TDT_MOUSE
ID TDT_MOUSE Reviewed; 510 AA.
AC P09838; Q99PD0; Q99PD1;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 4.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=DNA nucleotidylexotransferase;
DE EC=2.7.7.31 {ECO:0000269|PubMed:11938351, ECO:0000269|PubMed:23856622, ECO:0000269|PubMed:23968551};
DE EC=3.1.11.- {ECO:0000269|PubMed:11938351};
DE AltName: Full=Terminal addition enzyme;
DE AltName: Full=Terminal deoxynucleotidyltransferase {ECO:0000303|PubMed:3755527};
DE Short=TDT;
DE Short=Terminal transferase;
GN Name=Dntt; Synonyms=Tdt;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TDT-L).
RC TISSUE=Lymphoma;
RX PubMed=3755527; DOI=10.1093/nar/14.14.5777;
RA Koiwai O., Yokota T., Kageyama T., Hirose T., Yoshida S., Arai K.;
RT "Isolation and characterization of bovine and mouse terminal
RT deoxynucleotidyltransferase cDNAs expressible in mammalian cells.";
RL Nucleic Acids Res. 14:5777-5792(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TDT-S), FUNCTION, ALTERNATIVE SPLICING,
RP AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ; TISSUE=Thymus;
RX PubMed=8464703; DOI=10.1093/nar/21.5.1187;
RA Doyen N., Fanton D'Andon M., Bentolila L.A., Nguyen T.Q., Rougeon F.;
RT "Differential splicing in mouse thymus generates two forms of terminal
RT deoxynucleotidyl transferase.";
RL Nucleic Acids Res. 21:1187-1191(1993).
RN [3]
RP SEQUENCE REVISION TO 443-445.
RA Doyen N.;
RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS TDT-L AND TDT-S), FUNCTION, AND TISSUE
RP SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=11136823; DOI=10.1084/jem.193.1.89;
RA Benedict C.L., Gilfillan S., Kearney J.F.;
RT "The long isoform of terminal deoxynucleotidyl transferase (TdtL) enters
RT the nucleus and, rather than catalyzing N addition, modulates the catalytic
RT activity of the short isoform.";
RL J. Exp. Med. 193:89-99(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM TDT-L).
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP PROTEIN SEQUENCE OF 388-393, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=OF1; TISSUE=Hippocampus;
RA Lubec G., Sunyer B., Chen W.-Q.;
RL Submitted (JAN-2009) to UniProtKB.
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND ALTERNATIVE
RP SPLICING.
RX PubMed=7556063; DOI=10.1002/j.1460-2075.1995.tb00096.x;
RA Bentolila L.A., Fanton D'Andon M., Nguyen T.Q., Martinez O., Rougeon F.,
RA Doyen N.;
RT "The two isoforms of mouse terminal deoxynucleotidyl transferase differ in
RT both the ability to add N regions and subcellular localization.";
RL EMBO J. 14:4221-4229(1995).
RN [8]
RP FUNCTION, ALTERNATIVE SPLICING, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10878023; DOI=10.1074/jbc.m005544200;
RA Boule J.-B., Rougeon F., Papanicolaou C.;
RT "Comparison of the two murine terminal deoxynucleotidyltransferase
RT isoforms. A 20-amino acid insertion in the highly conserved carboxyl-
RT terminal region modifies the thermosensitivity but not the catalytic
RT activity.";
RL J. Biol. Chem. 275:28984-28988(2000).
RN [9]
RP ERRATUM OF PUBMED:10878023.
RX PubMed=11032847;
RA Boule J.-B., Rougeon F., Papanicolaou C.;
RL J. Biol. Chem. 275:33184-33184(2000).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, CHARACTERIZATION OF ISOFORMS TDT-L AND TDT-S,
RP AND MUTAGENESIS OF ASP-29; ASP-170 AND ASP-473.
