Full text data of FNTA
FNTA
[Confidence: low (only semi-automatic identification from reviews)]
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha; 2.5.1.58; 2.5.1.59 (CAAX farnesyltransferase subunit alpha; FTase-alpha; Ras proteins prenyltransferase subunit alpha; Type I protein geranyl-geranyltransferase subunit alpha; GGTase-I-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha; 2.5.1.58; 2.5.1.59 (CAAX farnesyltransferase subunit alpha; FTase-alpha; Ras proteins prenyltransferase subunit alpha; Type I protein geranyl-geranyltransferase subunit alpha; GGTase-I-alpha)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P49354
ID FNTA_HUMAN Reviewed; 379 AA.
AC P49354; A6NJW0; Q53XJ9; Q9UDC1;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 1.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha;
DE EC=2.5.1.58;
DE EC=2.5.1.59;
DE AltName: Full=CAAX farnesyltransferase subunit alpha;
DE AltName: Full=FTase-alpha;
DE AltName: Full=Ras proteins prenyltransferase subunit alpha;
DE AltName: Full=Type I protein geranyl-geranyltransferase subunit alpha;
DE Short=GGTase-I-alpha;
GN Name=FNTA;
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] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=8276393; DOI=10.1006/geno.1993.1432;
RA Andres D.A., Milatovich A., Ozcelik T., Wenzlau J.M., Brown M.S.,
RA Goldstein J.L., Francke U.;
RT "cDNA cloning of the two subunits of human CAAX farnesyltransferase
RT and chromosomal mapping of FNTA and FNTB loci and related sequences.";
RL Genomics 18:105-112(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-164.
RX PubMed=8419339;
RA Andres D.A., Goldstein J.L., Ho Y.K., Brown M.S.;
RT "Mutational analysis of alpha-subunit of protein farnesyltransferase.
RT Evidence for a catalytic role.";
RL J. Biol. Chem. 268:1383-1390(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF ASN-199.
RC TISSUE=Placenta;
RX PubMed=8494894; DOI=10.1021/bi00070a028;
RA Omer C.A., Kral A.M., Diehl R.E., Prendergast G.C., Powers S.,
RA Allen C.M., Gibbs J.B., Kohl N.E.;
RT "Characterization of recombinant human farnesyl-protein transferase:
RT cloning, expression, farnesyl diphosphate binding, and functional
RT homology with yeast prenyl-protein transferases.";
RL Biochemistry 32:5167-5176(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-261 (ISOFORM 2).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT;
RP FARNESYL DIPHOSPHATE AND INHIBITOR L-739,750.
RX PubMed=11687658; DOI=10.1073/pnas.241407898;
RA Long S.B., Hancock P.J., Kral A.M., Hellinga H.W., Beese L.S.;
RT "The crystal structure of human protein farnesyltransferase reveals
RT the basis for inhibition by CaaX tetrapeptides and their mimetics.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12948-12953(2001).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT;
RP FARNESYL DIPHOSPHATE AND INHIBITORS.
RX PubMed=12036349; DOI=10.1021/jm010531d;
RA Bell I.M., Gallicchio S.N., Abrams M., Beese L.S., Beshore D.C.,
RA Bhimnathwala H., Bogusky M.J., Buser C.A., Culberson J.C., Davide J.,
RA Ellis-Hutchings M., Fernandes C., Gibbs J.B., Graham S.L.,
RA Hamilton K.A., Hartman G.D., Heimbrook D.C., Homnick C.F., Huber H.E.,
RA Huff J.R., Kassahun K., Koblan K.S., Kohl N.E., Lobell R.B.,
RA Lynch J.J. Jr., Robinson R., Rodrigues A.D., Taylor J.S., Walsh E.S.,
RA Williams T.M., Zartman C.B.;
RT "3-aminopyrrolidinone farnesyltransferase inhibitors: design of
RT macrocyclic compounds with improved pharmacokinetics and excellent
RT cell potency.";
RL J. Med. Chem. 45:2388-2409(2002).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT;
RP FARNESYL DIPHOSPHATE AND INHIBITOR.
RX PubMed=12825937; DOI=10.1021/jm020587n;
RA deSolms S.J., Ciccarone T.M., MacTough S.C., Shaw A.W., Buser C.A.,
RA Ellis-Hutchings M., Fernandes C., Hamilton K.A., Huber H.E.,
RA Kohl N.E., Lobell R.B., Robinson R.G., Tsou N.N., Walsh E.S.,
RA Graham S.L., Beese L.S., Taylor J.S.;
RT "Dual protein farnesyltransferase-geranylgeranyltransferase-I
RT inhibitors as potential cancer chemotherapeutic agents.";
RL J. Med. Chem. 46:2973-2984(2003).
CC -!- FUNCTION: Catalyzes the transfer of a farnesyl or geranyl-geranyl
CC moiety from farnesyl or geranyl-geranyl pyrophosphate to a
CC cysteine at the fourth position from the C-terminus of several
CC proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.
CC The alpha subunit is thought to participate in a stable complex
CC with the substrate. The beta subunit binds the peptide substrate.
