ID   CAS10_MYCTU             Reviewed;         809 AA.
AC   P71629; L0TDG3;
DT   11-JUL-2012, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   11-DEC-2019, entry version 101.
DE   RecName: Full=CRISPR system single-strand-specific deoxyribonuclease Cas10/Csm1 (subtype III-A);
DE            Short=ssDNase Cas10;
DE            EC=3.1.-.-;
DE   AltName: Full=Cyclic oligoadenylate synthase;
DE            EC=2.7.7.- {ECO:0000250|UniProtKB:A0A0A7HFE1};
GN   Name=cas10; Synonyms=csm1; OrderedLocusNames=Rv2823c;
OS   Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83332;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=9634230; DOI=10.1038/31159;
RA   Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA   Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA   Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA   Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA   Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA   Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA   Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA   Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT   genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA   Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA   Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA   Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA   Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT   mass spectrometry.";
RL   Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN   [3]
RP   FUNCTION IN PLASMID RESISTANCE, SUBUNIT, AND DISRUPTION PHENOTYPE.
RC   STRAIN=H37Rv;
RX   PubMed=29979631; DOI=10.1096/fj.201800557rr;
RA   Wei W., Zhang S., Fleming J., Chen Y., Li Z., Fan S., Liu Y., Wang W.,
RA   Wang T., Liu Y., Ren B., Wang M., Jiao J., Chen Y., Zhou Y., Zhou Y.,
RA   Gu S., Zhang X., Wan L., Chen T., Zhou L., Chen Y., Zhang X.E., Li C.,
RA   Zhang H., Bi L.;
RT   "Mycobacterium tuberculosis type III-A CRISPR/Cas system crRNA and its
RT   maturation have atypical features.";
RL   FASEB J. 33:1496-1509(2019).
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 spacers, sequences complementary to
CC       antecedent mobile elements, and target invading nucleic acids. CRISPR
CC       clusters are transcribed and processed into CRISPR RNA (crRNA). The
CC       type III-A Csm effector complex binds crRNA and acts as a crRNA-guided
CC       RNase, DNase and cyclic oligoadenylate synthase; binding of target RNA
CC       cognate to the crRNA is required for all activities (Probable). This
CC       CRISPR-Cas system protects bacteria against transformation with
CC       plasmids containing DNA homologous to its spacer regions
CC       (PubMed:29979631). {ECO:0000269|PubMed:29979631,
CC       ECO:0000305|PubMed:29979631}.
CC   -!- FUNCTION: This subunit is a single-strand-specific deoxyribonuclease
CC       (ssDNase) which digests both linear and circular ssDNA; it has both
CC       exo- and endonuclease activity. {ECO:0000250|UniProtKB:B6YWB8}.
CC   -!- FUNCTION: ssDNase activity is stimulated in the ternary Csm effector
CC       complex; binding of cognate target RNA activates the ssDNase, as the
CC       target RNA is degraded ssDNA activity decreases.
CC       {ECO:0000250|UniProtKB:A0A0A7HFE1}.
CC   -!- FUNCTION: When associated with the ternary Csm effector complex (the
CC       crRNA, Cas proteins and a cognate target ssRNA) synthesizes cyclic
CC       oligoadenylates (cOA) from ATP. cOAs are second messengers that
CC       stimulate the ssRNase activity of Csm6, inducing an antiviral state
CC       important for defense against invading nucleic acids.
CC       {ECO:0000250|UniProtKB:A0A0A7HFE1}.
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000250|UniProtKB:A0A0A7HFE1};
CC   -!- SUBUNIT: Part of the Csm effector complex, that includes Cas10, Csm2,
CC       Csm3, Csm4, Csm5 and mature crRNA. {ECO:0000269|PubMed:29979631}.
CC   -!- DOMAIN: The N-terminal HD domain has ssDNase activity. The C-terminal
CC       GGDEF domain has the cOA synthesis activity.
CC       {ECO:0000250|UniProtKB:A0A0A7HFE1}.
CC   -!- DISRUPTION PHENOTYPE: Deletion of the entire CRISPR-Cas locus (cas6 to
CC       cas2, Rv2824c to Rv2816c) decreases resistance to plasmids encoding
CC       spacer elements about 6-fold. {ECO:0000269|PubMed:29979631}.
CC   -!- MISCELLANEOUS: Encoded in a type III-A CRISPR locus.
CC       {ECO:0000305|PubMed:29979631}.