RX PubMed=11938351; DOI=10.1038/ni788;
RA Thai T.H., Purugganan M.M., Roth D.B., Kearney J.F.;
RT "Distinct and opposite diversifying activities of terminal transferase
RT splice variants.";
RL Nat. Immunol. 3:457-462(2002).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-134, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 130-510 (ISOFORM TDT-S) IN
RP COMPLEXES WITH MAGNESIUM; COBALT AND ATP ANALOG.
RX PubMed=11823435; DOI=10.1093/emboj/21.3.427;
RA Delarue M., Boule J.-B., Lescar J., Expert-Bezancon N., Jourdan N.,
RA Sukumar N., Rougeon F., Papanicolaou C.;
RT "Crystal structures of a template-independent DNA polymerase: murine
RT terminal deoxynucleotidyltransferase.";
RL EMBO J. 21:427-439(2002).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 132-510 (ISOFORM TDT-S) IN
RP COMPLEXES WITH SYNTHETIC INHIBITORS AND NUCLEOTIDE, AND CATALYTIC ACTIVITY.
RX PubMed=23968551; DOI=10.1021/jm4010187;
RA Costi R., Crucitti G.C., Pescatori L., Messore A., Scipione L.,
RA Tortorella S., Amoroso A., Crespan E., Campiglia P., Maresca B., Porta A.,
RA Granata I., Novellino E., Gouge J., Delarue M., Maga G., Di Santo R.;
RT "New nucleotide-competitive non-nucleoside inhibitors of terminal
RT deoxynucleotidyl transferase: discovery, characterization, and crystal
RT structure in complex with the target.";
RL J. Med. Chem. 56:7431-7441(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 132-510 (ISOFORM TDT-S) IN
RP COMPLEXES WITH ATP; CTP; TTP; NUCLEOTIDE; MAGNESIUM; MANGANESE AND ZINC,
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF HIS-342;
RP LEU-398; ASP-399; HIS-400; LYS-403; ASP-473 AND HIS-475.
RX PubMed=23856622; DOI=10.1016/j.jmb.2013.07.009;
RA Gouge J., Rosario S., Romain F., Beguin P., Delarue M.;
RT "Structures of intermediates along the catalytic cycle of terminal
RT deoxynucleotidyltransferase: dynamical aspects of the two-metal ion
RT mechanism.";
RL J. Mol. Biol. 425:4334-4352(2013).
CC -!- FUNCTION: [Isoform TDT-S]: Transferase that catalyzes the nontemplated
CC addition of nucleoside triphosphate to coding ends during V(D)J
CC recombination (N addition). Involved in the generation of diversity in
CC the antigen-binding region of immunoglobulin heavy and light chains and
CC T-cell receptors during B- and T-cell development. Does not act on
CC double-stranded DNA with blunt ends. {ECO:0000269|PubMed:11136823,
CC ECO:0000269|PubMed:11938351, ECO:0000269|PubMed:23856622,
CC ECO:0000269|PubMed:7556063, ECO:0000269|PubMed:8464703}.
CC -!- FUNCTION: [Isoform TDT-L]: 3'-to-5' DNA exonuclease. Involved in the
CC generation of diversity in the antigen-binding region of immunoglobulin
CC heavy and light chains and T-cell receptors during B- and T-cell
CC development. Acts on single-stranded and double-stranded DNA with 3' or
CC 5' extensions, but not on double-stranded DNA with blunt ends.
CC Attenuates not only isoform TDT-S-catalyzed N addition, but also P
CC (palindromic) addition in coding joins (PubMed:11938351). Lacks
CC terminal transferase activity (PubMed:11136823, PubMed:7556063).
