Full text data of RABGGTA
RABGGTA
[Confidence: low (only semi-automatic identification from reviews)]
Geranylgeranyl transferase type-2 subunit alpha; 2.5.1.60 (Geranylgeranyl transferase type II subunit alpha; Rab geranyl-geranyltransferase subunit alpha; Rab GG transferase alpha; Rab GGTase alpha; Rab geranylgeranyltransferase subunit alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Geranylgeranyl transferase type-2 subunit alpha; 2.5.1.60 (Geranylgeranyl transferase type II subunit alpha; Rab geranyl-geranyltransferase subunit alpha; Rab GG transferase alpha; Rab GGTase alpha; Rab geranylgeranyltransferase subunit alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q92696
ID PGTA_HUMAN Reviewed; 567 AA.
AC Q92696; A8K5N2; D3DS69;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1999, sequence version 2.
DT 22-JAN-2014, entry version 127.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA 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
RT 3' end of the alpha-subunit gene overlaps with the transglutaminase 1
RT gene 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
RT related in 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION.
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-
RT RGGT 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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the transfer of a geranyl-geranyl moiety from
CC geranyl-geranyl pyrophosphate to both cysteines in Rab proteins
CC with an -XXCC, -XCXC and -CCXX C-terminal, such as RAB1A, RAB3A
CC and RAB5A respectively.
CC -!- CATALYTIC ACTIVITY: Geranylgeranyl diphosphate + protein-cysteine
CC = S-geranylgeranyl-protein + diphosphate.
CC -!- COFACTOR: Binds 1 zinc ion per dimer (By similarity).
CC -!- ENZYME REGULATION: The enzymatic reaction requires the aid of a
CC Rab escort protein (also called component A).
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit, collectively
CC called component B. The Rab GGTase dimer (RGGT) can associate with
CC CHM (component A) prior to Rab protein binding; the association is
CC stabilized by geranylgeranyl pyrophosphate (GGpp). The
CC CHM:RGGT:Rab complex is destabilized by GGpp.
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family.
CC -!- SIMILARITY: Contains 5 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 6 PFTA repeats.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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 PIR; JC5538; JC5538.
DR RefSeq; NP_004572.3; NM_004581.5.
DR RefSeq; NP_878256.1; NM_182836.2.
DR RefSeq; XP_005268015.1; XM_005267958.1.
DR UniGene; Hs.377992; -.
DR ProteinModelPortal; Q92696; -.
DR SMR; Q92696; 2-567.
DR STRING; 9606.ENSP00000216840; -.
DR BindingDB; Q92696; -.
DR PhosphoSite; Q92696; -.
DR DMDM; 6093707; -.
DR PaxDb; Q92696; -.
DR PRIDE; Q92696; -.
DR Ensembl; ENST00000216840; ENSP00000216840; ENSG00000100949.
DR Ensembl; ENST00000399409; ENSP00000382341; ENSG00000100949.
DR GeneID; 5875; -.
DR KEGG; hsa:5875; -.
DR UCSC; uc001wof.4; human.
DR CTD; 5875; -.
DR GeneCards; GC14M024734; -.
DR HGNC; HGNC:9795; RABGGTA.
DR HPA; HPA043488; -.
DR MIM; 601905; gene.
DR neXtProt; NX_Q92696; -.
DR PharmGKB; PA34156; -.
DR eggNOG; COG5536; -.
DR HOGENOM; HOG000007845; -.
DR HOVERGEN; HBG002171; -.
DR InParanoid; Q92696; -.
DR KO; K14050; -.
DR OMA; WNCRREV; -.
DR OrthoDB; EOG7PP56C; -.
DR GenomeRNAi; 5875; -.
DR NextBio; 22826; -.
DR PRO; PR:Q92696; -.
DR ArrayExpress; Q92696; -.
DR Bgee; Q92696; -.
DR CleanEx; HS_RABGGTA; -.
DR Genevestigator; Q92696; -.
DR GO; GO:0004663; F:Rab geranylgeranyltransferase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc.
