Q9NWX6 (THG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Probable tRNA(His) guanylyltransferase
EC=2.7.7.79

Alternative name(s):
Interphase cytoplasmic foci protein 45
tRNA-histidine guanylyltransferase

Gene names

Name:	THG1L
Synonyms:	ICF45

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	298 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage. This step is essential for proper recognition of the tRNA and for the fidelity of protein synthesis. Ref.8
Catalytic activity	p-tRNA(His) + ATP + GTP = pppG-P-tRNA(His) + AMP + diphosphate.
Cofactor	Binds 2 magnesium ions per subunit. Ref.8
Subunit structure	Homotetramer. Ref.8
Subcellular location	Cytoplasm. Note: Found near the nuclear membrane. Ref.1
Tissue specificity	Expressed in many tissues. Ref.1
Sequence similarities	Belongs to the tRNA(His) guanylyltransferase family.
Sequence caution	The sequence AAH01523.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH01852.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	tRNA processing
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	GTP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	protein homotetramerization Inferred from physical interaction Ref.8. Source: UniProtKB tRNA modification Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrion Inferred from direct assay. Source: LIFEdb
Molecular_function	ATP binding Inferred from direct assay Ref.8. Source: BHF-UCL GTP binding Inferred from direct assay Ref.8. Source: BHF-UCL magnesium ion binding Inferred from direct assay Ref.8. Source: BHF-UCL tRNA binding Traceable author statement Ref.8. Source: BHF-UCL tRNA guanylyltransferase activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 298

298

Probable tRNA(His) guanylyltransferase

PRO_0000284984

Regions

Nucleotide binding

58 – 63

6

GTP

Nucleotide binding

104 – 105

2

GTP

Sites

Metal binding

58

1

Magnesium 1; catalytic

Metal binding

58

1

Magnesium 2; catalytic

Metal binding

59

1

Magnesium 1; via carbonyl oxygen; catalytic

Metal binding

105

1

Magnesium 1; catalytic

Metal binding

105

1

Magnesium 2; catalytic

Amino acid modifications

Modified residue

251

1

Phosphothreonine By similarity

Natural variations

Natural variant

232

1

L → P. Ref.3 Ref.5 Ref.6 Ref.7
Corresponds to variant rs2270812 [ dbSNP | Ensembl ].

VAR_031871

Experimental info

Mutagenesis

58

1

D → A: Reduces activity by 99.5%. Ref.8

Mutagenesis

63

1

H → A: Slightly reduced enzyme activity. Ref.8

Mutagenesis

104

1

S → A: Slightly reduced enzyme activity. Ref.8

Mutagenesis

105

1

D → A: Loss of enzyme activity. Ref.8

Mutagenesis

106

1

E → A: Reduces activity by 95%. Ref.8

Mutagenesis

127

1

T → A: Abolishes oligomerization. Loss of enzyme activity. Ref.8

Mutagenesis

181

1

H → A: Loss of enzyme activity. Ref.8

Mutagenesis

216

1

K → A: Reduces activity by 98.5%. Ref.8

Mutagenesis

227

1

N → A: Loss of enzyme activity. Ref.8

Sequence conflict

57

1

L → Q in BAD96839. Ref.5

Secondary structure

1

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298

Helix Strand Turn

Details...

