RAE1_RAT
ID RAE1_RAT Reviewed; 650 AA.
AC P37727;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 25-MAY-2022, entry version 141.
DE RecName: Full=Rab proteins geranylgeranyltransferase component A 1;
DE AltName: Full=Choroideremia protein homolog;
DE AltName: Full=Rab escort protein 1;
DE Short=REP-1;
GN Name=Chm; Synonyms=Rep1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH RAB1A.
RC TISSUE=Brain;
RX PubMed=8513495; DOI=10.1016/0092-8674(93)90639-8;
RA Andres D.A., Seabra M.C., Brown M.S., Armstrong S.A., Smeland T.E.,
RA Cremers F.P.M., Goldstein J.L.;
RT "cDNA cloning of component A of Rab geranylgeranyl transferase and
RT demonstration of its role as a Rab escort protein.";
RL Cell 73:1091-1099(1993).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RC TISSUE=Brain;
RX PubMed=1525821; DOI=10.1016/0092-8674(92)90253-9;
RA Saebra M.C., Brown M.S., Slaughter C.A., Suedhof T.C., Goldstein J.L.;
RT "Purification of component A of Rab geranylgeranyl transferase: possible
RT identity with the choroideremia gene product.";
RL Cell 70:1049-1057(1992).
RN [3]
RP INTERACTION WITH RAB1B.
RX PubMed=11389151; DOI=10.1074/jbc.m101511200;
RA Overmeyer J.H., Wilson A.L., Maltese W.A.;
RT "Membrane targeting of a Rab GTPase that fails to associate with Rab escort
RT protein (REP) or guanine nucleotide dissociation inhibitor (GDI).";
RL J. Biol. Chem. 276:20379-20386(2001).
RN [4]
RP SUBUNIT.
RX PubMed=11675392; DOI=10.1074/jbc.m108241200;
RA Thoma N.H., Iakovenko A., Goody R.S., Alexandrov K.;
RT "Phosphoisoprenoids modulate association of Rab geranylgeranyltransferase
RT with REP-1.";
RL J. Biol. Chem. 276:48637-48643(2001).
RN [5]
RP FUNCTION, SUBUNIT, INTERACTION WITH RAB7A, AND SUBCELLULAR LOCATION.
RX PubMed=12356470; DOI=10.1016/s1046-5928(02)00506-5;
RA Sidorovitch V., Niculae A., Kan N., Ceacareanu A.C., Alexandrov K.;
RT "Expression of mammalian Rab Escort protein-1 and -2 in yeast Saccharomyces
RT cerevisiae.";
RL Protein Expr. Purif. 26:50-58(2002).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH RABGGTA AND RABGGTB,
RP MUTAGENESIS OF PHE-279, SUBUNIT, AND FUNCTION.
RX PubMed=12620235; DOI=10.1016/s1097-2765(03)00044-3;
RA Pylypenko O., Rak A., Reents R., Niculae A., Sidorovitch V., Cioaca M.D.,
RA Bessolitsyna E., Thomae N.H., Waldmann H., Schlichting I., Goody R.S.,
RA Alexandrov K.;
RT "Structure of Rab escort protein-1 in complex with Rab
RT geranylgeranyltransferase.";
RL Mol. Cell 11:483-494(2003).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH RAB7A, SUBUNIT,
RP FUNCTION, AND INTERACTION WITH RAB1A; RAB7A AND RAB27A.
RX PubMed=15186776; DOI=10.1016/j.cell.2004.05.017;
RA Rak A., Pylypenko O., Niculae A., Pyatkov K., Goody R.S., Alexandrov K.;
RT "Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab
RT prenylation and choroideremia disease.";
RL Cell 117:749-760(2004).
CC -!- FUNCTION: Substrate-binding subunit of the Rab
CC geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab
CC proteins and presents the substrate peptide to the catalytic component
CC B composed of RABGGTA and RABGGTB, and remains bound to it after the
CC geranylgeranyl transfer reaction. The component A is thought to be
CC regenerated by transferring its prenylated Rab back to the donor
CC membrane. Besides, a pre-formed complex consisting of CHM and the Rab
CC GGTase dimer (RGGT or component B) can bind to and prenylate Rab
CC proteins; this alternative pathway is proposed to be the predominant
CC pathway for Rab protein geranylgeranylation.
