Description: choroideremia isoform a RefSeq Summary (NM_000390): This gene encodes component A of the RAB geranylgeranyl transferase holoenzyme. In the dimeric holoenzyme, this subunit binds unprenylated Rab GTPases and then presents them to the catalytic Rab GGTase subunit for the geranylgeranyl transfer reaction. Rab GTPases need to be geranylgeranyled on either one or two cysteine residues in their C-terminus to localize to the correct intracellular membrane. Mutations in this gene are a cause of choroideremia; also known as tapetochoroidal dystrophy (TCD). This X-linked disease is characterized by progressive dystrophy of the choroid, retinal pigment epithelium and retina. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]. Transcript (Including UTRs) Position: hg18 chrX:85,002,841-85,189,222 Size: 186,382 Total Exon Count: 15 Strand: - Coding Region Position: hg18 chrX:85,006,291-85,189,192 Size: 182,902 Coding Exon Count: 15
ID:RAE1_HUMAN DESCRIPTION: RecName: Full=Rab proteins geranylgeranyltransferase component A 1; AltName: Full=Choroideraemia protein; AltName: Full=Rab escort protein 1; Short=REP-1; AltName: Full=TCD protein; FUNCTION: Binds unprenylated Rab proteins, presents it to the catalytic Rab GGTase dimer, and remains bound to it after the geranylgeranyl transfer reaction. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane. Also a pre-formed complex consisting of CHM and the Rab GGTase dimer (RGGT or component B) can bind to and prenylate Rab proteins; this alternative pathway is proposed to be the predominant pathway for Rab protein geranylgeranylation. SUBUNIT: Monomer. Can associate with the Rab GGTase dimer (RGGT or component B) prior to Rab protein binding; the association is stabilized by geranylgeranyl pyrophosphate (GGpp). The CHM:RGGT:Rab complex is destabilized by GGpp. Interacts with RAB1B; the interaction is required for RAB1B prenylation. Interacts with RABGGTA. DISEASE: Defects in CHM are the cause of choroideremia (CHM) [MIM:303100]. An X-linked recessive disease characterized by a slowly progressive degeneration of the choroid, photoreceptors, and retinal pigment epithelium. Affected males develop night blindness in their teenage years followed by loss of peripheral vision and complete blindness at middle age. Carrier females are generally asymptomatic but funduscopic examination often shows patchy areas of chorioretinal atrophy. SIMILARITY: Belongs to the Rab GDI family. WEB RESOURCE: Name=Mutations of the REP1 gene; Note=Retina International's Scientific Newsletter; URL="http://www.retina-international.org/files/sci-news/repmut.htm"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CHM"; WEB RESOURCE: Name=Retinal and hearing impairment genetic mutation database choroideremia (Rab escort protein 1) (CHM); Note=Leiden Open Variation Database (LOVD); URL="http://grenada.lumc.nl/LOVD2/Usher_montpellier/home.php?select_db=CHM"; WEB RESOURCE: Name=NGRL, Manchester LOVD choroideremia (Rab escort protein 1) (CHM); Note=Leiden Open Variation Database (LOVD); URL="http://ngrl.manchester.ac.uk/LOVDv.2.0/home.php?select_db=CHM";
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Genetic Association Studies of Complex Diseases and Disorders
Genetic Association Database (archive): CHM CDC HuGE Published Literature: CHM Positive Disease Associations: pinealoma Related Studies:
pinealoma Hotta Y et al. 1997, A hemizygous A to CC base change of the CHM gene causing choroideremia associated with pinealoma., Graefes Arch Clin Exp Ophthalmol. 1997 Oct;235(10):653-5.
