Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q04631 (FNTA_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha

EC=2.5.1.58
EC=2.5.1.59
Alternative name(s):
CAAX farnesyltransferase subunit alpha
FTase-alpha
Ras proteins prenyltransferase subunit alpha
Type I protein geranyl-geranyltransferase subunit alpha
Short name=GGTase-I-alpha
Gene names
Name:Fnta
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length377 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.13 Ref.16 Ref.17 Ref.18

Catalytic activity

Farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate. Ref.12 Ref.13 Ref.16 Ref.17 Ref.18

Geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate. Ref.12 Ref.13 Ref.16 Ref.17 Ref.18

Enzyme regulation

Activated by the AGRIN-induced phosphorylation which is mediated by MUSK By similarity.

Subunit structure

Interacts with MUSK; the interaction is direct and mediates AGRIN-induced phosphorylation of FNTA By similarity. Heterodimer of FNTA and FNTB (farnesyltransferase). Heterodimer of FNTA and PGGT1B (geranylgeranyltransferase). Ref.2 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18

Post-translational modification

Phosphorylated. Phosphorylation is mediated by MUSK upon AGRIN stimulation and results in the activation of FNTA By similarity.

Sequence similarities

Belongs to the protein prenyltransferase subunit alpha family.

Contains 5 PFTA repeats.

Ontologies

Keywords
   DomainRepeat
   Molecular functionPrenyltransferase
Transferase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of apoptotic process

Inferred from mutant phenotype PubMed 11313965. Source: RGD

negative regulation of nitric-oxide synthase biosynthetic process

Inferred from mutant phenotype PubMed 9153192. Source: RGD

positive regulation of cell cycle

Inferred from mutant phenotype PubMed 10544242. Source: RGD

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 10544242. Source: RGD

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from mutant phenotype PubMed 9153192. Source: RGD

protein farnesylation

Inferred from sequence or structural similarity. Source: UniProtKB

protein geranylgeranylation

Inferred from sequence or structural similarity. Source: UniProtKB

response to cytokine

Inferred from mutant phenotype PubMed 9153192. Source: RGD

response to inorganic substance

Inferred from mutant phenotype PubMed 18957540. Source: RGD

response to organic cyclic compound

Inferred from mutant phenotype PubMed 16257390. Source: RGD

   Cellular_componentCAAX-protein geranylgeranyltransferase complex

Inferred from direct assay PubMed 15248757. Source: RGD

cytoplasm

Inferred from direct assay PubMed 17192483. Source: RGD

protein farnesyltransferase complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionCAAX-protein geranylgeranyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein binding

Inferred from physical interaction Ref.7Ref.12PubMed 12657283PubMed 12657284Ref.11PubMed 12699757Ref.13Ref.14PubMed 15248757Ref.15. Source: IntAct

protein farnesyltransferase activity

Inferred from direct assay Ref.1. Source: RGD

protein geranylgeranyltransferase activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FntbQ0229314EBI-602447,EBI-602454
KRASP01116-22EBI-602447,EBI-367427From a different organism.
Pggt1bP536105EBI-602447,EBI-602610

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 377376Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha
PRO_0000119748

Regions

Repeat112 – 14635PFTA 1
Repeat147 – 18135PFTA 2
Repeat182 – 21433PFTA 3
Repeat215 – 24935PFTA 4
Repeat255 – 28935PFTA 5
Compositional bias22 – 309Pro-rich

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Secondary structure

..................................................... 377
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04631 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: DFFFECC1B88BC080

FASTA37744,049
        10         20         30         40         50         60 
MAATEGVGES APGGEPGQPE QPPPPPPPPP AQQPQEEEMA AEAGEAAASP MDDGFLSLDS 

        70         80         90        100        110        120 
PTYVLYRDRA EWADIDPVPQ NDGPSPVVQI IYSEKFRDVY DYFRAVLQRD ERSERAFKLT 

       130        140        150        160        170        180 
RDAIELNAAN YTVWHFRRVL LRSLQKDLQE EMNYIIAIIE EQPKNYQVWH HRRVLVEWLK 

       190        200        210        220        230        240 
DPSQELEFIA DILNQDAKNY HAWQHRQWVI QEFRLWDNEL QYVDQLLKED VRNNSVWNQR 

       250        260        270        280        290        300 
HFVISNTTGY SDRAVLEREV QYTLEMIKLV PHNESAWNYL KGILQDRGLS RYPNLLNQLL 

       310        320        330        340        350        360 
DLQPSHSSPY LIAFLVDIYE DMLENQCDNK EDILNKALEL CEILAKEKDT IRKEYWRYIG 

