Reviewed, UniProtKB/Swiss-Prot P04053 (TDT_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA nucleotidylexotransferase
    EC=2.7.7.31
Alternative name(s):
    Terminal addition enzyme
    Terminal deoxynucleotidyltransferase
      Short name=Terminal transferase

Gene names

Name:	DNTT
Synonyms:	TDT

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

General annotation (Comments)

Function	Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells.
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Magnesium.
Subunit structure	Interacts with PRP19 and DNTTIP1. Forms a ternary complex with DNTTIP2 and core histone. Released from this complex by PCNA. Ref.7 Ref.8 Ref.9
Subcellular location	Nucleus.
Involvement in disease	Very high levels of enzyme activity have been detected in certain acute leukemic cells.
Sequence similarities	Belongs to the DNA polymerase type-X family. Contains 1 BRCT domain.

Ontologies

Keywords
Biological process	Terminal addition
Cellular component	Nucleus
Ligand	Magnesium Metal-binding
Molecular function	Nucleotidyltransferase Transferase
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA modification Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	DNA binding Inferred from electronic annotation. Source: InterPro DNA nucleotidylexotransferase activity Ref.1 Traceable author statement. Source: ProtInc DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 509

509

DNA nucleotidylexotransferase

PRO_0000218791

Regions

Domain

27 – 124

98

BRCT

Region

151 – 509

359

Mediates interaction with DNTTIP2

Region

336 – 345

10

Involved in ssDNA binding By similarity

Sites

Metal binding

253

1

Sodium; via carbonyl oxygen By similarity

Metal binding

255

1

Sodium; via carbonyl oxygen By similarity

Metal binding

343

1

Magnesium By similarity

Metal binding

345

1

Magnesium By similarity

Metal binding

433

1

Magnesium By similarity

Experimental info

Sequence conflict

452

1

S → SP in AAA53100. Ref.2

Sequence conflict

454

1

Missing Ref.1

Sequence conflict

454

1

Missing Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

509

Helix Strand Turn

Details...

Beta strand

23 – 25

3

Beta strand

36 – 40

5

Turn

42 – 44

3

Helix

46 – 58

13

Beta strand

73 – 78

6

Helix

81 – 90

10

Beta strand

100 – 103

4

Helix

104 – 112

9

Beta strand

120 – 124

5

Sequences

	Sequence		Length	Mass (Da)
	P04053-1 [UniParc]. Last modified November 28, 2002. Version 2. Checksum: 4F33A95A983B7287	FASTA	509	58,437
	10 20 30 40 50 60 MDPPRASHLS PRKKRPRQTG ALMASSPQDI KFQDLVVFIL EKKMGTTRRA FLMELARRKG 70 80 90 100 110 120 FRVENELSDS VTHIVAENNS GSDVLEWLQA QKVQVSSQPE LLDVSWLIEC IGAGKPVEMT 130 140 150 160 170 180 GKHQLVVRRD YSDSTNPGPP KTPPIAVQKI SQYACQRRTT LNNCNQIFTD AFDILAENCE 190 200 210 220 230 240 FRENEDSCVT FMRAASVLKS LPFTIISMKD TEGIPCLGSK VKGIIEEIIE DGESSEVKAV 250 260 270 280 290 300 LNDERYQSFK LFTSVFGVGL KTSEKWFRMG FRTLSKVRSD KSLKFTRMQK AGFLYYEDLV 310 320 330 340 350 360 SCVTRAEAEA VSVLVKEAVW AFLPDAFVTM TGGFRRGKKM GHDVDFLITS PGSTEDEEQL 370 380 390 400 410 420 LQKVMNLWEK KGLLLYYDLV ESTFEKLRLP SRKVDALDHF QKCFLIFKLP RQRVDSDQSS 430 440 450 460 470 480 WQEGKTWKAI RVDLVLCPYE RRAFALLGWT GSRQFERDLR RYATHERKMI LDNHALYDKT 490 500 KRIFLKAESE EEIFAHLGLD YIEPWERNA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of human terminal deoxynucleotidyl transferase in Escherichia coli." Peterson R.C., Cheung L.C., Mattaliano R.J., White S.T., Chang L.M.S., Bollum F.J. J. Biol. Chem. 260:10495-10502(1985) [PubMed: 2863268] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human terminal deoxyribonucleotidyltransferase: molecular cloning and structural analysis of the gene and 5' flanking region." Riley L.K., Morrow J.K., Danton M.J., Coleman M.S. Proc. Natl. Acad. Sci. U.S.A. 85:2489-2493(1988) [PubMed: 2833741] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Terminal deoxynucleotidyltransferase is negatively regulated by direct interaction with proliferating cell nuclear antigen." Ibe S., Fujita K., Toyomoto T., Shimazaki N., Kaneko R., Tanabe A., Takebe I., Kuroda S., Kobayashi T., Toji S., Tamai K., Yamamoto H., Koiwai O. Genes Cells 6:815-824(2001) [PubMed: 11554927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"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]. Tissue: Testis.
[5]	"Molecular cloning of human terminal deoxynucleotidyltransferase." Peterson R.C., Cheung L.C., Mattaliano R.J., Chang L.M.S., Bollum F.J. Proc. Natl. Acad. Sci. U.S.A. 81:4363-4367(1984) [PubMed: 6087320] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 271-508.
[6]	"Isolation of putative promoter region for human terminal deoxynucleotidyltransferase gene." Koiwai O., Morita A. Biochem. Biophys. Res. Commun. 154:91-100(1988) [PubMed: 3395350] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
[7]	"Terminal deoxynucleotidyltransferase directly interacts with a novel nuclear protein that is homologous to p65." Yamashita N., Shimazaki N., Ibe S., Kaneko R., Tanabe A., Toyomoto T., Fujita K., Hasegawa T., Toji S., Tamai K., Yamamoto H., Koiwai O. Genes Cells 6:641-652(2001) [PubMed: 11473582] [Abstract] Cited for: INTERACTION WITH TDIF1. Tissue: Thymus.
[8]	"Terminal deoxynucleotidyltransferase forms a ternary complex with a novel chromatin remodeling protein with 82 kDa and core histone." Fujita K., Shimazaki N., Ohta Y., Kubota T., Ibe S., Toji S., Tamai K., Fujisaki S., Hayano T., Koiwai O. Genes Cells 8:559-571(2003) [PubMed: 12786946] [Abstract] Cited for: INTERACTION WITH DNTTIP2 AND CORE HISTONE.
[9]	"Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase." Mahajan K.N., Mitchell B.S. Proc. Natl. Acad. Sci. U.S.A. 100:10746-10751(2003) [PubMed: 12960389] [Abstract] Cited for: INTERACTION WITH PRP19.
[10]	"Mutational analysis of residues in the nucleotide binding domain of human terminal deoxynucleotidyl transferase." Yang B., Gathy K.N., Coleman M.S. J. Biol. Chem. 269:11859-11868(1994) [PubMed: 8163485] [Abstract] Cited for: MUTAGENESIS.
[11]	"Solution structure of BRCT domain of terminal deoxynucleotidyltransferase." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 19-125.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

