ESCRT-II, EAP45,(Kr.13q14.3), VPS36, C13orf9, CGI-148 , GLUE-domeeni

ESCRT-II

(EAP45 geenin virallinen nimi on VPS36) 

Also known as EAP45; C13orf9; CGI-145

Summary This gene encodes a protein that is a subunit of the endosomal sorting complex required for transport II (ESCRT-II). This protein complex functions in sorting of ubiquitinated membrane proteins during endocytosis. A similar protein complex in rat is associated with RNA polymerase elongation factor II. [provided by RefSeq, Aug 2013]

Expression Ubiquitous expression in skin (RPKM 25.0), thyroid (RPKM 15.1) and 25 other tissues See more

Preferred Names

vacuolar protein-sorting-associated protein 36

Names

ELL-associated protein of 45 kDa

ESCRT-II complex subunit VPS36

Conserved Domains (2) summary

cd13226
Location:1 → 119

PH-GRAM-like_Eap45; Pleckstrin homology-like domain or GLUE (GRAM-like ubiquitin-binding in Eap45) domain of Eap45

pfam04157
Location:146 → 360

EAP30; EAP30/Vps36 family

Peptide sequence

https://www.ncbi.nlm.nih.gov/protein/NP_001269098.1

Related articles in PubMed

1. Structural basis for ubiquitin recognition by the human ESCRT-II EAP45 GLUE domain. Alam SL, et al. Nat Struct Mol Biol, 2006 Nov. PMID 17057716 Abstract The ESCRT-I and ESCRT-II complexes help sort ubiquitinated proteins into vesicles that accumulate within multivesicular bodies (MVBs). Crystallographic and biochemical analyses reveal that the GLUE domain of the human ESCRT-II EAP45 (also called VPS36) subunit is a split pleckstrin-homology domain that binds ubiquitin along one edge of the beta-sandwich. The structure suggests how human ESCRT-II can couple recognition of ubiquitinated cargoes and endosomal phospholipids during MVB protein sorting
2. RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells. Worst TS, et al. Int J Oncol, 2017 Mar. PMID 28197629
3. Integrated structural model and membrane targeting mechanism of the human ESCRT-II complex. Im YJ, et al. Dev Cell, 2008 Jun. PMID 18539118, Free PMC Article
4. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. Gill DJ, et al. EMBO J, 2007 Jan 24. PMID 17215868, Free PMC Article
5. Evidence that the endosomal sorting complex required for transport-II (ESCRT-II) is required for efficient human immunodeficiency virus-1 (HIV-1) production. Meng B, et al. Retrovirology, 2015 Aug 14. PMID 26268989, Free PMC Article
   

See all (37) citations in PubMed
See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. RAB27A, RAB27B and VPS36 are frequently underexpressed in advanced prostate cancer and are inversely correlated with prostate cancer outcome. There seems to be a close relationship in the expression of RAB27A, RAB27B and VPS36, with RAB27A and RAB27B being dependent on VPS36.
2. mammalian ESCRTII is made up of hVps25p, hVps22p, and hVps36p and may be redundant, cargo-specific, or not required for protein sorting at the multivesicular body
3. Crystallographic and biochemical analyses reveal that the GLUE domain of the human ESCRT-II EAP45 (also called VPS36) subunit is a split pleckstrin-homology domain that binds ubiquitin along one edge of the beta-sandwich.
   

Eap45 in Mammalian ESCRT-II Binds Ubiquitin via a Phosphoinositide-interacting GLUE Domain^*,♦

• Thomas Slagsvold‡, Rein Aasland§, ^‡Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway, the ^§Department of Molecular Biology, University of Bergen, HIB, N-5020 Bergen, Norway, and the ^¶Structural Biology Research Center, Photon Factory, IMSS, KEK, Tsukuba, Ibaraki 305-0801, Japan Abstract Ubiquitination serves as a key sorting signal in the lysosomal degradation of endocytosed receptors through the ability of ubiquitinated membrane proteins to be recognized and sorted by ubiquitin-binding proteins along the endocytic route. The ESCRT-II complex in yeast contains one such protein, Vps36, which harbors a ubiquitin-binding NZF domain* and is required for vacuolar sorting of ubiquitinated membrane proteins.

https://www.researchgate.net/profile/Mark_Van_der_Giezen/publication/49784933/figure/fig1/AS:601633838878722@1520452093285/Model-of-ESCRT-complex-assembly-The-diagram-is-based-loosely-upon-one-previously.png    *

Surprisingly, the presumptive mammalian ortholog Eap45 lacks the ubiquitin-binding module of Vps36, and it is thus not clear whether mammalian ESCRT-II functions to bind ubiquitinated cargo. In this paper, we provide evidence that Eap45 contains a novel ubiquitin-binding domain, GLUE (GRAM-like ubiquitin-binding in Eap45), which binds ubiquitin with similar affinity and specificity as other ubiquitin-binding domains.**

The GLUE domain shares similarities in its primary and predicted secondary structures to phosphoinositide-binding GRAM and PH domains. 

** https://www.cell.com/cms/attachment/2119039383/2088388025/gr2.jpg 

Accordingly, we find that Eap45 binds to a subset of 3-phosphoinositides, suggesting that ubiquitin recognition could be coordinated with phosphoinositide binding.

Furthermore, we show that Eap45 colocalizes with ubiquitinated proteins on late endosomes. These results are consistent with a role for Eap45 in endosomal sorting of ubiquitinated cargo. Received February 9, 2005. Revision received March 7, 2005. The American Society for Biochemistry and Molecular Biology, Inc.

Muistiin 17.5. 2018