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{{Infobox protein family|Symbol=RH Domain|Name=Rubicon Homology Domain|image=Crystal structure of Human Rubicon protein bound to Rab7-GTP.png|caption=RH domain of human Rubicon (red) bound to Rab7-GTP (grey) ({{PDB|6WCW}})|InterPro=|Pfam=PF13901|Pfam_clan=CL0229|SMART=SM01175|PROSITE=|MEROPS=|SCOP=6WCW|CATH=|TCDB=|OPM family=|OPM protein=|CAZy=|CDD=|Membranome superfamily=|Membranome family=|class=<!-- to save space: mw-collapsible mw-collapsed -->}}
{{Infobox protein family|Symbol=RH Domain|Name=Rubicon Homology Domain|image=Crystal structure of Human Rubicon protein bound to Rab7-GTP.png|caption=RH domain of human Rubicon (red) bound to Rab7-GTP (grey) ({{PDB|6WCW}})|InterPro=|Pfam=PF13901|Pfam_clan=CL0229|SMART=SM01175|PROSITE=|MEROPS=|SCOP=6WCW|CATH=|TCDB=|OPM family=|OPM protein=|CAZy=|CDD=|Membranome superfamily=|Membranome family=|class=<!-- to save space: mw-collapsible mw-collapsed -->}}


The Rubicon homology domain (RH domain) is an evolutionarily conserved [[protein domain]] of approximately 250 [[Amino acid|amino acids]] that mediates protein–protein interaction.<ref>{{Cite web |title=Pfam: Family: zf-RING_9 (PF13901) |url=http://pfam.xfam.org/family/PF13901 |access-date=2022-05-31 |website=pfam.xfam.org}}</ref> RH domains are present in several human proteins involved in regulation of [[autophagy]] and [[Endosome|endosomal trafficking]].<ref name=":0" /> While not all RH domains have been characterized, those of human Rubicon and [[PLEKHM1]] mediate interaction with the [[RAB7A|small GTPase Rab7]], which is found on late endosomes and autophagosomes.<ref name=":0">{{Cite journal |last=Bhargava |first=Hersh K. |last2=Tabata |first2=Keisuke |last3=Byck |first3=Jordan M. |last4=Hamasaki |first4=Maho |last5=Farrell |first5=Daniel P. |last6=Anishchenko |first6=Ivan |last7=DiMaio |first7=Frank |last8=Im |first8=Young Jun |last9=Yoshimori |first9=Tamotsu |last10=Hurley |first10=James H. |date=2020-07-21 |title=Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex |url=https://pubmed.ncbi.nlm.nih.gov/32632011/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=117 |issue=29 |pages=17003–17010 |doi=10.1073/pnas.2008030117 |issn=1091-6490 |pmc=7382272 |pmid=32632011}}</ref><ref name=":1">{{Cite journal |last=Tabata |first=Keisuke |last2=Matsunaga |first2=Kohichi |last3=Sakane |first3=Ayuko |last4=Sasaki |first4=Takuya |last5=Noda |first5=Takeshi |last6=Yoshimori |first6=Tamotsu |date=December 2010 |title=Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain |url=https://pubmed.ncbi.nlm.nih.gov/20943950/ |journal=Molecular Biology of the Cell |volume=21 |issue=23 |pages=4162–4172 |doi=10.1091/mbc.E10-06-0495 |issn=1939-4586 |pmc=2993745 |pmid=20943950}}</ref>
The '''Rubicon homology domain''' (RH domain) is an evolutionarily conserved [[protein domain]] of approximately 250 [[Amino acid|amino acids]] that mediates protein–protein interaction.<ref>{{Cite web |title=Pfam: Family: zf-RING_9 (PF13901) |url=http://pfam.xfam.org/family/PF13901 |access-date=2022-05-31 |website=pfam.xfam.org}}</ref> RH domains are present in several human proteins involved in regulation of [[autophagy]] and [[Endosome|endosomal trafficking]].<ref name=":0" /> While not all RH domains have been characterized, those of human Rubicon and [[PLEKHM1]] mediate interaction with the [[RAB7A|small GTPase Rab7]], which is found on late endosomes and autophagosomes.<ref name=":0">{{Cite journal |last=Bhargava |first=Hersh K. |last2=Tabata |first2=Keisuke |last3=Byck |first3=Jordan M. |last4=Hamasaki |first4=Maho |last5=Farrell |first5=Daniel P. |last6=Anishchenko |first6=Ivan |last7=DiMaio |first7=Frank |last8=Im |first8=Young Jun |last9=Yoshimori |first9=Tamotsu |last10=Hurley |first10=James H. |date=2020-07-21 |title=Structural basis for autophagy inhibition by the human Rubicon-Rab7 complex |url=https://pubmed.ncbi.nlm.nih.gov/32632011/ |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=117 |issue=29 |pages=17003–17010 |doi=10.1073/pnas.2008030117 |issn=1091-6490 |pmc=7382272 |pmid=32632011}}</ref><ref name=":1">{{Cite journal |last=Tabata |first=Keisuke |last2=Matsunaga |first2=Kohichi |last3=Sakane |first3=Ayuko |last4=Sasaki |first4=Takuya |last5=Noda |first5=Takeshi |last6=Yoshimori |first6=Tamotsu |date=December 2010 |title=Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain |url=https://pubmed.ncbi.nlm.nih.gov/20943950/ |journal=Molecular Biology of the Cell |volume=21 |issue=23 |pages=4162–4172 |doi=10.1091/mbc.E10-06-0495 |issn=1939-4586 |pmc=2993745 |pmid=20943950}}</ref>


