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P24386 (RAE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 130. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rab proteins geranylgeranyltransferase component A 1
Alternative name(s):
Choroideremia protein
Rab escort protein 1
Short name=REP-1
TCD protein
Gene names
Name:CHM
Synonyms:REP1, TCD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length653 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Substrate-binding subunit of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B composed of RABGGTA and RABGGTB, 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. Besides, 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. Ref.8 Ref.9

Subunit structure

Monomer. Heterotrimer composed of RABGGTA, RABGGTB and CHM; within this trimer, RABGGTA and RABGGTB form the catalytic component B, while CHM (component A) mediates Rab protein binding. 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 RAB1A, RAB1B, RAB5A, RAB7A and RAB27A and mediates their prenylation. Ref.8 Ref.9 Ref.11

Subcellular location

Cytoplasmcytosol Ref.8.

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11 Ref.12 Ref.13

Sequence similarities

Belongs to the Rab GDI family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P24386-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P24386-2)

The sequence of this isoform differs from the canonical sequence as follows:
     105-110: SQDLHE → RSTLLL
     111-653: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 653653Rab proteins geranylgeranyltransferase component A 1
PRO_0000056686

Natural variations

Alternative sequence105 – 1106SQDLHE → RSTLLL in isoform 2.
VSP_042817
Alternative sequence111 – 653543Missing in isoform 2.
VSP_042818
Natural variant4711Q → L in CHM; may affect splicing. Ref.12
VAR_008273
Natural variant5071H → R in CHM; impairs the interaction with RABGGTA. Ref.11
VAR_066847
Natural variant5501L → P in CHM. Ref.13
VAR_066848

Experimental info

Mutagenesis2821F → L: Abolishes prenylation of RAB1A and association with RGGT. Ref.9
Mutagenesis2901V → F: Impairs prenylation of RAB1A and abolishes association with RGGT. Ref.9
Sequence conflict625 – 6262AS → RA in AAA61032. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 6, 2002. Version 3.
Checksum: 7CFFAECE7BA1F3AF

FASTA65373,476
        10         20         30         40         50         60 
MADTLPSEFD VIVIGTGLPE SIIAAACSRS GRRVLHVDSR SYYGGNWASF SFSGLLSWLK 

        70         80         90        100        110        120 
EYQENSDIVS DSPVWQDQIL ENEEAIALSR KDKTIQHVEV FCYASQDLHE DVEEAGALQK 

       130        140        150        160        170        180 
NHALVTSANS TEAADSAFLP TEDESLSTMS CEMLTEQTPS SDPENALEVN GAEVTGEKEN 

       190        200        210        220        230        240 
HCDDKTCVPS TSAEDMSENV PIAEDTTEQP KKNRITYSQI IKEGRRFNID LVSKLLYSRG 

       250        260        270        280        290        300 
LLIDLLIKSN VSRYAEFKNI TRILAFREGR VEQVPCSRAD VFNSKQLTMV EKRMLMKFLT 

       310        320        330        340        350        360 
FCMEYEKYPD EYKGYEEITF YEYLKTQKLT PNLQYIVMHS IAMTSETASS TIDGLKATKN 

       370        380        390        400        410        420 
FLHCLGRYGN TPFLFPLYGQ GELPQCFCRM CAVFGGIYCL RHSVQCLVVD KESRKCKAII 

       430        440        450        460        470        480 
DQFGQRIISE HFLVEDSYFP ENMCSRVQYR QISRAVLITD RSVLKTDSDQ QISILTVPAE 

       490        500        510        520        530        540 
EPGTFAVRVI ELCSSTMTCM KGTYLVHLTC TSSKTAREDL ESVVQKLFVP YTEMEIENEQ 

       550        560        570        580        590        600 
VEKPRILWAL YFNMRDSSDI SRSCYNDLPS NVYVCSGPDC GLGNDNAVKQ AETLFQEICP 

       610        620        630        640        650 
NEDFCPPPPN PEDIILDGDS LQPEASESSA IPEANSETFK ESTNLGNLEE SSE 

« Hide

Isoform 2 [UniParc].

Checksum: AD591A7B415DFD18
Show »

