membrane by a glycosylphosphatidylinositol (GPI) linkage and lack a cytoplasmic domain while ephrin-Bs are attached to the membrane by a single transmembrane domain that contains a short cytoplasmic PDZ-binding motif. The genes that encode the ephrin-A and ephrin-B proteins are designated as EFNA and EFNB respectively. Eph receptors in turn are classified as either EphAs or EphBs based on their binding affinity for either the ephrin-A or ephrin-B ligands.
Of the eight ephrins that have been identified in humans there are five known ephrin-A ligands (ephrin-A1-5) that interact with nine EphAs (EphA1-8 and EphA10) and three ephrin-B ligands (ephrin-B1-3) that interact with five EphBs (EphB1-4 and EphB6). Ephs of a particular subclass demonstrate an ability to bind with high affinity to all ephrins of the corresponding subcass, but in general have little to no cross-binding to ephrins of the opposing subclass. However, there are a few exceptions to this intrasubclass binding specificity as it has recently been shown that ephrin-B3 is able bind to and activate EPH receptor A4 and ephrin-A5 can bind to and activate Eph receptor B2. EphAs/ephrin-As typically bind with high affinity, which can partially be attributed to the fact that ephrinAs interact with EphAs by a "lock-and-key" mechanism that requires little conformational change of the EphAs upon ligand binding. In contrast EphBs typically bind with lower affinity than EphAs/ephring-As since they utilize an "induced fit" mechanism that requires a greater conformational change of EphBs to bind ephrin-Bs.
 Axon guidance
During the development of the central nervous system Eph/ephrin signaling plays a critical role in the cell-cell mediated migration of several types of neuronal axons to their target destinations. Eph/ephrin signaling controls the guidance of neuronal axons through their ability to inhibit the survival of axonal growth cones, which repels the migrating axon away from the site of Eph/ephrin activation. The growth cones of migrating axons do not simply respond to absolute levels of Ephs or ephrins in cells that they contact, but rather respond to relative levels of Eph and ephrin expression, which allows migrating axons that express either Ephs or ephrins to be directed along gradients of Eph or ephrin expressing cells towards a destination where axonal growth cone survival is no longer completely inhibited.
Although Eph-ephrin activation is usually associated with decreased growth cone survival and the repellence of migrating axons, it has recently been demonstrated that growth cone survival does not depend just on Eph-ephrin activation, but rather on the differential effects of "forward" signaling by the Eph receptor or "reverse" signaling by the ephrin ligand on growth cone survival(see "Ephrin Reverse Signaling" below).
 Retinotopic mapping
The formation of an organized retinotopic map in the superior colliculus (SC) (referred to as the optic tectum in lower vertebrates) requires the proper migration of the axons of retinal ganglion cells (RGCs) from the retina to specific regions in the SC that is mediated by gradients of Eph and ephrin expression in both the SC and in migrating RGCs leaving the retina. The decreased survival of axonal growth cones discussed above allows for a gradient of high posterior to low anterior ephrin-A ligand expression in the SC to direct migrating RGCs axons from the temporal region of the retina that express a high level of EphA receptors toward targets in the anterior SC and RGCs from the nasal retina that have low EphA expression toward their final destination in the posterior SC. Similarly, a gradient of ephrin-B1 expression along the medial-ventral axis of the SC directs the migration of dorsal and ventral EphB-expressing RGCs to the lateral and medial SC respectively.
 Reverse signaling
One unique property of the ephrin ligands is that many have the capacity to initiate a "reverse" signal that is separate and distinct from the intracellular signal activated in Eph receptor-expressing cells. Although the mechanisms by which "reverse" signaling occurs are not completely understood, both ephrin-As and ephrin-Bs have been shown to mediate cellular responses that are distinct from those associated with activation of their corresponding receptors. Specifically, ephrin-A5 was shown to stimulate growth cone spreading in spinal motor neurons and ephrin-B1 was shown to promote dendritic spine maturation.
- Egea, J.; Klein, R. D. (2007). "Bidirectional Eph–ephrin signaling during axon guidance". Trends in Cell Biology 17 (5): 230–238. doi:10.1016/j.tcb.2007.03.004. PMID 17420126.
- Rohani, N.; Canty, L.; Luu, O.; Fagotto, F. O.; Winklbauer, R. (2011). "EphrinB/EphB Signaling Controls Embryonic Germ Layer Separation by Contact-Induced Cell Detachment". In Hamada, Hiroshi. PLoS Biology 9 (3): e1000597. doi:10.1371/journal.pbio.1000597. PMC 3046958. PMID 21390298.
- Davy, A.; Soriano, P. (2005). "Ephrin signaling in vivo: Look both ways". Developmental Dynamics 232 (1): 1–10. doi:10.1002/dvdy.20200. PMID 15580616.
- Kullander, K.; Klein, R. D. (2002). "Mechanisms and functions of eph and ephrin signalling". Nature Reviews Molecular Cell Biology 3 (7): 475–486. doi:10.1038/nrm856. PMID 12094214.
- Kuijper, S.; Turner, C. J.; Adams, R. H. (2007). "Regulation of Angiogenesis by Eph–Ephrin Interactions". Trends in Cardiovascular Medicine 17 (5): 145–151. doi:10.1016/j.tcm.2007.03.003. PMID 17574121.
