ID   CAS3_METTH              Reviewed;         830 AA.
AC   O27158;
DT   18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 125.
DE   RecName: Full=CRISPR-associated nuclease/helicase Cas3;
DE            EC=3.1.-.-;
DE            EC=3.6.4.-;
GN   Name=cas3; OrderedLocusNames=MTH_1086;
OS   Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM
OS   10044 / NBRC 100330 / Delta H) (Methanobacterium thermoautotrophicum).
OC   Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC   Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX   NCBI_TaxID=187420;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H;
RX   PubMed=9371463; DOI=10.1128/jb.179.22.7135-7155.1997;
RA   Smith D.R., Doucette-Stamm L.A., Deloughery C., Lee H.-M., Dubois J.,
RA   Aldredge T., Bashirzadeh R., Blakely D., Cook R., Gilbert K., Harrison D.,
RA   Hoang L., Keagle P., Lumm W., Pothier B., Qiu D., Spadafora R., Vicare R.,
RA   Wang Y., Wierzbowski J., Gibson R., Jiwani N., Caruso A., Bush D.,
RA   Safer H., Patwell D., Prabhakar S., McDougall S., Shimer G., Goyal A.,
RA   Pietrovski S., Church G.M., Daniels C.J., Mao J.-I., Rice P., Noelling J.,
RA   Reeve J.N.;
RT   "Complete genome sequence of Methanobacterium thermoautotrophicum deltaH:
RT   functional analysis and comparative genomics.";
RL   J. Bacteriol. 179:7135-7155(1997).
RN   [2]
RP   FUNCTION AS A HELICASE, FUNCTION IN FORMING R-LOOPS, AND MUTAGENESIS OF
RP   ASP-347.
RC   STRAIN=ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H;
RX   PubMed=21699496; DOI=10.1042/bj20110901;
RA   Howard J.A., Delmas S., Ivancic-Bace I., Bolt E.L.;
RT   "Helicase dissociation and annealing of RNA-DNA hybrids by Escherichia coli
RT   Cas3 protein.";
RL   Biochem. J. 439:85-95(2011).
CC   -!- FUNCTION: CRISPR (clustered regularly interspaced short palindromic
CC       repeat), is an adaptive immune system that provides protection against
CC       mobile genetic elements (viruses, transposable elements and conjugative
CC       plasmids). CRISPR clusters contain sequences complementary to
CC       antecedent mobile elements and target invading nucleic acids. CRISPR
CC       clusters are transcribed and processed into CRISPR RNA (crRNA). Cas3
CC       plus Cascade participate in CRISPR interference, the third stage of
CC       CRISPR immunity. Anneals and unwinds R-loops (in which crRNA binds the
CC       target DNA, displacing the noncomplementary strand). Unwinding requires
CC       ATP, annealing does not. {ECO:0000269|PubMed:21699496}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC   -!- DOMAIN: Proteins of this family have an N-terminal nuclease domain and
CC       a C-terminal helicase/ATPase domain. In some CRISPR/Cas systems the
CC       domains are swapped, in others they are encoded separately.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the CRISPR-associated
CC       nuclease Cas3-HD family. {ECO:0000305}.
CC   -!- SIMILARITY: In the central section; belongs to the CRISPR-associated
CC       helicase Cas3 family. {ECO:0000305}.
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DR   EMBL; AE000666; AAB85575.1; -; Genomic_DNA.
DR   PIR; C69011; C69011.
DR   AlphaFoldDB; O27158; -.
DR   STRING; 187420.MTH_1086; -.
DR   EnsemblBacteria; AAB85575; AAB85575; MTH_1086.
DR   KEGG; mth:MTH_1086; -.
DR   PATRIC; fig|187420.15.peg.1064; -.
DR   HOGENOM; CLU_009347_0_0_2; -.
DR   OMA; AIAGPRY; -.
DR   Proteomes; UP000005223; Chromosome.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004386; F:helicase activity; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004518; F:nuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR   GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.3210.30; -; 1.