CC {ECO:0000269|PubMed:12356470, ECO:0000269|PubMed:12620235,
CC ECO:0000269|PubMed:15186776, ECO:0000269|PubMed:1525821,
CC ECO:0000269|PubMed:8513495}.
CC -!- SUBUNIT: Monomer (PubMed:8513495, PubMed:1525821). Heterotrimer
CC composed of RABGGTA, RABGGTB and CHM; within this trimer, RABGGTA and
CC RABGGTB form the catalytic component B, while CHM (component A)
CC mediates Rab protein binding (PubMed:12620235). Can associate with the
CC Rab GGTase dimer (RGGT or component B) prior to Rab protein binding;
CC the association is stabilized by geranylgeranyl pyrophosphate (GGpp).
CC The CHM:RGGT:Rab complex is destabilized by GGpp (By similarity).
CC Interacts with RAB1A, RAB1B, RAB7A and RAB27A and mediates their
CC prenylation (PubMed:11389151, PubMed:12356470, PubMed:15186776,
CC PubMed:8513495). Interacts with RAB5A (By similarity). Interacts with
CC the non-phosphorylated forms of RAB3A, RAB3B, RAB3C, RAB3D, RAB5B,
CC RAB5C RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (By similarity).
CC {ECO:0000250|UniProtKB:P24386, ECO:0000269|PubMed:11389151,
CC ECO:0000269|PubMed:12356470, ECO:0000269|PubMed:12620235,
CC ECO:0000269|PubMed:15186776, ECO:0000269|PubMed:1525821,
CC ECO:0000269|PubMed:8513495}.
CC -!- INTERACTION:
CC P37727; P09527: Rab7a; NbExp=2; IntAct=EBI-1039231, EBI-916225;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12356470,
CC ECO:0000269|PubMed:1525821, ECO:0000269|PubMed:8513495}.
CC -!- TISSUE SPECIFICITY: Most abundant in the heart, brain, and spleen.
CC Lower levels seen in the lung, liver, muscle and kidney. Extremely low
CC levels seen in the testis.
CC -!- SIMILARITY: Belongs to the Rab GDI family. {ECO:0000305}.
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DR EMBL; L13722; AAA87626.1; -; mRNA.
DR PIR; A40686; A40686.
DR RefSeq; NP_058763.1; NM_017067.1.
DR PDB; 1LTX; X-ray; 2.70 A; R=1-650.
DR PDB; 1VG0; X-ray; 2.20 A; A=1-650.
DR PDB; 1VG9; X-ray; 2.50 A; A/C/E/G=1-650.
DR PDBsum; 1LTX; -.
DR PDBsum; 1VG0; -.
DR PDBsum; 1VG9; -.
DR AlphaFoldDB; P37727; -.
DR SMR; P37727; -.
DR IntAct; P37727; 1.
DR STRING; 10116.ENSRNOP00000000174; -.
DR iPTMnet; P37727; -.
DR PhosphoSitePlus; P37727; -.
DR jPOST; P37727; -.
DR PaxDb; P37727; -.
DR PRIDE; P37727; -.
DR GeneID; 24942; -.
DR KEGG; rno:24942; -.
DR UCSC; RGD:2340; rat.
DR CTD; 1121; -.
DR RGD; 2340; Chm.
DR eggNOG; KOG4405; Eukaryota.
DR InParanoid; P37727; -.
DR OrthoDB; 1017439at2759; -.
DR PhylomeDB; P37727; -.
DR Reactome; R-RNO-6803205; TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain.
DR Reactome; R-RNO-8873719; RAB geranylgeranylation.
DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR EvolutionaryTrace; P37727; -.
