Summary: Vacuolar protein sorting protein 36 Vps36
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Vacuolar protein sorting protein 36 Vps36 Provide feedback
Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes .
Teo H, Gill DJ, Sun J, Perisic O, Veprintsev DB, Vallis Y, Emr SD, Williams RL; , Cell. 2006;125:99-111.: ESCRT-I core and ESCRT-II GLUE domain structures reveal role for GLUE in linking to ESCRT-I and membranes. PUBMED:16615893 EPMC:16615893
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This tab holds annotation information from the InterPro database.
InterPro entry IPR021648
Vps36 is a subunit of ESCRT-II, a protein involved in driving protein sorting from endosomes to lysosomes. The GLUE domain of Vps36 allows for a tight interaction to occur between the protein and Vps28, a subunit of ESCRT-I. This interaction is critical for ubiquitinated cargo progression from early to late endosomes [PUBMED:16615893].
The multivesicular body (MVB) protein-sorting pathway targets transmembrane proteins either for degradation or for function in the vacuole/lysosomes. The signal for entry into this pathway is monoubiquitination of protein cargo, which results in incorporation of cargo into luminal vesicles at late endosomes. Another crucial player is phosphatidylinositol 3-phosphate (PtdINS(3)P), which is enriched on early endosomes and on the luminal vesicles of MVBs. The ESCRT complexes are critical for MVB budding and sorting of monoubiquitinated cargo into the luminal vesicles. Various Ub-binding domains (UBDs), such as UIM, UEV and NZF are found in such machineries. The Vps 36 subunit of the ESCRT-II trafficking complex binds both phosphoinositides and ubiquitin. All members of the Vps36 family contain a divergent GRAM/PH-like domain and yeast and some other fungi have one or two NZF domains inserted in the GRAM/PH-like domain.
The N-terminal region of Vps36 (EAP45) has been named the GLUE (GRAM-like ubiquitin-binding in EAP45) domain. The GLUE domain acts as a central cog driving the endosomal ESCRT machinery, through simultaneous interactions with PtdIns3P-containing membranes, ubiquitin, and ESCRT-I. Like other known ubiquitin-binding domains, the GLUE domain interacts with the hydrophobic surface patch of ubiquitin. The GLUE domain is the first ubiquitin-binding domain shown to bind phosphoinositides, and the ability of the same domain to bind both ubiquitin and a phosphoinositide opens interesting possibilities for coordination of membrane interactions and cargo recognition [PUBMED:15755741, PUBMED:16615893, PUBMED:17057714, PUBMED:16615903, PUBMED:17034365].
The GLUE domain has a split PH-domain fold with two curved beta sheets and one long alpha helix. The two sheets (beta1-beta4 and beta5- beta7) form a beta barrel-like structure, the C-terminal alpha helix is wedged between the two beta sheets, covering a hydrophobic core. The Vps36 GLUE domain binds PtdIns3P via a positively charged lipid binding pocket, delineated by the variable loops beta1/beta2, beta5/beta6 and beta7/alpha1, in contrast to the vast majority of characterised PH domains, which use a different lipid binding pocket [PUBMED:16615893, PUBMED:17057714].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Molecular function||ubiquitin binding (GO:0043130)|
|phosphatidylinositol-3-phosphate binding (GO:0032266)|
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Members of this clan share a PH-like fold. Many families in this clan bind to short peptide motifs in proteins and are involved in signalling.
The clan contains the following 38 members:bPH_1 bPH_2 bPH_3 bPH_4 bPH_5 bPH_6 DCP1 DUF1448 DUF1681 FERM_C GRAM ICAP-1_inte_bdg IQ_SEC7_PH IRS Mcp5_PH PH PH_10 PH_11 PH_12 PH_13 PH_2 PH_3 PH_4 PH_5 PH_6 PH_8 PH_9 PH_BEACH PH_TFIIH PID PID_2 PTB Ran_BP1 Rtt106 SSrecog Voldacs Vps36_ESCRT-II WH1
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Curation and family details
|Number in seed:||21|
|Number in full:||481|
|Average length of the domain:||86.70 aa|
|Average identity of full alignment:||33 %|
|Average coverage of the sequence by the domain:||17.12 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||4|
|Download:||download the raw HMM for this family|
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There are 3 interactions for this family. More...
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 Vps36_ESCRT-II domain has been found. There are 4 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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