CC Through RAC1 prenylation and activation may positively regulate
CC neuromuscular junction development downstream of MUSK (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: Farnesyl diphosphate + protein-cysteine = S-
CC farnesyl protein + diphosphate.
CC -!- CATALYTIC ACTIVITY: Geranylgeranyl diphosphate + protein-cysteine
CC = S-geranylgeranyl-protein + diphosphate.
CC -!- ENZYME REGULATION: Activated by the AGRIN-induced phosphorylation
CC which is mediated by MUSK (By similarity).
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Interacts
CC with MUSK; the interaction is direct and mediates AGRIN-induced
CC phosphorylation of FNTA (By similarity).
CC -!- INTERACTION:
CC P49356:FNTB; NbExp=7; IntAct=EBI-602336, EBI-602349;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49354-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49354-2; Sequence=VSP_036468;
CC -!- PTM: Phosphorylated. Phosphorylation is mediated by MUSK upon
CC AGRIN stimulation and results in the activation of FNTA (By
CC similarity).
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family.
CC -!- SIMILARITY: Contains 5 PFTA repeats.
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DR EMBL; L10413; AAA86285.1; -; mRNA.
DR EMBL; L00634; AAA35853.1; -; mRNA.
DR EMBL; AC110275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BT009854; AAP88856.1; -; mRNA.
DR EMBL; AK292121; BAF84810.1; -; mRNA.
DR EMBL; AC113191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017029; AAH17029.2; -; mRNA.
DR EMBL; BC084566; AAH84566.1; -; mRNA.
DR EMBL; AL698961; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A47659; A47659.
DR RefSeq; NP_002018.1; NM_002027.2.
DR UniGene; Hs.370312; -.
DR PDB; 1JCQ; X-ray; 2.30 A; A=1-379.
DR PDB; 1LD7; X-ray; 2.00 A; A=1-379.
DR PDB; 1LD8; X-ray; 1.80 A; A=1-379.
DR PDB; 1MZC; X-ray; 2.00 A; A=1-379.
DR PDB; 1S63; X-ray; 1.90 A; A=1-379.
DR PDB; 1SA4; X-ray; 2.10 A; A=1-379.
DR PDB; 1TN6; X-ray; 1.80 A; A=1-379.
DR PDB; 2F0Y; X-ray; 2.70 A; A=1-379.
DR PDB; 2H6F; X-ray; 1.50 A; A=1-379.
DR PDB; 2H6G; X-ray; 1.85 A; A=1-379.
DR PDB; 2H6H; X-ray; 1.80 A; A=1-379.
DR PDB; 2H6I; X-ray; 3.00 A; A=1-379.
DR PDB; 2IEJ; X-ray; 1.80 A; A=1-379.
DR PDB; 3E37; X-ray; 1.80 A; A=1-379.
DR PDBsum; 1JCQ; -.
DR PDBsum; 1LD7; -.
DR PDBsum; 1LD8; -.
DR PDBsum; 1MZC; -.
DR PDBsum; 1S63; -.
DR PDBsum; 1SA4; -.
DR PDBsum; 1TN6; -.
DR PDBsum; 2F0Y; -.
DR PDBsum; 2H6F; -.
DR PDBsum; 2H6G; -.
DR PDBsum; 2H6H; -.
DR PDBsum; 2H6I; -.
DR PDBsum; 2IEJ; -.
DR PDBsum; 3E37; -.
DR DisProt; DP00558; -.
DR ProteinModelPortal; P49354; -.
DR SMR; P49354; 55-369.
DR IntAct; P49354; 12.
DR MINT; MINT-238861; -.
DR STRING; 9606.ENSP00000303423; -.
DR BindingDB; P49354; -.
DR ChEMBL; CHEMBL2094108; -.
DR PhosphoSite; P49354; -.
DR DMDM; 1346694; -.
DR PaxDb; P49354; -.
DR PRIDE; P49354; -.
DR DNASU; 2339; -.
DR Ensembl; ENST00000302279; ENSP00000303423; ENSG00000168522.
DR Ensembl; ENST00000342116; ENSP00000343931; ENSG00000168522.
DR GeneID; 2339; -.
DR KEGG; hsa:2339; -.
DR UCSC; uc003xps.3; human.
DR CTD; 2339; -.
DR GeneCards; GC08P042928; -.
DR HGNC; HGNC:3782; FNTA.
DR HPA; CAB010149; -.
DR HPA; HPA018830; -.
DR MIM; 134635; gene.
DR neXtProt; NX_P49354; -.
DR PharmGKB; PA28199; -.
DR eggNOG; COG5536; -.
DR HOGENOM; HOG000188957; -.
DR HOVERGEN; HBG004498; -.
DR InParanoid; P49354; -.
DR KO; K05955; -.
DR OMA; DATDYFR; -.
DR PhylomeDB; P49354; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR EvolutionaryTrace; P49354; -.
DR GeneWiki; FNTA; -.
DR GenomeRNAi; 2339; -.
DR NextBio; 9495; -.
DR PMAP-CutDB; P49354; -.
DR PRO; PR:P49354; -.
DR ArrayExpress; P49354; -.
DR Bgee; P49354; -.
DR CleanEx; HS_FNTA; -.
