P07884 (MOD5_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
tRNA dimethylallyltransferase, mitochondrial
Short name=DMATase
EC=2.5.1.75

Alternative name(s):
Isopentenyl-diphosphate: tRNA isopentenyltransferase
Short name=IPP transferase
Short name=IPPT
tRNA isopentenyltransferase
Short name=IPTase

Gene names

Name:	MOD5
Ordered Locus Names:	YOR274W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37 in the anticodon loop on a specific subset of tRNAs both in the cytosol and the mitochondrion, leading to the formation of N6-(dimethylallyl)adenosine (i6A). This modification optimizes the codon:anticodon fit in the ribosome and promotes translational fidelity. Competes with the farnesyl pyrophosphate synthase ERG20 for the common substrate dimethylallyl diphosphate (DMAPP). Ref.5 Ref.9 Ref.11
Catalytic activity	Dimethylallyl diphosphate + tRNA = diphosphate + tRNA containing 6-dimethylallyladenosine.
Subcellular location	Cytoplasm. Mitochondrion Ref.6 Ref.7 Ref.8 Ref.12. Nucleus Ref.6 Ref.7 Ref.8 Ref.12. Note: [MOD+] forms multicytoplasmic aggregates that do not colocalize to either mitochondria or nucleus. Ref.6 Ref.7 Ref.8 Ref.12 Isoform I: Cytoplasm. Mitochondrion Ref.6 Ref.7 Ref.8 Ref.12. Isoform II: Cytoplasm. Nucleus Ref.6 Ref.7 Ref.8 Ref.12.
Domain	The core aggregation region, although lacking the prion-typical Gln/Asn (Q/N)-rich domain, is required for the formation of the amyloid-like fibrillar aggregates.
Miscellaneous	[MOD+] is the prion form of MOD5. [MOD+] is the result of a conformational change of the cellular MOD5 protein that becomes self-propagating and infectious. This conformational change generates a form of MOD5 that assembles into amyloid-like fibrillar aggregates. [MOD+] aggregates sequester soluble MOD5, resulting in decreased levels of (i6A)-modified tRNAs and higher ergosterol levels, due to less competition for ERG20, which uses the same substrate DMAPP than MOD5. [MOD+] can be cured by GdnHCl and by deletion of the molecular chaperone HSP104, which is required for [MOD+] propagation. The [MOD+] state acquires resistance against antifungal agents such as flucanozole, ketoconazole and clotrimazole that inhibit ergosterol biosynthesis. De novo appearance of [MOD+] is favored in the presence of antifunagl agents, and the growth advantage of [MOD+] is lost when the cells are released from the selective pressure. Thus, the conformational switch of MOD5 from a soluble state to a prion state allows the cell to adapt to the harmful environment of anti-fungal drugs by up-regulating ergosterol biosynthesis at the expense of tRNA modification (Ref.12). Present with 2020 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the IPP transferase family. Contains 1 matrin-type zinc finger.

Ontologies

Keywords
Biological process	tRNA processing
Cellular component	Amyloid Cytoplasm Mitochondrion Nucleus
Coding sequence diversity	Alternative initiation
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Prion Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	tRNA modification Inferred from direct assay Ref.13. Source: SGD
Cellular_component	cytosol Inferred from direct assay PubMed 9872948. Source: SGD mitochondrion Inferred from direct assay PubMed 14576278PubMed 16823961PubMed 9872948. Source: SGD nucleolus Inferred from direct assay PubMed 9872948. Source: SGD
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW tRNA dimethylallyltransferase activity Inferred from direct assay Ref.13Ref.5. Source: SGD
Complete GO annotation...

Alternative products

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

Isoform I (identifier: P07884-1)

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 II (identifier: P07884-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-11: Missing.

Note: Produced by alternative initiation at Met-12 of isoform I.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 428

428

tRNA dimethylallyltransferase, mitochondrial

PRO_0000019025

Regions

Nucleotide binding

21 – 28

8

ATP Potential

Zinc finger

373 – 409

37

Matrin-type

Region

23 – 28

6

Substrate binding

Region

46 – 49

4

Interaction with substrate tRNA

Region

170 – 174

5

Interaction with substrate tRNA

Region

199 – 207

9

Core aggregation region

Region

210 – 232

23

Interaction with isopentenylpyrophosphate transferase

Region

256 – 258

3

Interaction with substrate tRNA

Region

284 – 302

19

Interaction with substrate tRNA

Region

294 – 301

8

Interaction with substrate tRNA By similarity

Sites

Site

112

1

Interaction with substrate tRNA

Site

193

1

Interaction with substrate tRNA

Natural variations

Alternative sequence

1 – 11

11

Missing in isoform II.