CC {ECO:0000269|PubMed:11136823, ECO:0000269|PubMed:11938351,
CC ECO:0000269|PubMed:7556063}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) =
CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339,
CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560,
CC ChEBI:CHEBI:173112; EC=2.7.7.31;
CC Evidence={ECO:0000269|PubMed:23856622, ECO:0000269|PubMed:23968551};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:23856622};
CC Note=Can also utilize other divalent cations, such as Mn(2+) and Co(2+)
CC (in vitro). {ECO:0000269|PubMed:23856622, ECO:0000305};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=300 uM for dATP (at 35 degrees Celsius)
CC {ECO:0000269|PubMed:10878023};
CC Note=In assays with isoform TDT-S. {ECO:0000269|PubMed:10878023};
CC -!- SUBUNIT: Interacts with PRP19 and DNTTIP1. Forms a ternary complex with
CC DNTTIP2 and core histone. Released from this complex by PCNA. Interacts
CC with TRERF1. {ECO:0000250|UniProtKB:P04053}.
CC -!- SUBCELLULAR LOCATION: [Isoform TDT-S]: Nucleus
CC {ECO:0000269|PubMed:7556063}.
CC -!- SUBCELLULAR LOCATION: [Isoform TDT-L]: Nucleus
CC {ECO:0000269|PubMed:11136823}. Cytoplasm {ECO:0000269|PubMed:7556063}.
CC Note=The subcellular location is controversial. Detected in the nucleus
CC (PubMed:11136823). Found mainly in the cytoplasm (PubMed:7556063).
CC {ECO:0000269|PubMed:11136823, ECO:0000269|PubMed:7556063}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=TDT-S; Synonyms=TDT-Small, TdtS {ECO:0000303|PubMed:8464703};
CC IsoId=P09838-2; Sequence=Displayed;
CC Name=TDT-L; Synonyms=TDT-Large, TdtL {ECO:0000303|PubMed:8464703};
CC IsoId=P09838-1; Sequence=VSP_059967;
CC -!- TISSUE SPECIFICITY: Isoform TDT-L: Expressed in the thymus, and, at
CC lower levels, in the bone marrow (PubMed:8464703, PubMed:11136823,
CC PubMed:7556063). Detected in both cycling and noncycling pro-B and pre-
CC B cells (at protein level) (PubMed:11938351). Isoform TDT-S: Expressed
CC in both cycling and noncycling pro-B, but not pre-B, cells (at protein
CC level) (PubMed:11938351). Not detected in mature peripheral or germinal
CC center B cells (PubMed:11938351). {ECO:0000269|PubMed:11136823,
CC ECO:0000269|PubMed:11938351, ECO:0000269|PubMed:7556063,
CC ECO:0000269|PubMed:8464703}.
CC -!- MISCELLANEOUS: [Isoform TDT-S]: Major form in the thymus and the bone
CC marrow (PubMed:8464703, PubMed:11136823). Catalyzes the nontemplated
CC addition of nucleoside triphosphate to coding ends during V(D)J
CC recombination (PubMed:23856622). May have a longer half-life than
CC isoform TDT-L (PubMed:7556063). {ECO:0000269|PubMed:11136823,
CC ECO:0000269|PubMed:11938351, ECO:0000269|PubMed:7556063,
CC ECO:0000269|PubMed:8464703}.
CC -!- MISCELLANEOUS: [Isoform TDT-L]: Exhibits 3'-to-5' DNA exonuclease
CC activity (EC=3.1.11.-) (PubMed:23856622). May have a shorter half-life
CC than isoform TDT-S (PubMed:7556063, PubMed:10878023).
CC {ECO:0000269|PubMed:10878023, ECO:0000269|PubMed:11938351,
CC ECO:0000269|PubMed:7556063}.
CC -!- SIMILARITY: Belongs to the DNA polymerase type-X family. {ECO:0000305}.
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DR EMBL; X04123; CAA27735.1; -; mRNA.
DR EMBL; X68670; CAA48634.2; -; mRNA.
DR EMBL; AF316014; AAK07884.1; -; mRNA.
DR EMBL; AF316015; AAK07885.1; -; mRNA.
DR EMBL; AK087978; BAC40071.1; -; mRNA.
DR EMBL; AK088709; BAC40518.1; -; mRNA.
