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79  structures 129  species 3  interactions 1269  sequences 50  architectures

Family: Ephrin_lbd (PF01404)

Summary: Ephrin receptor ligand binding 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 "Ephrin receptor". More...

Ephrin receptor Edit Wikipedia article

Eph receptor ligand binding domain
EphA5.png
Structure of the kinase domain of human eph type-A receptor 5 (EphA5)
Identifiers
Symbol Ephrin_lbd
Pfam PF01404
InterPro IPR001090
SCOP 1nuk
SUPERFAMILY 1nuk
CDD cd10319

Eph receptors (Ephs, after erythropoietin-producing human hepatocellular receptors) are a group of receptors that are activated in response to binding Eph receptor-interacting proteins (Ephrins). Ephs form the largest known subfamily of receptor tyrosine kinases (RTKs). Both Eph receptors and their corresponding ephrin ligands are membrane-bound proteins that require direct cell-cell interactions for Eph receptor activation. Eph/ephrin signaling has been implicated in the regulation of a host of processes critical to embryonic development including axon guidance,[1] formation of tissue boundaries,[2] cell migration, and segmentation.[3] Additionally, Eph/ephrin signaling has recently been identified to play a critical role in the maintenance of several processes during adulthood including long-term potentiation,[4] angiogenesis,[5] and stem cell differentiation and cancer.[6]

Subclasses

Ephs can be divided into two subclasses, EphAs and EphBs (encoded by the genetic loci designated EPHA and EPHB respectively), based on sequence similarity and on their binding affinity for either the glycosylphosphatidylinositol-linked ephrin-A ligands or the transmembrane-bound ephrin-B ligands.[7] Of the 16 Eph receptors (see above) that have been identified in animals, humans are known to express nine EphAs (EphA1-8 and EphA10) and five EphBs (EphB1-4 and EphB6).[8] In general, Ephs of a particular subclass bind preferentially to all ephrins of the corresponding subclass, but have little to no cross-binding to ephrins of the opposing subclass.[9] It has recently been proposed that the intrasubclass specificity of Eph/ephrin binding could be partially attributed to the different binding mechanisms used by EphAs and EphBs. There are exceptions to the intrasubclass binding specificity observed in Ephs, however, as it has recently been shown that ephrin-B3 can bind to and activate EphA4 and that ephrin-A5 can bind to and activate EphB2.[10] EphA/ephrinA interaction typically occur with higher affinity than EphB/ephrin-B interactions which can partially be attributed to the fact that ephrin-As bind via a "lock-and-key" mechanism that requires little conformational change of the EphAs in contrast to EphBs which utilize an "induced fit" mechanism that requires a greater amount of energy to alter the conformation of EphBs to bind to ephrin-Bs.[11]

16 Ephs have been identified in animals and are listed below:

Activation

The extracellular domain of Eph receptors is composed of a highly conserved globular ephrin ligand-binding domain, a cysteine-rich region and two fibronectin type III domains. The cytoplasmic domain of Eph receptors is composed of a juxtamembrane region with two conserved tyrosine residues, a tyrosine kinase domain, a sterile alpha motif (SAM), and a PDZ-binding motif.[4][11] Following binding of an ephrin ligand to the extracellular globular domain of an Eph receptor, tyrosine and serine residues in the juxtamembrane region of the Eph become phosphorylated[12] allowing the intracellular tyrosine kinase to convert into its active form and subsequently activate or repress downstream signaling cascades.[13] The structure of the trans-autophosphorylation of the juxtamembrane region of EPHA2 has been observed within a crystal of EPHA2.[14]

Function

The ability of Ephs and ephrins to mediate a variety of cell-cell interactions places the Eph/ephrin system in an ideal position to regulate a variety of different biological processes during embryonic development.

