MRE11_PYRFU
ID MRE11_PYRFU Reviewed; 426 AA.
AC Q8U1N9;
DT 21-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=DNA double-strand break repair protein Mre11 {ECO:0000255|HAMAP-Rule:MF_02044, ECO:0000305};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_02044, ECO:0000305};
DE AltName: Full=pfMre11 {ECO:0000303|PubMed:11029422};
GN Name=mre11 {ECO:0000255|HAMAP-Rule:MF_02044, ECO:0000303|PubMed:11029422};
GN OrderedLocusNames=PF1166;
OS Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=186497;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=10430560; DOI=10.1093/genetics/152.4.1299;
RA Maeder D.L., Weiss R.B., Dunn D.M., Cherry J.L., Gonzalez J.M.,
RA DiRuggiero J., Robb F.T.;
RT "Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P.
RT horikoshii inferred from complete genomic sequences.";
RL Genetics 152:1299-1305(1999).
RN [2]
RP FUNCTION, AND COFACTOR.
RC STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX PubMed=11029422; DOI=10.1128/jb.182.21.6036-6041.2000;
RA Hopfner K.-P., Karcher A., Shin D., Fairley C., Tainer J.A., Carney J.P.;
RT "Mre11 and Rad50 from Pyrococcus furiosus: cloning and biochemical
RT characterization reveal an evolutionarily conserved multiprotein machine.";
RL J. Bacteriol. 182:6036-6041(2000).
RN [3]
RP FUNCTION.
RX PubMed=18957200; DOI=10.1016/j.cell.2008.09.054;
RA Hopkins B.B., Paull T.T.;
RT "The P. furiosus mre11/rad50 complex promotes 5' strand resection at a DNA
RT double-strand break.";
RL Cell 135:250-260(2008).
RN [4]
RP ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=22102415; DOI=10.1074/jbc.m111.307041;
RA Majka J., Alford B., Ausio J., Finn R.M., McMurray C.T.;
RT "ATP hydrolysis by RAD50 protein switches MRE11 enzyme from endonuclease to
RT exonuclease.";
RL J. Biol. Chem. 287:2328-2341(2012).
RN [5]
RP ACTIVITY REGULATION.
RX PubMed=24493214; DOI=10.1002/embj.201386100;
RA Deshpande R.A., Williams G.J., Limbo O., Williams R.S., Kuhnlein J.,
RA Lee J.H., Classen S., Guenther G., Russell P., Tainer J.A., Paull T.T.;
RT "ATP-driven Rad50 conformations regulate DNA tethering, end resection, and
RT ATM checkpoint signaling.";
RL EMBO J. 33:482-500(2014).
RN [6] {ECO:0007744|PDB:1II7}
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-333 IN COMPLEX WITH MANGANESE,
RP COFACTOR, SUBUNIT, AND ACTIVE SITE.
RX PubMed=11371344; DOI=10.1016/s0092-8674(01)00335-x;
RA Hopfner K.-P., Karcher A., Craig L., Woo T.T., Carney J.P., Tainer J.A.;
RT "Structural biochemistry and interaction architecture of the DNA double-
RT strand break repair Mre11 nuclease and Rad50-ATPase.";
RL Cell 105:473-485(2001).
RN [7] {ECO:0007744|PDB:1S8E}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-333 OF MUTANT PFMRE11-3 IN
RP COMPLEX WITH MANGANESE, COFACTOR, AND ACTIVE SITE.
RX PubMed=15047855; DOI=10.1093/nar/gkh343;
RA Arthur L.M., Gustausson K., Hopfner K.P., Carson C.T., Stracker T.H.,
RA Karcher A., Felton D., Weitzman M.D., Tainer J., Carney J.P.;
RT "Structural and functional analysis of Mre11-3.";
RL Nucleic Acids Res. 32:1886-1893(2004).
RN [8] {ECO:0007744|PDB:3DSC, ECO:0007744|PDB:3DSD}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 1-343 IN COMPLEX WITH MANGANESE,
RP FUNCTION, DNA-BINDING, COFACTOR, SUBUNIT, AND MUTAGENESIS OF HIS-17;
RP HIS-52; LEU-61; HIS-85 AND LEU-97.
RX PubMed=18854158; DOI=10.1016/j.cell.2008.08.017;
RA Williams R.S., Moncalian G., Williams J.S., Yamada Y., Limbo O., Shin D.S.,
RA Groocock L.M., Cahill D., Hitomi C., Guenther G., Moiani D., Carney J.P.,
RA Russell P., Tainer J.A.;
RT "Mre11 dimers coordinate DNA end bridging and nuclease processing in
RT double-strand-break repair.";
RL Cell 135:97-109(2008).