DR Genevestigator; P49354; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005875; C:microtubule associated complex; IDA:BHF-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:BHF-UCL.
DR GO; GO:0004662; F:CAAX-protein geranylgeranyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008017; F:microtubule binding; IDA:BHF-UCL.
DR GO; GO:0004660; F:protein farnesyltransferase activity; TAS:ProtInc.
DR GO; GO:0004661; F:protein geranylgeranyltransferase activity; TAS:ProtInc.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR GO; GO:0090045; P:positive regulation of deacetylase activity; IDA:BHF-UCL.
DR GO; GO:0090044; P:positive regulation of tubulin deacetylation; IDA:BHF-UCL.
DR GO; GO:0018343; P:protein farnesylation; IDA:BHF-UCL.
DR GO; GO:0018344; P:protein geranylgeranylation; TAS:ProtInc.
DR GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0016056; P:rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
DR InterPro; IPR002088; Prenyl_trans_a.
DR Pfam; PF01239; PPTA; 5.
DR PROSITE; PS51147; PFTA; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Phosphoprotein; Prenyltransferase; Reference proteome; Repeat;
KW Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 379 Protein
FT farnesyltransferase/
FT geranylgeranyltransferase type-1 subunit
FT alpha.
FT /FTId=PRO_0000119746.
FT REPEAT 112 146 PFTA 1.
FT REPEAT 147 180 PFTA 2.
FT REPEAT 181 215 PFTA 3.
FT REPEAT 216 249 PFTA 4.
FT REPEAT 255 289 PFTA 5.
FT COMPBIAS 22 31 Pro-rich.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 373 373 Phosphoserine.
FT VAR_SEQ 68 134 Missing (in isoform 2).
FT /FTId=VSP_036468.
FT MUTAGEN 164 164 K->N: Reduced activity.
FT MUTAGEN 199 199 N->K: Reduced catalytic efficiency.
FT CONFLICT 241 241 Y -> H (in Ref. 2).
FT HELIX 66 68
FT HELIX 70 72
FT STRAND 87 90
FT HELIX 94 109
FT HELIX 114 126
FT HELIX 131 143
FT HELIX 148 161
FT HELIX 166 179
FT HELIX 185 195
FT HELIX 200 213
FT HELIX 216 218
FT HELIX 219 229
FT HELIX 234 246
FT HELIX 253 269
FT HELIX 274 284
FT TURN 285 287
FT HELIX 289 291
FT HELIX 293 302
FT TURN 303 305
FT HELIX 309 324
FT HELIX 330 346
FT HELIX 350 352
FT HELIX 353 367
SQ SEQUENCE 379 AA; 44409 MW; E933CBA874AB92B9 CRC64;
MAATEGVGEA AQGGEPGQPA QPPPQPHPPP PQQQHKEEMA AEAGEAVASP MDDGFVSLDS
PSYVLYRDRA EWADIDPVPQ NDGPNPVVQI IYSDKFRDVY DYFRAVLQRD ERSERAFKLT
RDAIELNAAN YTVWHFRRVL LKSLQKDLHE EMNYITAIIE EQPKNYQVWH HRRVLVEWLR
DPSQELEFIA DILNQDAKNY HAWQHRQWVI QEFKLWDNEL QYVDQLLKED VRNNSVWNQR
YFVISNTTGY NDRAVLEREV QYTLEMIKLV PHNESAWNYL KGILQDRGLS KYPNLLNQLL
DLQPSHSSPY LIAFLVDIYE DMLENQCDNK EDILNKALEL CEILAKEKDT IRKEYWRYIG
RSLQSKHSTE NDSPTNVQQ
//
ID FNTA_HUMAN Reviewed; 379 AA.
AC P49354; A6NJW0; Q53XJ9; Q9UDC1;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-FEB-1996, sequence version 1.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha;
DE EC=2.5.1.58;
DE EC=2.5.1.59;
DE AltName: Full=CAAX farnesyltransferase subunit alpha;
DE AltName: Full=FTase-alpha;
DE AltName: Full=Ras proteins prenyltransferase subunit alpha;
DE AltName: Full=Type I protein geranyl-geranyltransferase subunit alpha;
DE Short=GGTase-I-alpha;
GN Name=FNTA;
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] (ISOFORM 1).
RC TISSUE=Retina;
RX PubMed=8276393; DOI=10.1006/geno.1993.1432;
RA Andres D.A., Milatovich A., Ozcelik T., Wenzlau J.M., Brown M.S.,
RA Goldstein J.L., Francke U.;
RT "cDNA cloning of the two subunits of human CAAX farnesyltransferase
RT and chromosomal mapping of FNTA and FNTB loci and related sequences.";
RL Genomics 18:105-112(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF LYS-164.
RX PubMed=8419339;
RA Andres D.A., Goldstein J.L., Ho Y.K., Brown M.S.;
RT "Mutational analysis of alpha-subunit of protein farnesyltransferase.
RT Evidence for a catalytic role.";
RL J. Biol. Chem. 268:1383-1390(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF ASN-199.