Bi-directional signaling

Unlike most other RTKs, Ephs have a unique capacity to initiate an intercellular signal in both the receptor-bearing cell ("forward" signaling) and the opposing ephrin-bearing cell ("reverse" signaling) following cell-cell contact, which is known as bi-directional signaling.[15] Although the functional consequences of Eph/ephrin bi-directional signaling have not been completely elucidated, it is clear that such a unique signaling process allows for ephrin Ephs to have opposing effects on growth cone survival[16] and allows for the segregation of Eph-expressing cells from ephrin-expressing cells.[17]

Segmentation

Segmentation is a basic process of embryogenesis occurring in most invertebrates and all vertebrates by which the body is initially divided into functional units. In the segmented regions of the embryo, cells begin to present biochemical and morphological boundaries at which cell behavior is drastically different – vital for future differentiation and function.[18] In the hindbrain, segmentation is a precisely defined process. In the paraxial mesoderm, however, development is a dynamic and adaptive process that adjusts according to posterior body growth. Various Eph receptors and ephrins are expressed in these regions, and, through functional analysis, it has been determined that Eph signaling is crucial for the proper development and maintenance of these segment boundaries.[18] Similar studies conducted in zebrafish have shown similar segmenting processes within the somites containing a striped expression pattern of Eph receptors and their ligands, which is vital to proper segmentation - the disruption of expression resulting in misplaced or even absent boundaries.[19]

Axon guidance

As the nervous system develops, the patterning of neuronal connections is established by molecular guides that direct axons (axon guidance) along pathways by target and pathway derived signals.[20] Eph/ephrin signaling regulates the migration of axons to their target destinations largely by decreasing the survival of axonal growth cones and repelling the migrating axon away from the site of Eph/ephrin activation.[16][21] This mechanism of repelling migrating axons through decreased growth cone survival depends on relative levels of Eph and ephrin expression and allows gradients of Eph and ephrin expression in target cells to direct the migration of axon growth cones based on their own relative levels of Eph and ephrin expression. Typically, forward signaling by both EphA and EphB receptors mediates growth cone collapse while reverse signaling via ephrin-A and ephrin-B induces growth cone survival.[16][22]

The ability of Eph/ephrin signaling to direct migrating axons along Eph/ephrin expression gradients is evidenced in the formation of the retinotopic map in the visual system, with graded expression levels of both Eph receptors and ephrin ligands leading to the development of a resolved neuronal map[23] (for a more detailed description of Eph/ephrin signaling see "Formation of the Retinotopic Map" in ephrin). Further studies then showed the role of Eph’s in topographic mapping in other regions of the central nervous system, such as learning and memory via the formation of projections between the septum and hippocampus.[24]

In addition to the formation of topographic maps, Eph/ephrin signaling has been implicated in the proper guidance of motor neuron axons in the spinal cord. Although several members of Ephs and ephrins contribute to motor neuron guidance,[25] ephrin-A5 reverse signaling has been shown to play a critical role in the survival of motor neuron growth cones and to mediate growth cone migration by initiating repellence in EphA-expressing migrating axons.[16]

Cell migration

More than just axonal guidance, Ephs have been implicated in the migration of neural crest cells during gastrulation.[26] In the chick and rat embryo trunk, the migration of crest cells is partially mediated by EphB receptors. Similar mechanisms have been shown to control crest movement in the hindbrain within rhombomeres 4, 5, and 7, which distribute crest cells to brachial arches 2, 3, and 4 respectively. In C. elegans a knockout of the vab-1 gene, known to encode an Eph receptor, and its Ephrin ligand vab-2 results in two cell migratory processes being affected.[27][28]

Angiogenesis

Eph receptors are present in high degrees during vasculogenesis (angiogenesis) and other early development of the circulatory system. This development is disturbed without it. It is thought to distinguish arterial and venous endothelium, stimulating the production of capillary sprouts as well as in the differentiation of mesenchyme into perivascular support cells.

