P04053 (TDT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	509 AA.
Sequence status	Complete.
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.9 Ref.10 Ref.11
Subcellular location	Nucleus.
Sequence similarities	Belongs to the DNA polymerase type-X family. Contains 1 BRCT domain.

Ontologies

Keywords
Biological process	Terminal addition
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Magnesium Metal-binding
Molecular function	Nucleotidyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA modification Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	DNA binding Inferred from electronic annotation. Source: InterPro DNA nucleotidylexotransferase activity Traceable author statement Ref.1. Source: ProtInc DNA-directed DNA polymerase activity Inferred from electronic annotation. Source: InterPro metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P04053-1)

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: P04053-2)

The sequence of this isoform differs from the canonical sequence as follows:
     454-454: Missing.

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

Natural variations

Alternative sequence

454

1

Missing in isoform 2.

VSP_038397

Natural variant

112

1

R → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs6584066 [ dbSNP | Ensembl ].

VAR_058200

Experimental info

Sequence conflict

51

1

F → L in BAD97037. Ref.4

Sequence conflict

299

1

L → P in BAD97037. Ref.4

Sequence conflict

329

1

T → A in BAD97037. Ref.4

Sequence conflict

383

1

T → A in BAD97037. Ref.4

Sequence conflict

389

1

L → M in BAD97037. Ref.4

Sequence conflict

452

1

S → SP in AAA53100. Ref.2

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)
	Isoform 1 [UniParc]. Last modified November 2, 2010. Version 3. Checksum: 0EC01E380FA7E5A2	FASTA	509	58,536
	10 20 30 40 50 60 MDPPRASHLS PRKKRPRQTG ALMASSPQDI KFQDLVVFIL EKKMGTTRRA FLMELARRKG 70 80 90 100 110 120 FRVENELSDS VTHIVAENNS GSDVLEWLQA QKVQVSSQPE LLDVSWLIEC IRAGKPVEMT 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
	Isoform 2 [UniParc]. Checksum: C72DABE3ACAEADD1	FASTA	508	58,408
	10 20 30 40 50 60 MDPPRASHLS PRKKRPRQTG ALMASSPQDI KFQDLVVFIL EKKMGTTRRA FLMELARRKG 70 80 90 100 110 120 FRVENELSDS VTHIVAENNS GSDVLEWLQA QKVQVSSQPE LLDVSWLIEC IRAGKPVEMT 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 GSRFERDLRR YATHERKMIL DNHALYDKTK 490 500 RIFLKAESEE EIFAHLGLDY IEPWERNA

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT GLY-112.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-112.
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-112.
[4]	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] (ISOFORM 1), VARIANT GLY-112. Tissue: Thymus.
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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] (ISOFORM 1), VARIANT GLY-112. Tissue: Testis.
[7]	"Isolation of putative promoter region for human terminal deoxynucleotidyltransferase gene." Koiwai O., Morita A. Biochem. Biophys. Res. Commun. 154:91-100(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-67.
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 271-508 (ISOFORM 2).
[9]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TDIF1. Tissue: Thymus.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DNTTIP2 AND CORE HISTONE.
[11]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PRP19.
[12]	"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] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[13]	"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

EMBL
GenBank
DDBJ

M11722 mRNA. Translation: AAA36726.1.
M20703 , M22968, M20694, M20695, M20696, M20697, M20698, M20699, M20700, M20701, M20702 mRNA. Translation: AAA53100.1.
AB046378 mRNA. Translation: BAB72001.1.
AK223317 mRNA. Translation: BAD97037.1.
AL136181 Genomic DNA. Translation: CAH72984.1.
BC012920 mRNA. Translation: AAH12920.1.
M21195 Genomic DNA. Translation: AAA61137.1.
K01919 mRNA. Translation: AAA61136.1.

IPI

IPI00219676.
IPI00604441.

PIR

WXHU. A23924.

RefSeq

NP_001017520.1. NM_001017520.1.
NP_004079.3. NM_004088.3.

UniGene

Hs.534206.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P04053.

SMR

P04053. Positions 21-125, 148-509.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04053. 1 interaction.

STRING

9606.ENSP00000360216.

PTM databases

PhosphoSite

P04053.

Polymorphism databases

DMDM

311033533.

Proteomic databases

PaxDb

P04053.

PRIDE

P04053.

Protocols and materials databases

DNASU

1791.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000371174; ENSP00000360216; ENSG00000107447.
ENST00000419175; ENSP00000401169; ENSG00000107447.

GeneID

1791.

KEGG

hsa:1791.

UCSC

uc001kmf.3. human.
uc001kmg.3. human.

Organism-specific databases

CTD

1791.

GeneCards

GC10P098054.

H-InvDB

HIX0009072.

HGNC

HGNC:2983. DNTT.

HPA

HPA044194.

MIM

187410. gene.

neXtProt

NX_P04053.

PharmGKB

PA27449.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1796.

HOGENOM

HOG000263600.

HOVERGEN

HBG003670.

InParanoid

P04053.

KO

K00977.

OMA

RRTTLNN.

OrthoDB

EOG4SQWWN.

PhylomeDB

P04053.

Enzyme and pathway databases

SABIO-RK

P04053.

Gene expression databases

Bgee

P04053.

CleanEx

HS_DNTT.

Genevestigator

P04053.

GermOnline

ENSG00000107447. Homo sapiens.

Family and domain databases

InterPro

IPR001357. BRCT_dom.
IPR002054. DNA-dir_DNA_pol_X.
IPR019843. DNA_pol-X_BS.
IPR010996. DNA_pol_b-like_N.
IPR018944. DNA_pol_lambd_fingers_domain.
IPR022312. DNA_pol_X.
IPR002934. Nucleotidyltransferase.
IPR027292. TdT.
IPR001726. TdT/Mu.
[Graphical view]

PANTHER

PTHR11276:SF6. PTHR11276:SF6. 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.
PIRSF501175. TDT. 1 hit.

PRINTS

PR00869. DNAPOLX.
PR00871. DNAPOLXTDT.

SMART

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

SUPFAM

SSF52113. BRCT. 1 hit.
SSF81585. DNA_pol_lambd_fingers_domain. 1 hit.
SSF47802. DNApol_B_N_like. 1 hit.

PROSITE

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

ProtoNet

Search...

Other

BindingDB

P04053.

ChEMBL

CHEMBL4810.

EvolutionaryTrace

P04053.

GenomeRNAi

1791.

NextBio

7299.

SOURCE

Search...

Entry information

Entry name

TDT_HUMAN

Accession

Primary (citable) accession number: P04053
Secondary accession number(s): Q53FH1, Q5W103, Q96E50

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 148 of the entry and version 3 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.