RC TISSUE=Placenta;
RX PubMed=8494894; DOI=10.1021/bi00070a028;
RA Omer C.A., Kral A.M., Diehl R.E., Prendergast G.C., Powers S.,
RA Allen C.M., Gibbs J.B., Kohl N.E.;
RT "Characterization of recombinant human farnesyl-protein transferase:
RT cloning, expression, farnesyl diphosphate binding, and functional
RT homology with yeast prenyl-protein transferases.";
RL Biochemistry 32:5167-5176(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, and 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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-261 (ISOFORM 2).
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H.,
RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K.,
RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT;
RP FARNESYL DIPHOSPHATE AND INHIBITOR L-739,750.
RX PubMed=11687658; DOI=10.1073/pnas.241407898;
RA Long S.B., Hancock P.J., Kral A.M., Hellinga H.W., Beese L.S.;
RT "The crystal structure of human protein farnesyltransferase reveals
RT the basis for inhibition by CaaX tetrapeptides and their mimetics.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:12948-12953(2001).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT;
RP FARNESYL DIPHOSPHATE AND INHIBITORS.
RX PubMed=12036349; DOI=10.1021/jm010531d;
RA Bell I.M., Gallicchio S.N., Abrams M., Beese L.S., Beshore D.C.,
RA Bhimnathwala H., Bogusky M.J., Buser C.A., Culberson J.C., Davide J.,
RA Ellis-Hutchings M., Fernandes C., Gibbs J.B., Graham S.L.,
RA Hamilton K.A., Hartman G.D., Heimbrook D.C., Homnick C.F., Huber H.E.,
RA Huff J.R., Kassahun K., Koblan K.S., Kohl N.E., Lobell R.B.,
RA Lynch J.J. Jr., Robinson R., Rodrigues A.D., Taylor J.S., Walsh E.S.,
RA Williams T.M., Zartman C.B.;
RT "3-aminopyrrolidinone farnesyltransferase inhibitors: design of
RT macrocyclic compounds with improved pharmacokinetics and excellent
RT cell potency.";
RL J. Med. Chem. 45:2388-2409(2002).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT;
RP FARNESYL DIPHOSPHATE AND INHIBITOR.
RX PubMed=12825937; DOI=10.1021/jm020587n;
RA deSolms S.J., Ciccarone T.M., MacTough S.C., Shaw A.W., Buser C.A.,
RA Ellis-Hutchings M., Fernandes C., Hamilton K.A., Huber H.E.,
RA Kohl N.E., Lobell R.B., Robinson R.G., Tsou N.N., Walsh E.S.,
RA Graham S.L., Beese L.S., Taylor J.S.;
RT "Dual protein farnesyltransferase-geranylgeranyltransferase-I
RT inhibitors as potential cancer chemotherapeutic agents.";
RL J. Med. Chem. 46:2973-2984(2003).
CC -!- FUNCTION: Catalyzes the transfer of a farnesyl or geranyl-geranyl
CC moiety from farnesyl or geranyl-geranyl pyrophosphate to a
CC cysteine at the fourth position from the C-terminus of several
CC proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X.
CC The alpha subunit is thought to participate in a stable complex
CC with the substrate. The beta subunit binds the peptide substrate.
CC Through RAC1 prenylation and activation may positively regulate
CC neuromuscular junction development downstream of MUSK (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: Farnesyl diphosphate + protein-cysteine = S-
CC farnesyl protein + diphosphate.
CC -!- CATALYTIC ACTIVITY: Geranylgeranyl diphosphate + protein-cysteine
CC = S-geranylgeranyl-protein + diphosphate.
CC -!- ENZYME REGULATION: Activated by the AGRIN-induced phosphorylation
CC which is mediated by MUSK (By similarity).
CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. Interacts
CC with MUSK; the interaction is direct and mediates AGRIN-induced
CC phosphorylation of FNTA (By similarity).
CC -!- INTERACTION:
CC P49356:FNTB; NbExp=7; IntAct=EBI-602336, EBI-602349;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49354-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49354-2; Sequence=VSP_036468;
CC -!- PTM: Phosphorylated. Phosphorylation is mediated by MUSK upon
CC AGRIN stimulation and results in the activation of FNTA (By
CC similarity).
CC -!- SIMILARITY: Belongs to the protein prenyltransferase subunit alpha
CC family.
CC -!- SIMILARITY: Contains 5 PFTA repeats.
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DR EMBL; L10413; AAA86285.1; -; mRNA.
DR EMBL; L00634; AAA35853.1; -; mRNA.
DR EMBL; AC110275; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BT009854; AAP88856.1; -; mRNA.
DR EMBL; AK292121; BAF84810.1; -; mRNA.
DR EMBL; AC113191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017029; AAH17029.2; -; mRNA.
DR EMBL; BC084566; AAH84566.1; -; mRNA.
DR EMBL; AL698961; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A47659; A47659.
DR RefSeq; NP_002018.1; NM_002027.2.
DR UniGene; Hs.370312; -.
DR PDB; 1JCQ; X-ray; 2.30 A; A=1-379.
DR PDB; 1LD7; X-ray; 2.00 A; A=1-379.
DR PDB; 1LD8; X-ray; 1.80 A; A=1-379.
DR PDB; 1MZC; X-ray; 2.00 A; A=1-379.