       370 
RSLQSKHSRE SDIPASV 

« Hide

References

[1]"Cloning and expression of a cDNA encoding the alpha subunit of rat p21ras protein farnesyltransferase."
Chen W.-J., Andres D.A., Goldstein J.L., Brown M.S.
Proc. Natl. Acad. Sci. U.S.A. 88:11368-11372(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
Tissue: Brain.
[2]"Crystal structure of protein farnesyltransferase at 2.25-A resolution."
Park H.-W., Boduluri S.R., Mooomaw J.F., Casey P.J., Beese L.S.
Science 275:1800-1804(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS), SUBUNIT.
[3]Erratum
Park H.-W., Boduluri S.R., Mooomaw J.F., Casey P.J., Beese L.S.
Science 276:21-21(1997)
[4]"Protein farnesyltransferase: structure and implications for substrate binding."
Dunten P., Kammlott U., Crowther R., Weber D., Palermo R., Birktoft J.
Biochemistry 37:7907-7912(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 1-377 IN COMPLEX WITH FNTB, SUBUNIT.
[5]"Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate."
Long S.B., Casey P.J., Beese L.S.
Biochemistry 37:9612-9618(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS)IN COMPLEX WITH FNTB, SUBUNIT.
[6]"Crystal structure of farnesyl protein transferase complexed with a CaaX peptide and farnesyl diphosphate analogue."
Strickland C.L., Windsor W.T., Syto R., Wang L., Bond R., Wu Z., Schwartz J., Le H.V., Beese L.S., Weber P.C.
Biochemistry 37:16601-16611(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 45-377 IN COMPLEX WITH FNTB, SUBUNIT.
[7]"Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships."
Strickland C.L., Weber P.C., Windsor W.T., Wu Z., Le H.V., Albanese M.M., Alvarez C.S., Cesarz D., del Rosario J., Deskus J., Mallams A.K., Njoroge F.G., Piwinski J.J., Remiszewski S., Rossman R.R., Taveras A.G., Vibulbhan B., Doll R.J., Girijavallabhan V.M., Ganguly A.K.
J. Med. Chem. 42:2125-2135(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-377 IN COMPLEX WITH FNTB, SUBUNIT.
[8]"The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures."
Long S.B., Casey P.J., Beese L.S.
Structure 8:209-222(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1-377 IN COMPLEX WITH FNTB, SUBUNIT.
[9]"The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics."
Long S.B., Hancock P.J., Kral A.M., Hellinga H.W., Beese L.S.
Proc. Natl. Acad. Sci. U.S.A. 98:12948-12953(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH FNTB, SUBUNIT.
[10]"Reaction path of protein farnesyltransferase at atomic resolution."
Long S.B., Casey P.J., Beese L.S.
Nature 419:645-650(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-377 IN COMPLEX WITH FNTB, SUBUNIT.
[11]"Biochemical and structural studies with prenyl diphosphate analogues provide insights into isoprenoid recognition by protein farnesyl transferase."
Turek-Etienne T.C., Strickland C.L., Distefano M.D.
Biochemistry 42:3716-3724(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-377 IN COMPLEX WITH FNTB, SUBUNIT.
[12]"Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives."
Gwaltney S.L., O'Connor S.J., Nelson L.T., Sullivan G.M., Imade H., Wang W., Hasvold L., Li Q., Cohen J., Gu W.Z., Tahir S.K., Bauch J., Marsh K., Ng S.C., Frost D.J., Zhang H., Muchmore S., Jakob C.G. expand/collapse author list , Stoll V., Hutchins C., Rosenberg S.H., Sham H.L.
Bioorg. Med. Chem. Lett. 13:1359-1362(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 55-369 IN COMPLEX WITH FNTB, SUBUNIT, CATALYTIC ACTIVITY.
[13]"Structure of mammalian protein geranylgeranyltransferase type-I."
Taylor J.S., Reid T.S., Terry K.L., Casey P.J., Beese L.S.
EMBO J. 22:5963-5974(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH PGGT1B, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION.
[14]"Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity."
Reid T.S., Beese L.S.
Biochemistry 43:6877-6884(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) IN COMPLEX WITH FNTB, SUBUNIT.
[15]"Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity."
