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   24-JAN-2024, entry version 199.
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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; 94.
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; 9606-ENSP00000382341; -.
DR   PeptideAtlas; Q92696; -.
DR   ProteomicsDB; 75413; -.
DR   Pumba; Q92696; -.
DR   Antibodypedia; 22812; 104 antibodies from 23 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   AGR; HGNC:9795; -.
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; PKSYNAW; -.
DR   OrthoDB; 5489560at2759; -.
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; 702 hits in 1164 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 97 other cell types or tissues.
DR   ExpressionAtlas; Q92696; baseline and differential.
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; 1.25.40.120; Protein prenylyltransferase; 1.
DR   Gene3D; 2.60.40.1130; Rab geranylgeranyltransferase alpha-subunit, insert domain; 1.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 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   PANTHER; PTHR11129:SF2; GERANYLGERANYL TRANSFERASE TYPE-2 SUBUNIT ALPHA; 1.
DR   PANTHER; PTHR11129; PROTEIN FARNESYLTRANSFERASE ALPHA SUBUNIT/RAB GERANYLGERANYL TRANSFERASE ALPHA SUBUNIT; 1.
DR   Pfam; PF00560; LRR_1; 1.
DR   Pfam; PF01239; PPTA; 4.
DR   Pfam; PF07711; RabGGT_insert; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   SUPFAM; SSF48439; Protein prenylyltransferase; 1.
DR   SUPFAM; SSF49594; Rab geranylgeranyltransferase alpha-subunit, insert domain; 1.
DR   PROSITE; PS51450; LRR; 5.
DR   PROSITE; PS51147; PFTA; 6.
DR   Genevisible; Q92696; HS.
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
//