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Description:
Thymidylate synthase (EC 2.1.1.45) (TS) (TSase).
Molecular weight: 35585
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 )
Important dates:
13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
01-JUL-1989, sequence version 2.
07-FEB-2006, entry version 70.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein TYSY_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X02308 | CAA26178.1 | - |
| EMBL | D00596 | BAA00472.1 | - |
| EMBL | AB062290 | BAB93473.1 | - |
| EMBL | BC002567 | AAH02567.1 | - |
| EMBL | BC013919 | AAH13919.1 | - |
| EMBL | BC083512 | AAH83512.1 | - |
| EMBL | D00517 | BAA00404.1 | - |
| PIR | A23047 | YXHUT. | |
| PDB | 1HVY | X-ray | A/B/C/D=25-312. |
| PDB | 1HW3 | X-ray | A=1-312. |
| PDB | 1HW4 | X-ray | A=1-312. |
| PDB | 1HZW | X-ray | A/B=29-312. |
| PDB | 1I00 | X-ray | A/B=29-312. |
| PDB | 1JU6 | X-ray | A/B/C/D=1-312. |
| PDB | 1JUJ | X-ray | A/B/C/D=1-312. |
| Ensembl | ENSG00000176890 | Homo sapiens.1 | |
| H-InvDB | HIX0017793 | -.1 | |
| HGNC | HGNC:12441 | TYMS.1 | |
| MIM | 188350 | gene. | |
| Reactome | P04818 | -.1 | |
| GO | GO:0009157 | P:deoxyribonucleoside monophosphate biosynthesis | TAS. |
| GO | GO:0006281 | P:DNA repair | NAS. |
| GO | GO:0006260 | P:DNA replication | NAS. |
| GO | GO:0006139 | P:nucleobase, nucleoside, nucleotide and nucl... | TAS. |
| GO | GO:0048015 | P:phosphoinositide-mediated signaling | NAS. |
| InterPro | IPR000398 | Thymidylat_synth. | |
| Pfam | PF00303 | Thymidylat_synt | 1. |
| PRINTS | PR00108 | THYMDSNTHASE. | |
| ProDom | PD001180 | Thymidylat_synth | 1. |
| PROSITE | PS00091 | THYMIDYLATE_SYNTHASE | 1. |
Keywords:
3D-structure; Direct protein sequencing; Methyltransferase; Nucleotide biosynthesis; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX MEDLINE=85215597; PubMed=2987839;
RA Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T.;
RT "Nucleotide sequence of a functional cDNA for human thymidylate
RT synthase.";
RL Nucleic Acids Res. 13:2035-2043(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX MEDLINE=91056070; PubMed=2243092;
RA Kaneda S., Nalbantoglu J., Takeishi K., Shimizu K., Gotoh O., Seno T.,
RA Ayusawa D.;
RT "Structural and functional analysis of the human thymidylate synthase
RT gene.";
RL J. Biol. Chem. 265:20277-20284(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow, Placenta, and Skin;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 1-67.
RX MEDLINE=90110051; PubMed=2532645;
RA Takeishi K., Kaneda S., Ayusawa D., Shimizu K., Gotoh O., Seno T.;
RT "Human thymidylate synthase gene: isolation of phage clones which
RT cover a functionally active gene and structural analysis of the region
RT upstream from the translation initiation codon.";
RL J. Biochem. 106:575-583(1989).
RN [6]
RP PROTEIN SEQUENCE OF 1-24.
RX MEDLINE=85261174; PubMed=3839505;
RA Shimizu K., Ayusawa D., Takeishi K., Seno T.;
RT "Purification and NH2-terminal amino acid sequence of human
RT thymidylate synthase in an overproducing transformant of mouse FM3A
RT cells.";
RL J. Biochem. 97:845-850(1985).
RN [7]
RP PROTEIN SEQUENCE OF 1-9.