DR   Gene3D; 3.40.50.300; -; 2.
DR   InterPro; IPR035011; Cas3.
DR   InterPro; IPR006483; CRISPR-assoc_Cas3_HD.
DR   InterPro; IPR038257; CRISPR-assoc_Cas3_HD_sf.
DR   InterPro; IPR011545; DEAD/DEAH_box_helicase_dom.
DR   InterPro; IPR014001; Helicase_ATP-bd.
DR   InterPro; IPR006474; Helicase_Cas3_CRISPR-ass_core.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   PANTHER; PTHR47959:SF5; PTHR47959:SF5; 1.
DR   Pfam; PF00270; DEAD; 1.
DR   Pfam; PF18019; HD_6; 1.
DR   SMART; SM00487; DEXDc; 1.
DR   SUPFAM; SSF52540; SSF52540; 1.
DR   TIGRFAMs; TIGR01587; cas3_core; 1.
DR   TIGRFAMs; TIGR01596; cas3_HD; 1.
DR   PROSITE; PS51643; HD_CAS3; 1.
DR   PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR   PROSITE; PS51194; HELICASE_CTER; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; ATP-binding; Helicase; Hydrolase; Magnesium;
KW   Metal-binding; Nuclease; Nucleotide-binding; Reference proteome.
FT   CHAIN           1..830
FT                   /note="CRISPR-associated nuclease/helicase Cas3"
FT                   /id="PRO_0000416953"
FT   DOMAIN          15..250
FT                   /note="HD Cas3-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00974"
FT   DOMAIN          286..471
FT                   /note="Helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   DOMAIN          503..660
FT                   /note="Helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT   BINDING         67
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         135
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255"
FT   BINDING         299..306
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT   MUTAGEN         347
FT                   /note="D->A: Loss of R-loop unwinding."
FT                   /evidence="ECO:0000269|PubMed:21699496"
SQ   SEQUENCE   830 AA;  96329 MW;  6DEE12EA4F047604 CRC64;
     MAMMELIDII RAKSNDQRNY LLKDHLKETV ARIDDFHNFY QTNREKFSYK IGEKTFRALA
     MASIIHDLGK IDYNFQKKLM GDDSEAWEVL EEFLSPLKPL KRSPRHEILS IIWSTFLLGN
     DDLDAMMRTA ILLHHYNEYF LNDKDLMEII FTYRDAFEIY LNFIIEKKET LRIFIEDILN
     YIQNSLESDL VISAADEIRS NMDFEKPELL LEKIKEYDDD ISEFAAFYEP EERSADILIL
     SGILRRADYS ASAGVDIELF SEEVFRDIDE KITSKIGGAP WQIRLMGELG GPKKMVLVAP
     TGSGKTEFSI LWAAKHGRKF IYTLPLRVAL NDIFMRLRDS DGYFSEDEID ILHSTAFIEY
     LKEERLGRGT DLDSMMTSAR LMASPALLTT PDQVLITSLN YFGSDKVISV YPFASMILDE
     IQTYNEEMAA VIIKTLELVN EVDGNILVMT ATLPPYFRSF LDAMNFEVMD VAAIPGAHDI
     KNLNLKRHVP QLIEEPLFND ELEVSDKLGK ILDENSEKNV LIVVNNVQKA IELYREYQDD
     PDVYLLHSRL LEKVKSQRIG EVKKRSQDER GLTVISTQII EASVDIDFDL MITEISTIDS
     QIQRWGRIHR NRDADYDSGD PNIIIFTDSD RRTSLIYDKK VLDATRAILE RYDGQILDYN
     LERSMIEEVF QEEIDGSTLK EIYENQIRET ISDLDYFTVE KRTQAQRLFR NMAGYKVFIP
     DAVLRYSESE IERTFAELIK GDYRLWKDIL GEIERITGEK TTMWDLKKVL YEYSVNVPVF
     YEEKSDFWSR TTGEFKGFYV WGSMEDDDVE LLEELGLDSI FGETESSLIV