The construction of blood vessels requires the coordination of endothelial and supportive mesenchymal cells through multiple phases to develop the intricate networks required for a fully functional circulatory system.[29] The dynamic nature and expression patterns of the Ephs make them, therefore, ideal for roles in angiogenesis. Mouse embryonic models show expression of EphA1 in mesoderm and pre-endocardial cells, later spreading up into the dorsal aorta then primary head vein, intersomitic vessels, and limb bud vasculature, as would be consistent with a role in angiogenesis. Different class A Eph receptors have also been detected in the lining of the aorta, brachial arch arteries, umbilical vein, and endocardium.[29] Complementary expression of EphB2/ephrin-B4 was detected in developing arterial endothelial cells and EphB4 in venous endothelial cells.[30] Expression of EphB2 and ephrin-B2 was also detected on supportive mesenchymal cells, suggesting a role in wall development through mediation of endothelial-mesenchymal interactions.[31] Blood vessel formation during embryogenesis consists of vasculogenesis, the formation of a primary capillary network followed by a second remodeling and restructuring into a finer tertiary network - studies utilizing ephrin-B2 deficient mice showed a disruption of the embryonic vasculature as a result of a deficiency in the restructuring of the primary network.[18] Functional analysis of other mutant mice have led to the development of a hypothesis by which Ephs and ephrins contribute to vascular development by restricting arterial and venous endothelial mixing, thus stimulating the production of capillary sprouts as well as in the differentiation of mesenchyme into perivascular support cells, an ongoing area of research.[29]

Limb development

While there is currently little evidence to support this (and mounting evidence to refute it), some early studies implicated the Ephs to play a part in the signaling of limb development.[18] In chicks, EphA4 is expressed in the developing wing and leg buds, as well as in the feather and scale primordia.[32] This expression is seen in the distal end of the limb buds, where cells are still undifferentiated and dividing, and appears to be under the regulation of retinoic acid, FGF2, FGF4, and BMP-2 – known to regulate limb patterning. EphA4 defective mice do not present abnormalities in limb morphogenesis (personal communication between Andrew Boyd and Nigel Holder), so it is possible that these expression patterns are related to neuronal guidance or vascularisation of the limb with further studies being required to confirm or deny a potential role of Eph in limb development.

Cancer

As a member of the RTK family and with responsibilities as diverse as Ephs, it is not surprising to learn that the Ephs have been implicated in several aspects of cancer. While used extensively throughout development, Ephs are rarely detected in adult tissues. Elevated levels of expression and activity have been correlated with the growth of solid tumors, with Eph receptors of both classes A and B being over expressed in a wide range of cancers including melanoma, breast, prostate, pancreatic, gastric, esophageal, and colon cancer, as well as hematopoietic tumors.[33][34][35] Increased expression was also correlated with more malignant and metastatic tumors, consistent with the role of Ephs in governing cell movement.[29]

It is possible that the increased expression of Eph in cancer plays several roles, first, by acting as survival factors or as a promoter of abnormal growth.[36] The angiogenic properties of the Eph system may increase vascularisation of and thus growth capacity of tumors.[29] Second, elevated Eph levels may disrupt cell-cell adhesion via cadherin, known to alter expression and localisation of Eph receptors and ephrins, which is known to further disrupt cellular adhesion, a key feature of metastatic cancers.[36] Third, Eph activity may alter cell matrix interactions via integrins by the sequestering of signaling molecules following Eph receptor activation, as well as providing potential adherence via ephrin ligand binding following metastasis.[35][36]

Discovery and history

The Eph receptors were initially identified in 1987 following a search for tyrosine kinases with possible roles in cancer, earning their name from the erythropoietin-producing hepatocellular carcinoma cell line from which their cDNA was obtained.[37] These transmembranous receptors were initially classed as orphan receptors with no known ligands or functions, and it was some time before possible functions of the receptors were known.[20]

When it was shown that almost all Eph receptors were expressed during various well-defined stages of development in assorted locations and concentrations, a role in cell positioning was proposed, initiating research that revealed the Eph/ephrin families as a principle cell guidance system during vertebrate and invertebrate development.[38]

