Biology:Rubicon homology domain
| Rubicon homology domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
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| Identifiers | |||||||||
| Symbol | RH Domain | ||||||||
| Pfam | PF13901 | ||||||||
| Pfam clan | CL0229 | ||||||||
| InterPro | IPR025258 | ||||||||
| SMART | SM01175 | ||||||||
| SCOP2 | 6WCW / SCOPe / SUPFAM | ||||||||
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The Rubicon homology domain (also known as RH domain) is an evolutionarily conserved protein domain of approximately 250 amino acids that mediates protein–protein interaction.[1] RH domains are present in several human proteins involved in regulation of autophagy and endosomal trafficking.[2] While not all RH domains have been characterized, those of human Rubicon and PLEKHM1 mediate interaction with the small GTPase Rab7, which is found on late endosomes and autophagosomes.[2][3]
RH domains contain 16 conserved cysteine and histidine residues that bind zinc atoms and form at least 4 zinc finger motifs.[2][3] Amino acid residues toward the C-terminus of the RH domain of Rubicon have been shown to be essential for interaction with Rab7.[2]
Structure
The 3D atomic structure of the Rubicon RH domain in complex with Rab7 has been determined by X-ray crystallography.[2] The structure of the RH domain has an "L" shape, with the base of the "L" making contact with the switch regions of Rab7.[2] The structure is predominantly alpha helical, with short beta strand regions present in the vicinity of zinc finger motifs.[2] The N-terminal region of the Rubicon RH domain resembles a FYVE domain, however the basic residues required for canonical FYVE domain binding of PI3P are not present.[2]
Proteins containing an RH domain
RH domains are found in a number of proteins, including (in humans):
- Rubicon, the defining member of the RH domain-containing family of proteins and a negative regulator of autophagy[4]
- PLEKHM1, a protein implicated in osteopetrosis
- Pacer, a positive regulator of autophagy
- DEF8, a regulator of lysosome peripheral distribution[5]
- PLEKHM3, involved in skeletal muscle differentiation[6]
References
- ↑ "Pfam: Family: zf-RING_9 (PF13901)". http://pfam.xfam.org/family/PF13901.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 "Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex". Proceedings of the National Academy of Sciences of the United States of America 117 (29): 17003–17010. July 2020. doi:10.1073/pnas.2008030117. PMID 32632011.
- ↑ 3.0 3.1 "Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain". Molecular Biology of the Cell 21 (23): 4162–4172. December 2010. doi:10.1091/mbc.E10-06-0495. PMID 20943950.
- ↑ "RUBCN - Run domain Beclin-1-interacting and cysteine-rich domain-containing protein - Homo sapiens (Human) - RUBCN gene & protein" (in en). https://www.uniprot.org/uniprot/Q92622.
- ↑ "Def8 - Differentially expressed in FDCP 8 - Mus musculus (Mouse) - Def8 gene & protein" (in en). https://www.uniprot.org/uniprot/Q99J78.
- ↑ "PLEKHM3 - Pleckstrin homology domain-containing family M member 3 - Homo sapiens (Human) - PLEKHM3 gene & protein" (in en). https://www.uniprot.org/uniprot/Q6ZWE6.
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