Entry - *618001 - RAB11 EFFECTOR CONTAINING LIS1 HOMOLOGY DOMAIN, COILED-COIL DOMAINS, AND HEAT REPEATS; RELCH - OMIM

 
 
* 618001

RAB11 EFFECTOR CONTAINING LIS1 HOMOLOGY DOMAIN, COILED-COIL DOMAINS, AND HEAT REPEATS; RELCH


Alternative titles; symbols

KIAA1468


HGNC Approved Gene Symbol: RELCH

Cytogenetic location: 18q21.33     Genomic coordinates (GRCh38): 18:62,187,255-62,310,249 (from NCBI)


TEXT

▼ Description

RELCH regulates intracellular cholesterol distribution through interactions with RAB11 (see RAB11A, 605570) and oxysterol-binding protein (OSBP; 167040) (Sobajima et al., 2018).


▼ Cloning and Expression

By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (2000) cloned RELCH, which they designated KIAA1468. RT-PCR ELISA detected RELCH expression in all adult and fetal human tissues examined, with highest expression in adult brain. Expression was high in all specific adult brain regions examined.

Sobajima et al. (2018) cloned mouse Relch. The deduced 1,216-amino acid protein contains a LIS1 (PAFAH1B1; 601545) homology (LISH) domain, 2 coiled-coil domains, and 2 HEAT repeat motifs. Mouse Relch had an apparent molecular mass of 130 kD.


▼ Gene Function

Using protein pull-down assays, Sobajima et al. (2018) showed that mouse Relch interacted directly with mouse Rab11. Yeast 2-hybrid assays showed that Relch bound Rab11a, Rab11b (604198), and, weakly, Rab25 (612942), but not other Rab proteins. Mutation analysis revealed that the region containing the first HEAT repeat motif of Relch was necessary for binding to Rab11. Immunofluorescence analysis of transfected HeLa cells showed colocalization of Relch with Rab11a in recycling endosomes. Immunoprecipitation and mass spectrometry analyses revealed that mouse Relch bound directly to mouse and human OSBP. Binding required the region containing the second HEAT repeat of Relch and the C-terminal ligand-binding region of OSBP. Knockdown and reconstitution experiments showed that RELCH formed a ternary complex with RAB11 and OSBP, tethering OSBP-bound and RAB11-bound membranes and promoting OSBP-mediated nonvesicular cholesterol transport between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes.


▼ Mapping

Gross (2018) mapped the RELCH gene to chromosome 18q21.33 based on an alignment of the RELCH sequence (GenBank BC011992) with the genomic sequence (GRCh38).

▼ REFERENCES

  1. Gross, M. B. Personal Communication. Baltimore, Md. 5/31/2018.

  2. Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 143-150, 2000. [PubMed: 10819331, related citations] [Full Text]

  3. Sobajima, T., Yoshimura, S., Maeda, T., Miyata, H., Miyoshi, E., Harada, A. The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution. J. Cell Biol. 217: 1777-1796, 2018. [PubMed: 29514919, related citations] [Full Text]


Contributors:
Matthew B. Gross - updated : 05/31/2018
Creation Date:
Bao Lige : 05/31/2018
Edit History:
mgross : 06/01/2018
mgross : 05/31/2018
mgross : 05/31/2018

* 618001

RAB11 EFFECTOR CONTAINING LIS1 HOMOLOGY DOMAIN, COILED-COIL DOMAINS, AND HEAT REPEATS; RELCH


Alternative titles; symbols

KIAA1468


HGNC Approved Gene Symbol: RELCH

Cytogenetic location: 18q21.33     Genomic coordinates (GRCh38): 18:62,187,255-62,310,249 (from NCBI)


TEXT

Description

RELCH regulates intracellular cholesterol distribution through interactions with RAB11 (see RAB11A, 605570) and oxysterol-binding protein (OSBP; 167040) (Sobajima et al., 2018).


Cloning and Expression

By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (2000) cloned RELCH, which they designated KIAA1468. RT-PCR ELISA detected RELCH expression in all adult and fetal human tissues examined, with highest expression in adult brain. Expression was high in all specific adult brain regions examined.

Sobajima et al. (2018) cloned mouse Relch. The deduced 1,216-amino acid protein contains a LIS1 (PAFAH1B1; 601545) homology (LISH) domain, 2 coiled-coil domains, and 2 HEAT repeat motifs. Mouse Relch had an apparent molecular mass of 130 kD.


Gene Function

Using protein pull-down assays, Sobajima et al. (2018) showed that mouse Relch interacted directly with mouse Rab11. Yeast 2-hybrid assays showed that Relch bound Rab11a, Rab11b (604198), and, weakly, Rab25 (612942), but not other Rab proteins. Mutation analysis revealed that the region containing the first HEAT repeat motif of Relch was necessary for binding to Rab11. Immunofluorescence analysis of transfected HeLa cells showed colocalization of Relch with Rab11a in recycling endosomes. Immunoprecipitation and mass spectrometry analyses revealed that mouse Relch bound directly to mouse and human OSBP. Binding required the region containing the second HEAT repeat of Relch and the C-terminal ligand-binding region of OSBP. Knockdown and reconstitution experiments showed that RELCH formed a ternary complex with RAB11 and OSBP, tethering OSBP-bound and RAB11-bound membranes and promoting OSBP-mediated nonvesicular cholesterol transport between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes.


Mapping

Gross (2018) mapped the RELCH gene to chromosome 18q21.33 based on an alignment of the RELCH sequence (GenBank BC011992) with the genomic sequence (GRCh38).

REFERENCES

  1. Gross, M. B. Personal Communication. Baltimore, Md. 5/31/2018.

  2. Nagase, T., Kikuno, R., Ishikawa, K., Hirosawa, M., Ohara, O. Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 7: 143-150, 2000. [PubMed: 10819331] [Full Text: https://doi.org/10.1093/dnares/7.2.143]

  3. Sobajima, T., Yoshimura, S., Maeda, T., Miyata, H., Miyoshi, E., Harada, A. The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution. J. Cell Biol. 217: 1777-1796, 2018. [PubMed: 29514919] [Full Text: https://doi.org/10.1083/jcb.201709123]


Contributors:
Matthew B. Gross - updated : 05/31/2018

Creation Date:
Bao Lige : 05/31/2018

Edit History:
mgross : 06/01/2018
mgross : 05/31/2018
mgross : 05/31/2018



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.
Printed: June 2, 2024