- Genander, M.; Frisén, J. (2010). "Ephrins and Eph receptors in stem cells and cancer". Current Opinion in Cell Biology 22 (5): 611–616. doi:10.1016/j.ceb.2010.08.005. PMID 20810264.
- Ephnomenclaturecommittee (1997). "Unified nomenclature for Eph family receptors and their ligands, the ephrins. Eph Nomenclature Committee". Cell 90 (3): 403–404. doi:10.1016/S0092-8674(00)80500-0. PMID 9267020.
- Pitulescu, M. E.; Adams, R. H. (2010). "Eph/ephrin molecules—a hub for signaling and endocytosis". Genes & Development 24 (22): 2480–2492. doi:10.1101/gad.1973910. PMC 2975924. PMID 21078817.
- Pasquale, E. B. (1997). "The Eph family of receptors". Current opinion in cell biology 9 (5): 608–615. doi:10.1016/S0955-0674(97)80113-5. PMID 9330863.
- Himanen, J. P.; Chumley, M. J.; Lackmann, M.; Li, C.; Barton, W. A.; Jeffrey, P. D.; Vearing, C.; Geleick, D. et al. (2004). "Repelling class discrimination: Ephrin-A5 binds to and activates EphB2 receptor signaling". Nature Neuroscience 7 (5): 501–509. doi:10.1038/nn1237. PMID 15107857.
- Himanen, J. P. (2011). "Ectodomain structures of Eph receptors". Seminars in Cell & Developmental Biology 23 (1): 35–42. doi:10.1016/j.semcdb.2011.10.025. PMID 22044883.
- Marquardt, T.; Shirasaki, R.; Ghosh, S.; Andrews, S. E.; Carter, N.; Hunter, T.; Pfaff, S. L. (2005). "Coexpressed EphA Receptors and Ephrin-A Ligands Mediate Opposing Actions on Growth Cone Navigation from Distinct Membrane Domains". Cell 121 (1): 127–139. doi:10.1016/j.cell.2005.01.020. PMID 15820684.
- Reber, M. L.; Burrola, P.; Lemke, G. (2004). "A relative signalling model for the formation of a topographic neural map". Nature 431 (7010): 847–853. doi:10.1038/nature02957. PMID 15483613.
- Petros, T. J.; Bryson, J. B.; Mason, C. (2010). "Ephrin-B2 elicits differential growth cone collapse and axon retraction in retinal ganglion cells from distinct retinal regions". Developmental Neurobiology 70 (11): 781–794. doi:10.1002/dneu.20821. PMC 2930402. PMID 20629048.
- Triplett, J. W.; Feldheim, D. A. (2011). "Eph and ephrin signaling in the formation of topographic maps". Seminars in Cell & Developmental Biology 23 (1): 7–15. doi:10.1016/j.semcdb.2011.10.026. PMID 22044886.
- Wilkinson, D. G. (2001). "Multiple roles of EPH receptors and ephrins in neural development". Nature Reviews Neuroscience 2 (3): 155–164. doi:10.1038/35058515. PMID 11256076.
- Cheng, H. J.; Nakamoto, M.; Bergemann, A. D.; Flanagan, J. G. (1995). "Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map". Cell 82 (3): 371–381. doi:10.1016/0092-8674(95)90426-3. PMID 7634327.
- Drescher, U.; Kremoser, C.; Handwerker, C.; Löschinger, J.; Noda, M.; Bonhoeffer, F. (1995). "In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases". Cell 82 (3): 359–370. doi:10.1016/0092-8674(95)90425-5. PMID 7634326.
- Mann, F.; Ray, S.; Harris, W.; Holt, C. (2002). "Topographic mapping in dorsoventral axis of the Xenopus retinotectal system depends on signaling through ephrin-B ligands". Neuron 35 (3): 461–473. doi:10.1016/S0896-6273(02)00786-9. PMID 12165469.
- Segura, I.; Essmann, C. L.; Weinges, S.; Acker-Palmer, A. (2007). "Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation". Nature Neuroscience 10 (3): 301–310. doi:10.1038/nn1858. PMID 17310244.
Ephrin Provide feedback
No Pfam abstract.
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001799
Ephrins are a family of proteins [PUBMED:7838529] that are ligands of class V (EPH-related) receptor protein-tyrosine kinases. These receptors and their ligands have been implicated in regulating neuronal axon guidance and in patterning of the developing nervous system and may also serve a patterning and compartmentalisation role outside of the nervous system as well.
Ephrins are membrane-attached proteins of 205 to 340 residues. Attachment appears to be crucial for their normal function. Type-A ephrins are linked to the membrane via a glycosylphosphatidylinositol (GPI)-linkage, while type-B ephrins are type-I membrane proteins.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Loading domain graphics...
Many of the proteins in this family contain multiple similar copies of this plastocyanin-like domain.
The clan contains the following 9 members:Copper-bind COX2 Cu-oxidase Cu-oxidase_2 Cu-oxidase_3 Cu_bind_like Cupredoxin_1 Ephrin SoxE
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Seed source:||Pfam-B_1390 (release 2.1)|
|Number in seed:||14|
|Number in full:||554|
|Average length of the domain:||131.80 aa|
|Average identity of full alignment:||39 %|
|Average coverage of the sequence by the domain:||52.16 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||12|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
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 Ephrin domain has been found. There are 31 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.
Loading structure mapping...