FASTA11012,301

References

« Hide 'large scale' references
[1]"Cloning and characterization of the human choroideremia gene."
van Bokhoven H., van den Hurk J.A., Bogerd L., Philippe C., Gilgenkrantz S., de Jong P., Ropers H.-H., Cremers F.P.
Hum. Mol. Genet. 3:1041-1046(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retina.
[2]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[4]"Isolation of a candidate gene for choroideremia."
Merry D.E., Janne P.A., Landers J.E., Lewis R.A., Nussbaum R.L.
Proc. Natl. Acad. Sci. U.S.A. 89:2135-2139(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 289-653 (ISOFORM 1).
Tissue: Retina.
[5]"Cloning of a gene that is rearranged in patients with choroideraemia."
Cremers F.P.M., van de Pol D.J.R., van Kerkhoff L.P.M., Wieringa B., Ropers H.-H.
Nature 347:674-677(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 338-653 (ISOFORM 1).
[6]"Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing."
van den Hurk J.A.J.M., van de Pol T.J.R., Molloy C.M., Brunsmann F., Ruther K., Zrenner E., Pinckers A.J.L.G., Pawlowitzki I.H., Bleeker-Wagemakers E.M., Wieringa B., Ropers H.-H., Cremers F.P.M.
Am. J. Hum. Genet. 50:1195-1202(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 451-590.
[7]"Analysis of choroideraemia gene."
Fodor E., Lee R.T., O'Donnell J.J.
Nature 351:614-614(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SIMILARITY TO SMG P25A GDI.
[8]"Rab escort protein-1 is a multifunctional protein that accompanies newly prenylated rab proteins to their target membranes."
Alexandrov K., Horiuchi H., Steele-Mortimer O., Seabra M.C., Zerial M.
EMBO J. 13:5262-5273(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH RAB5A AND RAB7A.
[9]"Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate."
Baron R.A., Seabra M.C.
Biochem. J. 415:67-75(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF PHE-282 AND VAL-290.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a missense variant that prevents the binding of REP1 with rab geranylgeranyl transferase."
Esposito G., De Falco F., Tinto N., Testa F., Vitagliano L., Tandurella I.C., Iannone L., Rossi S., Rinaldi E., Simonelli F., Zagari A., Salvatore F.
Hum. Mutat. 32:1460-1469(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RABGGTA, VARIANT CHM ARG-507, CHARACTERIZATION OF VARIANT CHM ARG-507.
[12]"Missense mutation in the choroideremia gene."
Donnelly P., Menet H., Fouanon C., Herbert O., Moisan J.P., Le Roux M.G., Pascal O.
Hum. Mol. Genet. 3:1017-1017(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHM LEU-471.
[13]"The functional effect of pathogenic mutations in Rab escort protein 1."
Sergeev Y.V., Smaoui N., Sui R., Stiles D., Gordiyenko N., Strunnikova N., Macdonald I.M.
Mutat. Res. 665:44-50(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CHM PRO-550.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X78121 mRNA. Translation: CAA55011.1.
AL009175, AL022401, AL035451 Genomic DNA. Translation: CAI42098.1.
AL022401, AL009175, AL035451 Genomic DNA. Translation: CAI43163.1.
AL035451, AL009175 Genomic DNA. Translation: CAI42042.1.
AL035451, AL009175, AL022401 Genomic DNA. Translation: CAI42043.1.
AL009175, AL035451 Genomic DNA. Translation: CAI42097.1.
AL138748 Genomic DNA. No translation available.
BC130494 mRNA. Translation: AAI30495.1.
BC130496 mRNA. Translation: AAI30497.1.
M83773 mRNA. Translation: AAA61032.1.
X57637 mRNA. Translation: CAA40855.1.
S37423 expand/collapse EMBL AC list , S37416, S37417, S37422 Genomic DNA. Translation: AAD13814.1.
PIRI37234.
RefSeqNP_000381.1. NM_000390.2.
NP_001138886.1. NM_001145414.1.
UniGeneHs.496449.

3D structure databases

ProteinModelPortalP24386.
SMRP24386. Positions 3-617.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107545. 6 interactions.
IntActP24386. 47 interactions.
STRING9606.ENSP00000350386.

PTM databases

PhosphoSiteP24386.

Polymorphism databases

DMDM21431807.

Proteomic databases

PaxDbP24386.
PRIDEP24386.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357749; ENSP00000350386; ENSG00000188419. [P24386-1]
ENST00000358786; ENSP00000362228; ENSG00000188419. [P24386-2]
GeneID1121.
KEGGhsa:1121.
UCSCuc004eet.3. human. [P24386-1]
uc004eev.4. human. [P24386-2]

Organism-specific databases

CTD1121.
GeneCardsGC0XM085116.
HGNCHGNC:1940. CHM.
HPACAB016171.
HPA003231.
MIM300390. gene.
303100. phenotype.
neXtProtNX_P24386.
Orphanet180. Choroideremia.
PharmGKBPA26471.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5044.
HOGENOMHOG000220905.
HOVERGENHBG004961.
InParanoidP24386.
OMALQKNHAS.
OrthoDBEOG7Q5HCQ.
PhylomeDBP24386.
TreeFamTF320813.

Gene expression databases

ArrayExpressP24386.
BgeeP24386.
CleanExHS_CHM.
GenevestigatorP24386.

Family and domain databases

InterProIPR018203. GDP_dissociation_inhibitor.
IPR001738. Rab_escort.
IPR016664. Rab_geranylTrfase_A_euk.
[Graphical view]
PfamPF00996. GDI. 2 hits.
[Graphical view]
PIRSFPIRSF016550. Rab_ger_ger_transf_A_euk. 1 hit.
PRINTSPR00893. RABESCORT.
PR00891. RABGDIREP.
ProtoNetSearch...

Other

GeneWikiRab_escort_protein.
GenomeRNAi1121.
NextBio4654.
PROP24386.
SOURCESearch...

Entry information

Entry nameRAE1_HUMAN
AccessionPrimary (citable) accession number: P24386
Secondary accession number(s): A1L4D2, O43732
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: June 6, 2002
Last modified: April 16, 2014
This is version 130 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM