Reviewed, UniProtKB/Swiss-Prot P49354 (FNTA_HUMAN)

Names and origin

Protein names

Recommended 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
    Ras proteins prenyltransferase subunit alpha
    FTase-alpha
    Type I protein geranyl-geranyltransferase subunit alpha
      Short name=GGTase-I-alpha

Gene names

Name:

FNTA

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	379 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of several proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. The alpha subunit is thought to participate in a stable complex with the substrate. The beta subunit binds the peptide substrate.
Catalytic activity	Farnesyl diphosphate + protein-cysteine = S-farnesyl protein + diphosphate. Geranylgeranyl diphosphate + protein-cysteine = S-geranylgeranyl-protein + diphosphate.
Subunit structure	Heterodimer of an alpha and a beta subunit. Ref.9 Ref.10 Ref.11
Sequence similarities	Belongs to the protein prenyltransferase subunit alpha family. Contains 5 PFTA repeats.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Prenyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid farnesylation Ref.3 Traceable author statement. Source: ProtInc protein amino acid geranylgeranylation Traceable author statement. Source: ProtInc transforming growth factor beta receptor signaling pathway Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	CAAX-protein geranylgeranyltransferase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: IntAct protein farnesyltransferase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FNTB	P49356	5	EBI-602336,EBI-602349
PTP4A2	Q12974	1	EBI-602336,EBI-1046324

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49354-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P49354-2)

The sequence of this isoform differs from the canonical sequence as follows:
     68-134: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 379

379

Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha

PRO_0000119746

Regions

Repeat

112 – 146

35

PFTA 1

Repeat

147 – 180

34

PFTA 2

Repeat

181 – 215

35

PFTA 3

Repeat

216 – 249

34

PFTA 4

Repeat

255 – 289

35

PFTA 5

Compositional bias

22 – 31

10

Pro-rich

Amino acid modifications

Modified residue

373

1

Phosphoserine Ref.7

Natural variations

Alternative sequence

68 – 134

67

Missing in isoform 2.

VSP_036468

Experimental info

Mutagenesis

164

1

K → N: Reduced activity. Ref.2

Mutagenesis

199

1

N → K: Reduced catalytic efficiency. Ref.3

Sequence conflict

241

1

Y → H Ref.2

Secondary structure

1

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379

Helix Strand Turn

Details...

