PGTB2_RAT
ID PGTB2_RAT Reviewed; 331 AA.
AC Q08603;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Geranylgeranyl transferase type-2 subunit beta;
DE EC=2.5.1.60 {ECO:0000269|PubMed:18399557, ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725, ECO:0000269|PubMed:22480322, ECO:0000269|PubMed:22963166, ECO:0000269|PubMed:8505342};
DE AltName: Full=Geranylgeranyl transferase type II subunit beta;
DE Short=GGTase-II-beta;
DE AltName: Full=Rab geranyl-geranyltransferase subunit beta;
DE Short=Rab GG transferase beta;
DE Short=Rab GGTase beta;
DE AltName: Full=Rab geranylgeranyltransferase subunit beta;
DE AltName: Full=Type II protein geranyl-geranyltransferase subunit beta;
GN Name=Rabggtb; Synonyms=Ggtb;
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, SUBUNIT,
RP CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
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 SUBUNIT, AND ACTIVITY REGULATION.
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 [3]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH RABGGTA AND ZINC
RP IONS, SUBUNIT, AND COFACTOR.
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 [4]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH ZINC IONS;
RP GERANYGERANYL PHOSPHATE ANALOG; RAB7A; RABGGTA AND CHM, SUBUNIT, AND
RP COFACTOR.
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 [5]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH RABGGTA; INHIBITOR
RP AND ZINC IONS, FUNCTION, SUBUNIT, COFACTOR, AND CATALYTIC ACTIVITY.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEXES WITH RABGGTA; RAB7A;
RP GERANYLGERANYL DIPHOSPHATE AND ZINC IONS, COFACTOR, SUBUNIT, FUNCTION, AND
RP CATALYTIC ACTIVITY.
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 [7]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH RABGGTA; ZINC IONS
RP AND INHIBITOR, SUBUNIT, COFACTOR, FUNCTION, AND CATALYTIC ACTIVITY.
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 [8]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH RABGGTA; ZINC IONS,
RP SUBUNIT, COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=22480322; DOI=10.1021/ja211305j;
RA Deraeve C., Guo Z., Bon R.S., Blankenfeldt W., DiLucrezia R., Wolf A.,
RA Menninger S., Stigter E.A., Wetzel S., Choidas A., Alexandrov K.,
RA Waldmann H., Goody R.S., Wu Y.W.;
RT "Psoromic acid is a selective and covalent Rab-prenylation inhibitor
RT targeting autoinhibited RabGGTase.";
RL J. Am. Chem. Soc. 134:7384-7391(2012).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH RABGGTA; ZINC IONS,
RP SUBUNIT, COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION.
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:22480322,
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:18399557, ECO:0000269|PubMed:18756270,
CC ECO:0000269|PubMed:19894725, ECO:0000269|PubMed:22480322,
CC ECO:0000269|PubMed:22963166, ECO:0000269|PubMed:8505342};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10745007, ECO:0000269|PubMed:12620235,
CC ECO:0000269|PubMed:18399557, ECO:0000269|PubMed:18756270,
CC ECO:0000269|PubMed:19894725, ECO:0000269|PubMed:22480322,
CC ECO:0000269|PubMed:22963166};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:10745007,
CC ECO:0000269|PubMed:12620235, ECO:0000269|PubMed:18399557,
CC ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725,
CC ECO:0000269|PubMed:22480322, 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 {ECO:0000269|PubMed:11675392}.
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:10745007,
CC PubMed:12620235, PubMed:18399557, PubMed:18756270, PubMed:19894725,
CC PubMed:22480322, PubMed:8505342, PubMed:22963166). The Rab GGTase dimer
CC (RGGT) interacts with CHM (component A) prior to Rab protein binding;
CC the association is stabilized by geranylgeranyl pyrophosphate (GGpp)
CC (PubMed:11675392). The CHM:RGGT:Rab complex is destabilized by GGpp
CC (PubMed:11675392). Interaction of RABGGTB with prenylated PTP4A2
CC precludes its association with RABGGTA and inhibits enzyme activity (By
CC similarity). Interacts with CHODL (By similarity). Interacts with non-
CC phosphorylated form of RAB8A; phosphorylation of RAB8A at 'Thr-72'
CC disrupts this interaction (By similarity).
CC {ECO:0000250|UniProtKB:P53611, ECO:0000250|UniProtKB:P53612,
CC ECO:0000269|PubMed:10745007, ECO:0000269|PubMed:11675392,
CC ECO:0000269|PubMed:12620235, ECO:0000269|PubMed:18399557,
CC ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725,
CC ECO:0000269|PubMed:22480322, ECO:0000269|PubMed:22963166,
CC 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 more abundant than the subunit alpha. {ECO:0000269|PubMed:8505342}.
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit beta
CC family. {ECO:0000305}.
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DR EMBL; L10416; AAA41999.1; -; mRNA.
DR EMBL; S62097; AAB27019.1; -; mRNA.
DR PIR; B45977; B45977.
DR RefSeq; NP_619715.1; NM_138708.2.
DR PDB; 1DCE; X-ray; 2.00 A; B/D=1-331.
DR PDB; 1LTX; X-ray; 2.70 A; B=1-331.
DR PDB; 3C72; X-ray; 2.30 A; B=1-331.
DR PDB; 3DSS; X-ray; 1.80 A; B=1-331.
DR PDB; 3DST; X-ray; 1.90 A; B=1-331.
DR PDB; 3DSU; X-ray; 1.90 A; B=1-331.
DR PDB; 3DSV; X-ray; 2.10 A; B=1-331.
DR PDB; 3DSW; X-ray; 2.15 A; B=1-331.
DR PDB; 3DSX; X-ray; 2.10 A; B=1-331.
