PGTA_RAT
ID PGTA_RAT Reviewed; 567 AA.
AC Q08602;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Geranylgeranyl transferase type-2 subunit alpha;
DE EC=2.5.1.60;
DE AltName: Full=Geranylgeranyl transferase type II subunit alpha;
DE AltName: Full=Rab geranyl-geranyltransferase subunit alpha;
DE Short=Rab GG transferase alpha;
DE Short=Rab GGTase alpha;
DE AltName: Full=Rab geranylgeranyltransferase subunit alpha;
GN Name=Rabggta; Synonyms=Ggta;
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], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP SUBUNIT.
RC TISSUE=Brain;
RX PubMed=8505342; DOI=10.1016/s0021-9258(19)50329-5;
RA Armstrong S.A., Seabra M.C., Suedhof T.C., Goldstein J.L., Brown M.S.;
RT "cDNA cloning and expression of the alpha and beta subunits of rat Rab
RT geranylgeranyl transferase.";
RL J. Biol. Chem. 268:12221-12229(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
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 [4]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH RABGGTB, AND SUBUNIT.
RX PubMed=10745007; DOI=10.1016/s0969-2126(00)00102-7;
RA Zhang H., Seabra M.C., Deisenhofer J.;
RT "Crystal structure of Rab geranylgeranyltransferase at 2.0 A resolution.";
RL Structure 8:241-251(2000).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH GERANYGERANYL
RP PHOSPHATE ANALOG; RABGGTB AND CHM/REP1, AND SUBUNIT.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-441 IN COMPLEX WITH INHIBITOR,
RP FUNCTION, AND SUBUNIT.
RX PubMed=18399557; DOI=10.1002/anie.200705795;
RA Guo Z., Wu Y.W., Tan K.T., Bon R.S., Guiu-Rozas E., Delon C., Nguyen T.U.,
RA Wetzel S., Arndt S., Goody R.S., Blankenfeldt W., Alexandrov K.,
RA Waldmann H.;
RT "Development of selective RabGGTase inhibitors and crystal structure of a
RT RabGGTase-inhibitor complex.";
RL Angew. Chem. Int. Ed. Engl. 47:3747-3750(2008).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-441, FUNCTION, CATALYTIC
RP ACTIVITY, AND SUBUNIT.
RX PubMed=18756270; DOI=10.1038/emboj.2008.164;
RA Guo Z., Wu Y.W., Das D., Delon C., Cramer J., Yu S., Thuns S., Lupilova N.,
RA Waldmann H., Brunsveld L., Goody R.S., Alexandrov K., Blankenfeldt W.;
RT "Structures of RabGGTase-substrate/product complexes provide insights into
RT the evolution of protein prenylation.";
RL EMBO J. 27:2444-2456(2008).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 1-441, FUNCTION, CATALYTIC
RP ACTIVITY, AND SUBUNIT.
RX PubMed=19894725; DOI=10.1021/jm901117d;
RA Tan K.T., Guiu-Rozas E., Bon R.S., Guo Z., Delon C., Wetzel S., Arndt S.,
RA Alexandrov K., Waldmann H., Goody R.S., Wu Y.W., Blankenfeldt W.;
RT "Design, synthesis, and characterization of peptide-based rab
RT geranylgeranyl transferase inhibitors.";
RL J. Med. Chem. 52:8025-8037(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-441, FUNCTION, CATALYTIC
RP ACTIVITY, AND SUBUNIT.
RX PubMed=21520375; DOI=10.1002/anie.201101210;
RA Bon R.S., Guo Z., Stigter E.A., Wetzel S., Menninger S., Wolf A.,
RA Choidas A., Alexandrov K., Blankenfeldt W., Goody R.S., Waldmann H.;
RT "Structure-guided development of selective RabGGTase inhibitors.";
RL Angew. Chem. Int. Ed. Engl. 50:4957-4961(2011).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1-441, FUNCTION, CATALYTIC
RP ACTIVITY, AND SUBUNIT.
