Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha

Details

Name
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha
Synonyms
  • 2.5.1.58
  • 2.5.1.59
  • CAAX farnesyltransferase subunit alpha
  • FTase-alpha
  • GGTase-I-alpha
  • Ras proteins prenyltransferase subunit alpha
  • Type I protein geranyl-geranyltransferase subunit alpha
Gene Name
FNTA
UniProtKB Entry
P49354Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0004661|Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha
MAATEGVGEAAQGGEPGQPAQPPPQPHPPPPQQQHKEEMAAEAGEAVASPMDDGFVSLDS
PSYVLYRDRAEWADIDPVPQNDGPNPVVQIIYSDKFRDVYDYFRAVLQRDERSERAFKLT
RDAIELNAANYTVWHFRRVLLKSLQKDLHEEMNYITAIIEEQPKNYQVWHHRRVLVEWLR
DPSQELEFIADILNQDAKNYHAWQHRQWVIQEFKLWDNELQYVDQLLKEDVRNNSVWNQR
YFVISNTTGYNDRAVLEREVQYTLEMIKLVPHNESAWNYLKGILQDRGLSKYPNLLNQLL
DLQPSHSSPYLIAFLVDIYEDMLENQCDNKEDILNKALELCEILAKEKDTIRKEYWRYIG
RSLQSKHSTENDSPTNVQQ
Number of residues
379
Molecular Weight
44408.32
Theoretical pI
4.72
GO Classification
Functions
alpha-tubulin binding / CAAX-protein geranylgeranyltransferase activity / microtubule binding / protein farnesyltransferase activity / protein geranylgeranyltransferase activity / Rab geranylgeranyltransferase activity
Processes
positive regulation of deacetylase activity / positive regulation of tubulin deacetylation / protein farnesylation / protein geranylgeranylation / transforming growth factor beta receptor signaling pathway
Components
CAAX-protein geranylgeranyltransferase complex / cytoplasm / cytosol / microtubule associated complex / protein farnesyltransferase complex
General Function
Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. Contributes to the transfer of a farnesyl or geranylgeranyl moiety from farnesyl or geranylgeranyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. May positively regulate neuromuscular junction development downstream of MUSK via its function in RAC1 prenylation and activation
Specific Function
alpha-tubulin binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0011702|Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (FNTA)
ATGGCGGCCACCGAGGGGGTCGGGGAGGCTGCGCAAGGGGGCGAGCCCGGGCAGCCGGCG
CAACCCCCGCCCCAGCCGCACCCACCGCCGCCCCAGCAGCAGCACAAGGAAGAGATGGCG
GCCGAGGCTGGGGAAGCCGTGGCGTCCCCCATGGACGACGGGTTTGTGAGCCTGGACTCG
CCCTCCTATGTCCTGTACAGGGACAGAGCAGAATGGGCTGATATAGATCCGGTGCCGCAG
AATGATGGCCCCAATCCCGTGGTCCAGATCATTTATAGTGACAAATTTAGAGATGTTTAT
GATTACTTCCGAGCTGTCCTGCAGCGTGATGAAAGAAGTGAACGAGCTTTTAAGCTAACC
CGGGATGCTATTGAGTTAAATGCAGCCAATTATACAGTGTGGCATTTCCGGAGAGTTCTT
TTGAAGTCACTTCAGAAGGATCTACATGAGGAAATGAACTACATCACTGCAATAATTGAG
GAGCAGCCCAAAAACTATCAAGTTTGGCATCATAGGCGAGTATTAGTGGAATGGCTAAGA
GATCCATCTCAGGAGCTTGAATTTATTGCTGATATTCTTAATCAGGATGCAAAGAATTAT
CATGCCTGGCAGCATCGACAATGGGTTATTCAGGAATTTAAACTTTGGGATAATGAGCTG
CAGTATGTGGACCAACTTCTGAAAGAGGATGTGAGAAATAACTCTGTCTGGAACCAAAGA
TACTTCGTTATTTCTAACACCACTGGCTACAATGATCGTGCTGTATTGGAGAGAGAAGTC
CAATACACTCTGGAAATGATTAAACTAGTACCACATAATGAAAGTGCATGGAACTATTTG
AAAGGGATTTTGCAGGATCGTGGTCTTTCCAAATATCCTAATCTGTTAAATCAATTACTT
GATTTACAACCAAGTCATAGTTCCCCCTACCTAATTGCCTTTCTTGTGGATATCTATGAA
GACATGCTAGAAAATCAGTGTGACAATAAGGAAGACATTCTTAATAAAGCATTAGAGTTA
TGTGAAATCCTAGCTAAAGAAAAGGACACTATAAGAAAGGAATATTGGAGATACATTGGA
AGATCCCTTCAAAGCAAACACAGCACAGAAAATGACTCACCAACAAATGTACAGCAATAA
Chromosome Location
8
Locus
8p11.21
External Identifiers
ResourceLink
UniProtKB IDP49354
UniProtKB Entry NameFNTA_HUMAN
GenBank Gene IDL10413
GeneCard IDFNTA
GenAtlas IDFNTA
HGNC IDHGNC:3782
PDB ID(s)1JCQ, 1LD7, 1LD8, 1MZC, 1S63, 1SA4, 1TN6, 2F0Y, 2H6F, 2H6G, 2H6H, 2H6I, 2IEJ, 3E37
KEGG IDhsa:2339
NCBI Gene ID2339
General References
  1. Andres DA, Milatovich A, Ozcelik T, Wenzlau JM, Brown MS, Goldstein JL, Francke U: cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences. Genomics. 1993 Oct;18(1):105-12. [Article]
  2. Andres DA, Goldstein JL, Ho YK, Brown MS: Mutational analysis of alpha-subunit of protein farnesyltransferase. Evidence for a catalytic role. J Biol Chem. 1993 Jan 15;268(2):1383-90. [Article]