DR PDB; 3HXB; X-ray; 2.25 A; B=1-331.
DR PDB; 3HXC; X-ray; 1.95 A; B=1-331.
DR PDB; 3HXD; X-ray; 1.95 A; B=1-331.
DR PDB; 3HXE; X-ray; 1.95 A; B=1-331.
DR PDB; 3HXF; X-ray; 1.90 A; B=1-331.
DR PDB; 4EHM; X-ray; 2.20 A; B=2-331.
DR PDB; 4GTS; X-ray; 2.45 A; B=2-331.
DR PDB; 4GTT; X-ray; 2.05 A; B=2-331.
DR PDB; 4GTV; X-ray; 1.95 A; B=2-331.
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; 4EHM; -.
DR PDBsum; 4GTS; -.
DR PDBsum; 4GTT; -.
DR PDBsum; 4GTV; -.
DR AlphaFoldDB; Q08603; -.
DR SMR; Q08603; -.
DR ComplexPortal; CPX-2249; Protein geranylgeranyltransferase type II complex.
DR DIP; DIP-6138N; -.
DR STRING; 10116.ENSRNOP00000061541; -.
DR BindingDB; Q08603; -.
DR ChEMBL; CHEMBL4523995; -.
DR PaxDb; Q08603; -.
DR GeneID; 25533; -.
DR KEGG; rno:25533; -.
DR CTD; 5876; -.
DR RGD; 3530; Rabggtb.
DR eggNOG; KOG0366; Eukaryota.
DR InParanoid; Q08603; -.
DR OrthoDB; 1042804at2759; -.
DR PhylomeDB; Q08603; -.
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; Q08603; -.
DR PRO; PR:Q08603; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005968; C:Rab-protein geranylgeranyltransferase complex; IDA:UniProtKB.
DR GO; GO:0019840; F:isoprenoid binding; IDA:CAFA.
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; IDA:UniProtKB.
DR GO; GO:0018344; P:protein geranylgeranylation; IDA:UniProtKB.
DR GO; GO:0018342; P:protein prenylation; IBA:GO_Central.
DR CDD; cd02894; GGTase-II; 1.
DR InterPro; IPR001330; PFTB_repeat.
DR InterPro; IPR045089; PGGT1B-like.
DR InterPro; IPR026873; Ptb1.
DR InterPro; IPR008930; Terpenoid_cyclase/PrenylTrfase.
DR PANTHER; PTHR11774; PTHR11774; 1.
DR Pfam; PF00432; Prenyltrans; 5.
DR SUPFAM; SSF48239; SSF48239; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Metal-binding;
KW Phosphoprotein; Prenyltransferase; Reference proteome; Repeat; Transferase;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P53611"
FT CHAIN 2..331
FT /note="Geranylgeranyl transferase type-2 subunit beta"
FT /id="PRO_0000119774"
FT REPEAT 20..61
FT /note="PFTB 1"
FT REPEAT 68..109
FT /note="PFTB 2"
FT REPEAT 116..157
FT /note="PFTB 3"
FT REPEAT 164..205
FT /note="PFTB 4"
FT REPEAT 212..253
FT /note="PFTB 5"
FT REPEAT 260..302
FT /note="PFTB 6"
FT BINDING 190..192
FT /ligand="geranylgeranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57533"
FT /evidence="ECO:0000269|PubMed:18756270,
FT ECO:0007744|PDB:3DST, ECO:0007744|PDB:3DSX"
FT BINDING 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18399557,
FT ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725,
FT ECO:0000269|PubMed:22480322, ECO:0000269|PubMed:22963166"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18399557,
FT ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725,
FT ECO:0000269|PubMed:22480322, ECO:0000269|PubMed:22963166"
FT BINDING 241..244
FT /ligand="geranylgeranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57533"
FT /evidence="ECO:0007744|PDB:3DST, ECO:0007744|PDB:3DSV"
FT BINDING 290
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:18399557,
FT ECO:0000269|PubMed:18756270, ECO:0000269|PubMed:19894725,
FT ECO:0000269|PubMed:22480322, ECO:0000269|PubMed:22963166"
FT MOD_RES 2
FT /note="N-acetylglycine"
FT /evidence="ECO:0000250|UniProtKB:P53611"
FT MOD_RES 3
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P53611"
FT HELIX 20..29
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 40..45
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 46..59
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 68..77
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 85..88
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 95..107
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 116..125
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 143..156
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 164..172
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 191..203
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 212..220
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 231..234
FT /evidence="ECO:0007829|PDB:1LTX"
FT HELIX 239..251
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 260..269
FT /evidence="ECO:0007829|PDB:3DSS"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:3HXF"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:3DSS"
FT TURN 311..313
FT /evidence="ECO:0007829|PDB:3DSS"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:3DSS"
FT HELIX 317..323
FT /evidence="ECO:0007829|PDB:3DSS"
SQ SEQUENCE 331 AA; 36856 MW; 4B12DEC0245979D6 CRC64;
MGTQQKDVTI KSDAPDTLLL EKHADYIASY GSKKDDYEYC MSEYLRMSGV YWGLTVMDLM
GQLHRMNKEE ILVFIKSCQH ECGGVSASIG HDPHLLYTLS AVQILTLYDS IHVINVDKVV
AYVQSLQKED GSFAGDIWGE IDTRFSFCAV ATLALLGKLD AINVEKAIEF VLSCMNFDGG
FGCRPGSESH AGQIYCCTGF LAITSQLHQV NSDLLGWWLC ERQLPSGGLN GRPEKLPDVC
YSWWVLASLK IIGRLHWIDR EKLRSFILAC QDEETGGFAD RPGDMVDPFH TLFGIAGLSL
LGEEQIKPVS PVFCMPEEVL QRVNVQPELV S
