ATL1_SCHPO
ID ATL1_SCHPO Reviewed; 108 AA.
AC Q9UTN9;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 25-MAY-2022, entry version 117.
DE RecName: Full=Alkyltransferase-like protein 1 {ECO:0000303|PubMed:16679453};
GN Name=atl1 {ECO:0000303|PubMed:16679453};
GN ORFNames=SPAC1250.04c {ECO:0000312|PomBase:SPAC1250.04c};
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [2]
RP FUNCTION.
RX PubMed=16679453; DOI=10.1093/nar/gkl270;
RA Pearson S.J., Wharton S., Watson A.J., Begum G., Butt A., Glynn N.,
RA Williams D.M., Shibata T., Santibanez-Koref M.F., Margison G.P.;
RT "A novel DNA damage recognition protein in Schizosaccharomyces pombe.";
RL Nucleic Acids Res. 34:2347-2354(2006).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH SUBSTRATE DNA, AND
RP FUNCTION.
RX PubMed=19516334; DOI=10.1038/nature08076;
RA Tubbs J.L., Latypov V., Kanugula S., Butt A., Melikishvili M.,
RA Kraehenbuehl R., Fleck O., Marriott A., Watson A.J., Verbeek B., McGown G.,
RA Thorncroft M., Santibanez-Koref M.F., Millington C., Arvai A.S.,
RA Kroeger M.D., Peterson L.A., Williams D.M., Fried M.G., Margison G.P.,
RA Pegg A.E., Tainer J.A.;
RT "Flipping of alkylated DNA damage bridges base and nucleotide excision
RT repair.";
RL Nature 459:808-813(2009).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS), AND FUNCTION.
RX PubMed=22658721; DOI=10.1016/j.molcel.2012.04.028;
RA Latypov V.F., Tubbs J.L., Watson A.J., Marriott A.S., McGown G.,
RA Thorncroft M., Wilkinson O.J., Senthong P., Butt A., Arvai A.S.,
RA Millington C.L., Povey A.C., Williams D.M., Santibanez-Koref M.F.,
RA Tainer J.A., Margison G.P.;
RT "Atl1 regulates choice between global genome and transcription-coupled
RT repair of O(6)-alkylguanines.";
RL Mol. Cell 47:50-60(2012).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS), FUNCTION, AND MUTAGENESIS OF
RP ARG-69.
RX PubMed=23112169; DOI=10.1073/pnas.1209451109;
RA Wilkinson O.J., Latypov V., Tubbs J.L., Millington C.L., Morita R.,
RA Blackburn H., Marriott A., McGown G., Thorncroft M., Watson A.J.,
RA Connolly B.A., Grasby J.A., Masui R., Hunter C.A., Tainer J.A.,
RA Margison G.P., Williams D.M.;
RT "Alkyltransferase-like protein (Atl1) distinguishes alkylated guanines for
RT DNA repair using cation-pi interactions.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:18755-18760(2012).
CC -!- FUNCTION: Involved in DNA damage recognition. Binds DNA containing
CC O(6)-methylguanine and larger O(6)-alkylguanine adducts. The DNA is
CC bent, the damaged base is rotated out of the DNA duplex into a
CC hydrophobic binding pocket (nucleotide flipping), with Arg-39 donating
CC a hydrogen bond to the orphaned cytosine to stabilize the extrahelical
CC DNA conformation. This structural change in DNA presents the lesion to
CC the nucleotide excision repair (NER) pathway (PubMed:16679453,
CC PubMed:19516334, PubMed:23112169). The affinity for O(6)-alkylguanine
CC adducts increases with the size of the alkyl group. Low affinity small
CC O(6)-alkylguanines are directed to the global genome repair pathway of
CC NER via rhp7-rhp16 and rhp41-rhp23, while strong binding to bulky O(6)-
CC alkylguanines stalls the transcription machinery and diverts the damage
CC to the transcription-coupled repair pathway of NER via rhp26
CC (PubMed:22658721). {ECO:0000269|PubMed:16679453,
CC ECO:0000269|PubMed:19516334, ECO:0000269|PubMed:22658721,
CC ECO:0000269|PubMed:23112169}.
CC -!- MISCELLANEOUS: Does not have alkyltransferase activity. A tryptophan
CC residue replaces the cysteine at the known active site of MGMT.
CC {ECO:0000269|PubMed:19516334}.
CC -!- SIMILARITY: Belongs to the MGMT family. ATL subfamily. {ECO:0000305}.
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DR EMBL; CU329670; CAB54827.1; -; Genomic_DNA.
DR PIR; T37558; T37558.
DR RefSeq; NP_594858.1; NM_001020287.2.
DR PDB; 3GVA; X-ray; 2.00 A; A/B=1-108.