Reid T.S., Terry K.L., Casey P.J., Beese L.S.
J. Mol. Biol. 343:417-433(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) IN COMPLEX WITH FNTB, SUBUNIT.
[16]"Caged protein prenyltransferase substrates: tools for understanding protein prenylation."
DeGraw A.J., Hast M.A., Xu J., Mullen D., Beese L.S., Barany G., Distefano M.D.
Chem. Biol. Drug Des. 72:171-181(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH FNTB, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION.
[17]"Analysis of the eukaryotic prenylome by isoprenoid affinity tagging."
Nguyen U.T., Guo Z., Delon C., Wu Y., Deraeve C., Franzel B., Bon R.S., Blankenfeldt W., Goody R.S., Waldmann H., Wolters D., Alexandrov K.
Nat. Chem. Biol. 5:227-235(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS), SUBUNIT, CATALYTIC ACTIVITY, FUNCTION.
[18]"Development of selective, potent RabGGTase inhibitors."
Stigter E.A., Guo Z., Bon R.S., Wu Y.W., Choidas A., Wolf A., Menninger S., Waldmann H., Blankenfeldt W., Goody R.S.
J. Med. Chem. 55:8330-8340(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) IN COMPLEX WITH FNTB, SUBUNIT, CATALYTIC ACTIVITY, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M81225 mRNA. Translation: AAA41833.1.
PIRA41625.
RefSeqNP_036979.1. NM_012847.1.
UniGeneRn.5990.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1D8DX-ray2.00A1-377[»]
1D8EX-ray3.00A1-377[»]
1FPPX-ray2.75A1-377[»]
1FT1X-ray2.25A1-377[»]
1FT2X-ray3.40A55-369[»]
1FTImodel-A55-369[»]
1HZ7model-A116-247[»]
1JCRX-ray2.00A1-377[»]
1JCSX-ray2.20A1-377[»]
1KZOX-ray2.20A1-377[»]
1KZPX-ray2.10A1-377[»]
1KZRmodel-A55-377[»]
1N4PX-ray2.65A/C/E/G/I/K1-377[»]
1N4QX-ray2.40A/C/E/G/I/K1-377[»]
1N4RX-ray2.80A/C/E/G/I/K1-377[»]
1N4SX-ray2.60A/C/E/G/I/K1-377[»]
1N94X-ray3.50A55-369[»]
1N95X-ray2.30A55-369[»]
1N9AX-ray3.20A55-369[»]
1NI1X-ray2.30A55-369[»]
1NL4X-ray2.70A55-366[»]
1O1RX-ray2.30A1-377[»]
1O1SX-ray2.30A1-377[»]
1O1TX-ray2.10A1-377[»]
1O5MX-ray2.30A1-377[»]
1QBQX-ray2.40A45-377[»]
1QE2model-A116-247[»]
1S64X-ray2.55A/C/E/G/I/K1-377[»]
1SA5X-ray2.60A1-377[»]
1TN7X-ray2.30A1-377[»]
1TN8X-ray2.25A1-377[»]
1TNBX-ray2.85A/C/E/G/I/K1-377[»]
1TNOX-ray2.70A/C/E/G/I/K1-377[»]
1TNUX-ray2.70A/C/E/G/I/K1-377[»]
1TNYX-ray2.70A/C/E/G/I/K1-377[»]
1TNZX-ray2.90A/C/E/G/I/K1-377[»]
1X81X-ray3.50A55-369[»]
2BEDX-ray2.70A54-366[»]
2FTImodel-A55-369[»]
2R2LX-ray2.23A54-368[»]
2ZIRX-ray2.40A1-377[»]
2ZISX-ray2.60A1-377[»]
3DPYX-ray2.70A1-377[»]
3E30X-ray2.45A1-377[»]
3E32X-ray2.45A1-377[»]
3E33X-ray1.90A1-377[»]
3E34X-ray2.05A1-377[»]
3EU5X-ray2.80A1-377[»]
3EUVX-ray2.75A1-377[»]
3FTImodel-A55-369[»]
3KSLX-ray2.05A1-377[»]
3KSQX-ray2.10A1-377[»]
4GTMX-ray2.20A1-377[»]
4GTOX-ray2.15A1-377[»]
4GTPX-ray2.75A1-377[»]
4GTQX-ray2.60A1-377[»]
4GTRX-ray2.20A1-377[»]
ProteinModelPortalQ04631.
SMRQ04631. Positions 55-377.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-6131N.
IntActQ04631. 8 interactions.
MINTMINT-121907.
STRING10116.ENSRNOP00000019594.

Chemistry

BindingDBQ04631.
ChEMBLCHEMBL2095197.

PTM databases

PhosphoSiteQ04631.

Proteomic databases

PaxDbQ04631.
PRIDEQ04631.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25318.
KEGGrno:25318.
UCSCRGD:2625. rat.

Organism-specific databases

CTD2339.
RGD2625. Fnta.

Phylogenomic databases

eggNOGCOG5536.
HOGENOMHOG000188957.
HOVERGENHBG004498.
InParanoidQ04631.
KOK05955.
PhylomeDBQ04631.

Enzyme and pathway databases

SABIO-RKQ04631.

Gene expression databases

GenevestigatorQ04631.

Family and domain databases

InterProIPR002088. Prenyl_trans_a.
[Graphical view]
PfamPF01239. PPTA. 5 hits.
[Graphical view]
PROSITEPS51147. PFTA. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ04631.
NextBio606153.
PROQ04631.

Entry information

Entry nameFNTA_RAT
AccessionPrimary (citable) accession number: Q04631
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: June 11, 2014
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references