Helix

66 – 68

3

Helix

70 – 72

3

Beta strand

87 – 90

4

Helix

94 – 109

16

Helix

114 – 126

13

Helix

131 – 143

13

Helix

148 – 161

14

Helix

166 – 179

14

Helix

185 – 195

11

Helix

200 – 212

13

Helix

219 – 229

11

Helix

234 – 246

13

Helix

253 – 269

17

Helix

274 – 284

11

Turn

285 – 287

3

Helix

289 – 291

3

Helix

293 – 306

14

Helix

309 – 324

16

Helix

330 – 346

17

Helix

350 – 352

3

Helix

353 – 366

14

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: E933CBA874AB92B9	FASTA	379	44,409
	10 20 30 40 50 60 MAATEGVGEA AQGGEPGQPA QPPPQPHPPP PQQQHKEEMA AEAGEAVASP MDDGFVSLDS 70 80 90 100 110 120 PSYVLYRDRA EWADIDPVPQ NDGPNPVVQI IYSDKFRDVY DYFRAVLQRD ERSERAFKLT 130 140 150 160 170 180 RDAIELNAAN YTVWHFRRVL LKSLQKDLHE EMNYITAIIE EQPKNYQVWH HRRVLVEWLR 190 200 210 220 230 240 DPSQELEFIA DILNQDAKNY HAWQHRQWVI QEFKLWDNEL QYVDQLLKED VRNNSVWNQR 250 260 270 280 290 300 YFVISNTTGY NDRAVLEREV QYTLEMIKLV PHNESAWNYL KGILQDRGLS KYPNLLNQLL 310 320 330 340 350 360 DLQPSHSSPY LIAFLVDIYE DMLENQCDNK EDILNKALEL CEILAKEKDT IRKEYWRYIG 370 RSLQSKHSTE NDSPTNVQQ
	Isoform 2. Checksum: 789D43774B90D5DA	FASTA	312	36,493
	10 20 30 40 50 60 MAATEGVGEA AQGGEPGQPA QPPPQPHPPP PQQQHKEEMA AEAGEAVASP MDDGFVSLDS 70 80 90 100 110 120 PSYVLYRHFR RVLLKSLQKD LHEEMNYITA IIEEQPKNYQ VWHHRRVLVE WLRDPSQELE 130 140 150 160 170 180 FIADILNQDA KNYHAWQHRQ WVIQEFKLWD NELQYVDQLL KEDVRNNSVW NQRYFVISNT 190 200 210 220 230 240 TGYNDRAVLE REVQYTLEMI KLVPHNESAW NYLKGILQDR GLSKYPNLLN QLLDLQPSHS 250 260 270 280 290 300 SPYLIAFLVD IYEDMLENQC DNKEDILNKA LELCEILAKE KDTIRKEYWR YIGRSLQSKH 310 STENDSPTNV QQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of the two subunits of human CAAX farnesyltransferase and chromosomal mapping of FNTA and FNTB loci and related sequences." Andres D.A., Milatovich A., Ozcelik T., Wenzlau J.M., Brown M.S., Goldstein J.L., Francke U. Genomics 18:105-112(1993) [PubMed: 8276393] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Retina.
[2]	"Mutational analysis of alpha-subunit of protein farnesyltransferase. Evidence for a catalytic role." Andres D.A., Goldstein J.L., Ho Y.K., Brown M.S. J. Biol. Chem. 268:1383-1390(1993) [PubMed: 8419339] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF LYS-164.
[3]	"Characterization of recombinant human farnesyl-protein transferase: cloning, expression, farnesyl diphosphate binding, and functional homology with yeast prenyl-protein transferases." Omer C.A., Kral A.M., Diehl R.E., Prendergast G.C., Powers S., Allen C.M., Gibbs J.B., Kohl N.E. Biochemistry 32:5167-5176(1993) [PubMed: 8494894] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF ASN-199. Tissue: Placenta.
[4]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon and Lung.
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., 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. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-261 (ISOFORM 2).
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, MASS SPECTROMETRY.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 11687658] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT; FARNESYL DIPHOSPHATE AND INHIBITOR L-739,750.
[10]	"3-aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency." Bell I.M., Gallicchio S.N., Abrams M., Beese L.S., Beshore D.C., Bhimnathwala H., Bogusky M.J., Buser C.A., Culberson J.C., Davide J., Ellis-Hutchings M., Fernandes C., Gibbs J.B., Graham S.L., Hamilton K.A., Hartman G.D., Heimbrook D.C., Homnick C.F. , Huber H.E., Huff J.R., Kassahun K., Koblan K.S., Kohl N.E., Lobell R.B., Lynch J.J. Jr., Robinson R., Rodrigues A.D., Taylor J.S., Walsh E.S., Williams T.M., Zartman C.B. J. Med. Chem. 45:2388-2409(2002) [PubMed: 12036349] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT; FARNESYL DIPHOSPHATE AND INHIBITORS.
[11]	"Dual protein farnesyltransferase-geranylgeranyltransferase-I inhibitors as potential cancer chemotherapeutic agents." deSolms S.J., Ciccarone T.M., MacTough S.C., Shaw A.W., Buser C.A., Ellis-Hutchings M., Fernandes C., Hamilton K.A., Huber H.E., Kohl N.E., Lobell R.B., Robinson R.G., Tsou N.N., Walsh E.S., Graham S.L., Beese L.S., Taylor J.S. J. Med. Chem. 46:2973-2984(2003) [PubMed: 12825937] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH BETA SUBUNIT; FARNESYL DIPHOSPHATE AND INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L10413 mRNA. Translation: AAA86285.1.
L00634 mRNA. Translation: AAA35853.1.
AC110275 Genomic DNA. No translation available.
AC113191 Genomic DNA. No translation available.
BC017029 mRNA. Translation: AAH17029.2.
BC084566 mRNA. Translation: AAH84566.1.
AL698961 mRNA. No translation available.

IPI

IPI00026813.
IPI00607601.

PIR

A47659.

RefSeq

NP_001018196.1.
NP_002018.1.

UniGene

Hs.370312

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JCQ	X-ray	2.30	A	1-379	[»]
1LD7	X-ray	2.00	A	1-379	[»]
1LD8	X-ray	1.80	A	1-379	[»]
1MZC	X-ray	2.00	A	1-379	[»]
1S63	X-ray	1.90	A	1-379	[»]
1SA4	X-ray	2.10	A	1-379	[»]
1TN6	X-ray	1.80	A	1-379	[»]
2F0Y	X-ray	2.70	A	1-379	[»]
2H6F	X-ray	1.50	A	1-379	[»]
2H6G	X-ray	1.85	A	1-379	[»]
2H6H	X-ray	1.80	A	1-379	[»]
2H6I	X-ray	3.00	A	1-379	[»]
2IEJ	X-ray	1.80	A	1-379	[»]
3E37	X-ray	1.80	A	1-379	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P49354. 4 interactions.

PTM databases

PhosphoSite

P49354.

Proteomic databases

PRIDE

P49354.

Genome annotation databases

Ensembl

ENSG00000168522. Homo sapiens. [Contig view]

GeneID

2339.

KEGG

hsa:2339.

Organism-specific databases

GeneCards

GC08P043030.

H-InvDB

HIX0022455.

HGNC

HGNC:3782. FNTA.

HPA

CAB010149.
HPA018830.

MIM

134635. gene.

PharmGKB

PA28199.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P49354.

HOVERGEN

P49354.

OMA

P49354. TVWHYRR.

Enzyme and pathway databases

BRENDA

2.5.1.58. 247.
2.5.1.59. 247.

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

P49354.

Bgee

P49354.

CleanEx

HS_FNTA.

GermOnline

ENSG00000168522. Homo sapiens.

Family and domain databases

InterPro

IPR002088. Prenyl_trans_a.
IPR008940. Prenyltransferase.
[Graphical view]

Gene3D

G3DSA:1.25.40.120. Prenyl_trans. 1 hit.

Pfam

PF01239. PPTA. 5 hits.
[Graphical view]

PROSITE

PS51147. PFTA. 5 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

9495.

PMAP-CutDB

P49354.

SOURCE

Search...

Entry information

Entry name

FNTA_HUMAN

Accession

Primary (citable) accession number: P49354
Secondary accession number(s): Q9UDC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	June 16, 2009
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)