DR PRO; PR:P37727; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005968; C:Rab-protein geranylgeranyltransferase complex; IDA:UniProtKB.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; IEA:InterPro.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:CAFA.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0018344; P:protein geranylgeranylation; IDA:UniProtKB.
DR GO; GO:0006612; P:protein targeting to membrane; ISS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
DR DisProt; DP00458; -.
DR Gene3D; 3.50.50.60; -; 2.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR018203; GDP_dissociation_inhibitor.
DR InterPro; IPR001738; Rab_escort.
DR PANTHER; PTHR11787; PTHR11787; 1.
DR Pfam; PF00996; GDI; 2.
DR PIRSF; PIRSF016550; Rab_ger_ger_transf_A_euk; 1.
DR PRINTS; PR00893; RABESCORT.
DR PRINTS; PR00891; RABGDIREP.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; GTPase activation;
KW Reference proteome.
FT CHAIN 1..650
FT /note="Rab proteins geranylgeranyltransferase component A
FT 1"
FT /id="PRO_0000056688"
FT REGION 156..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 603..650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 174..189
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 190..208
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 618..650
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 279
FT /note="F->A: Abolishes association with RGGT."
FT /evidence="ECO:0000269|PubMed:12620235"
FT STRAND 10..14
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 18..29
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 39..43
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 52..61
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 75..78
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 83..88
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 95..102
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 214..219
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 238..246
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 259..270
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 275..280
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 286..300
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 306..310
FT /evidence="ECO:0007829|PDB:1VG0"
FT TURN 311..314
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 317..321
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 328..337
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 343..345
FT /evidence="ECO:0007829|PDB:1VG9"
FT HELIX 348..361
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 364..373
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 379..390
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 394..398
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 401..407
FT /evidence="ECO:0007829|PDB:1VG0"
FT TURN 408..410
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 413..418
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 427..432
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:1VG0"
FT TURN 438..443
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 447..458
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 478..480
FT /evidence="ECO:0007829|PDB:1LTX"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 491..493
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:1VG9"
FT STRAND 501..508
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 513..524
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 542..553
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 559..561
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 562..564
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 569..572
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 577..581
FT /evidence="ECO:0007829|PDB:1VG0"
FT HELIX 582..595
FT /evidence="ECO:0007829|PDB:1VG0"
FT STRAND 596..598
FT /evidence="ECO:0007829|PDB:1VG9"
FT STRAND 610..613
FT /evidence="ECO:0007829|PDB:1VG9"
SQ SEQUENCE 650 AA; 72480 MW; 5BF42B445E546282 CRC64;
MADNLPSDFD VIVIGTGLPE SIIAAACSRS GQRVLHVDSR SYYGGNWASF SFSGLLSWLK
EYQENNDVVT ENSMWQEQIL ENEEAIPLSS KDKTIQHVEV FCYASQDLHK DVEEAGALQK
NHASVTSAQS AEAAEAAETS CLPTAVEPLS MGSCEIPAEQ SQCPGPESSP EVNDAEATGK
KENSDAKSST EEPSENVPKV QDNTETPKKN RITYSQIIKE GRRFNIDLVS QLLYSRGLLI
DLLIKSNVSR YAEFKNITRI LAFREGTVEQ VPCSRADVFN SKQLTMVEKR MLMKFLTFCV
EYEEHPDEYR AYEGTTFSEY LKTQKLTPNL QYFVLHSIAM TSETTSCTVD GLKATKKFLQ
CLGRYGNTPF LFPLYGQGEL PQCFCRMCAV FGGIYCLRHS VQCLVVDKES RKCKAVIDQF
GQRIISKHFI IEDSYLSENT CSRVQYRQIS RAVLITDGSV LKTDADQQVS ILAVPAEEPG
SFGVRVIELC SSTMTCMKGT YLVHLTCMSS KTAREDLERV VQKLFTPYTE IEAENEQVEK
PRLLWALYFN MRDSSDISRD CYNDLPSNVY VCSGPDSGLG NDNAVKQAET LFQQICPNED
FCPAPPNPED IVLDGDSSQQ EVPESSVTPE TNSETPKEST VLGNPEEPSE