RN [9] {ECO:0007744|PDB:3QKR, ECO:0007744|PDB:3QKS, ECO:0007744|PDB:3QKU}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 348-381, AND SUBUNIT.
RX PubMed=21441914; DOI=10.1038/nsmb.2038;
RA Williams G.J., Williams R.S., Williams J.S., Moncalian G., Arvai A.S.,
RA Limbo O., Guenther G., SilDas S., Hammel M., Russell P., Tainer J.A.;
RT "ABC ATPase signature helices in Rad50 link nucleotide state to Mre11
RT interface for DNA repair.";
RL Nat. Struct. Mol. Biol. 18:423-431(2011).
RN [10] {ECO:0007744|PDB:4HD0}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1-333 OF MUTANT ARG-204 IN
RP COMPLEX WITH MANGANESE, AND COFACTOR.
RX PubMed=23080121; DOI=10.1093/nar/gks954;
RA Limbo O., Moiani D., Kertokalio A., Wyman C., Tainer J.A., Russell P.;
RT "Mre11 ATLD17/18 mutation retains Tel1/ATM activity but blocks DNA double-
RT strand break repair.";
RL Nucleic Acids Res. 40:11435-11449(2012).
CC -!- FUNCTION: Part of the Rad50/Mre11 complex, which is involved in the
CC early steps of DNA double-strand break (DSB) repair (PubMed:11029422,
CC PubMed:18854158, PubMed:18957200). The complex may facilitate opening
CC of the processed DNA ends to aid in the recruitment of HerA and NurA
CC (PubMed:18957200). Mre11 binds to DSB ends and has both double-stranded
CC 3'-5' exonuclease activity and single-stranded endonuclease activity
CC (PubMed:11029422, PubMed:18854158, PubMed:18957200).
CC {ECO:0000269|PubMed:11029422, ECO:0000269|PubMed:18854158,
CC ECO:0000269|PubMed:18957200}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_02044,
CC ECO:0000269|PubMed:11029422, ECO:0000269|PubMed:11371344,
CC ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
CC ECO:0000269|PubMed:23080121};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_02044, ECO:0000269|PubMed:11371344,
CC ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
CC ECO:0000269|PubMed:23080121};
CC -!- ACTIVITY REGULATION: Nuclease activity is regulated by Rad50.
CC {ECO:0000255|HAMAP-Rule:MF_02044, ECO:0000269|PubMed:22102415,
CC ECO:0000269|PubMed:24493214}.
CC -!- SUBUNIT: Homodimer (PubMed:18854158). Forms a heterotetramer composed
CC of two Mre11 subunits and two Rad50 subunits (PubMed:11371344,
CC PubMed:21441914, PubMed:22102415). Homodimerization facilitates DNA
CC binding (PubMed:18854158). {ECO:0000269|PubMed:11371344,
CC ECO:0000269|PubMed:18854158, ECO:0000269|PubMed:21441914,
CC ECO:0000269|PubMed:22102415}.
CC -!- INTERACTION:
CC Q8U1N9; Q8U1N9: mre11; NbExp=3; IntAct=EBI-2014945, EBI-2014945;
CC Q8U1N9; P58301: rad50; NbExp=11; IntAct=EBI-2014945, EBI-2505704;
CC -!- SIMILARITY: Belongs to the MRE11/RAD32 family. {ECO:0000255|HAMAP-
CC Rule:MF_02044, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL81290.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AE009950; AAL81290.1; ALT_INIT; Genomic_DNA.
DR PDB; 1II7; X-ray; 2.20 A; A/B=1-333.
DR PDB; 1S8E; X-ray; 2.30 A; A/B=1-333.
DR PDB; 3DSC; X-ray; 2.70 A; A=1-343.
DR PDB; 3DSD; X-ray; 2.20 A; A/B=1-343.
DR PDB; 3QKR; X-ray; 3.40 A; C=348-381.
DR PDB; 3QKS; X-ray; 2.10 A; C=348-381.
DR PDB; 3QKU; X-ray; 3.30 A; C=348-381.
DR PDB; 4HD0; X-ray; 2.30 A; A/B=1-333.
DR PDBsum; 1II7; -.
DR PDBsum; 1S8E; -.
DR PDBsum; 3DSC; -.
DR PDBsum; 3DSD; -.
DR PDBsum; 3QKR; -.
DR PDBsum; 3QKS; -.
DR PDBsum; 3QKU; -.
DR PDBsum; 4HD0; -.
DR AlphaFoldDB; Q8U1N9; -.
DR SMR; Q8U1N9; -.
DR DIP; DIP-52386N; -.
DR IntAct; Q8U1N9; 1.
DR MINT; Q8U1N9; -.
DR STRING; 186497.PF1166; -.
DR EnsemblBacteria; AAL81290; AAL81290; PF1166.
DR KEGG; pfu:PF1166; -.