CC   -!- SIMILARITY: Belongs to the CRISPR-associated Cas10/Csm1 family.
CC       {ECO:0000305}.
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DR   EMBL; AL123456; CCP45623.1; -; Genomic_DNA.
DR   PIR; B70692; B70692.
DR   RefSeq; NP_217339.1; NC_000962.3.
DR   RefSeq; WP_003911999.1; NZ_NVQJ01000006.1.
DR   STRING; 83332.Rv2823c; -.
DR   PaxDb; P71629; -.
DR   PRIDE; P71629; -.
DR   EnsemblBacteria; CCP45623; CCP45623; Rv2823c.
DR   GeneID; 887735; -.
DR   KEGG; mtu:Rv2823c; -.
DR   KEGG; mtv:RVBD_2823c; -.
DR   TubercuList; Rv2823c; -.
DR   eggNOG; ENOG410695F; Bacteria.
DR   eggNOG; COG1353; LUCA.
DR   HOGENOM; HOG000220575; -.
DR   InParanoid; P71629; -.
DR   KO; K07016; -.
DR   OMA; LKMDVDN; -.
DR   PhylomeDB; P71629; -.
DR   BioCyc; MTBH37RV:G185E-7073-MONOMER; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR   CDD; cd09680; Cas10_III; 1.
DR   InterPro; IPR013408; Cas10/Csm1.
DR   InterPro; IPR041062; Csm1_B.
DR   InterPro; IPR000160; GGDEF_dom.
DR   InterPro; IPR003607; HD/PDEase_dom.
DR   Pfam; PF18211; Csm1_B; 1.
DR   TIGRFAMs; TIGR02578; cas_TM1811_Csm1; 1.
DR   PROSITE; PS50887; GGDEF; 1.
DR   PROSITE; PS51831; HD; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; ATP-binding; Endonuclease; Exonuclease; Hydrolase;
KW   Nuclease; Nucleotide-binding; Reference proteome; RNA-binding; Transferase.
FT   CHAIN           1..809
FT                   /note="CRISPR system single-strand-specific
FT                   deoxyribonuclease Cas10/Csm1 (subtype III-A)"
FT                   /id="PRO_0000418224"
FT   DOMAIN          1..98
FT                   /note="HD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01175"
FT   DOMAIN          547..700
FT                   /note="GGDEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00095"
SQ   SEQUENCE   809 AA;  90747 MW;  E7328ED485D73531 CRC64;
     MNPQLIEAII GCLLHDIGKP VQRAALGYPG RHSAIGRAFM KKVWLRDSRN PSQFTDEVDE
     ADIGVSDRRI LDAISYHHSS ALRTAAENGR LAADAPAYIA YNIAAGTDRR KADSDDGHGA
     STWDPDTPLY SMFNRFGSGT ANLAFAPEML DDRKPINIPS PRRIEFDKDR YAAIVNKLKA
     ILVDLERSDT YLASLLNVLE ATLSFVPSST DASEVVDVSL FDHLKLTGAL GACIWHYLQA
     TGQSDFKSAL FDKQDTFYNE KAFLLTTFDV SGIQDFIYTI HSSGAAKMLR ARSFYLEMLT
     EHLIDELLAR VGLSRANLNY SGGGHAYLLL PNTESARKSV EQFEREANDW LLENFATRLF
     IATGSVPLAA NDLMRRPNES ASQASNRALR YSGLYRELSE QLSAKKLARY SADQLRELNS
     RDHDGQKGDR ECSVCHTVNR TVSADDEPKC SLCQALTAAS SQIQSESRRF LLISDGATKG
     LPLPFGATLT FCSRADADKA LQQPQTRRRY AKNKFFAGEC LGTGLWVGDY VAQMEFGDYV
     KRASGIARLG VLRLDVDNLG QAFTHGFMEQ GNGKFNTISR TAAFSRMLSL FFRQHINYVL
     ARPKLRPITG DDPARPREAT IIYSGGDDVF VVGAWDDVIE FGIELRERFH EFTQGKLTVS
     AGIGMFPDKY PISVMAREVG DLEDAAKSLP GKNGVALFDR EFTFGWDELL SKVIEEKYRH
     IADYFSGNEE RGMAFIYKLL ELLAERDDRI TKARWVYFLT RMRNPTGDTA PFQQFANRLH
     QWFQDPTDAK QLKTALHLYI YRTRKEESE
//