  3. Omer CA, Kral AM, Diehl RE, Prendergast GC, Powers S, Allen CM, Gibbs JB, Kohl NE: Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases. Biochemistry. 1993 May 18;32(19):5167-76. [Article]
  4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  5. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. [Article]
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  7. Bechtel S, Rosenfelder H, Duda A, Schmidt CP, Ernst U, Wellenreuther R, Mehrle A, Schuster C, Bahr A, Blocker H, Heubner D, Hoerlein A, Michel G, Wedler H, Kohrer K, Ottenwalder B, Poustka A, Wiemann S, Schupp I: The full-ORF clone resource of the German cDNA Consortium. BMC Genomics. 2007 Oct 31;8:399. [Article]
  8. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [Article]
  9. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [Article]
  11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  13. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  14. Long SB, Hancock PJ, Kral AM, Hellinga HW, Beese LS: The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics. Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12948-53. Epub 2001 Oct 30. [Article]
  15. Bell IM, Gallicchio SN, Abrams M, Beese LS, Beshore DC, Bhimnathwala H, Bogusky MJ, Buser CA, Culberson JC, Davide J, Ellis-Hutchings M, Fernandes C, Gibbs JB, Graham SL, Hamilton KA, Hartman GD, Heimbrook DC, Homnick CF, Huber HE, Huff JR, Kassahun K, Koblan KS, Kohl NE, Lobell RB, Lynch JJ Jr, Robinson R, Rodrigues AD, Taylor JS, Walsh ES, Williams TM, Zartman CB: 3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency. J Med Chem. 2002 Jun 6;45(12):2388-409. [Article]
  16. deSolms SJ, Ciccarone TM, MacTough SC, Shaw AW, Buser CA, Ellis-Hutchings M, Fernandes C, Hamilton KA, Huber HE, Kohl NE, Lobell RB, Robinson RG, Tsou NN, Walsh ES, Graham SL, Beese LS, Taylor JS: Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents. J Med Chem. 2003 Jul 3;46(14):2973-84. [Article]
  17. Reid TS, Beese LS: Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochemistry. 2004 Jun 8;43(22):6877-84. [Article]
  18. Reid TS, Terry KL, Casey PJ, Beese LS: Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J Mol Biol. 2004 Oct 15;343(2):417-33. [Article]
  19. Terry KL, Casey PJ, Beese LS: Conversion of protein farnesyltransferase to a geranylgeranyltransferase. Biochemistry. 2006 Aug 15;45(32):9746-55. [Article]
  20. Hast MA, Fletcher S, Cummings CG, Pusateri EE, Blaskovich MA, Rivas K, Gelb MH, Van Voorhis WC, Sebti SM, Hamilton AD, Beese LS: Structural basis for binding and selectivity of antimalarial and anticancer ethylenediamine inhibitors to protein farnesyltransferase. Chem Biol. 2009 Feb 27;16(2):181-92. doi: 10.1016/j.chembiol.2009.01.014. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
AZD3409investigationalunknowntargetDetails
Lonafarnibapproved, investigationalyestargetinhibitorDetails
2-CHLORO-5-(3-CHLORO-PHENYL)-6-[(4-CYANO-PHENYL)-(3-METHYL-3H-IMIDAZOL-4-YL)- METHOXYMETHYL]-NICOTINONITRILEexperimentalunknowntargetDetails
(11S)-8-CHLORO-11-[1-(METHYLSULFONYL)PIPERIDIN-4-YL]-6-PIPERAZIN-1-YL-11H-BENZO[5,6]CYCLOHEPTA[1,2-B]PYRIDINEexperimentalunknowntargetDetails
L-778123experimentalyestargetmodulatorDetails
[(3,7,11-TRIMETHYL-DODECA-2,6,10-TRIENYLOXYCARBAMOYL)-METHYL]-PHOSPHONIC ACIDexperimentalunknowntargetDetails
Farnesyl diphosphateexperimentalunknowntargetDetails
Geranylgeranyl diphosphateexperimentalyestargetinhibitorDetails
ALPHA-HYDROXYFARNESYLPHOSPHONIC ACIDexperimentalunknowntargetDetails
2-[METHYL-(5-GERANYL-4-METHYL-PENT-3-ENYL)-AMINO]-ETHYL-DIPHOSPHATEexperimentalunknowntargetDetails
(20S)-19,20,21,22-TETRAHYDRO-19-OXO-5H-18,20-ETHANO-12,14-ETHENO-6,10-METHENO-18H-BENZ[D]IMIDAZO[4,3-K][1,6,9,12]OXATRIAZA-CYCLOOCTADECOSINE-9-CARBONITRILEexperimentalunknowntargetDetails
(20S)-19,20,22,23-TETRAHYDRO-19-OXO-5H,21H-18,20-ETHANO-12,14-ETHENO-6,10-METHENOBENZ[D]IMIDAZO[4,3-L][1,6,9,13]OXATRIAZACYCLONOADECOSINE-9-CARBONITRILEexperimentalunknowntargetDetails
PTX-100investigationalyestargetmodulatorDetails
BMS-214662investigationalyestargetmodulatorDetails
TipifarnibinvestigationalyestargetmodulatorDetails