DR PDB; 1S63; X-ray; 1.90 A; A=1-379.
DR PDB; 1SA4; X-ray; 2.10 A; A=1-379.
DR PDB; 1TN6; X-ray; 1.80 A; A=1-379.
DR PDB; 2F0Y; X-ray; 2.70 A; A=1-379.
DR PDB; 2H6F; X-ray; 1.50 A; A=1-379.
DR PDB; 2H6G; X-ray; 1.85 A; A=1-379.
DR PDB; 2H6H; X-ray; 1.80 A; A=1-379.
DR PDB; 2H6I; X-ray; 3.00 A; A=1-379.
DR PDB; 2IEJ; X-ray; 1.80 A; A=1-379.
DR PDB; 3E37; X-ray; 1.80 A; A=1-379.
DR PDBsum; 1JCQ; -.
DR PDBsum; 1LD7; -.
DR PDBsum; 1LD8; -.
DR PDBsum; 1MZC; -.
DR PDBsum; 1S63; -.
DR PDBsum; 1SA4; -.
DR PDBsum; 1TN6; -.
DR PDBsum; 2F0Y; -.
DR PDBsum; 2H6F; -.
DR PDBsum; 2H6G; -.
DR PDBsum; 2H6H; -.
DR PDBsum; 2H6I; -.
DR PDBsum; 2IEJ; -.
DR PDBsum; 3E37; -.
DR DisProt; DP00558; -.
DR ProteinModelPortal; P49354; -.
DR SMR; P49354; 55-369.
DR IntAct; P49354; 12.
DR MINT; MINT-238861; -.
DR STRING; 9606.ENSP00000303423; -.
DR BindingDB; P49354; -.
DR ChEMBL; CHEMBL2094108; -.
DR PhosphoSite; P49354; -.
DR DMDM; 1346694; -.
DR PaxDb; P49354; -.
DR PRIDE; P49354; -.
DR DNASU; 2339; -.
DR Ensembl; ENST00000302279; ENSP00000303423; ENSG00000168522.
DR Ensembl; ENST00000342116; ENSP00000343931; ENSG00000168522.
DR GeneID; 2339; -.
DR KEGG; hsa:2339; -.
DR UCSC; uc003xps.3; human.
DR CTD; 2339; -.
DR GeneCards; GC08P042928; -.
DR HGNC; HGNC:3782; FNTA.
DR HPA; CAB010149; -.
DR HPA; HPA018830; -.
DR MIM; 134635; gene.
DR neXtProt; NX_P49354; -.
DR PharmGKB; PA28199; -.
DR eggNOG; COG5536; -.
DR HOGENOM; HOG000188957; -.
DR HOVERGEN; HBG004498; -.
DR InParanoid; P49354; -.
DR KO; K05955; -.
DR OMA; DATDYFR; -.
DR PhylomeDB; P49354; -.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR Reactome; REACT_578; Apoptosis.
DR EvolutionaryTrace; P49354; -.
DR GeneWiki; FNTA; -.
DR GenomeRNAi; 2339; -.
DR NextBio; 9495; -.
DR PMAP-CutDB; P49354; -.
DR PRO; PR:P49354; -.
DR ArrayExpress; P49354; -.
DR Bgee; P49354; -.
DR CleanEx; HS_FNTA; -.
DR Genevestigator; P49354; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005875; C:microtubule associated complex; IDA:BHF-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:BHF-UCL.
DR GO; GO:0004662; F:CAAX-protein geranylgeranyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008017; F:microtubule binding; IDA:BHF-UCL.
DR GO; GO:0004660; F:protein farnesyltransferase activity; TAS:ProtInc.
DR GO; GO:0004661; F:protein geranylgeranyltransferase activity; TAS:ProtInc.
DR GO; GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
DR GO; GO:0090045; P:positive regulation of deacetylase activity; IDA:BHF-UCL.
DR GO; GO:0090044; P:positive regulation of tubulin deacetylation; IDA:BHF-UCL.
DR GO; GO:0018343; P:protein farnesylation; IDA:BHF-UCL.
DR GO; GO:0018344; P:protein geranylgeranylation; TAS:ProtInc.
DR GO; GO:0022400; P:regulation of rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0016056; P:rhodopsin mediated signaling pathway; TAS:Reactome.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:ProtInc.
DR InterPro; IPR002088; Prenyl_trans_a.
DR Pfam; PF01239; PPTA; 5.
DR PROSITE; PS51147; PFTA; 5.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Phosphoprotein; Prenyltransferase; Reference proteome; Repeat;
KW Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 379 Protein
FT farnesyltransferase/
FT geranylgeranyltransferase type-1 subunit
FT alpha.
FT /FTId=PRO_0000119746.
FT REPEAT 112 146 PFTA 1.
FT REPEAT 147 180 PFTA 2.
FT REPEAT 181 215 PFTA 3.
FT REPEAT 216 249 PFTA 4.
FT REPEAT 255 289 PFTA 5.
FT COMPBIAS 22 31 Pro-rich.
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 373 373 Phosphoserine.
FT VAR_SEQ 68 134 Missing (in isoform 2).
FT /FTId=VSP_036468.
FT MUTAGEN 164 164 K->N: Reduced activity.
