PGTA_HUMAN
ID PGTA_HUMAN Reviewed; 567 AA.
AC Q92696; A8K5N2; D3DS69;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 191.
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;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fetal brain;
RX PubMed=8954794; DOI=10.1006/geno.1996.0608;
RA van Bokhoven H., Rawson R.B., Merkx G.F.M., Cremers F.P.M., Seabra M.C.;
RT "cDNA cloning and chromosomal localization of the genes encoding the
RT alpha- and beta-subunits of human Rab geranylgeranyl transferase: the 3'
RT end of the alpha-subunit gene overlaps with the transglutaminase 1 gene
RT promoter.";
RL Genomics 38:133-140(1996).
RN [2]
RP SEQUENCE REVISION.
RA van Bokhoven H.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9196026; DOI=10.1006/bbrc.1997.6717;
RA Song H.-J., Rossi A., Ceci R., Kim I.-G., Anzano M.A., Jang S.-I.,
RA De Laurenzi V., Steinert P.M.;
RT "The genes encoding geranylgeranyl transferase alpha-subunit and
RT transglutaminase 1 are very closely linked but not functionally related in
RT terminally differentiating keratinocytes.";
RL Biochem. Biophys. Res. Commun. 235:10-14(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-420.
RC TISSUE=Thymus, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [7]
RP FUNCTION, SUBUNIT, AND CATALYTIC ACTIVITY.
RX PubMed=7991565; DOI=10.1073/pnas.91.25.11963;
RA Farnsworth C.C., Seabra M.C., Ericsson L.H., Gelb M.H., Glomset J.A.;
RT "Rab geranylgeranyl transferase catalyzes the geranylgeranylation of
RT adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:11963-11967(1994).
RN [8]
RP SUBUNIT.
RX PubMed=18532927; DOI=10.1042/bj20080662;
RA Baron R.A., Seabra M.C.;
RT "Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT
RT complex and is regulated by geranylgeranyl pyrophosphate.";
RL Biochem. J. 415:67-75(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH RAB8A.
RX PubMed=26824392; DOI=10.7554/elife.12813;
RA Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S.,
RA Lorentzen E., Duddy G., Wilson S., Baptista M.A., Fiske B.K., Fell M.J.,
RA Morrow J.A., Reith A.D., Alessi D.R., Mann M.;
RT "Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates
RT a subset of Rab GTPases.";
RL Elife 5:0-0(2016).
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:7991565}.
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:7991565};
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:7991565). 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). The CHM:RGGT:Rab complex is destabilized by GGpp
CC (PubMed:18532927). Interacts with non-phosphorylated form of RAB8A;
CC phosphorylation of RAB8A at 'Thr-72' disrupts this interaction
CC (PubMed:26824392). {ECO:0000269|PubMed:18532927,
CC ECO:0000269|PubMed:26824392, ECO:0000269|PubMed:7991565}.
CC -!- INTERACTION:
CC Q92696; P24386: CHM; NbExp=2; IntAct=EBI-9104196, EBI-2515129;
CC Q92696; P53611: RABGGTB; NbExp=4; IntAct=EBI-9104196, EBI-536715;
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family. {ECO:0000305}.
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DR EMBL; Y08200; CAA69382.1; -; mRNA.
DR EMBL; AK291347; BAF84036.1; -; mRNA.
DR EMBL; AK292613; BAF85302.1; -; mRNA.
DR EMBL; CH471078; EAW66044.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW66045.1; -; Genomic_DNA.
DR EMBL; BC003093; AAH03093.1; -; mRNA.
DR CCDS; CCDS45088.1; -.
DR PIR; JC5538; JC5538.
DR RefSeq; NP_004572.3; NM_004581.5.
DR RefSeq; NP_878256.1; NM_182836.2.
DR AlphaFoldDB; Q92696; -.
DR SMR; Q92696; -.
DR BioGRID; 111813; 75.
DR ComplexPortal; CPX-2919; Protein geranylgeranyltransferase type II complex.
DR CORUM; Q92696; -.
DR IntAct; Q92696; 23.
DR MINT; Q92696; -.
DR STRING; 9606.ENSP00000382341; -.
DR ChEMBL; CHEMBL5249; -.
DR DrugBank; DB07780; Farnesyl diphosphate.
DR DrugBank; DB07841; Geranylgeranyl diphosphate.
DR DrugBank; DB04464; N-Formylmethionine.
DR GlyGen; Q92696; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92696; -.
DR PhosphoSitePlus; Q92696; -.
DR BioMuta; RABGGTA; -.
DR DMDM; 6093707; -.
DR EPD; Q92696; -.
DR jPOST; Q92696; -.
DR MassIVE; Q92696; -.