DR CCDS; CCDS29807.1; -. [P09838-1]
DR CCDS; CCDS37984.1; -. [P09838-2]
DR PIR; B23595; B23595.
DR RefSeq; NP_001036693.1; NM_001043228.1. [P09838-2]
DR RefSeq; NP_033371.2; NM_009345.2. [P09838-1]
DR PDB; 1JMS; X-ray; 2.36 A; A=130-510.
DR PDB; 1KDH; X-ray; 3.00 A; A=148-510.
DR PDB; 1KEJ; X-ray; 3.00 A; A=148-510.
DR PDB; 4I27; X-ray; 2.60 A; A=132-510.
DR PDB; 4I28; X-ray; 2.15 A; A=132-510.
DR PDB; 4I29; X-ray; 2.20 A; A=132-510.
DR PDB; 4I2A; X-ray; 1.90 A; A=132-510.
DR PDB; 4I2B; X-ray; 2.20 A; A=132-510.
DR PDB; 4I2C; X-ray; 2.10 A; A=132-510.
DR PDB; 4I2D; X-ray; 2.30 A; A=132-510.
DR PDB; 4I2E; X-ray; 2.00 A; A=132-510.
DR PDB; 4I2F; X-ray; 2.10 A; A=132-510.
DR PDB; 4I2G; X-ray; 2.50 A; A=132-510.
DR PDB; 4I2H; X-ray; 2.75 A; A=132-510.
DR PDB; 4I2I; X-ray; 2.50 A; A=132-510.
DR PDB; 4I2J; X-ray; 2.70 A; A=132-510.
DR PDB; 4IQT; X-ray; 2.60 A; A=132-510.
DR PDB; 4IQU; X-ray; 2.40 A; A=132-510.
DR PDB; 4IQV; X-ray; 2.90 A; A=132-510.
DR PDB; 4IQW; X-ray; 2.60 A; A=132-510.
DR PDB; 4QZ8; X-ray; 2.70 A; A=132-510.
DR PDB; 4QZ9; X-ray; 2.05 A; A=132-510.
DR PDB; 4QZA; X-ray; 2.15 A; A=132-510.
DR PDB; 4QZB; X-ray; 2.15 A; A=132-510.
DR PDB; 4QZC; X-ray; 2.75 A; A=132-510.
DR PDB; 4QZD; X-ray; 2.70 A; A=132-510.
DR PDB; 4QZE; X-ray; 2.25 A; A=132-510.
DR PDB; 4QZF; X-ray; 2.60 A; A=132-510.
DR PDB; 4QZG; X-ray; 2.75 A; A=132-510.
DR PDB; 4QZH; X-ray; 2.60 A; A=132-510.
DR PDB; 4QZI; X-ray; 2.65 A; A=132-510.
DR PDB; 5D46; X-ray; 2.80 A; A=132-510.
DR PDB; 5D49; X-ray; 1.99 A; A=132-510.
DR PDB; 5D4B; X-ray; 2.66 A; A/B=132-510.
DR PDB; 6GO3; X-ray; 2.20 A; A=132-377, A=409-510.
DR PDB; 6GO4; X-ray; 1.96 A; A=132-377, A=409-510.
DR PDB; 6GO5; X-ray; 2.35 A; A/B=132-377, A/B=409-510.
DR PDB; 6GO6; X-ray; 2.09 A; A=132-377, A=409-510.
DR PDB; 6GO7; X-ray; 2.55 A; A=132-377, A=409-510.
DR PDBsum; 1JMS; -.
DR PDBsum; 1KDH; -.
DR PDBsum; 1KEJ; -.
DR PDBsum; 4I27; -.
DR PDBsum; 4I28; -.
DR PDBsum; 4I29; -.
DR PDBsum; 4I2A; -.
DR PDBsum; 4I2B; -.
DR PDBsum; 4I2C; -.
DR PDBsum; 4I2D; -.
DR PDBsum; 4I2E; -.
DR PDBsum; 4I2F; -.
DR PDBsum; 4I2G; -.
DR PDBsum; 4I2H; -.
DR PDBsum; 4I2I; -.
DR PDBsum; 4I2J; -.
DR PDBsum; 4IQT; -.
DR PDBsum; 4IQU; -.
DR PDBsum; 4IQV; -.
DR PDBsum; 4IQW; -.
DR PDBsum; 4QZ8; -.
DR PDBsum; 4QZ9; -.
DR PDBsum; 4QZA; -.
DR PDBsum; 4QZB; -.
DR PDBsum; 4QZC; -.
DR PDBsum; 4QZD; -.
DR PDBsum; 4QZE; -.
DR PDBsum; 4QZF; -.
DR PDBsum; 4QZG; -.
DR PDBsum; 4QZH; -.
DR PDBsum; 4QZI; -.
DR PDBsum; 5D46; -.
DR PDBsum; 5D49; -.
DR PDBsum; 5D4B; -.
DR PDBsum; 6GO3; -.
DR PDBsum; 6GO4; -.
DR PDBsum; 6GO5; -.
DR PDBsum; 6GO6; -.
DR PDBsum; 6GO7; -.
DR AlphaFoldDB; P09838; -.
DR SMR; P09838; -.
DR BioGRID; 204095; 4.
DR STRING; 10090.ENSMUSP00000062078; -.
DR iPTMnet; P09838; -.
DR PhosphoSitePlus; P09838; -.
DR jPOST; P09838; -.
DR MaxQB; P09838; -.
DR PaxDb; P09838; -.
DR PRIDE; P09838; -.
DR ProteomicsDB; 263150; -. [P09838-2]
DR ProteomicsDB; 263151; -. [P09838-2]
DR Antibodypedia; 16924; 603 antibodies from 40 providers.
DR DNASU; 21673; -.
DR Ensembl; ENSMUST00000051806; ENSMUSP00000062078; ENSMUSG00000025014. [P09838-1]
DR Ensembl; ENSMUST00000112200; ENSMUSP00000107819; ENSMUSG00000025014. [P09838-2]
DR GeneID; 21673; -.
DR KEGG; mmu:21673; -.
DR UCSC; uc008hlo.1; mouse. [P09838-2]
DR CTD; 1791; -.
DR MGI; MGI:98659; Dntt.
DR VEuPathDB; HostDB:ENSMUSG00000025014; -.
DR eggNOG; KOG2534; Eukaryota.
DR GeneTree; ENSGT00940000158584; -.
DR HOGENOM; CLU_008698_0_0_1; -.
DR InParanoid; P09838; -.
DR OMA; PKVINLW; -.
DR OrthoDB; 1212057at2759; -.
DR PhylomeDB; P09838; -.
DR TreeFam; TF103012; -.
DR BRENDA; 2.7.7.31; 3474.
DR BioGRID-ORCS; 21673; 7 hits in 73 CRISPR screens.
DR ChiTaRS; Dntt; mouse.
DR EvolutionaryTrace; P09838; -.
DR PRO; PR:P09838; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; P09838; protein.
DR Bgee; ENSMUSG00000025014; Expressed in thymus and 24 other tissues.
DR ExpressionAtlas; P09838; baseline and differential.
DR Genevisible; P09838; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0003912; F:DNA nucleotidylexotransferase activity; IDA:MGI.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:InterPro.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006259; P:DNA metabolic process; IDA:MGI.
DR GO; GO:0006304; P:DNA modification; IEA:UniProtKB-KW.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IBA:GO_Central.
DR CDD; cd00141; NT_POLXc; 1.
DR Gene3D; 1.10.150.110; -; 1.
DR Gene3D; 3.30.210.10; -; 1.
DR Gene3D; 3.30.460.10; -; 1.
DR Gene3D; 3.40.50.10190; -; 1.
DR InterPro; IPR001357; BRCT_dom.
DR InterPro; IPR036420; BRCT_dom_sf.