RH domains contain 16 conserved cysteine and histidine residues that bind zinc atoms and form at least 4 [[Zinc finger|zinc finger motifs]].<ref name=":0" /><ref name=":1" /> Amino acid residues toward the C-terminus of the RH domain of Rubicon have been shown to be essential for interaction with Rab7.<ref name=":0" />
RH domains contain 16 conserved cysteine and histidine residues that bind zinc atoms and form at least 4 [[Zinc finger|zinc finger motifs]].<ref name=":0" /><ref name=":1" /> Amino acid residues toward the C-terminus of the RH domain of Rubicon have been shown to be essential for interaction with Rab7.<ref name=":0" />

Revision as of 08:16, 6 June 2022

Rubicon Homology Domain
RH domain of human Rubicon (red) bound to Rab7-GTP (grey) (PDB: 6WCW​)
Identifiers
SymbolRH Domain
PfamPF13901
Pfam clanCL0229
SMARTSM01175
SCOP26WCW / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

The Rubicon homology domain (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

  1. ^ "Pfam: Family: zf-RING_9 (PF13901)". pfam.xfam.org. Retrieved 2022-05-31.
  2. ^ a b c d e f g h Bhargava, Hersh K.; Tabata, Keisuke; Byck, Jordan M.; Hamasaki, Maho; Farrell, Daniel P.; Anishchenko, Ivan; DiMaio, Frank; Im, Young Jun; Yoshimori, Tamotsu; Hurley, James H. (2020-07-21). "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. doi:10.1073/pnas.2008030117. ISSN 1091-6490. PMC 7382272. PMID 32632011.
  3. ^ a b Tabata, Keisuke; Matsunaga, Kohichi; Sakane, Ayuko; Sasaki, Takuya; Noda, Takeshi; Yoshimori, Tamotsu (December 2010). "Rubicon and PLEKHM1 negatively regulate the endocytic/autophagic pathway via a novel Rab7-binding domain". Molecular Biology of the Cell. 21 (23): 4162–4172. doi:10.1091/mbc.E10-06-0495. ISSN 1939-4586. PMC 2993745. PMID 20943950.
  4. ^ "RUBCN - Run domain Beclin-1-interacting and cysteine-rich domain-containing protein - Homo sapiens (Human) - RUBCN gene & protein". www.uniprot.org. Retrieved 2022-05-31.
  5. ^ "Def8 - Differentially expressed in FDCP 8 - Mus musculus (Mouse) - Def8 gene & protein". www.uniprot.org. Retrieved 2022-05-31.
  6. ^ "PLEKHM3 - Pleckstrin homology domain-containing family M member 3 - Homo sapiens (Human) - PLEKHM3 gene & protein". www.uniprot.org. Retrieved 2022-05-31.