RX PubMed=22963166; DOI=10.1021/jm300624s;
RA Stigter E.A., Guo Z., Bon R.S., Wu Y.W., Choidas A., Wolf A., Menninger S.,
RA Waldmann H., Blankenfeldt W., Goody R.S.;
RT "Development of selective, potent RabGGTase inhibitors.";
RL J. Med. Chem. 55:8330-8340(2012).
CC -!- FUNCTION: Catalyzes the transfer of a geranylgeranyl moiety from
CC geranylgeranyl diphosphate to both cysteines of Rab proteins with the
CC C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A
CC and RAB7A. {ECO:0000269|PubMed:18399557, ECO:0000269|PubMed:18756270,
CC ECO:0000269|PubMed:19894725, ECO:0000269|PubMed:21520375,
CC ECO:0000269|PubMed:22963166, ECO:0000269|PubMed:8505342}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=geranylgeranyl diphosphate + L-cysteinyl-[protein] =
CC diphosphate + S-geranylgeranyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:21240, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11537,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:33019, ChEBI:CHEBI:57533,
CC ChEBI:CHEBI:86021; EC=2.5.1.60;
CC Evidence={ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725,
CC ECO:0000269|PubMed:21520375, ECO:0000269|PubMed:22963166};
CC -!- ACTIVITY REGULATION: The enzymatic reaction requires the aid of a Rab
CC escort protein (also called component A), such as CHM.
CC -!- SUBUNIT: Heterotrimer composed of RABGGTA, RABGGTB and CHM; within this
CC trimer, RABGGTA and RABGGTB form the catalytic component B, while CHM
CC (component A) mediates peptide substrate binding (PubMed:11675392,
CC PubMed:10745007, PubMed:12620235, PubMed:18399557, PubMed:18756270,
CC PubMed:19894725, PubMed:21520375, PubMed:22963166, PubMed:8505342). The
CC Rab GGTase dimer (RGGT) interacts with CHM (component A) prior to Rab
CC protein binding; the association is stabilized by geranylgeranyl
CC pyrophosphate (GGpp) (PubMed:12620235). The CHM:RGGT:Rab complex is
CC destabilized by GGpp (PubMed:12620235). Interacts with non-
CC phosphorylated form of RAB8A; phosphorylation of RAB8A at 'Thr-72'
CC disrupts this interaction (By similarity).
CC {ECO:0000250|UniProtKB:Q92696, ECO:0000269|PubMed:10745007,
CC ECO:0000269|PubMed:11675392, ECO:0000269|PubMed:12620235,
CC ECO:0000269|PubMed:18399557, ECO:0000269|PubMed:18756270,
CC ECO:0000269|PubMed:19894725, ECO:0000269|PubMed:21520375,
CC ECO:0000269|PubMed:22963166, ECO:0000269|PubMed:8505342}.
CC -!- TISSUE SPECIFICITY: Most abundant in the heart, brain, spleen and
CC liver. Less in the lung, muscle, kidney and testis; in these tissues
CC less abundant than the beta subunit.
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family. {ECO:0000305}.
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DR EMBL; L10415; AAA41998.1; -; mRNA.
DR EMBL; S62096; AAB27018.1; -; mRNA.
DR EMBL; BC086547; AAH86547.1; -; mRNA.
DR PIR; A45977; A45977.
DR RefSeq; NP_113842.1; NM_031654.2.
DR RefSeq; XP_006252071.1; XM_006252009.3.
DR RefSeq; XP_006252072.1; XM_006252010.3.
DR PDB; 1DCE; X-ray; 2.00 A; A/C=1-567.
DR PDB; 1LTX; X-ray; 2.70 A; A=1-567.
DR PDB; 3C72; X-ray; 2.30 A; A=1-236, A=353-441.
DR PDB; 3DSS; X-ray; 1.80 A; A=1-237, A=353-441.
DR PDB; 3DST; X-ray; 1.90 A; A=1-237, A=353-441.
DR PDB; 3DSU; X-ray; 1.90 A; A=1-237, A=353-441.
DR PDB; 3DSV; X-ray; 2.10 A; A=1-237, A=353-441.