DR GO; GO:0018344; P:protein geranylgeranylation; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 2.60.40.1130; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR002088; Prenyl_trans_a.
DR InterPro; IPR009087; RabGGT_asu_insert-domain.
DR Pfam; PF00560; LRR_1; 1.
DR Pfam; PF01239; PPTA; 5.
DR Pfam; PF07711; RabGGT_insert; 1.
DR ProDom; PD331837; RabGG_trans_A; 1.
DR SUPFAM; SSF49594; SSF49594; 1.
DR PROSITE; PS51450; LRR; 5.
DR PROSITE; PS51147; PFTA; 6.
PE 1: Evidence at protein level;
KW Complete proteome; Leucine-rich repeat; Metal-binding; Polymorphism;
KW Prenyltransferase; Reference proteome; Repeat; Transferase; Zinc.
FT CHAIN 1 567 Geranylgeranyl transferase type-2 subunit
FT alpha.
FT /FTId=PRO_0000119757.
FT REPEAT 44 78 PFTA 1.
FT REPEAT 88 122 PFTA 2.
FT REPEAT 124 158 PFTA 3.
FT REPEAT 159 193 PFTA 4.
FT REPEAT 207 241 PFTA 5.
FT REPEAT 363 397 PFTA 6.
FT REPEAT 442 463 LRR 1.
FT REPEAT 464 486 LRR 2.
FT REPEAT 487 508 LRR 3.
FT REPEAT 509 530 LRR 4.
FT REPEAT 534 555 LRR 5.
FT METAL 2 2 Zinc (By similarity).
FT VARIANT 420 420 T -> A (in dbSNP:rs729421).
FT /FTId=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
//
ID PGTA_HUMAN Reviewed; 567 AA.
AC Q92696; A8K5N2; D3DS69;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1999, sequence version 2.
DT 22-JAN-2014, entry version 127.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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.,
RA 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
RT 3' end of the alpha-subunit gene overlaps with the transglutaminase 1
RT gene 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
RT related in 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP CHARACTERIZATION.
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-
RT RGGT 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.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Catalyzes the transfer of a geranyl-geranyl moiety from
CC geranyl-geranyl pyrophosphate to both cysteines in Rab proteins
CC with an -XXCC, -XCXC and -CCXX C-terminal, such as RAB1A, RAB3A
CC and RAB5A respectively.
CC -!- CATALYTIC ACTIVITY: Geranylgeranyl diphosphate + protein-cysteine
CC = S-geranylgeranyl-protein + diphosphate.
CC -!- COFACTOR: Binds 1 zinc ion per dimer (By similarity).
CC -!- ENZYME REGULATION: The enzymatic reaction requires the aid of a
CC Rab escort protein (also called component A).
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit, collectively
CC called component B. The Rab GGTase dimer (RGGT) can associate with
CC CHM (component A) prior to Rab protein binding; the association is
CC stabilized by geranylgeranyl pyrophosphate (GGpp). The
CC CHM:RGGT:Rab complex is destabilized by GGpp.
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family.
CC -!- SIMILARITY: Contains 5 LRR (leucine-rich) repeats.
CC -!- SIMILARITY: Contains 6 PFTA repeats.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs 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 PIR; JC5538; JC5538.
DR RefSeq; NP_004572.3; NM_004581.5.
DR RefSeq; NP_878256.1; NM_182836.2.
DR RefSeq; XP_005268015.1; XM_005267958.1.
DR UniGene; Hs.377992; -.
DR ProteinModelPortal; Q92696; -.
DR SMR; Q92696; 2-567.
DR STRING; 9606.ENSP00000216840; -.
DR BindingDB; Q92696; -.
DR PhosphoSite; Q92696; -.
DR DMDM; 6093707; -.
DR PaxDb; Q92696; -.
DR PRIDE; Q92696; -.
DR Ensembl; ENST00000216840; ENSP00000216840; ENSG00000100949.
DR Ensembl; ENST00000399409; ENSP00000382341; ENSG00000100949.
DR GeneID; 5875; -.