DR PATRIC; fig|186497.12.peg.1226; -.
DR eggNOG; arCOG00397; Archaea.
DR HOGENOM; CLU_026621_5_1_2; -.
DR OMA; RWDFGDY; -.
DR PhylomeDB; Q8U1N9; -.
DR EvolutionaryTrace; Q8U1N9; -.
DR Proteomes; UP000001013; Chromosome.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0045027; F:DNA end binding; IDA:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR GO; GO:0000403; F:Y-form DNA binding; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR CDD; cd00840; MPP_Mre11_N; 1.
DR Gene3D; 3.60.21.10; -; 1.
DR HAMAP; MF_02044; Mre11; 1.
DR InterPro; IPR004843; Calcineurin-like_PHP_ApaH.
DR InterPro; IPR029052; Metallo-depent_PP-like.
DR InterPro; IPR032885; Mre11_archaea-type.
DR InterPro; IPR041796; Mre11_N.
DR Pfam; PF00149; Metallophos; 1.
DR SUPFAM; SSF56300; SSF56300; 1.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; Endonuclease; Exonuclease; Hydrolase;
KW Manganese; Metal-binding; Nuclease; Reference proteome.
FT CHAIN 1..426
FT /note="DNA double-strand break repair protein Mre11"
FT /id="PRO_0000138696"
FT ACT_SITE 85
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_02044,
FT ECO:0000305|PubMed:11371344, ECO:0000305|PubMed:15047855"
FT BINDING 8
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 10
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 49
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 49
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 84
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 173
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 206
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT BINDING 208
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11371344,
FT ECO:0000269|PubMed:15047855, ECO:0000269|PubMed:18854158,
FT ECO:0000269|PubMed:23080121, ECO:0007744|PDB:1II7,
FT ECO:0007744|PDB:1S8E, ECO:0007744|PDB:3DSD,
FT ECO:0007744|PDB:4HD0"
FT MUTAGEN 17
FT /note="H->A: Decreases 3'-5' exonuclease activity."
FT /evidence="ECO:0000269|PubMed:18854158"
FT MUTAGEN 52
FT /note="H->S: Lacks 3'-5' exonuclease activity. Slight
FT decrease in endonuclease activity."
FT /evidence="ECO:0000269|PubMed:18854158"
FT MUTAGEN 61
FT /note="L->K: Decreases affinity for ssDNA and dsDNA, but
FT does not affect exonuclease and endonuclease activities."
FT /evidence="ECO:0000269|PubMed:18854158"
FT MUTAGEN 85
FT /note="H->S: Lacks both 3'-5' exonuclease and endonuclease
FT activities."
FT /evidence="ECO:0000269|PubMed:18854158"
FT MUTAGEN 97
FT /note="L->D: Decreases affinity for ssDNA and dsDNA, but
FT does not affect exonuclease and endonuclease activities."
FT /evidence="ECO:0000269|PubMed:18854158"
FT STRAND 2..6
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 19..38
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 42..48
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 58..72
FT /evidence="ECO:0007829|PDB:1II7"
FT TURN 73..75
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:1II7"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 94..100
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 129..135
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 148..152
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 157..161
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 166..173
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 177..181
FT /evidence="ECO:0007829|PDB:1II7"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 242..249
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 254..259
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 262..267
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 282..292
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 301..310
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 315..320
FT /evidence="ECO:0007829|PDB:1II7"
FT STRAND 324..332
FT /evidence="ECO:0007829|PDB:1II7"
FT HELIX 354..361
FT /evidence="ECO:0007829|PDB:3QKS"
FT HELIX 370..376
FT /evidence="ECO:0007829|PDB:3QKS"
SQ SEQUENCE 426 AA; 49456 MW; 639092C2F9C24DCD CRC64;
MKFAHLADIH LGYEQFHKPQ REEEFAEAFK NALEIAVQEN VDFILIAGDL FHSSRPSPGT
LKKAIALLQI PKEHSIPVFA IEGNHDRTQR GPSVLNLLED FGLVYVIGMR KEKVENEYLT
SERLGNGEYL VKGVYKDLEI HGMKYMSSAW FEANKEILKR LFRPTDNAIL MLHQGVREVS
EARGEDYFEI GLGDLPEGYL YYALGHIHKR YETSYSGSPV VYPGSLERWD FGDYEVRYEW
DGIKFKERYG VNKGFYIVED FKPRFVEIKV RPFIDVKIKG SEEEIRKAIK RLIPLIPKNA
YVRLNIGWRK PFDLTEIKEL LNVEYLKIDT WRIKERTDEE SGKIGLPSDF FTEFELKIID
ILGEKDFDDF DYIIKLITEG KVEEEGPLEE AVKKVSEEKG KTVRQKIESI PKKKRGTLDS
WLGGAR