DR PDB; 3DSW; X-ray; 2.15 A; A=1-237, A=353-441.
DR PDB; 3DSX; X-ray; 2.10 A; A=1-237, A=353-441.
DR PDB; 3HXB; X-ray; 2.25 A; A=1-237, A=353-441.
DR PDB; 3HXC; X-ray; 1.95 A; A=1-237, A=353-441.
DR PDB; 3HXD; X-ray; 1.95 A; A=1-237, A=353-441.
DR PDB; 3HXE; X-ray; 1.95 A; A=1-237, A=353-441.
DR PDB; 3HXF; X-ray; 1.90 A; A=1-237, A=353-441.
DR PDB; 3PZ1; X-ray; 1.95 A; A=1-237, A=353-441.
DR PDB; 3PZ2; X-ray; 2.35 A; A=1-237, A=353-441.
DR PDB; 3PZ3; X-ray; 2.00 A; A=1-237, A=353-441.
DR PDB; 4EHM; X-ray; 2.20 A; A=1-237, A=353-441.
DR PDB; 4GTS; X-ray; 2.45 A; A=1-237, A=353-441.
DR PDB; 4GTT; X-ray; 2.05 A; A=1-237, A=353-441.
DR PDB; 4GTV; X-ray; 1.95 A; A=1-237, A=353-441.
DR PDBsum; 1DCE; -.
DR PDBsum; 1LTX; -.
DR PDBsum; 3C72; -.
DR PDBsum; 3DSS; -.
DR PDBsum; 3DST; -.
DR PDBsum; 3DSU; -.
DR PDBsum; 3DSV; -.
DR PDBsum; 3DSW; -.
DR PDBsum; 3DSX; -.
DR PDBsum; 3HXB; -.
DR PDBsum; 3HXC; -.
DR PDBsum; 3HXD; -.
DR PDBsum; 3HXE; -.
DR PDBsum; 3HXF; -.
DR PDBsum; 3PZ1; -.
DR PDBsum; 3PZ2; -.
DR PDBsum; 3PZ3; -.
DR PDBsum; 4EHM; -.
DR PDBsum; 4GTS; -.
DR PDBsum; 4GTT; -.
DR PDBsum; 4GTV; -.
DR AlphaFoldDB; Q08602; -.
DR SMR; Q08602; -.
DR BioGRID; 248714; 3.
DR ComplexPortal; CPX-2249; Protein geranylgeranyltransferase type II complex.
DR DIP; DIP-6137N; -.
DR IntAct; Q08602; 1.
DR STRING; 10116.ENSRNOP00000049261; -.
DR BindingDB; Q08602; -.
DR ChEMBL; CHEMBL4523995; -.
DR jPOST; Q08602; -.
DR PaxDb; Q08602; -.
DR PRIDE; Q08602; -.
DR GeneID; 58983; -.
DR KEGG; rno:58983; -.
DR UCSC; RGD:621697; rat.
DR CTD; 5875; -.
DR RGD; 621697; Rabggta.
DR VEuPathDB; HostDB:ENSRNOG00000030483; -.
DR eggNOG; KOG0529; Eukaryota.
DR HOGENOM; CLU_031996_3_2_1; -.
DR InParanoid; Q08602; -.
DR OMA; YNAWHHR; -.
DR OrthoDB; 1527547at2759; -.
DR PhylomeDB; Q08602; -.
DR TreeFam; TF315057; -.
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 EvolutionaryTrace; Q08602; -.
DR PRO; PR:Q08602; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000030483; Expressed in skeletal muscle tissue and 20 other tissues.
DR Genevisible; Q08602; RN.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005968; C:Rab-protein geranylgeranyltransferase complex; IDA:UniProtKB.
DR GO; GO:0004663; F:Rab geranylgeranyltransferase activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0018344; P:protein geranylgeranylation; IDA:UniProtKB.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR002088; Prenyl_trans_a.
DR InterPro; IPR036254; RabGGT_asu_insert-dom_sf.
DR InterPro; IPR009087; RabGGT_asu_insert-domain.
