150:, which is critical for normal embryonic development. Notch Signaling is dependent on the proteolytic cleavage of the Notch receptor intracellular domain. Epsin's role in Notch Signaling is due to Notch's reliance on ligand endocytosis to release the Notch intracellular domain. This occurs through ubiquitination of the D114 notch ligand which provides a docking location of the epsin UIM domain. Current research suggest that this directing of cargo material aids in the recycling in Notch signaling as well. A study on knock out epsins 1 and 2 in mice showed
250:), has been studied for a possible relationship to schizophrenia in four independent studies, though no conclusive evidence has been found in the analysis of SNPs believed to be associated with schizophrenia (rs1186922, rs254664, rs10046055). A genetic abnormality in CLINT1 is assumed to change the way internalisation of neurotransmitter receptors occurs in the brains of people with
43:
100:
225:
genes encoding epsin family members, Epsin1, Epsin2 and Epsin3 that differ in molecular weight and C - terminal domains. Epsin1 has highest expression in cotyledons and flowers while Epsin2 and Epsin3 expression is currently unknown. Little is known about the role plant Epsin plays in clathrin coated
234:
Epsin is thought to have role in the angiogenesis of tumors; thus, epsin has the potential to be a target for anti-cancer therapies. Several cancers including prostate, breast, lung and skin display an upregulation in epsin. Research indicates that the overexpression could affect the regulation of
95:
In general, most vertebrates contain at least two epsin paralogs. The two paralogs, epsin-1 and epsin-2 are members that contribute to the clathrin coated endocytotic machinery and are localized at the plasma membrane. In mammals, the two main classes of Epsins are expressed throughout tissues but
712:
Escamilla M, Lee BD, Ontiveros A, Raventos H, Nicolini H, Mendoza R, Jerez A, Munoz R, Medina R, Figueroa A, Walss-Bass C, Armas R, Contreras S, Ramirez ME, Dassori A (Dec 2008). "The epsin 4 gene is associated with psychotic disorders in families of Latin
American origin".
508:
Chang, Baojun; Tessneer, Kandice L.; McManus, John; Liu, Xiaolei; Hahn, Scott; Pasula, Satish; Wu, Hao; Song, Hoogeun; Chen, Yiyuan; Cai, Xiaofeng; Dong, Yunzhou; Brophy, Megan L.; Rahman, Ruby; Ma, Jian-Xing; Xia, Lijun; Chen, Hong (16 March 2015).
71:
and an eighth helix that is not aligned with the seven helices that make up a superhelical fold. The role of the ENTH domain is to bind membrane lipids which is currently thought to aid in the invagination of the plasma membrane to form
138:
Epsins may be the major membrane curvature-driving proteins in many clathrin-coated vesicle budding events. In addition to its primary role as an endocytic adapter, there is evidence the epsins play a role in regulating
431:
Holstein, Susanne E. H.; Oliviusson, Peter (20 October 2005). "Sequence analysis of
Arabidopsis thaliana E/ANTH-domain-containing proteins: membrane tethers of the clathrin-dependent vesicle budding machinery".
135:. As such, epsins are able to bind to membranes with specific cargo and connect them with the endocytosis machinery, so one may understand epsins as something like Swiss army knives for endocytosis.
558:
Pimm J, McQuillin A, Thirumalai S, Lawrence J, Quested D, Bass N, Lamb G, Moorey H, Datta SR, Kalsi G, Badacsonyi A, Kelly K, Morgan J, Punukollu B, Curtis D, Gurling H (May 2005).
781:
Chen H, Fre S, Slepnev VI, Capua MR, Takei K, Butler MH, Di Fiore PP, De
Camilli P (Aug 1998). "Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis".
839:
Cai X, Pasula S, Chang B, Hahn S, McManus J, Chen H (April 2013). "Upregulation of epsin in breast cancer and critical role of epsin in promoting cancer growth and metastasis".
677:
Gurling H, Pimm J, McQuillin A (Jan 2007). "Replication of genetic association studies between markers at the Epsin 4 gene locus and schizophrenia in two Han
Chinese samples".
119:, meaning that it binds a lipid of biological membranes. It has also been postulated that this is a site for cargo-binding. In the middle of the epsin sequence are two UIMs (
83:
Following the ENTH domain there is not as much conservation in structure across species. However, in higher eukaryotes there are several conserved motifs such as the
607:
Tang RQ, Zhao XZ, Shi YY, Tang W, Gu NF, Feng GY, Xing YL, Zhu SM, Sang H, Liang PJ, He L (Apr 2006). "Family-based association study of Epsin 4 and
Schizophrenia".
461:"Arabidopsis EPSIN1 Plays an Important Role in Vacuolar Trafficking of Soluble Cargo Proteins in Plant Cells via Interactions with Clathrin, AP-1, VTI11, and VSR1"
67:. ENTH stands for Epsin N-Terminal Homolog. The ENTH domain is approximately 150 amino acids long and is highly conserved across species. It is composed of seven
560:"The Epsin 4 gene on chromosome 5q, which encodes the clathrin-associated protein enthoprotin, is involved in the genetic susceptibility to schizophrenia"
642:
Liou YJ, Lai IC, Wang YC, Bai YM, Lin CC, Lin CY, Chen TT, Chen JY (Jun 2006). "Genetic analysis of the human ENTH (Epsin 4) gene and schizophrenia".