DR MaxQB; Q92696; -.
DR PaxDb; Q92696; -.
DR PeptideAtlas; Q92696; -.
DR PRIDE; Q92696; -.
DR ProteomicsDB; 75413; -.
DR Antibodypedia; 22812; 90 antibodies from 22 providers.
DR DNASU; 5875; -.
DR Ensembl; ENST00000216840.11; ENSP00000216840.6; ENSG00000100949.15.
DR Ensembl; ENST00000399409.7; ENSP00000382341.3; ENSG00000100949.15.
DR Ensembl; ENST00000644383.1; ENSP00000494636.1; ENSG00000285193.1.
DR Ensembl; ENST00000646658.1; ENSP00000496595.1; ENSG00000285193.1.
DR GeneID; 5875; -.
DR KEGG; hsa:5875; -.
DR MANE-Select; ENST00000216840.11; ENSP00000216840.6; NM_182836.3; NP_878256.1.
DR UCSC; uc001wof.5; human.
DR CTD; 5875; -.
DR DisGeNET; 5875; -.
DR GeneCards; RABGGTA; -.
DR HGNC; HGNC:9795; RABGGTA.
DR HPA; ENSG00000100949; Tissue enhanced (esophagus).
DR MIM; 601905; gene.
DR neXtProt; NX_Q92696; -.
DR OpenTargets; ENSG00000100949; -.
DR PharmGKB; PA34156; -.
DR VEuPathDB; HostDB:ENSG00000100949; -.
DR eggNOG; KOG0529; Eukaryota.
DR GeneTree; ENSGT00550000075121; -.
DR InParanoid; Q92696; -.
DR OMA; YNAWHHR; -.
DR OrthoDB; 1527547at2759; -.
DR PhylomeDB; Q92696; -.
DR TreeFam; TF315057; -.
DR PathwayCommons; Q92696; -.
DR Reactome; R-HSA-6803205; TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR SignaLink; Q92696; -.
DR SIGNOR; Q92696; -.
DR BioGRID-ORCS; 5875; 668 hits in 1085 CRISPR screens.
DR ChiTaRS; RABGGTA; human.
DR GenomeRNAi; 5875; -.
DR Pharos; Q92696; Tdark.
DR PRO; PR:Q92696; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q92696; protein.
DR Bgee; ENSG00000100949; Expressed in lower esophagus mucosa and 95 other tissues.
DR ExpressionAtlas; Q92696; baseline and differential.
DR Genevisible; Q92696; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005968; C:Rab-protein geranylgeranyltransferase complex; ISS:UniProtKB.
DR GO; GO:0004663; F:Rab geranylgeranyltransferase activity; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0018344; P:protein geranylgeranylation; ISS:UniProtKB.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
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; PS51450; LRR; 5.
DR PROSITE; PS51147; PFTA; 6.
PE 1: Evidence at protein level;
KW Leucine-rich repeat; Phosphoprotein; Prenyltransferase; Reference proteome;
KW Repeat; Transferase.
FT CHAIN 1..567
FT /note="Geranylgeranyl transferase type-2 subunit alpha"
FT /id="PRO_0000119757"
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 VARIANT 420
FT /note="T -> A (in dbSNP:rs729421)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_020406"
SQ SEQUENCE 567 AA; 65072 MW; ABA1AFFC8A496C5F CRC64;
MHGRLKVKTS EEQAEAKRLE REQKLKLYQS ATQAVFQKRQ AGELDESVLE LTSQILGANP
DFATLWNCRR EVLQQLETQK SPEELAALVK AELGFLESCL RVNPKSYGTW HHRCWLLGRL
PEPNWTRELE LCARFLEVDE RNFHCWDYRR FVATQAAVPP AEELAFTDSL ITRNFSNYSS
WHYRSCLLPQ LHPQPDSGPQ GRLPEDVLLK ELELVQNAFF TDPNDQSAWF YHRWLLGRAD
PQDALRCLHV SRDEACLTVS FSRPLLVGSR MEILLLMVDD SPLIVEWRTP DGRNRPSHVW
LCDLPAASLN DQLPQHTFRV IWTAGDVQKE CVLLKGRQEG WCRDSTTDEQ LFRCELSVEK
STVLQSELES CKELQELEPE NKWCLLTIIL LMRALDPLLY EKETLQYFQT LKAVDPMRAT
YLDDLRSKFL LENSVLKMEY AEVRVLHLAH KDLTVLCHLE QLLLVTHLDL SHNRLRTLPP
ALAALRCLEV LQASDNAIES LDGVTNLPRL QELLLCNNRL QQPAVLQPLA SCPRLVLLNL
QGNPLCQAVG ILEQLAELLP SVSSVLT