DR InterPro; IPR002054; DNA-dir_DNA_pol_X.
DR InterPro; IPR019843; DNA_pol-X_BS.
DR InterPro; IPR010996; DNA_pol_b-like_N.
DR InterPro; IPR028207; DNA_pol_B_palm_palm.
DR InterPro; IPR018944; DNA_pol_lambd_fingers_domain.
DR InterPro; IPR027421; DNA_pol_lamdba_lyase_dom_sf.
DR InterPro; IPR037160; DNA_Pol_thumb_sf.
DR InterPro; IPR022312; DNA_pol_X.
DR InterPro; IPR043519; NT_sf.
DR InterPro; IPR029398; PolB_thumb.
DR InterPro; IPR027292; TdT.
DR InterPro; IPR001726; TdT/Mu.
DR PANTHER; PTHR11276; PTHR11276; 1.
DR Pfam; PF00533; BRCT; 1.
DR Pfam; PF14792; DNA_pol_B_palm; 1.
DR Pfam; PF14791; DNA_pol_B_thumb; 1.
DR Pfam; PF10391; DNA_pol_lambd_f; 1.
DR Pfam; PF14716; HHH_8; 1.
DR PIRSF; PIRSF000817; DNA_NT; 1.
DR PIRSF; PIRSF501175; TDT; 1.
DR PRINTS; PR00869; DNAPOLX.
DR PRINTS; PR00871; DNAPOLXTDT.
DR SMART; SM00292; BRCT; 1.
DR SMART; SM00483; POLXc; 1.
DR SUPFAM; SSF47802; SSF47802; 1.
DR SUPFAM; SSF52113; SSF52113; 1.
DR SUPFAM; SSF81301; SSF81301; 1.
DR PROSITE; PS50172; BRCT; 1.
DR PROSITE; PS00522; DNA_POLYMERASE_X; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Hydrolase; Magnesium; Metal-binding; Nucleotidyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; Terminal addition; Transferase.
FT CHAIN 1..510
FT /note="DNA nucleotidylexotransferase"
FT /id="PRO_0000218792"
FT DOMAIN 27..124
FT /note="BRCT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00033"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 151..510
FT /note="Mediates interaction with DNTTIP2"
FT /evidence="ECO:0000250|UniProtKB:P04053"
FT REGION 258..262
FT /note="Involved in DNA binding"
FT /evidence="ECO:0000269|PubMed:11823435,
FT ECO:0000269|PubMed:23856622"
FT MOTIF 11..17
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P06526"
FT BINDING 333..338
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000305, ECO:0007744|PDB:4I2B,
FT ECO:0007744|PDB:4I2C, ECO:0007744|PDB:4I2D,
FT ECO:0007744|PDB:4I2E"
FT BINDING 342..345
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000305, ECO:0007744|PDB:4I2B,
FT ECO:0007744|PDB:4I2C, ECO:0007744|PDB:4I2D,
FT ECO:0007744|PDB:4I2E"
FT BINDING 343
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305, ECO:0007744|PDB:1JMS,
FT ECO:0007744|PDB:4I2B"
FT BINDING 345
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305, ECO:0007744|PDB:1JMS,
FT ECO:0007744|PDB:4I2B"
FT BINDING 434
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000305, ECO:0007744|PDB:1JMS,
FT ECO:0007744|PDB:4I2B"
FT BINDING 449..450
FT /ligand="a 2'-deoxyribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61560"
FT /evidence="ECO:0000305, ECO:0007744|PDB:4I2B,
FT ECO:0007744|PDB:4I2C, ECO:0007744|PDB:4I2D,
FT ECO:0007744|PDB:4I2E"
FT MOD_RES 134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 482
FT /note="K -> KGKTVTISPLDGKVSKLQKAL (in isoform TDT-L)"
FT /evidence="ECO:0000303|PubMed:11136823,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:3755527"
FT /id="VSP_059967"
FT MUTAGEN 29
FT /note="D->A: Almost complete loss of exonuclease activity
FT in TDT-L; when associated with A-170 and A-473. Decreased
FT transferase activity in TDT-S; when associated with A-170
FT and A-473."