FT MUTAGEN 199 199 N->K: Reduced catalytic efficiency.
FT CONFLICT 241 241 Y -> H (in Ref. 2).
FT HELIX 66 68
FT HELIX 70 72
FT STRAND 87 90
FT HELIX 94 109
FT HELIX 114 126
FT HELIX 131 143
FT HELIX 148 161
FT HELIX 166 179
FT HELIX 185 195
FT HELIX 200 213
FT HELIX 216 218
FT HELIX 219 229
FT HELIX 234 246
FT HELIX 253 269
FT HELIX 274 284
FT TURN 285 287
FT HELIX 289 291
FT HELIX 293 302
FT TURN 303 305
FT HELIX 309 324
FT HELIX 330 346
FT HELIX 350 352
FT HELIX 353 367
SQ SEQUENCE 379 AA; 44409 MW; E933CBA874AB92B9 CRC64;
MAATEGVGEA AQGGEPGQPA QPPPQPHPPP PQQQHKEEMA AEAGEAVASP MDDGFVSLDS
PSYVLYRDRA EWADIDPVPQ NDGPNPVVQI IYSDKFRDVY DYFRAVLQRD ERSERAFKLT
RDAIELNAAN YTVWHFRRVL LKSLQKDLHE EMNYITAIIE EQPKNYQVWH HRRVLVEWLR
DPSQELEFIA DILNQDAKNY HAWQHRQWVI QEFKLWDNEL QYVDQLLKED VRNNSVWNQR
YFVISNTTGY NDRAVLEREV QYTLEMIKLV PHNESAWNYL KGILQDRGLS KYPNLLNQLL
DLQPSHSSPY LIAFLVDIYE DMLENQCDNK EDILNKALEL CEILAKEKDT IRKEYWRYIG
RSLQSKHSTE NDSPTNVQQ
//
MIM
134635
*RECORD*
*FIELD* NO
134635
*FIELD* TI
*134635 FARNESYLTRANSFERASE, CAAX BOX, ALPHA; FNTA
;;PROTEIN GERANYLGERANYLTRANSFERASE TYPE I, ALPHA SUBUNIT; PGGT1A
read more*FIELD* TX
DESCRIPTION
The FNTA gene encodes the alpha subunit for the heterodimeric enzymes
CAAX farnesyltransferase and CAAX geranylgeranyltransferase (Zhang et
al., 1994). The beta subunits are encoded by the FNTB (134636) and
PGGT1B (602031) genes, respectively.
GENE FAMILY
Eukaryotic cells contain 3 distinct prenyltransferases that attach
either a farnesyl group (15 carbons) or a geranylgeranyl group (20
carbons) in thioether linkage to C-terminal cysteine residues in a
variety of cellular proteins (Schafer and Rine, 1992). These
posttranslational modifications provide a mechanism for membrane
localization of proteins that lack a transmembrane domain. Prenylation
is a frequent covalent modification of proteins; Epstein et al. (1991)
estimated that approximately 0.5% of all proteins in mammalian tissues
are prenylated. The best characterized of the prenyltransferases, CAAX
farnesyltransferase (FTase), attaches a farnesyl group from farnesyl
pyrophosphate to cysteine residues at the fourth position from the C
terminus of proteins that end in the so-called CAAX box, where C is
cysteine, A is usually but not always an aliphatic amino acid, and X is
typically methionine or serine. This enzyme has the remarkable property
of farnesylating peptides as short as 4 residues in length that conform
to the CAAX consensus sequence (summary by Andres et al., 1993).
CLONING
Epstein et al. (1991) noted that full-length cDNAs for the alpha and
beta subunits of the rat farnesyltransferase were cloned, and both were
shown to be essential for catalytic activity. Andres et al. (1993) used
the rat cDNAs to clone cDNAs for the human alpha and beta (134636)
subunits. The human and rat amino acid sequences show 93% identity for
the alpha subunit and 96% identity for the beta subunit.
GENE FUNCTION
CAAX farnesyltransferase is an alpha-beta heterodimeric enzyme with a
molecular mass of approximately 100 kD. Geranylgeranyltransferase type I
(GGTase-I) is also a heterodimeric enzyme. Zhang et al. (1994) analyzed
tryptic digests of the bovine GGTase-I alpha subunit and showed that it
is identical to that of bovine FTase; GGTase-I uses a different beta
chain (PGGT1B; 602031). Coexpression of human PGGT1B and FNTA cDNAs in
E. coli produced recombinant GGTase-I with electrophoretic and enzymatic
properties indistinguishable from those of native GGTase-I. The beta
chains of both FTase (FNTB; 134636) and GGTase are catalytic for
specific substrates (e.g., p21ras; see 190020).
A role for the alpha subunit had been uncertain until Wang et al. (1996)
showed, using the 2-hybrid yeast assay, that FNTA is a specific
cytoplasmic interactor of the transforming growth factor-beta (190180)
and activin type I (102576) receptors. Wang et al. (1996) stated that
because of these interactions FNTA is likely to be a key component of
the signaling pathway which involves p21ras, an important substrate for
farnesyltransferase. Membrane localization and activity of RAS is
dependent on farnesylation; Wang et al. (1996) proposed that the actions
of TGF-beta and activin on cell growth may be mediated through their
ability to affect ras farnesylation via FNTA.