DR InterPro; IPR032955; RabGGTase_alpha.
DR PANTHER; PTHR11129:SF2; PTHR11129:SF2; 1.
DR Pfam; PF01239; PPTA; 5.
DR Pfam; PF07711; RabGGT_insert; 1.
DR SUPFAM; SSF49594; SSF49594; 1.
DR PROSITE; PS51147; PFTA; 6.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Leucine-rich repeat;
KW Phosphoprotein; Prenyltransferase; Reference proteome; Repeat; Transferase.
FT CHAIN 1..567
FT /note="Geranylgeranyl transferase type-2 subunit alpha"
FT /id="PRO_0000119759"
FT REPEAT 44..78
FT /note="PFTA 1"
FT REPEAT 88..122
FT /note="PFTA 2"
FT REPEAT 124..158
FT /note="PFTA 3"
FT REPEAT 159..193
FT /note="PFTA 4"
FT REPEAT 207..241
FT /note="PFTA 5"
FT REPEAT 363..397
FT /note="PFTA 6"
FT REPEAT 442..463
FT /note="LRR 1"
FT REPEAT 464..486
FT /note="LRR 2"
FT REPEAT 487..508
FT /note="LRR 3"
FT REPEAT 509..530
FT /note="LRR 4"
FT REPEAT 534..555
FT /note="LRR 5"
FT MOD_RES 98
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JHK4"
FT CONFLICT 169
FT /note="S -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="S -> Q (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 13..40
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 63..79
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 82..102
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 107..119
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:3C72"
FT HELIX 125..138
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 143..155
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 160..173
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 178..191
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 205..221
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 245..251
FT /evidence="ECO:0007829|PDB:1DCE"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 256..265
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 267..269
FT /evidence="ECO:0007829|PDB:1LTX"
FT STRAND 274..283
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 296..303
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 313..322
FT /evidence="ECO:0007829|PDB:1DCE"
FT TURN 323..326
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 327..334
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 338..343
FT /evidence="ECO:0007829|PDB:1DCE"
FT TURN 347..350
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 358..377
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 382..395
FT /evidence="ECO:0007829|PDB:3DSS"
FT TURN 397..400
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 401..414
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 416..418
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 419..438
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 444..447
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 459..462
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 467..469
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 480..484
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 502..504
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 527..531
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 544..547
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 548..550
FT /evidence="ECO:0007829|PDB:1DCE"
FT HELIX 554..558
FT /evidence="ECO:0007829|PDB:1DCE"
FT STRAND 563..566
FT /evidence="ECO:0007829|PDB:1DCE"
SQ SEQUENCE 567 AA; 64904 MW; 1F9D235F973EABD5 CRC64;
MHGRLKVKTS EEQAEAKRLE REQKLKLYQS ATQAVFQKRQ AGELDESVLE LTSQILGANP
DFATLWNCRR EVLQHLETEK SPEESAALVK AELGFLESCL RVNPKSYGTW HHRCWLLSRL
PEPNWARELE LCARFLEADE RNFHCWDYRR FVAAQAAVAP AEELAFTDSL ITRNFSNYSS
WHYRSCLLPQ LHPQPDSGPQ GRLPENVLLK ELELVQNAFF TDPNDQSAWF YHRWLLGRAE
PHDVLCCVHV SREEACLSVC FSRPLTVGSR MGTLLLMVDE APLSVEWRTP DGRNRPSHVW
LCDLPAASLN DQLPQHTFRV IWTGSDSQKE CVLLKDRPEC WCRDSATDEQ LFRCELSVEK
STVLQSELES CKELQELEPE NKWCLLTIIL LMRALDPLLY EKETLQYFST LKAVDPMRAA
YLDDLRSKFL LENSVLKMEY ADVRVLHLAH KDLTVLCHLE QLLLVTHLDL SHNRLRALPP
ALAALRCLEV LQASDNALEN VDGVANLPRL QELLLCNNRL QQSAAIQPLV SCPRLVLLNL
QGNSLCQEEG IQERLAEMLP SVSSILT