FT /evidence="ECO:0000269|PubMed:11938351"
FT MUTAGEN 170
FT /note="D->A: Almost complete loss of exonuclease activity
FT in TDT-L; when associated with A-29 and A-473. Decreased
FT transferase activity in TDT-S; when associated with A-29
FT and A-473."
FT /evidence="ECO:0000269|PubMed:11938351"
FT MUTAGEN 342
FT /note="H->A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT MUTAGEN 398
FT /note="L->A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT MUTAGEN 399
FT /note="D->A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT MUTAGEN 400
FT /note="H->A: Reduces enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT MUTAGEN 403
FT /note="K->A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT MUTAGEN 473
FT /note="D->A: Almost complete loss of exonuclease activity
FT in TDT-L; when associated with A-29 and A-170. Decreased
FT transferase activity in TDT-S; when associated with A-29
FT and A-170."
FT /evidence="ECO:0000269|PubMed:11938351"
FT MUTAGEN 473
FT /note="D->A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT MUTAGEN 475
FT /note="H->A: Nearly abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:23856622"
FT CONFLICT 26
FT /note="T -> M (in Ref. 2; CAA48634)"
FT /evidence="ECO:0000305"
FT CONFLICT 99
FT /note="L -> F (in Ref. 2; CAA48634)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="R -> G (in Ref. 1; CAA27735)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="Q -> K (in Ref. 1; CAA27735)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="E -> Q (in Ref. 1; CAA27735)"
FT /evidence="ECO:0000305"
FT CONFLICT 367
FT /note="D -> H (in Ref. 1; CAA27735)"
FT /evidence="ECO:0000305"
FT CONFLICT 441..445
FT /note="DRRAF -> ECAC (in Ref. 1; CAA27735)"
FT /evidence="ECO:0000305"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 166..181
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 185..199
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 208..211
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 219..231
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 235..242
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 260..268
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 274..279
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 287..294
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 296..300
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 305..322
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 332..335
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 339..342
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 344..349
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 355..372
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 375..381
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 387..389
FT /evidence="ECO:0007829|PDB:5D49"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 401..411
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 425..437
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 443..451
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 454..468
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:4I2A"
FT TURN 480..483
FT /evidence="ECO:0007829|PDB:4I2A"
FT STRAND 484..486
FT /evidence="ECO:0007829|PDB:4I2E"
FT HELIX 491..498
FT /evidence="ECO:0007829|PDB:4I2A"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:4I2A"
SQ SEQUENCE 510 AA; 58266 MW; CF6E850EE36EE3BF CRC64;
MDPLQAVHLG PRKKRPRQLG TPVASTPYDI RFRDLVLFIL EKKMGTTRRA FLMELARRKG
FRVENELSDS VTHIVAENNS GSDVLEWLQL QNIKASSELE LLDISWLIEC MGAGKPVEMM
GRHQLVVNRN SSPSPVPGSQ NVPAPAVKKI SQYACQRRTT LNNYNQLFTD ALDILAENDE
LRENEGSCLA FMRASSVLKS LPFPITSMKD TEGIPCLGDK VKSIIEGIIE DGESSEAKAV
LNDERYKSFK LFTSVFGVGL KTAEKWFRMG FRTLSKIQSD KSLRFTQMQK AGFLYYEDLV
SCVNRPEAEA VSMLVKEAVV TFLPDALVTM TGGFRRGKMT GHDVDFLITS PEATEDEEQQ
LLHKVTDFWK QQGLLLYCDI LESTFEKFKQ PSRKVDALDH FQKCFLILKL DHGRVHSEKS
GQQEGKGWKA IRVDLVMCPY DRRAFALLGW TGSRQFERDL RRYATHERKM MLDNHALYDR
TKRVFLEAES EEEIFAHLGL DYIEPWERNA
