P24386 (RAE1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	653 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.9
Subunit structure	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. Ref.9 Ref.10
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.10 Ref.11 Ref.12
Sequence similarities	Belongs to the Rab GDI family.

Ontologies

Keywords
Biological process	Sensory transduction Vision
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Molecular function	GTPase activation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel development Inferred from electronic annotation. Source: Compara intracellular protein transport Inferred from electronic annotation. Source: InterPro positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC protein geranylgeranylation Traceable author statement PubMed 8380507. Source: ProtInc response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Traceable author statement Ref.1. Source: ProtInc
Cellular_component	Rab-protein geranylgeranyltransferase complex Traceable author statement PubMed 8380507. Source: ProtInc
Molecular_function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW Rab geranylgeranyltransferase activity Traceable author statement PubMed 8380507. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 653	653	Rab proteins geranylgeranyltransferase component A 1		PRO_0000056686
Natural variations
	Alternative sequence	105 – 110	6	SQDLHE → RSTLLL in isoform 2.		VSP_042817
	Alternative sequence	111 – 653	543	Missing in isoform 2.		VSP_042818
	Natural variant	471	1	Q → L in CHM; may affect splicing. Ref.11		VAR_008273
	Natural variant	507	1	H → R in CHM; impairs the interaction with RABGGTA. Ref.10		VAR_066847
	Natural variant	550	1	L → P in CHM. Ref.12		VAR_066848
Experimental info
	Mutagenesis	282	1	F → L: Abolishes prenylation of RAB1A and association with RGGT. Ref.9
	Mutagenesis	290	1	V → F: Impairs prenylation of RAB1A and abolishes association with RGGT. Ref.9
	Sequence conflict	625 – 626	2	AS → RA in AAA61032. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 6, 2002. Version 3. Checksum: 7CFFAECE7BA1F3AF	FASTA	653	73,476
	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
	Isoform 2 [UniParc]. Checksum: AD591A7B415DFD18	FASTA	110	12,301
	10 20 30 40 50 60 MADTLPSEFD VIVIGTGLPE SIIAAACSRS GRRVLHVDSR SYYGGNWASF SFSGLLSWLK 70 80 90 100 110 EYQENSDIVS DSPVWQDQIL ENEEAIALSR KDKTIQHVEV FCYARSTLLL

References

	« Hide 'large scale' referencesShow '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. , 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: CHARACTERIZATION.
[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]	"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.
[11]	"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.
[12]	"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.

Web resources

Mutations of the REP1 gene

Retina International's Scientific Newsletter

GeneReviews

Retinal and hearing impairment genetic mutation database choroideremia (Rab escort protein 1) (CHM)

Leiden Open Variation Database (LOVD)

NGRL, Manchester LOVD choroideremia (Rab escort protein 1) (CHM)

Leiden Open Variation Database (LOVD)

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 , S37416, S37417, S37422 Genomic DNA. Translation: AAD13814.1.
IPI	IPI00028099. IPI00641814.
PIR	I37234.
RefSeq	NP_000381.1. NM_000390.2. NP_001138886.1. NM_001145414.1.
UniGene	Hs.496449.
3D structure databases
ProteinModelPortal	P24386.
ModBase	Search...
Protein-protein interaction databases
IntAct	P24386. 47 interactions.
STRING	9606.ENSP00000350386.
PTM databases
PhosphoSite	P24386.
Polymorphism databases
DMDM	21431807.
Proteomic databases
PaxDb	P24386.
PRIDE	P24386.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000357749; ENSP00000350386; ENSG00000188419. ENST00000358786; ENSP00000362228; ENSG00000188419.
GeneID	1121.
KEGG	hsa:1121.
UCSC	uc004eet.3. human.
Organism-specific databases
CTD	1121.
GeneCards	GC0XM085116.
HGNC	HGNC:1940. CHM.
HPA	CAB016171. HPA003231.
MIM	300390. gene. 303100. phenotype.
neXtProt	NX_P24386.
Orphanet	180. Choroideremia.
PharmGKB	PA26471.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5044.
HOGENOM	HOG000220905.
HOVERGEN	HBG004961.
InParanoid	P24386.
OMA	GEKENHC.
OrthoDB	EOG441QBB.
PhylomeDB	P24386.
Gene expression databases
ArrayExpress	P24386.
Bgee	P24386.
CleanEx	HS_CHM.
Genevestigator	P24386.
GermOnline	ENSG00000188419. Homo sapiens.
Family and domain databases
InterPro	IPR018203. GDP_dissociation_inhibitor. IPR001738. Rab_escort. IPR016664. Rab_geranylTrfase_A_euk. [Graphical view]
Pfam	PF00996. GDI. 2 hits. [Graphical view]
PIRSF	PIRSF016550. Rab_ger_ger_transf_A_euk. 1 hit.
PRINTS	PR00893. RABESCORT. PR00891. RABGDIREP.
ProtoNet	Search...
Other
GenomeRNAi	1121.
NextBio	4654.
SOURCE	Search...

Entry information

Entry name

RAE1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.