References

  1. ^ Egea J, Klein R (May 2007). "Bidirectional Eph-ephrin signaling during axon guidance". Trends Cell Biol. 17 (5): 230–8. doi:10.1016/j.tcb.2007.03.004. PMID 17420126. 
  2. ^ Rohani N, Canty L, Luu O, Fagotto F, Winklbauer R (March 2011). Hamada, Hiroshi, ed. "EphrinB/EphB signaling controls embryonic germ layer separation by contact-induced cell detachment". PLoS Biol. 9 (3): e1000597. doi:10.1371/journal.pbio.1000597. PMC 3046958. PMID 21390298. 
  3. ^ Davy A, Soriano P (January 2005). "Ephrin signaling in vivo: look both ways". Dev. Dyn. 232 (1): 1–10. doi:10.1002/dvdy.20200. PMID 15580616. 
  4. ^ a b Kullander K, Klein R (July 2002). "Mechanisms and functions of Eph and ephrin signalling". Nat. Rev. Mol. Cell Biol. 3 (7): 475–86. doi:10.1038/nrm856. PMID 12094214. 
  5. ^ Kuijper S, Turner CJ, Adams RH (July 2007). "Regulation of angiogenesis by Eph-ephrin interactions". Trends Cardiovasc. Med. 17 (5): 145–51. doi:10.1016/j.tcm.2007.03.003. PMID 17574121. 
  6. ^ Genander M, Frisén J (October 2010). "Ephrins and Eph receptors in stem cells and cancer". Curr. Opin. Cell Biol. 22 (5): 611–6. doi:10.1016/j.ceb.2010.08.005. PMID 20810264. 
  7. ^ Eph Nomenclature Committee (August 1997). "Unified nomenclature for Eph family receptors and their ligands, the ephrins". Cell 90 (3): 403–4. doi:10.1016/S0092-8674(00)80500-0. PMID 9267020. 
  8. ^ Pitulescu ME, Adams RH (November 2010). "Eph/ephrin molecules--a hub for signaling and endocytosis". Genes Dev. 24 (22): 2480–92. doi:10.1101/gad.1973910. PMC 2975924. PMID 21078817. 
  9. ^ Pasquale EB (October 1997). "The Eph family of receptors". Curr. Opin. Cell Biol. 9 (5): 608–15. doi:10.1016/S0955-0674(97)80113-5. PMID 9330863. 
  10. ^ Himanen JP, Chumley MJ, Lackmann M, Li C, Barton WA, Jeffrey PD, Vearing C, Geleick D, Feldheim DA, Boyd AW, Henkemeyer M, Nikolov DB (May 2004). "Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling". Nat. Neurosci. 7 (5): 501–9. doi:10.1038/nn1237. PMID 15107857. 
  11. ^ a b Himanen JP (February 2012). "Ectodomain structures of Eph receptors". Semin. Cell Dev. Biol. 23 (1): 35–42. doi:10.1016/j.semcdb.2011.10.025. PMID 22044883. 
  12. ^ Kalo MS, Pasquale EB (October 1999). "Multiple in vivo tyrosine phosphorylation sites in EphB receptors". Biochemistry 38 (43): 14396–408. doi:10.1021/bi991628t. PMID 10572014. 
  13. ^ McClelland AC, Hruska M, Coenen AJ, Henkemeyer M, Dalva MB (May 2010). "Trans-synaptic EphB2-ephrin-B3 interaction regulates excitatory synapse density by inhibition of postsynaptic MAPK signaling". Proc. Natl. Acad. Sci. U.S.A. 107 (19): 8830–5. doi:10.1073/pnas.0910644107. PMC 2889310. PMID 20410461. 
  14. ^ Xu, Q.; Malecka, K. L.; Fink, L.; Jordan, E. J.; Duffy, E.; Kolander, S.; Peterson, J. R.; Dunbrack, R. L. (1 December 2015). "Identifying three-dimensional structures of autophosphorylation complexes in crystals of protein kinases". Science Signaling 8 (405): rs13. doi:10.1126/scisignal.aaa6711. 
  15. ^ Daar IO (February 2012). "Non-SH2/PDZ reverse signaling by ephrins". Semin. Cell Dev. Biol. 23 (1): 65–74. doi:10.1016/j.semcdb.2011.10.012. PMC 3288889. PMID 22040914. 
  16. ^ a b c d Marquardt T, Shirasaki R, Ghosh S, Andrews SE, Carter N, Hunter T, Pfaff SL (April 2005). "Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains". Cell 121 (1): 127–39. doi:10.1016/j.cell.2005.01.020. PMID 15820684. 
  17. ^ Jørgensen C, Sherman A, Chen GI, Pasculescu A, Poliakov A, Hsiung M, Larsen B, Wilkinson DG, Linding R, Pawson T (December 2009). "Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells". Science 326 (5959): 1502–9. doi:10.1126/science.1176615. PMID 20007894. 
  18. ^ a b c d Holder N, Klein R (May 1999). "Eph receptors and ephrins: effectors of morphogenesis". Development 126 (10): 2033–44. PMID 10207129. 
  19. ^ Durbin L, Brennan C, Shiomi K, Cooke J, Barrios A, Shanmugalingam S, Guthrie B, Lindberg R, Holder N (October 1998). "Eph signaling is required for segmentation and differentiation of the somites". Genes Dev. 12 (19): 3096–109. doi:10.1101/gad.12.19.3096. PMC 317186. PMID 9765210. 
  20. ^ a b Flanagan JG, Vanderhaeghen P (1998). "The ephrins and Eph receptors in neural development". Annu. Rev. Neurosci. 21: 309–45. doi:10.1146/annurev.neuro.21.1.309. PMID 9530499. 
  21. ^ Triplett JW, Feldheim DA (February 2012). "Eph and ephrin signaling in the formation of topographic maps". Semin. Cell Dev. Biol. 23 (1): 7–15. doi:10.1016/j.semcdb.2011.10.026. PMC 3288406. PMID 22044886. 
  22. ^ Petros TJ, Bryson JB, Mason C (September 2010). "Ephrin-B2 elicits differential growth cone collapse and axon retraction in retinal ganglion cells from distinct retinal regions". Dev Neurobiol 70 (11): 781–94. doi:10.1002/dneu.20821. PMC 2930402. PMID 20629048. 
  23. ^ Cheng HJ, Nakamoto M, Bergemann AD, Flanagan JG (August 1995). "Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map". Cell 82 (3): 371–81. doi:10.1016/0092-8674(95)90426-3. PMID 7634327. 
  24. ^ Gao PP, Zhang JH, Yokoyama M, Racey B, Dreyfus CF, Black IB, Zhou R (October 1996). "Regulation of topographic projection in the brain: Elf-1 in the hippocamposeptal system". Proc. Natl. Acad. Sci. U.S.A. 93 (20): 11161–6. doi:10.1073/pnas.93.20.11161. PMC 38301. PMID 8855326. 
  25. ^ Kao TJ, Law C, Kania A (February 2012). "Eph and ephrin signaling: lessons learned from spinal motor neurons". Semin. Cell Dev. Biol. 23 (1): 83–91. doi:10.1016/j.semcdb.2011.10.016. PMID 22040916. 
  26. ^ Robinson V, Smith A, Flenniken AM, Wilkinson DG (November 1997). "Roles of Eph receptors and ephrins in neural crest pathfinding". Cell Tissue Res. 290 (2): 265–74. doi:10.1007/s004410050931. PMID 9321688. 
  27. ^ George SE, Simokat K, Hardin J, Chisholm AD (1998)."The VAB-1 Eph receptor tyrosine kinase functions in neural and epithelial morphogenesis in C. elegans." Cell. 1998 Mar 6;92(5):633-43.. PMID 10619431
  28. ^ Chin-Sang ID, George SE, Ding M, Moseley SL, Lynch AS, Chisholm AD (1999). "The ephrin VAB-2/EFN-1 functions in neuronal signaling to regulate epidermal morphogenesis in C. elegans." Cell. 1999 Dec 23;99(7):781-90. PMID 10619431
  29. ^ a b c d e Cheng N, Brantley DM, Chen J (February 2002). "The ephrins and Eph receptors in angiogenesis". Cytokine Growth Factor Rev. 13 (1): 75–85. doi:10.1016/S1359-6101(01)00031-4. PMID 11750881. 
  30. ^ Wang HU, Chen ZF, Anderson DJ (May 1998). "Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4". Cell 93 (5): 741–53. doi:10.1016/S0092-8674(00)81436-1. PMID 9630219. 
  31. ^ Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R (February 1999). "Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis". Genes Dev. 13 (3): 295–306. doi:10.1101/gad.13.3.295. PMC 316426. PMID 9990854. 
  32. ^ Patel K, Nittenberg R, D'Souza D, Irving C, Burt D, Wilkinson DG, Tickle C (April 1996). "Expression and regulation of Cek-8, a cell to cell signalling receptor in developing chick limb buds". Development 122 (4): 1147–55. PMID 8620841. 
  33. ^ Wicks IP, Wilkinson D, Salvaris E, Boyd AW (March 1992). "Molecular cloning of HEK, the gene encoding a receptor tyrosine kinase expressed by human lymphoid tumor cell lines". Proc. Natl. Acad. Sci. U.S.A. 89 (5): 1611–5. doi:10.1073/pnas.89.5.1611. PMC 48502. PMID 1311845. 
  34. ^ Kiyokawa E, Takai S, Tanaka M, Iwase T, Suzuki M, Xiang YY, Naito Y, Yamada K, Sugimura H, Kino I (July 1994). "Overexpression of ERK, an EPH family receptor protein tyrosine kinase, in various human tumors". Cancer Res. 54 (14): 3645–50. PMID 8033077. 
  35. ^ a b Easty DJ, Herlyn M, Bennett DC (January 1995). "Abnormal protein tyrosine kinase gene expression during melanoma progression and metastasis". Int. J. Cancer 60 (1): 129–36. doi:10.1002/ijc.2910600119. PMID 7814145. 
  36. ^ a b c Surawska H, Ma PC, Salgia R (December 2004). "The role of ephrins and Eph receptors in cancer". Cytokine Growth Factor Rev. 15 (6): 419–33. doi:10.1016/j.cytogfr.2004.09.002. PMID 15561600. 
  37. ^ Murai KK, Pasquale EB (July 2003). "'Eph'ective signaling: forward, reverse and crosstalk". J. Cell. Sci. 116 (Pt 14): 2823–32. doi:10.1242/jcs.00625. PMID 12808016. 
  38. ^ Boyd AW, Lackmann M (December 2001). "Signals from Eph and ephrin proteins: a developmental tool kit". Sci. STKE 2001 (112): re20. doi:10.1126/stke.2001.112.re20. PMID 11741094. 