VSP_018811

Experimental info

Sequence conflict

313

1

Missing in AAA34785. Ref.1

Sequence conflict

375

1

C → R in AAA34785. Ref.1

Secondary structure

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428

Helix Strand Turn

Details...

Beta strand

15 – 21

7

Beta strand

23 – 26

4

Helix

27 – 38

12

Beta strand

40 – 44

5

Turn

47 – 50

4

Beta strand

51 – 53

3

Turn

55 – 59

5

Helix

63 – 65

3

Turn

66 – 68

3

Beta strand

71 – 73

3

Helix

85 – 100

16

Turn

101 – 103

3

Beta strand

105 – 109

5

Helix

113 – 120

8

Beta strand

127 – 129

3

Helix

135 – 141

7

Beta strand

144 – 148

5

Helix

149 – 155

7

Helix

158 – 161

4

Helix

169 – 182

14

Helix

186 – 191

6

Beta strand

198 – 207

10

Helix

210 – 226

17

Helix

229 – 240

12

Turn

241 – 244

4

Helix

247 – 249

3

Helix

253 – 256

4

Helix

261 – 267

7

Helix

278 – 302

25

Helix

304 – 307

4

Turn

308 – 310

3

Beta strand

312 – 316

5

Turn

320 – 322

3

Turn

324 – 327

4

Helix

328 – 339

12

Helix

351 – 357

7

Helix

359 – 361

3

Helix

363 – 365

3

Beta strand

372 – 379

8

Beta strand

385 – 390

6

Helix

391 – 398

8

Helix

401 – 418

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform I [UniParc]. Last modified November 1, 1997. Version 2. Checksum: A956B17ABC05161F	FASTA	428	50,237
	10 20 30 40 50 60 MLKGPLKGCL NMSKKVIVIA GTTGVGKSQL SIQLAQKFNG EVINSDSMQV YKDIPIITNK 70 80 90 100 110 120 HPLQEREGIP HHVMNHVDWS EEYYSHRFET ECMNAIEDIH RRGKIPIVVG GTHYYLQTLF 130 140 150 160 170 180 NKRVDTKSSE RKLTRKQLDI LESTDPDVIY NTLVKCDPDI ATKYHPNDYR RVQRMLEIYY 190 200 210 220 230 240 KTGKKPSETF NEQKITLKFD TLFLWLYSKP EPLFQRLDDR VDDMLERGAL QEIKQLYEYY 250 260 270 280 290 300 SQNKFTPEQC ENGVWQVIGF KEFLPWLTGK TDDNTVKLED CIERMKTRTR QYAKRQVKWI 310 320 330 340 350 360 KKMLIPDIKG DIYLLDATDL SQWDTNASQR AIAISNDFIS NRPIKQERAP KALEELLSKG 370 380 390 400 410 420 ETTMKKLDDW THYTCNVCRN ADGKNVVAIG EKYWKIHLGS RRHKSNLKRN TRQADFEKWK INKKETVE
	Isoform II [UniParc]. Checksum: 2E3553D49DA2E0AC	FASTA	417	49,081
	10 20 30 40 50 60 MSKKVIVIAG TTGVGKSQLS IQLAQKFNGE VINSDSMQVY KDIPIITNKH PLQEREGIPH 70 80 90 100 110 120 HVMNHVDWSE EYYSHRFETE CMNAIEDIHR RGKIPIVVGG THYYLQTLFN KRVDTKSSER 130 140 150 160 170 180 KLTRKQLDIL ESTDPDVIYN TLVKCDPDIA TKYHPNDYRR VQRMLEIYYK TGKKPSETFN 190 200 210 220 230 240 EQKITLKFDT LFLWLYSKPE PLFQRLDDRV DDMLERGALQ EIKQLYEYYS QNKFTPEQCE 250 260 270 280 290 300 NGVWQVIGFK EFLPWLTGKT DDNTVKLEDC IERMKTRTRQ YAKRQVKWIK KMLIPDIKGD 310 320 330 340 350 360 IYLLDATDLS QWDTNASQRA IAISNDFISN RPIKQERAPK ALEELLSKGE TTMKKLDDWT 370 380 390 400 410 HYTCNVCRNA DGKNVVAIGE KYWKIHLGSR RHKSNLKRNT RQADFEKWKI NKKETVE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"DNA sequence and transcript mapping of MOD5: features of the 5' region which suggest two translational starts." Najarian D., Dihanich M.E., Martin N.C., Hopper A.K. Mol. Cell. Biol. 7:185-191(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"DNA sequence analysis of the VPH1-SNF2 region on chromosome XV of Saccharomyces cerevisiae." Cheret G., Bernardi A., Sor F.J. Yeast 12:1059-1064(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XV." Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D. , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K. Nature 387:98-102(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[4]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[5]	"Isolation and characterization of MOD5, a gene required for isopentenylation of cytoplasmic and mitochondrial tRNAs of Saccharomyces cerevisiae." Dihanich M.E., Najarian D., Clark R., Gillman E.C., Martin N.C., Hopper A.K. Mol. Cell. Biol. 7:177-184(1987) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"mRNA leader length and initiation codon context determine alternative AUG selection for the yeast gene MOD5." Slusher L.B., Gillman E.C., Martin N.C., Hopper A.K. Proc. Natl. Acad. Sci. U.S.A. 88:9789-9793(1991) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION, SUBCELLULAR LOCATION.
[7]	"MOD5 translation initiation sites determine N6-isopentenyladenosine modification of mitochondrial and cytoplasmic tRNA." Gillman E.C., Slusher L.B., Martin N.C., Hopper A.K. Mol. Cell. Biol. 11:2382-2390(1991) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION, SUBCELLULAR LOCATION.
[8]	"Subcellular locations of MOD5 proteins: mapping of sequences sufficient for targeting to mitochondria and demonstration that mitochondrial and nuclear isoforms commingle in the cytosol." Boguta M., Hunter L.A., Shen W.C., Gillman E.C., Martin N.C., Hopper A.K. Mol. Cell. Biol. 14:2298-2306(1994) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE INITIATION, SUBCELLULAR LOCATION.
[9]	"Competition between a sterol biosynthetic enzyme and tRNA modification in addition to changes in the protein synthesis machinery causes altered nonsense suppression." Benko A.L., Vaduva G., Martin N.C., Hopper A.K. Proc. Natl. Acad. Sci. U.S.A. 97:61-66(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[11]	"Plasticity and diversity of tRNA anticodon determinants of substrate recognition by eukaryotic A37 isopentenyltransferases." Lamichhane T.N., Blewett N.H., Maraia R.J. RNA 17:1846-1857(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"A yeast prion, Mod5, promotes acquired drug resistance and cell survival under environmental stress." Suzuki G., Shimazu N., Tanaka M. Science 336:355-359(2012) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION, SUBCELLULAR LOCATION.
[13]	"Crystallographic snapshots of eukaryotic dimethylallyltransferase acting on tRNA: insight into tRNA recognition and reaction mechanism." Zhou C., Huang R.H. Proc. Natl. Acad. Sci. U.S.A. 105:16142-16147(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) OF 13-421 IN COMPLEXES WITH SUBSTRATE TRNA; ISOPENTENYL DIPHOSPHATE AND ZINC IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M15991 Genomic DNA. Translation: AAA34785.1.
X89633 Genomic DNA. Translation: CAA61780.1.
Z75182 Genomic DNA. Translation: CAA99499.1.
BK006948 Genomic DNA. Translation: DAA11040.1.