DR KEGG; hsa:5875; -.
DR UCSC; uc001wof.4; human.
DR CTD; 5875; -.
DR GeneCards; GC14M024734; -.
DR HGNC; HGNC:9795; RABGGTA.
DR HPA; HPA043488; -.
DR MIM; 601905; gene.
DR neXtProt; NX_Q92696; -.
DR PharmGKB; PA34156; -.
DR eggNOG; COG5536; -.
DR HOGENOM; HOG000007845; -.
DR HOVERGEN; HBG002171; -.
DR InParanoid; Q92696; -.
DR KO; K14050; -.
DR OMA; WNCRREV; -.
DR OrthoDB; EOG7PP56C; -.
DR GenomeRNAi; 5875; -.
DR NextBio; 22826; -.
DR PRO; PR:Q92696; -.
DR ArrayExpress; Q92696; -.
DR Bgee; Q92696; -.
DR CleanEx; HS_RABGGTA; -.
DR Genevestigator; Q92696; -.
DR GO; GO:0004663; F:Rab geranylgeranyltransferase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc.
DR GO; GO:0018344; P:protein geranylgeranylation; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 2.60.40.1130; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR002088; Prenyl_trans_a.
DR InterPro; IPR009087; RabGGT_asu_insert-domain.
DR Pfam; PF00560; LRR_1; 1.
DR Pfam; PF01239; PPTA; 5.
DR Pfam; PF07711; RabGGT_insert; 1.
DR ProDom; PD331837; RabGG_trans_A; 1.
DR SUPFAM; SSF49594; SSF49594; 1.
DR PROSITE; PS51450; LRR; 5.
DR PROSITE; PS51147; PFTA; 6.
PE 1: Evidence at protein level;
KW Complete proteome; Leucine-rich repeat; Metal-binding; Polymorphism;
KW Prenyltransferase; Reference proteome; Repeat; Transferase; Zinc.
FT CHAIN 1 567 Geranylgeranyl transferase type-2 subunit
FT alpha.
FT /FTId=PRO_0000119757.
FT REPEAT 44 78 PFTA 1.
FT REPEAT 88 122 PFTA 2.
FT REPEAT 124 158 PFTA 3.
FT REPEAT 159 193 PFTA 4.
FT REPEAT 207 241 PFTA 5.
FT REPEAT 363 397 PFTA 6.
FT REPEAT 442 463 LRR 1.
FT REPEAT 464 486 LRR 2.
FT REPEAT 487 508 LRR 3.
FT REPEAT 509 530 LRR 4.
FT REPEAT 534 555 LRR 5.
FT METAL 2 2 Zinc (By similarity).
FT VARIANT 420 420 T -> A (in dbSNP:rs729421).
FT /FTId=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
//
MIM
601905
*RECORD*
*FIELD* NO
601905
*FIELD* TI
*601905 RAB GERANYLGERANYL TRANSFERASE, ALPHA SUBUNIT; RABGGTA
*FIELD* TX
See RABGGTB (179080) for general information about RAB geranylgeranyl
read moretransferase.
CLONING
Van Bokhoven et al. (1996) cloned the human RABGGTA gene from a fetal
brain library. The gene encodes a 567-amino acid polypeptide. Homology
to the transglutaminase gene, TGM1 (190195), which maps to 14q11,
indicated that this subunit was located on the same chromosomal band;
Southern blot analysis confirmed this locus. Van Bokhoven et al. (1996)
found that the 3-prime end of the RABGGTA cDNA sequence overlaps the
promoter region of TGM1. Further analysis revealed that the RABGGTA and
TGM1 genes are located only 2 kb apart in head-to-tail tandem
arrangement; however, these 2 genes are not likely to be functionally
related.
GENE FUNCTION
Seabra et al. (1991) presented evidence that 2 prenyltransferases,
farnesyltransferase and geranylgeranyltransferase (GGTase), are
heterodimers that share a common alpha subunit with different beta
subunits. The third identified prenyltransferase is a GGTase that
recognizes proteins that terminate in the sequence cys-X-cys or cys-cys.
