ID   CAS6_MYCTU              Reviewed;         314 AA.
AC   P9WPJ1; F2GLB0; L0TCC6; P71628; Q7D6I1;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 32.
DE   RecName: Full=CRISPR-associated endoribonuclease Cas6;
DE            EC=3.1.-.- {ECO:0000269|PubMed:29979631};
GN   Name=cas6; OrderedLocusNames=Rv2824c;
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, FUNCTION IN PRE-CRRNA PROCESSING, COFACTOR,
RP   ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, DISRUPTION PHENOTYPE,
RP   MUTAGENESIS OF HIS-99 AND 295-GLY--GLY-297, AND RNA-BINDING.
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 sequences complementary to
CC       antecedent mobile elements (spacers) and target invading nucleic acids.
CC       CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).
CC       The type III-A Csm effector complex binds crRNA and acts as a crRNA-
CC       guided RNase, DNase and cyclic oligoadenylate synthase; binding of
CC       target RNA cognate to the crRNA is required for all activities
CC       (Probable). This CRISPR-Cas system protects bacteria against
CC       transformation with plasmids containing DNA homologous to its spacer
CC       regions (PubMed:29979631). {ECO:0000269|PubMed:29979631,
CC       ECO:0000305|PubMed:29979631}.
CC   -!- FUNCTION: Processes pre-crRNA into individual crRNA units; accurate
CC       cleavage of pre-crRNA depends on a 3' stem-loop and the sequence of the
CC       bases in the stem. The mature crRNA is unusual for type III-A systems
CC       as it doe snot undergo 3' processing after Cas6 cleavage. Mature crRNA
CC       is about 71 nucleotides (nt long) with an 8 nt 5' handle and 28 nt
CC       repeat with a 10 nt stem-loop at the 3' end.
CC       {ECO:0000269|PubMed:29979631}.
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000269|PubMed:29979631};
CC       Note=Ca(2+) and Mn(2+) stimulate processing of pre-crRNA.
CC       {ECO:0000269|PubMed:29979631};
CC   -!- ACTIVITY REGULATION: Pre-crRNA processing is inhibited by EDTA.
CC       {ECO:0000269|PubMed:29979631}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=8.395 uM for repeat pre-crRNA in presence of 0.125 mM CaCl(2)
CC         {ECO:0000269|PubMed:29979631};
CC         Note=kcat is 12.156 min(-1) in presence of CaCl(2).
CC         {ECO:0000269|PubMed:29979631};
CC   -!- DISRUPTION PHENOTYPE: Deletion of this gene alone blocks maturation of
CC       pre-crRNA (PubMed:29979631). Deletion of the entire CRISPR-Cas locus
CC       (cas6 to cas2, Rv2824c to Rv2816c) decreases resistance to plasmids
CC       encoding spacer elements about 6-fold (PubMed:29979631).
CC       {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 protein Cas6/Cse3/CasE
CC       family. {ECO:0000305}.
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DR   EMBL; AL123456; CCP45624.1; -; Genomic_DNA.
DR   PIR; C70692; C70692.
DR   RefSeq; NP_217340.1; NC_000962.3.
DR   RefSeq; WP_003899496.1; NC_000962.3.
DR   AlphaFoldDB; P9WPJ1; -.
DR   SMR; P9WPJ1; -.
DR   STRING; 83332.Rv2824c; -.
DR   PaxDb; P9WPJ1; -.
DR   DNASU; 888945; -.
DR   GeneID; 888945; -.
DR   KEGG; mtu:Rv2824c; -.
DR   TubercuList; Rv2824c; -.
DR   eggNOG; COG5551; Bacteria.
DR   OMA; RSIMIQF; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR   InterPro; IPR019267; CRISPR-assoc_Cas6_C.
DR   InterPro; IPR010156; CRISPR-assoc_prot_Cas6.
DR   Pfam; PF10040; CRISPR_Cas6; 1.
DR   TIGRFAMs; TIGR01877; cas_cas6; 1.
PE   1: Evidence at protein level;
KW   Antiviral defense; Endonuclease; Hydrolase; Nuclease; Reference proteome;
KW   RNA-binding.
FT   CHAIN           1..314
FT                   /note="CRISPR-associated endoribonuclease Cas6"
FT                   /id="PRO_0000418222"
FT   REGION          1..29
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MUTAGEN         99
FT                   /note="H->A: Incorrect processing of pre-crRNA, binds pre-
FT                   crRNA."
FT                   /evidence="ECO:0000269|PubMed:29979631"
FT   MUTAGEN         295..297
FT                   /note="GMG->AMA: Incorrect processing of pre-crRNA, no
FT                   longer binds pre-crRNA."
FT                   /evidence="ECO:0000269|PubMed:29979631"
SQ   SEQUENCE   314 AA;  34432 MW;  0351BF2BA94419D2 CRC64;
     MAARRGGIRR TDLLRRSGQP RGRHRASAAE SGLTWISPTL ILVGFSHRGD RRMTEHLSRL
     TLTLEVDAPL ERARVATLGP HLHGVLMESI PADYVQTLHT VPVNPYSQYA LARSTTSLEW
     KISTLTNEAR QQIVGPINDA AFAGFRLRAS GIATQVTSRS LEQNPLSQFA RIFYARPETR
     KFRVEFLTPT AFKQSGEYVF WPDPRLVFQS LAQKYGAIVD GEEPDPGLIA EFGQSVRLSA
     FRVASAPFAV GAARVPGFTG SATFTVRGVD TFASYIAALL WFGEFSGCGI KASMGMGAIR
     VQPLAPREKC VPKP