DR PDB; 3GX4; X-ray; 2.70 A; X=1-108.
DR PDB; 3GYH; X-ray; 2.80 A; X=1-108.
DR PDB; 4ENJ; X-ray; 3.10 A; A=1-108.
DR PDB; 4ENK; X-ray; 3.04 A; A=1-108.
DR PDB; 4ENM; X-ray; 2.84 A; A=1-108.
DR PDB; 4ENN; X-ray; 2.84 A; A/B=1-108.
DR PDB; 4HDU; X-ray; 2.85 A; A=1-108.
DR PDB; 4HDV; X-ray; 2.70 A; A=1-108.
DR PDBsum; 3GVA; -.
DR PDBsum; 3GX4; -.
DR PDBsum; 3GYH; -.
DR PDBsum; 4ENJ; -.
DR PDBsum; 4ENK; -.
DR PDBsum; 4ENM; -.
DR PDBsum; 4ENN; -.
DR PDBsum; 4HDU; -.
DR PDBsum; 4HDV; -.
DR AlphaFoldDB; Q9UTN9; -.
DR SMR; Q9UTN9; -.
DR BioGRID; 278199; 19.
DR DIP; DIP-60450N; -.
DR IntAct; Q9UTN9; 1.
DR STRING; 4896.SPAC1250.04c.1; -.
DR MaxQB; Q9UTN9; -.
DR PaxDb; Q9UTN9; -.
DR EnsemblFungi; SPAC1250.04c.1; SPAC1250.04c.1:pep; SPAC1250.04c.
DR GeneID; 2541704; -.
DR KEGG; spo:SPAC1250.04c; -.
DR PomBase; SPAC1250.04c; atl1.
DR VEuPathDB; FungiDB:SPAC1250.04c; -.
DR eggNOG; KOG4062; Eukaryota.
DR HOGENOM; CLU_000445_52_5_1; -.
DR InParanoid; Q9UTN9; -.
DR OMA; PRHSRHV; -.
DR PhylomeDB; Q9UTN9; -.
DR EvolutionaryTrace; Q9UTN9; -.
DR PRO; PR:Q9UTN9; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; HDA:PomBase.
DR GO; GO:0003824; F:catalytic activity; IEA:InterPro.
DR GO; GO:0003684; F:damaged DNA binding; IDA:PomBase.
DR GO; GO:0032132; F:O6-alkylguanine-DNA binding; IDA:PomBase.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IDA:PomBase.
DR CDD; cd06445; ATase; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR014048; MethylDNA_cys_MeTrfase_DNA-bd.
DR InterPro; IPR036217; MethylDNA_cys_MeTrfase_DNAb.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF01035; DNA_binding_1; 1.
DR SUPFAM; SSF46767; SSF46767; 1.
DR TIGRFAMs; TIGR00589; ogt; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; DNA-binding; Reference proteome.
FT CHAIN 1..108
FT /note="Alkyltransferase-like protein 1"
FT /id="PRO_0000249237"
FT SITE 25
FT /note="Required for phosphate rotation/nucleotide flipping"
FT /evidence="ECO:0000305|PubMed:19516334"
FT SITE 39
FT /note="Arg finger, required for nucleotide flipping"
FT /evidence="ECO:0000305|PubMed:19516334"
FT SITE 69
FT /note="Critical for recognition of O(6)-alkylguanines,
FT probes the electrostatic potential of the flipped base to
FT distinguish between O(6)-alkylguanine and guanine"
FT /evidence="ECO:0000269|PubMed:23112169"
FT MUTAGEN 69
FT /note="R->A,F: Reduces discrimination of modified bases 10-
FT 100-fold and increases sensitivity toward alkylating
FT agents."
FT /evidence="ECO:0000269|PubMed:23112169"
FT HELIX 3..14
FT /evidence="ECO:0007829|PDB:3GVA"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:3GX4"
FT HELIX 25..31
FT /evidence="ECO:0007829|PDB:3GVA"
FT HELIX 35..37
FT /evidence="ECO:0007829|PDB:4ENN"
FT HELIX 38..46
FT /evidence="ECO:0007829|PDB:3GVA"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:3GVA"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:4ENJ"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:4HDV"
FT HELIX 73..84
FT /evidence="ECO:0007829|PDB:3GVA"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:4ENN"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:3GX4"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:3GVA"
SQ SEQUENCE 108 AA; 12670 MW; 7F8B3BA12CED07F1 CRC64;
MRMDEFYTKV YDAVCEIPYG KVSTYGEIAR YVGMPSYARQ VGQAMKHLHP ETHVPWHRVI
NSRGTISKRD ISAGEQRQKD RLEEEGVEIY QTSLGEYKLN LPEYMWKP