BIOCHEMICAL FEATURES
Long et al. (2002) presented a complete series of structures
representing the major steps along the reaction coordinate of the enzyme
protein farnesyltransferase. From these observations, Long et al. (2002)
deduced the determinants of substrate specificity and an unusual
mechanism in which product release requires binding of substrate,
analogous to classically processive enzymes. A structural model for the
transition state consistent with previous mechanistic studies was also
constructed.
MAPPING
By Southern blot hybridization and PCR analyses of panels of
human/Chinese hamster somatic cell hybrid lines and by fluorescence
chromosomal in situ hybridization, Andres et al. (1993) mapped the FNTA
gene to 8p22-q11. Two genes related to FNTA were also identified: FNTAL1
(FNTAP1) was assigned to 11q13.4-q14.1 and FNTAL2 (FNTAP2) to chromosome
13.
Using interspecific backcross analysis, Porter and Messer (1996) mapped
the Fnta gene to mouse chromosome 8.
*FIELD* RF
1. Andres, D. A.; Milatovich, A.; Ozcelik, T.; Wenzlau, J. M.; Brown,
M. S.; Goldstein, J. L.; Francke, U.: cDNA cloning of the two subunits
of human CAAX farnesyltransferase and chromosomal mapping of FNTA
and FNTB loci and related sequences. Genomics 18: 105-112, 1993.
2. Epstein, W. W.; Lever, D.; Leining, L. M.; Bruenger, E.; Rilling,
H. C.: Quantitation of prenylcysteines by a selective cleavage reaction. Proc.
Nat. Acad. Sci. 88: 9668-9670, 1991.
3. Long, S. B.; Casey, P. J.; Beese, L. S.: Reaction path of protein
farnesyltransferase at atomic resolution. Nature 419: 645-650, 2002.
4. Porter, J. C.; Messer, A.: Genetic mapping of farnesyltransferase
alpha(Fnta) to mouse chromosome 8. Mammalian Genome 7: 622-623,
1996.
5. Schafer, W. R.; Rine, J.: Protein prenylation: genes, enzymes,
targets, and functions. Annu. Rev. Genet. 26: 209-237, 1992.
6. Wang, T.; Danielson, P. D.; Li, B.; Shah, P. C.; Kim, S. D.; Donahoe,
P. K.: The p21ras farnesyltransferase alpha subunit in TGF-beta and
activin signaling. Science 271: 1120-1122, 1996.
7. Zhang, F. L.; Diehl, R. E.; Kohl, N. E.; Gibbs, J. B.; Giros, B.;
Casey, P. J.; Omer, C. A.: cDNA cloning and expression of rat and
human protein geranylgeranyltransferase type-I. J. Biol. Chem. 269:
3175-3180, 1994.
*FIELD* CN
Ada Hamosh - updated: 10/18/2002
Mark H. Paalman - updated: 10/3/1997
Alan F. Scott - updated: 4/22/1996
*FIELD* CD
Victor A. McKusick: 10/14/1993
*FIELD* ED
carol: 11/21/2011
alopez: 3/15/2010
alopez: 10/21/2002
terry: 10/18/2002
alopez: 11/3/1997
mark: 10/7/1997
terry: 10/3/1997
mark: 10/3/1997
terry: 11/14/1996
mark: 4/22/1996
terry: 4/22/1996
mark: 4/22/1996
carol: 10/14/1993
*RECORD*
*FIELD* NO
134635
*FIELD* TI
*134635 FARNESYLTRANSFERASE, CAAX BOX, ALPHA; FNTA
;;PROTEIN GERANYLGERANYLTRANSFERASE TYPE I, ALPHA SUBUNIT; PGGT1A
read more*FIELD* TX
DESCRIPTION
The FNTA gene encodes the alpha subunit for the heterodimeric enzymes
CAAX farnesyltransferase and CAAX geranylgeranyltransferase (Zhang et
al., 1994). The beta subunits are encoded by the FNTB (134636) and
PGGT1B (602031) genes, respectively.
GENE FAMILY
Eukaryotic cells contain 3 distinct prenyltransferases that attach
either a farnesyl group (15 carbons) or a geranylgeranyl group (20
carbons) in thioether linkage to C-terminal cysteine residues in a
variety of cellular proteins (Schafer and Rine, 1992). These
posttranslational modifications provide a mechanism for membrane
localization of proteins that lack a transmembrane domain. Prenylation
is a frequent covalent modification of proteins; Epstein et al. (1991)
estimated that approximately 0.5% of all proteins in mammalian tissues
are prenylated. The best characterized of the prenyltransferases, CAAX
farnesyltransferase (FTase), attaches a farnesyl group from farnesyl
pyrophosphate to cysteine residues at the fourth position from the C
terminus of proteins that end in the so-called CAAX box, where C is
cysteine, A is usually but not always an aliphatic amino acid, and X is
typically methionine or serine. This enzyme has the remarkable property
of farnesylating peptides as short as 4 residues in length that conform
to the CAAX consensus sequence (summary by Andres et al., 1993).