PIR

S67176.

RefSeq

NP_014917.3. NM_001183693.3.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3EPH	X-ray	2.95	A/B	13-421	[»]
3EPJ	X-ray	3.10	A/B	13-421	[»]
3EPK	X-ray	3.20	A/B	13-421	[»]
3EPL	X-ray	3.60	A/B	13-421	[»]

ProteinModelPortal

P07884.

SMR

P07884. Positions 13-421.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-4094N.

IntAct

P07884. 2 interactions.

MINT

MINT-536616.

STRING

4932.YOR274W.

Proteomic databases

PaxDb

P07884.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YOR274W; YOR274W; YOR274W.

GeneID

854448.

KEGG

sce:YOR274W.

Organism-specific databases

CYGD

YOR274w.

SGD

S000005800. MOD5.

Phylogenomic databases

eggNOG

COG0324.

GeneTree

ENSGT00390000015214.

HOGENOM

HOG000039995.

KO

K00791.

OMA

PIITNKH.

OrthoDB

EOG42RHH4.

Enzyme and pathway databases

BioCyc

YEAST:YOR274W-MONOMER.

Gene expression databases

Genevestigator

P07884.

GermOnline

YOR274W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR002627. IPPT.
IPR027417. P-loop_NTPase.
IPR018022. tRNA_delta_PyrP_Trfase.
[Graphical view]

PANTHER

PTHR11088. PTHR11088. 1 hit.

Pfam

PF01715. IPPT. 1 hit.
[Graphical view]

SUPFAM

SSF52540. SSF52540. 1 hit.

TIGRFAMs

TIGR00174. miaA. 1 hit.

PROSITE

PS50171. ZF_MATRIN. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P07884.

NextBio

976706.

Entry information

Entry name

MOD5_YEAST

Accession

Primary (citable) accession number: P07884
Secondary accession number(s): D6W2X4, Q12203

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	November 1, 1997
Last modified:	May 29, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program