[PubMed 9349950]
The hemizygous mutation was detected in a patient and the heterozygous pattern in his mother, the carrier, suggesting that this mutation caused the disease.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P24386
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006612 protein targeting to membrane GO:0006886 intracellular protein transport GO:0007264 small GTPase mediated signal transduction GO:0007601 visual perception GO:0018344 protein geranylgeranylation GO:0042981 regulation of apoptotic process GO:0043547 positive regulation of GTPase activity GO:0043687 post-translational protein modification GO:0050790 regulation of catalytic activity GO:0050896 response to stimulus
AK095883 - Homo sapiens cDNA FLJ38564 fis, clone HCHON2004359. AK291160 - Homo sapiens cDNA FLJ78016 complete cds, highly similar to Homo sapiens choroideremia (Rab escort protein 1) (CHM), transcript variant, mRNA. X57637 - H.sapiens mRNA involved in tapetochoroidal dystrophy (TCD). AK299323 - Homo sapiens cDNA FLJ58404 complete cds, highly similar to Rab proteins geranylgeranyltransferase component A 1. M83773 - Human TCD protein mRNA, complete cds. X78121 - Homo sapiens choroideremia mRNA. BC172532 - Synthetic construct Homo sapiens clone IMAGE:100069226, MGC:199237 choroideremia (Rab escort protein 1) (CHM) mRNA, encodes complete protein. AK312443 - Homo sapiens cDNA, FLJ92793. BC156457 - Synthetic construct Homo sapiens clone IMAGE:100062979, MGC:190649 choroideremia (Rab escort protein 1) (CHM) mRNA, encodes complete protein. BC105969 - Homo sapiens choroideremia (Rab escort protein 1), mRNA (cDNA clone IMAGE:4186344), complete cds. BC065702 - Homo sapiens choroideremia (Rab escort protein 1), mRNA (cDNA clone IMAGE:6527430), complete cds. BC073987 - Homo sapiens choroideremia (Rab escort protein 1), mRNA (cDNA clone IMAGE:5735390), complete cds. AY255796 - Homo sapiens HSD-32 mRNA, complete cds. JD509468 - Sequence 490492 from Patent EP1572962. JD349908 - Sequence 330932 from Patent EP1572962. JD458808 - Sequence 439832 from Patent EP1572962. JD362405 - Sequence 343429 from Patent EP1572962. JD504190 - Sequence 485214 from Patent EP1572962. JD355217 - Sequence 336241 from Patent EP1572962. JD411333 - Sequence 392357 from Patent EP1572962. JD533625 - Sequence 514649 from Patent EP1572962. JD381240 - Sequence 362264 from Patent EP1572962. JD306001 - Sequence 287025 from Patent EP1572962. JD048802 - Sequence 29826 from Patent EP1572962. JD052641 - Sequence 33665 from Patent EP1572962. JD306135 - Sequence 287159 from Patent EP1572962. JD110475 - Sequence 91499 from Patent EP1572962. JD177559 - Sequence 158583 from Patent EP1572962. JD344234 - Sequence 325258 from Patent EP1572962. JD199700 - Sequence 180724 from Patent EP1572962. JD203131 - Sequence 184155 from Patent EP1572962. BC032237 - Homo sapiens choroideremia (Rab escort protein 1), mRNA (cDNA clone IMAGE:5248651), with apparent retained intron. BC063522 - Homo sapiens cDNA clone IMAGE:4358313, partial cds. BC130494 - Homo sapiens choroideremia (Rab escort protein 1), mRNA (cDNA clone IMAGE:40146525), complete cds. BC130496 - Homo sapiens choroideremia (Rab escort protein 1), mRNA (cDNA clone IMAGE:40146527), complete cds. JD338706 - Sequence 319730 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P24386 (Reactome details) participates in the following event(s):
R-HSA-6801109 CHM binds RGGT R-HSA-8870465 RGGT binds the RAB-binding subunit R-HSA-8875318 RAB3 GEFs exchange GTP for GDP on RAB3A R-HSA-8875320 RAB5 GEFs exchange GTP for GDP on RAB5 R-HSA-8876188 DENND4s exchange GTP for GDP on RAB10 R-HSA-8876190 RAB8 GEFs exchange GTP for GDP on RAB8 R-HSA-8876191 RAB9 GEFs exchange GTP for GDP on RAB9 R-HSA-8876193 RIC1-RGP1 exchanges GTP for GDP on RAB6 R-HSA-8876454 DENND3 exchanges GTP for GDP on RAB12 R-HSA-8876615 RAB13 GEFs exchange GTP for GDP on RAB13 R-HSA-8876616 DENND6A,B exchange GTP for GDP on RAB14 R-HSA-8876837 RAB21 GEFs exchange GTP for GDP on RAB21 R-HSA-8877308 MADD exchanges GTP for GDP on RAB27 R-HSA-8877311 RAB31 GEFs exchange GTP for GDP on RAB31 R-HSA-8877451 MON1:CCZ1 exchanges GTP for GDP on RAB7 R-HSA-8877475 TRAPPC complexes exchange GTP for GDP on RAB1 R-HSA-8877612 DENND1s exchange GTP for GDP on RAB35 R-HSA-8877760 HPS1:HPS4 exchange GTP for GDP on RAB32 and RAB38 R-HSA-8877813 DENND5A,B exchange GTP for GDP on RAB39 R-HSA-8877998 RAB3GAP1:RAB3GAP2 exchanges GTP for GDP on RAB18 R-HSA-8870469 RGGT geranylgeranylates RAB proteins R-HSA-8870466 RGGT:CHM binds RABs R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain R-HSA-8873719 RAB geranylgeranylation R-HSA-8876198 RAB GEFs exchange GTP for GDP on RABs R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes R-HSA-597592 Post-translational protein modification R-HSA-9007101 Rab regulation of trafficking R-HSA-3700989 Transcriptional Regulation by TP53 R-HSA-392499 Metabolism of proteins R-HSA-199991 Membrane Trafficking R-HSA-212436 Generic Transcription Pathway R-HSA-5653656 Vesicle-mediated transport R-HSA-73857 RNA Polymerase II Transcription R-HSA-74160 Gene expression (Transcription)
US Server
Sequence and Links to Tools and Databases 