Its substrates include a large family of related membrane-associated
GTP-binding proteins termed RAB proteins. According to van Bokhoven et
al. (1996), RAB proteins are the only known substrates of RAB GGTase.
RAB GGTase is composed of 2 tightly associated subunits, alpha (RABGGTA)
and beta (RABGGTB, 179080). The enzyme from rat brain contains 2
components, A and B. Seabra et al. (1992) reported the purification of
component A, a single 95-kD polypeptide. The holoenzyme attaches
(3)H-geranylgeranyl to cysteines in 2 GTP-binding proteins, RAB3A
(179490) and RAB1A (179508). Six peptides from rat component A showed
striking similarity to the product of a defective gene in choroideremia
(303100). Seabra et al. (1992) hypothesized that component A binds
conserved sequences in RAB and that component B transfers
geranylgeranyl. Seabra et al. (1993) demonstrated a marked deficiency in
the activity of component A in lymphoblasts from subjects with
choroideremia.
ANIMAL MODEL
Mice homozygous for 'gunmetal' (gm), a spontaneous, recessive mutation,
have prolonged bleeding caused by defects in platelets and
megakaryocytes (Swank et al., 1993; Novak et al., 1995). These mice also
have macrothrombocytopenia and reduced platelet alpha- and delta-granule
contents (storage pool deficiency, SPD). Megakaryocytes, the progenitors
of platelets, are more plentiful in gm mice, but have abnormal
intracellular membranes, increased emperipolesis (the active movement of
1 cell through another), and decreased platelet synthesis. In addition,
gm homozygotes have partial cutaneous albinism, the feature that gives
the mutation its name. Detter et al. (2000) noted that the phenotype
resembles human gray platelet syndrome (GPS; 139090) and platelet alpha-
and delta-SPD (185050).
By positional cloning, Detter et al. (2000) showed that gm results from
a G-to-A substitution in a splice acceptor site within the alpha-subunit
of RAB geranylgeranyl transferase (Rabggta). Most Rabggta mRNAs from gm
tissues skipped exon 1 and lacked a start codon. Levels of the protein
and of enzyme activity were reduced 4-fold in gm platelets.
Geranylgeranylation and membrane association of Rab27 (603868), a RAB
GGTase substrate, were significantly decreased in gm platelets. These
findings indicated that geranylgeranylation of RAB GTPases is critical
for hemostasis. Detter et al. (2000) suggested that Rab GGTase
inhibition may represent a therapeutic approach for thrombocytosis and
clotting disorders.
*FIELD* RF
1. Detter, J. C.; Zhang, Q.; Mules, E. H.; Novak, E. K.; Mishra, V.
S.; Li, W.; McMurtrie, E. B.; Tchernev, V. T.; Wallace, M. R.; Seabra,
M. C.; Swank, R. T.; Kingsmore, S. F.: Rab geranylgeranyl transferase
alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet
synthesis. Proc. Nat. Acad. Sci. 97: 4144-4149, 2000.
2. Novak, E. K.; Reddington, M.; Zhen, L.; Stenberg, P. E.; Jackson,
C. W.; McGarry, M. P.; Swank, R. T.: Inherited thrombocytopenia caused
by reduced platelet production in mice with the gunmetal pigment gene
mutation. Blood 85: 1781-1789, 1995.
3. Seabra, M. C.; Brown, M. S.; Goldstein, J. L.: Retinal degeneration
in choroideremia: deficiency of Rab geranylgeranyl transferase. Science 259:
377-381, 1993.
4. Seabra, M. C.; Brown, M. S.; Slaughter, C. A.; Sudhof, T. C.; Goldstein,
J. L.: Purification of component A of Rab geranylgeranyl transferase:
possible identity with the choroideremia gene product. Cell 70:
1049-1057, 1992.
5. Seabra, M. C.; Reiss, Y.; Casey, P. J.; Brown, M. S.; Goldstein,
J. L.: Protein farnesyltransferase and geranylgeranyltransferase
share a common alpha subunit. Cell 65: 429-434, 1991.