RX MEDLINE=89255401; PubMed=2656695;
RA Davisson V.J., Sirawaraporn W., Santi D.V.;
RT "Expression of human thymidylate synthase in Escherichia coli.";
RL J. Biol. Chem. 264:9145-9148(1989).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX MEDLINE=96110704; PubMed=8845352;
RA Schiffer C.A., Clifton I.J., Davisson V.J., Santi D.V., Stroud R.M.;
RT "Crystal structure of human thymidylate synthase: a structural
RT mechanism for guiding substrates into the active site.";
RL Biochemistry 34:16279-16287(1995).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX MEDLINE=21229106; PubMed=11329255; DOI=10.1021/bi002413i;
RA Phan J., Koli S., Minor W., Dunlap R.B., Berger S.H., Lebioda L.;
RT "Human thymidylate synthase is in the closed conformation when
RT complexed with dUMP and raltitrexed, an antifolate drug.";
RL Biochemistry 40:1897-1902(2001).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX MEDLINE=21216721; PubMed=11278511; DOI=10.1074/jbc.M009493200;
RA Phan J., Steadman D.J., Koli S., Ding W.C., Minor W., Dunlap R.B.,
RA Berger S.H., Lebioda L.;
RT "Structure of human thymidylate synthase suggests advantages of
RT chemotherapy with noncompetitive inhibitors.";
RL J. Biol. Chem. 276:14170-14177(2001).
Feature:
INIT_MET 0 0
CHAIN 1 312 Thymidylate synthase.
/FTId=PRO_0000140901.
ACT_SITE 194 194
TURN 28 28
HELIX 29 42
STRAND 44 46
TURN 49 50
STRAND 51 52
STRAND 54 65
TURN 67 68
TURN 74 77
HELIX 80 91
TURN 92 93
STRAND 96 96
HELIX 97 101
TURN 102 104
TURN 107 108
STRAND 109 109
HELIX 110 112
STRAND 113 113
HELIX 114 119
TURN 120 121
TURN 123 124
STRAND 125 125
TURN 127 128
STRAND 129 129
STRAND 132 132
HELIX 134 140
STRAND 141 141
TURN 142 142
STRAND 143 143
TURN 148 149
TURN 153 154
STRAND 156 157
HELIX 159 169
TURN 171 172
TURN 174 175
STRAND 177 179
TURN 183 185
HELIX 186 188
STRAND 190 191
STRAND 194 203
TURN 204 205
STRAND 206 217
TURN 218 220
HELIX 221 239
TURN 240 241
STRAND 243 257
HELIX 258 268
TURN 269 269
STRAND 270 270
STRAND 277 280
STRAND 282 282
STRAND 286 286
HELIX 287 289
HELIX 292 294
STRAND 295 299
Comments:
-!- CATALYTIC ACTIVITY: 5,10-methylenetetrahydrofolate + dUMP =
dihydrofolate + dTMP.
-!- PATHWAY: Nucleotide biosynthesis; deoxyribonucleotide
biosynthesis.
-!- SUBUNIT: Homodimer.
-!- SIMILARITY: Belongs to the thymidylate synthase family.
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Sequence length: 312
PVAGSELPRR PLPPAAQERD AEPRPPHGEL QYLGQIQHIL RCGVRKDDRT GTGTLSVFGM
QARYSLRDEF PLLTTKRVFW KGVLEELLWF IKGSTNAKEL SSKGVKIWDA NGSRDFLDSL
GFSTREEGDL GPVYGFQWRH FGAEYRDMES DYSGQGVDQL QRVIDTIKTN PDDRRIIMCA
WNPRDLPLMA LPPCHALCQF YVVNSELSCQ LYQRSGDMGL GVPFNIASYA LLTYMIAHIT
GLKPGDFIHT LGDAHIYLNH IEPLKIQLQR EPRPFPKLRI LRKVEKIDDF KAEDFQIEGY
NPHPTIKMEM AV