K01919 mRNA. Translation: AAA61136.1.
M20703 , M22968, M20694, M20695, M20696, M20697, M20698, M20699, M20700, M20701, M20702 mRNA. Translation: AAA53100.1.
AB046378 mRNA. Translation: BAB72001.1.
BC012920 mRNA. Translation: AAH12920.1.
M11722 mRNA. Translation: AAA36726.1.
M21195 Genomic DNA. Translation: AAA61137.1.

IPI

IPI00219676.

PIR

WXHU. A23924.

RefSeq

NP_001017520.1.
NP_004079.3.

UniGene

Hs.534206

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2COE	NMR	-	A	19-125	[»]

SMR

P04053. Positions 148-509.

ModBase

Search...

PTM databases

PhosphoSite

P04053.

Proteomic databases

PRIDE

P04053.

Genome annotation databases

Ensembl

ENSG00000107447. Homo sapiens. [Contig view]

GeneID

1791.

KEGG

hsa:1791.

Organism-specific databases

GeneCards

GC10P098054.

H-InvDB

HIX0009072.

HGNC

HGNC:2983. DNTT.

MIM

187410. gene.

PharmGKB

PA27449.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P04053.

HOVERGEN

P04053.

Enzyme and pathway databases

BRENDA

2.7.7.31. 247.

Gene expression databases

ArrayExpress

P04053.

Bgee

P04053.

CleanEx

HS_DNTT.

GermOnline

ENSG00000107447. Homo sapiens.

Family and domain databases

InterPro

IPR001357. BRCT.
IPR002054. DNA-dir_DNA_pol_X.
IPR010996. DNA-dir_DNA_pol_X_beta-like_N.
IPR001726. DNA_nucleotidylexotransferase.
IPR019843. DNA_pol-X_BS.
IPR018944. DNA_pol_lambd_fingers_domain.
IPR002934. Nucleotidyltransferase.
[Graphical view]

Gene3D

G3DSA:1.10.150.110. DNA_pol_b_N-like. 1 hit.

PANTHER

PTHR11276:SF6. DNA_polXtrans. 1 hit.

Pfam

PF00533. BRCT. 1 hit.
PF10391. DNA_pol_lambd_f. 1 hit.
PF01909. NTP_transf_2. 1 hit.
[Graphical view]

PIRSF

PIRSF000817. DNA_NT. 1 hit.

PRINTS

PR00869. DNAPOLX.
PR00871. DNAPOLXTDT.

SMART

SM00292. BRCT. 1 hit.
SM00483. POLXc. 1 hit.
[Graphical view]

PROSITE

PS50172. BRCT. 1 hit.
PS00522. DNA_POLYMERASE_X. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

7299.

SOURCE

Search...

Entry information

Entry name

TDT_HUMAN

Accession

Primary (citable) accession number: P04053
Secondary accession number(s): Q96E50

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 28, 2002
Last modified:	June 16, 2009
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)