6. Swank, R. T.; Jiang, S. Y.; Reddington, M.; Conway, J.; Stephenson,
D.; McGarry, M. P.; Novak, E. K.: Inherited abnormalities in platelet
organelles and platelet formation and associated altered expression
of low molecular weight guanosine triphosphate-binding proteins in
the mouse pigment mutant gunmetal. Blood 81: 2626-2635, 1993.
7. van Bokhoven, H.; Rawson, R. B.; Merkx, G. F. M.; Cremers, F. P.
M.; Seabra, M. C.: cDNA cloning and chromosomal localization of the
genes encoding the alpha- and beta-subunits of human Rab geranylgeranyl
transferase: the 3-prime end of the alpha-subunit gene overlaps with
the transglutaminase 1 gene promoter. Genomics 38: 133-140, 1996.
*FIELD* CN
Victor A. McKusick - updated: 10/14/2002
Jennifer P. Macke - updated: 4/29/1997
*FIELD* CD
Victor A. McKusick: 3/27/1992
*FIELD* ED
terry: 01/02/2003
tkritzer: 10/28/2002
tkritzer: 10/17/2002
terry: 10/14/2002
alopez: 3/3/1998
mark: 10/6/1997
alopez: 7/16/1997
alopez: 6/26/1997
*RECORD*
*FIELD* NO
601905
*FIELD* TI
*601905 RAB GERANYLGERANYL TRANSFERASE, ALPHA SUBUNIT; RABGGTA
*FIELD* TX
See RABGGTB (179080) for general information about RAB geranylgeranyl
read moretransferase.
CLONING
Van Bokhoven et al. (1996) cloned the human RABGGTA gene from a fetal
brain library. The gene encodes a 567-amino acid polypeptide. Homology
to the transglutaminase gene, TGM1 (190195), which maps to 14q11,
indicated that this subunit was located on the same chromosomal band;
Southern blot analysis confirmed this locus. Van Bokhoven et al. (1996)
found that the 3-prime end of the RABGGTA cDNA sequence overlaps the
promoter region of TGM1. Further analysis revealed that the RABGGTA and
TGM1 genes are located only 2 kb apart in head-to-tail tandem
arrangement; however, these 2 genes are not likely to be functionally
related.
GENE FUNCTION
Seabra et al. (1991) presented evidence that 2 prenyltransferases,
farnesyltransferase and geranylgeranyltransferase (GGTase), are
heterodimers that share a common alpha subunit with different beta
subunits. The third identified prenyltransferase is a GGTase that
recognizes proteins that terminate in the sequence cys-X-cys or cys-cys.
Its substrates include a large family of related membrane-associated
GTP-binding proteins termed RAB proteins. According to van Bokhoven et
al. (1996), RAB proteins are the only known substrates of RAB GGTase.
RAB GGTase is composed of 2 tightly associated subunits, alpha (RABGGTA)
and beta (RABGGTB, 179080). The enzyme from rat brain contains 2
components, A and B. Seabra et al. (1992) reported the purification of
component A, a single 95-kD polypeptide. The holoenzyme attaches
(3)H-geranylgeranyl to cysteines in 2 GTP-binding proteins, RAB3A
(179490) and RAB1A (179508). Six peptides from rat component A showed
striking similarity to the product of a defective gene in choroideremia
(303100). Seabra et al. (1992) hypothesized that component A binds
conserved sequences in RAB and that component B transfers
geranylgeranyl. Seabra et al. (1993) demonstrated a marked deficiency in
the activity of component A in lymphoblasts from subjects with
choroideremia.