CLONING
Epstein et al. (1991) noted that full-length cDNAs for the alpha and
beta subunits of the rat farnesyltransferase were cloned, and both were
shown to be essential for catalytic activity. Andres et al. (1993) used
the rat cDNAs to clone cDNAs for the human alpha and beta (134636)
subunits. The human and rat amino acid sequences show 93% identity for
the alpha subunit and 96% identity for the beta subunit.
GENE FUNCTION
CAAX farnesyltransferase is an alpha-beta heterodimeric enzyme with a
molecular mass of approximately 100 kD. Geranylgeranyltransferase type I
(GGTase-I) is also a heterodimeric enzyme. Zhang et al. (1994) analyzed
tryptic digests of the bovine GGTase-I alpha subunit and showed that it
is identical to that of bovine FTase; GGTase-I uses a different beta
chain (PGGT1B; 602031). Coexpression of human PGGT1B and FNTA cDNAs in
E. coli produced recombinant GGTase-I with electrophoretic and enzymatic
properties indistinguishable from those of native GGTase-I. The beta
chains of both FTase (FNTB; 134636) and GGTase are catalytic for
specific substrates (e.g., p21ras; see 190020).
A role for the alpha subunit had been uncertain until Wang et al. (1996)
showed, using the 2-hybrid yeast assay, that FNTA is a specific
cytoplasmic interactor of the transforming growth factor-beta (190180)
and activin type I (102576) receptors. Wang et al. (1996) stated that
because of these interactions FNTA is likely to be a key component of
the signaling pathway which involves p21ras, an important substrate for
farnesyltransferase. Membrane localization and activity of RAS is
dependent on farnesylation; Wang et al. (1996) proposed that the actions
of TGF-beta and activin on cell growth may be mediated through their
ability to affect ras farnesylation via FNTA.
BIOCHEMICAL FEATURES
Long et al. (2002) presented a complete series of structures
representing the major steps along the reaction coordinate of the enzyme
protein farnesyltransferase. From these observations, Long et al. (2002)
deduced the determinants of substrate specificity and an unusual
mechanism in which product release requires binding of substrate,
analogous to classically processive enzymes. A structural model for the
transition state consistent with previous mechanistic studies was also
constructed.
MAPPING
By Southern blot hybridization and PCR analyses of panels of
human/Chinese hamster somatic cell hybrid lines and by fluorescence
chromosomal in situ hybridization, Andres et al. (1993) mapped the FNTA
gene to 8p22-q11. Two genes related to FNTA were also identified: FNTAL1
(FNTAP1) was assigned to 11q13.4-q14.1 and FNTAL2 (FNTAP2) to chromosome
13.
Using interspecific backcross analysis, Porter and Messer (1996) mapped
the Fnta gene to mouse chromosome 8.
*FIELD* RF
1. Andres, D. A.; Milatovich, A.; Ozcelik, T.; Wenzlau, J. M.; Brown,
M. S.; Goldstein, J. L.; Francke, U.: cDNA cloning of the two subunits
of human CAAX farnesyltransferase and chromosomal mapping of FNTA
and FNTB loci and related sequences. Genomics 18: 105-112, 1993.
2. Epstein, W. W.; Lever, D.; Leining, L. M.; Bruenger, E.; Rilling,
H. C.: Quantitation of prenylcysteines by a selective cleavage reaction. Proc.
Nat. Acad. Sci. 88: 9668-9670, 1991.
3. Long, S. B.; Casey, P. J.; Beese, L. S.: Reaction path of protein
farnesyltransferase at atomic resolution. Nature 419: 645-650, 2002.
4. Porter, J. C.; Messer, A.: Genetic mapping of farnesyltransferase
alpha(Fnta) to mouse chromosome 8. Mammalian Genome 7: 622-623,
1996.
5. Schafer, W. R.; Rine, J.: Protein prenylation: genes, enzymes,
targets, and functions. Annu. Rev. Genet. 26: 209-237, 1992.
6. Wang, T.; Danielson, P. D.; Li, B.; Shah, P. C.; Kim, S. D.; Donahoe,
P. K.: The p21ras farnesyltransferase alpha subunit in TGF-beta and
activin signaling. Science 271: 1120-1122, 1996.
7. Zhang, F. L.; Diehl, R. E.; Kohl, N. E.; Gibbs, J. B.; Giros, B.;
Casey, P. J.; Omer, C. A.: cDNA cloning and expression of rat and
human protein geranylgeranyltransferase type-I. J. Biol. Chem. 269:
3175-3180, 1994.
*FIELD* CN
Ada Hamosh - updated: 10/18/2002
Mark H. Paalman - updated: 10/3/1997
Alan F. Scott - updated: 4/22/1996
*FIELD* CD
Victor A. McKusick: 10/14/1993
*FIELD* ED
carol: 11/21/2011
alopez: 3/15/2010
alopez: 10/21/2002
terry: 10/18/2002
alopez: 11/3/1997
mark: 10/7/1997
terry: 10/3/1997
mark: 10/3/1997
terry: 11/14/1996
mark: 4/22/1996
terry: 4/22/1996
mark: 4/22/1996
carol: 10/14/1993