Helix

36 – 41

6

Beta strand

51 – 59

9

Helix

62 – 68

7

Helix

77 – 93

17

Beta strand

94 – 103

10

Beta strand

106 – 111

6

Turn

117 – 120

4

Helix

122 – 139

18

Helix

141 – 144

4

Beta strand

146 – 148

3

Beta strand

156 – 165

10

Helix

166 – 195

30

Helix

201 – 208

8

Helix

213 – 224

12

Helix

228 – 230

3

Helix

233 – 237

5

Beta strand

239 – 243

5

Beta strand

274 – 277

4

Beta strand

281 – 283

3

Helix

284 – 289

6

Helix

292 – 295

4

Sequences

	Sequence		Length	Mass (Da)
	Q9NWX6 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: A6C941B75611C448	FASTA	298	34,831
	10 20 30 40 50 60 MWGACKVKVH DSLATISITL RRYLRLGATM AKSKFEYVRD FEADDTCLAH CWVVVRLDGR 70 80 90 100 110 120 NFHRFAEKHN FAKPNDSRAL QLMTKCAQTV MEELEDIVIA YGQSDEYSFV FKRKTNWFKR 130 140 150 160 170 180 RASKFMTHVA SQFASSYVFY WRDYFEDQPL LYPPGFDGRV VVYPSNQTLK DYLSWRQADC 190 200 210 220 230 240 HINNLYNTVF WALIQQSGLT PVQAQGRLQG TLAADKNEIL FSEFNINYNN ELPMYRKGTV 250 260 270 280 290 LIWQKVDEVM TKEIKLPTEM EGKKMAVTRT RTKPVPLHCD IIGDAFWKEH PEILDEDS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of a novel cytoplasm protein ICF45 that is involved in cell cycle regulation." Guo D., Hu K., Lei Y., Wang Y., Ma T., He D. J. Biol. Chem. 279:53498-53505(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-232.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-232.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-232.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-232. Tissue: Brain and Muscle.
[8]	"tRNA(His) guanylyltransferase (THG1), a unique 3'-5' nucleotidyl transferase, shares unexpected structural homology with canonical 5'-3' DNA polymerases." Hyde S.J., Eckenroth B.E., Smith B.A., Eberley W.A., Heintz N.H., Jackman J.E., Doublie S. Proc. Natl. Acad. Sci. U.S.A. 107:20305-20310(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 30-298 IN COMPLEX WITH MAGNESIUM; TRIPHOSPHATE AND GTP, FUNCTION, COFACTOR, SUBUNIT, MUTAGENESIS OF ASP-58; HIS-63; SER-104; ASP-105; GLU-106; THR-127; HIS-181; LYS-216 AND ASN-227.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY463216 mRNA. Translation: AAS21134.1.
AL136669 mRNA. Translation: CAB66604.1.
AK000553 mRNA. Translation: BAA91249.1.
AK021663 mRNA. Translation: BAB13870.1.
CR533503 mRNA. Translation: CAG38534.1.
AK223119 mRNA. Translation: BAD96839.1.
CH471062 Genomic DNA. Translation: EAW61590.1.
CH471062 Genomic DNA. Translation: EAW61591.1.
BC001523 mRNA. Translation: AAH01523.2. Different initiation.
BC001852 mRNA. Translation: AAH01852.2. Different initiation.
BC023521 mRNA. Translation: AAH23521.1.

IPI

IPI00016559.

RefSeq

NP_060342.2. NM_017872.3.

UniGene

Hs.353090.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3OTB	X-ray	2.95	A/B	30-298	[»]
3OTC	X-ray	3.01	A/B	30-298	[»]
3OTD	X-ray	2.28	A/B	30-298	[»]
3OTE	X-ray	2.56	A/B	30-298	[»]

ProteinModelPortal

Q9NWX6.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-59479N.

IntAct

Q9NWX6. 1 interaction.

MINT

MINT-4873002.

STRING

9606.ENSP00000231198.

PTM databases

PhosphoSite

Q9NWX6.

Polymorphism databases

DMDM

146325755.

Proteomic databases

PaxDb

Q9NWX6.

PeptideAtlas

Q9NWX6.

PRIDE

Q9NWX6.

Protocols and materials databases

DNASU

54974.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000231198; ENSP00000231198; ENSG00000113272.

GeneID

54974.

KEGG

hsa:54974.

UCSC

uc003lxd.3. human.

Organism-specific databases

CTD

54974.

GeneCards

GC05P157159.

HGNC

HGNC:26053. THG1L.

HPA

HPA035877.
HPA035878.

neXtProt

NX_Q9NWX6.

PharmGKB

PA162405691.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4021.

HOGENOM

HOG000204890.

HOVERGEN

HBG054289.

InParanoid

Q9NWX6.

KO

K10761.

OMA

WRQADVH.

OrthoDB

EOG4JHCG5.

PhylomeDB

Q9NWX6.

Gene expression databases

ArrayExpress

Q9NWX6.

Bgee

Q9NWX6.

CleanEx

HS_THG1L.

Genevestigator

Q9NWX6.

Family and domain databases

InterPro

IPR025845. Thg1_C_dom.
IPR024956. tRNAHis_GuaTrfase_cat.
IPR007537. tRNAHis_GuaTrfase_Thg1.
[Graphical view]

PANTHER

PTHR12729. PTHR12729. 1 hit.

Pfam

PF04446. Thg1. 1 hit.
PF14413. Thg1C. 1 hit.
[Graphical view]

PIRSF

PIRSF028980. tRNAHis_guanylyltransferase. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

THG1L. human.

EvolutionaryTrace

Q9NWX6.

GenomeRNAi

54974.

NextBio

58226.

Entry information

Entry name

THG1_HUMAN

Accession

Primary (citable) accession number: Q9NWX6
Secondary accession number(s): D3DQJ5 , Q53G12, Q7L5R3, Q9H0S2

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 1, 2007
Last sequence update:	May 1, 2007
Last modified:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.