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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.

Ephrin receptor ligand binding domain Provide feedback

The Eph receptors, which bind to ephrins PF00812 are a large family of receptor tyrosine kinases. This family represents the amino terminal domain which binds the ephrin ligand [1].

Literature references

  1. Himanen JP, Henkemeyer M, Nikolov DB; , Nature 1998;396:486-491.: Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2. PUBMED:9853759 EPMC:9853759

External database links

SCOP: 1nuk

This tab holds annotation information from the InterPro database.

InterPro entry IPR001090

The Eph receptors, which bind a group of cell-membrane-anchored ligands known as ephrins, represent the largest subfamily of receptor tyrosine kinases (RTKs). The Eph receptors and their ephrin ligands control a diverse array of cell-cell interactions in the nervous and vascular systems. On ephrin binding, the Eph kinase domain is activated, initiating 'forward' signaling in the receptor-expressing cells. Simultaneously, signals are also induced in the ligand-expressing cells a phenomenon referred to as 'reverse' signalling. The extracellular Eph receptor region contains a conserved 180- amino-acid N-terminal ligand-binding domain (LBD) which is both necessary and sufficient for bindings of the receptors to their ephrin ligands. An adjacent cysteine-rich region might be involved in receptor-receptor oligomerization often observed on ligand binding, whereas the next two fibronectin type III repeats have yet to be assigned a clear biological function. The cytoplasmic Eph receptor region contains a kinase domain, a sterile alpha motif (SAM) domain, and a PDZ-binding motif. The ligand-binding domain (LBD) of Eph receptors is unique to this family of RTKs ans shares no significant amino-acid-sequence homology with other known proteins [PUBMED:9853759, PUBMED:11780069, PUBMED:19525919].

The Eph LBD domain forms a compact globular structure which folds into a jellyroll beta-sandwich composed of 11 antiparallel beta-strands. It has two antiparallel beta-sheets, with the usual left-handed twist, packed against each other to form a compact beta-sandwich, and a short 3(10) helix [PUBMED:9853759, PUBMED:11780069, PUBMED:19525919].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Biological process ephrin receptor signaling pathway (GO:0048013)

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 GBD (CL0202), which has the following description:

This large superfamily contains beta sandwich domains with a jelly roll topology. Many of these families are involved in carbohydrate recognition. Despite sharing little sequence similarity they do share a weak sequence motif, with a conserved bulge in the C-terminal beta sheet. The probable role of this bulge is in bending of the beta sheet that contains the bulge. This enables the curvature of the sheet forming the sugar binding site [1].

The clan contains the following 32 members:

Allantoicase ANAPC10 Bac_rhamnosid_N BetaGal_dom4_5 CBM-like CBM27 CBM60 CBM_11 CBM_15 CBM_17_28 CBM_35 CBM_4_9 CBM_6 CIA30 DUF5000 DUF642 Endotoxin_C Ephrin_lbd F5_F8_type_C FBA Glyco_hydro_2_N Laminin_N Lyase_N Muskelin_N NPCBM P_proprotein PA-IL PepX_C PITH PPC Sad1_UNC XRCC1_N

Alignments

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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics 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
(68)		 Full
(1269)		 Representative proteomes UniProt
(1875)		 NCBI
(5636)		 Meta
(0)
RP15
(159)		 RP35
(348)		 RP55
(740)		 RP75
(1006)
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, — not available.

Format an alignment

  Seed
(68)		 Full
(1269)		 Representative proteomes UniProt
(1875)		 NCBI
(5636)		 Meta
(0)
RP15
(159)		 RP35
(348)		 RP55
(740)		 RP75
(1006)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(68)		 Full
(1269)		 Representative proteomes UniProt
(1875)		 NCBI
(5636)		 Meta
(0)
RP15
(159)		 RP35
(348)		 RP55
(740)		 RP75
(1006)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download    
Gzipped Download   Download   Download   Download   Download   Download   Download   Download    

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.

Note: You can also download the data file for the tree.

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: [1]
Previous IDs: EPH_lbd;
Type: Domain
Author: Bateman A
Number in seed: 68
Number in full: 1269
Average length of the domain: 167.40 aa
Average identity of full alignment: 52 %
Average coverage of the sequence by the domain: 19.12 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 19.8 19.8
Trusted cut-off 20.0 19.9
Noise cut-off 19.2 19.6
Model length: 178
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

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Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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The tree shows the occurrence of this domain across different species. More...

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Interactions

There are 3 interactions for this family. More...

Ephrin_lbd Ephrin Ephrin

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 Ephrin_lbd domain has been found. There are 79 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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