ANIMAL MODEL
Mice homozygous for 'gunmetal' (gm), a spontaneous, recessive mutation,
have prolonged bleeding caused by defects in platelets and
megakaryocytes (Swank et al., 1993; Novak et al., 1995). These mice also
have macrothrombocytopenia and reduced platelet alpha- and delta-granule
contents (storage pool deficiency, SPD). Megakaryocytes, the progenitors
of platelets, are more plentiful in gm mice, but have abnormal
intracellular membranes, increased emperipolesis (the active movement of
1 cell through another), and decreased platelet synthesis. In addition,
gm homozygotes have partial cutaneous albinism, the feature that gives
the mutation its name. Detter et al. (2000) noted that the phenotype
resembles human gray platelet syndrome (GPS; 139090) and platelet alpha-
and delta-SPD (185050).
By positional cloning, Detter et al. (2000) showed that gm results from
a G-to-A substitution in a splice acceptor site within the alpha-subunit
of RAB geranylgeranyl transferase (Rabggta). Most Rabggta mRNAs from gm
tissues skipped exon 1 and lacked a start codon. Levels of the protein
and of enzyme activity were reduced 4-fold in gm platelets.
Geranylgeranylation and membrane association of Rab27 (603868), a RAB
GGTase substrate, were significantly decreased in gm platelets. These
findings indicated that geranylgeranylation of RAB GTPases is critical
for hemostasis. Detter et al. (2000) suggested that Rab GGTase
inhibition may represent a therapeutic approach for thrombocytosis and
clotting disorders.
*FIELD* RF
1. Detter, J. C.; Zhang, Q.; Mules, E. H.; Novak, E. K.; Mishra, V.
S.; Li, W.; McMurtrie, E. B.; Tchernev, V. T.; Wallace, M. R.; Seabra,
M. C.; Swank, R. T.; Kingsmore, S. F.: Rab geranylgeranyl transferase
alpha mutation in the gunmetal mouse reduces Rab prenylation and platelet
synthesis. Proc. Nat. Acad. Sci. 97: 4144-4149, 2000.
2. Novak, E. K.; Reddington, M.; Zhen, L.; Stenberg, P. E.; Jackson,
C. W.; McGarry, M. P.; Swank, R. T.: Inherited thrombocytopenia caused
by reduced platelet production in mice with the gunmetal pigment gene
mutation. Blood 85: 1781-1789, 1995.
3. Seabra, M. C.; Brown, M. S.; Goldstein, J. L.: Retinal degeneration
in choroideremia: deficiency of Rab geranylgeranyl transferase. Science 259:
377-381, 1993.
4. Seabra, M. C.; Brown, M. S.; Slaughter, C. A.; Sudhof, T. C.; Goldstein,
J. L.: Purification of component A of Rab geranylgeranyl transferase:
possible identity with the choroideremia gene product. Cell 70:
1049-1057, 1992.
5. Seabra, M. C.; Reiss, Y.; Casey, P. J.; Brown, M. S.; Goldstein,
J. L.: Protein farnesyltransferase and geranylgeranyltransferase
share a common alpha subunit. Cell 65: 429-434, 1991.
6. Swank, R. T.; Jiang, S. Y.; Reddington, M.; Conway, J.; Stephenson,
D.; McGarry, M. P.; Novak, E. K.: Inherited abnormalities in platelet
organelles and platelet formation and associated altered expression
of low molecular weight guanosine triphosphate-binding proteins in
the mouse pigment mutant gunmetal. Blood 81: 2626-2635, 1993.
7. van Bokhoven, H.; Rawson, R. B.; Merkx, G. F. M.; Cremers, F. P.
M.; Seabra, M. C.: cDNA cloning and chromosomal localization of the
genes encoding the alpha- and beta-subunits of human Rab geranylgeranyl
transferase: the 3-prime end of the alpha-subunit gene overlaps with
the transglutaminase 1 gene promoter. Genomics 38: 133-140, 1996.
*FIELD* CN
Victor A. McKusick - updated: 10/14/2002
Jennifer P. Macke - updated: 4/29/1997
*FIELD* CD
Victor A. McKusick: 3/27/1992
*FIELD* ED
terry: 01/02/2003
tkritzer: 10/28/2002
tkritzer: 10/17/2002
terry: 10/14/2002
alopez: 3/3/1998
mark: 10/6/1997
alopez: 7/16/1997
alopez: 6/26/1997