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tumor angiogenesis through defects in the notch pathway. There is also evidence that Epsin could lead to colon cancer through impaired
87:-binding motifs which bind clathrin heavy chain, these motifs flank a cluster of up to eight DP repeats which bind to AP2.
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has the highest expression in the brain, whereas the third Epsin has higher expression in the epidermis and the stomach.
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Tessneer, KL; Cai, X; Pasula, S; Dong, Y; Liu, X; Chang, B; McManus, J; Hahn, S; Yu, L; Chen, H (1 July 2013).
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147:
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Horvath CA, Vanden Broeck D, Boulet GA, Bogers J, De Wolf MJ (2007). "Epsin: inducing membrane curvature".
195:
236:
511:"Epsin is required for Dishevelled stability and Wnt signalling activation in colon cancer development"
221:
810:
Chen X, Irani NG, Firml, J (2011). "Clathrin - mediated endocytosis: the gateway into plant cells".
107:
Epsins have many different domains to interact with various proteins related to endocytosis. At its
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activity which provides an alternative mechanism for epsin's role in cell polarity and migration.
76:-coated vesicles. Additionally, located toward the C-terminus of the ENTH domain are two to three
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at day 10. Further investigation showed vascular defects in the embryo proper, placenta and
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335:"Epsin Family of Endocytic Adaptor Proteins as Oncogenic Regulators of Cancer Progression"
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Epsin 4, which encodes the protein enthoprotin, now known as clathrin interactor 1 (
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Epsin contains various protein domains that aid in function. Starting at the
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281:"The epsin protein family: coordinators of endocytosis and signaling"
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and was first identified due to its role in eye patterning in flies.
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384:"Notch ligand endocytosis: mechanistic basis of signaling activity"
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interacting motifs which aids in ubiquitin dependent recruitment.
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There are four human genes encoding epsin family members:
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Musse, AA; Meloty-Kapella, L; Weinmaster, G (June 2012).
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Sen A, Madhivanan K, Mukherjee D, Aguilar RC (Apr 2012).
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which are characteristic of a loss in notch signaling.
243:, making epsin a possible target for pharmaceuticals.
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326:
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is EPN-1. EPN-1 conserves the UIM, ENTH domain, and
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In addition, Epsin is thought to play a role in the
27:. Epsins contribute to membrane deformations like
127:contains multiple binding sites, for example for
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239:by reducing the stability of the Wnt effector
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388:Seminars in Cell & Developmental Biology
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46:Crystal Structure of the ENTH Domain of
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117:phosphatidylinositol (4,5)-bisphosphate
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564:American Journal of Human Genetics
339:Journal of Cancer Research Updates
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103:Clathrin Coated Vesicle Formation
19:are a family of highly conserved
812:Current Opinion in Plant Biology
23:that are important in creating
868:Endocytosis.org entry on epsin
351:10.6000/1929-2279.2013.02.03.2
1:
853:10.1158/1538-7445.AM2013-5128
459:Song, J. (1 September 2006).
888:Peripheral membrane proteins
766:10.1016/j.biocel.2006.12.004
727:10.1016/j.schres.2008.09.005
691:10.1016/j.schres.2006.08.024
656:10.1016/j.schres.2006.02.021
400:10.1016/j.semcdb.2012.01.011
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123:-interacting motifs). The
824:10.1016/j.pbi.2011.08.006
446:10.1007/s00709-005-0105-7
209:Drosophila melanogaster
206:The epsin homologue of
193:The epsin homologue of
148:Notch Signaling Pathway
715:Schizophrenia Research
679:Schizophrenia Research
644:Schizophrenia Research
477:10.1105/tpc.105.039123
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621:10.1038/sj.mp.4001780
515:Nature Communications
465:The Plant Cell Online
297:10.1515/bmc-2011-0060
285:Biomolecular Concepts
230:Clinical significance
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609:Molecular Psychiatry
222:Arabidopsis thaliana
226:vesicle formation.
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25:membrane curvature
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133:AP2 adaptors
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31:, and block
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434:Protoplasma
241:dishevelled
115:that binds
113:ENTH domain
65:ENTH domain
29:endocytosis
258:References
196:C. elegans
125:C-terminus
109:N-terminus
61:N-terminus
121:ubiquitin
78:ubiquitin
69:α-helices
55:Structure
882:Category
847:: 5128.
832:21945181
774:17276129
735:18929466
699:17070672
664:16616458
629:16402136
594:15793701
545:25871009
521:: 6380.
495:16905657
418:22306180
369:24501612
315:22942912
201:clathrin
156:yolk sac
129:clathrin
91:Function
85:clathrin
74:clathrin
803:9723620
585:1199380
536:4397653
486:1560928
409:3507467
360:3911794
306:3431554
63:is the
37:mitosis
33:vesicle
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248:CLINT1
184:, and
141:GTPase
111:is an
50:Epsin1
17:Epsins
828:PMID
799:PMID
770:PMID
731:PMID
695:PMID
660:PMID
625:PMID
590:PMID
541:PMID
491:PMID
414:PMID
365:PMID
311:PMID
187:EPN4
181:EPN3
175:EPN2
169:EPN1
131:and
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820:doi
791:doi
787:394
762:doi
723:doi
719:106
687:doi
652:doi
617:doi
580:PMC
572:doi
531:PMC
523:doi
481:PMC
473:doi
442:doi
438:226
404:PMC
396:doi
355:PMC
347:doi
301:PMC
293:doi
212:is
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