CAS10_ENTI1
ID CAS10_ENTI1 Reviewed; 755 AA.
AC E6LHV7;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAR-2011, sequence version 1.
DT 25-MAY-2022, entry version 38.
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 {ECO:0000303|PubMed:28722012};
DE EC=2.7.7.- {ECO:0000269|PubMed:28722012};
DE AltName: Full=EiCas10 {ECO:0000303|PubMed:28722012};
GN Name=cas10; Synonyms=csm1; ORFNames=HMPREF9088_1947;
OS Enterococcus italicus (strain DSM 15952 / CCUG 50447 / LMG 22039 / TP 1.5).
OC Bacteria; Firmicutes; Bacilli; Lactobacillales; Enterococcaceae;
OC Enterococcus.
OX NCBI_TaxID=888064;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 15952 / CCUG 50447 / LMG 22039 / TP 1.5;
RA Muzny D., Qin X., Deng J., Jiang H., Liu Y., Qu J., Song X.-Z., Zhang L.,
RA Thornton R., Coyle M., Francisco L., Jackson L., Javaid M., Korchina V.,
RA Kovar C., Mata R., Mathew T., Ngo R., Nguyen L., Nguyen N., Okwuonu G.,
RA Ongeri F., Pham C., Simmons D., Wilczek-Boney K., Hale W., Jakkamsetti A.,
RA Pham P., Ruth R., San Lucas F., Warren J., Zhang J., Zhao Z., Zhou C.,
RA Zhu D., Lee S., Bess C., Blankenburg K., Forbes L., Fu Q., Gubbala S.,
RA Hirani K., Jayaseelan J.C., Lara F., Munidasa M., Palculict T., Patil S.,
RA Pu L.-L., Saada N., Tang L., Weissenberger G., Zhu Y., Hemphill L.,
RA Shang Y., Youmans B., Ayvaz T., Ross M., Santibanez J., Aqrawi P.,
RA Gross S., Joshi V., Fowler G., Nazareth L., Reid J., Worley K.,
RA Petrosino J., Highlander S., Gibbs R.;
RL Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION IN PHAGE RESISTANCE, FUNCTION IN COA FORMATION, COFACTOR, ACTIVITY
RP REGULATION, SUBUNIT, AND MUTAGENESIS OF 14-HIS-ASP-15 AND 584-ASP-ASP-585.
RC STRAIN=DSM 15952 / CCUG 50447 / LMG 22039 / TP 1.5;
RX PubMed=28722012; DOI=10.1038/nature23467;
RA Niewoehner O., Garcia-Doval C., Rostoel J.T., Berk C., Schwede F.,
RA Bigler L., Hall J., Marraffini L.A., Jinek M.;
RT "Type III CRISPR-Cas systems produce cyclic oligoadenylate second
RT messengers.";
RL Nature 548:543-548(2017).
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. In a heterologous
CC host the appropriately targeted Csm effector complex prevents growth of
CC dsDNA phage phiNM1-gamma6. {ECO:0000269|PubMed:28722012}.
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: 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: 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, producing (mostly) cyclic hexaadenylate
CC (cA6). cA6 synthesis occurs in the Csm effector complex and requires
CC cognate target RNA and ATP; other NTPs are not incorporated. cOAs are
CC second messengers that induce an antiviral state important for defense
CC against invading nucleic acids. {ECO:0000269|PubMed:28722012}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6 ATP = cyclic hexaadenylate + 6 diphosphate;
CC Xref=Rhea:RHEA:58276, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:142456; Evidence={ECO:0000269|PubMed:28722012};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:28722012};
CC Note=Synthesis of cA6 requires Mg(2+). {ECO:0000269|PubMed:28722012};
CC -!- ACTIVITY REGULATION: Synthesis of cA6 is inhibited by EDTA.
CC {ECO:0000269|PubMed:28722012}.
CC -!- SUBUNIT: Part of the Csm effector complex that includes Cas10, Csm2,
CC Csm3, Csm4 and Csm5. {ECO:0000269|PubMed:28722012}.
CC -!- DOMAIN: The N-terminal HD domain has ssDNase activity. The C-terminal
CC GGDEF domain has the cOA synthesis activity.
CC {ECO:0000269|PubMed:28722012}.
CC -!- MISCELLANEOUS: Encoded in a type III-A CRISPR locus.
CC {ECO:0000269|PubMed:28722012}.
CC -!- SIMILARITY: Belongs to the CRISPR-associated Cas10/Csm1 family.
CC {ECO:0000305}.
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DR EMBL; AEPV01000074; EFU73217.1; -; Genomic_DNA.
DR RefSeq; WP_007208958.1; NZ_JXKT01000007.1.
DR AlphaFoldDB; E6LHV7; -.
DR SMR; E6LHV7; -.
DR STRING; 888064.HMPREF9088_1947; -.
DR EnsemblBacteria; EFU73217; EFU73217; HMPREF9088_1947.
DR PATRIC; fig|888064.11.peg.2085; -.
DR eggNOG; COG1353; Bacteria.
DR HOGENOM; CLU_017487_1_0_9; -.
DR OMA; PSAFYYS; -.
DR OrthoDB; 423797at2; -.
DR Proteomes; UP000010296; Unassembled WGS sequence.
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 Gene3D; 3.30.70.270; -; 1.
DR InterPro; IPR013408; Cas10/Csm1.
DR InterPro; IPR041062; Csm1_B.
DR InterPro; IPR000160; GGDEF_dom.
DR InterPro; IPR043128; Rev_trsase/Diguanyl_cyclase.
DR Pfam; PF18211; Csm1_B; 1.
DR TIGRFAMs; TIGR02578; cas_TM1811_Csm1; 1.
DR PROSITE; PS50887; GGDEF; 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..755
FT /note="CRISPR system single-strand-specific
FT deoxyribonuclease Cas10/Csm1 (subtype III-A)"
FT /id="PRO_0000446111"
FT DOMAIN 522..656
FT /note="GGDEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00095"
FT REGION 1..87
FT /note="HD domain"
FT /evidence="ECO:0000305"
FT MUTAGEN 14..15
FT /note="HD->AN: Wild-type synthesis of the cA6 activator."
FT /evidence="ECO:0000269|PubMed:28722012"
FT MUTAGEN 584..585
FT /note="DD->AA: No longer synthesizes the cA6 activator."
FT /evidence="ECO:0000269|PubMed:28722012"
SQ SEQUENCE 755 AA; 85841 MW; 89707E26C2128EB7 CRC64;
MNKKLELMYG SLLHDIGKIV YRSNSVDFAK GTHSKIGSQF LNKFKPFQLS GIVDSVSYHH
YKELASSSLL DDSVAYITYI ADNIASGTDR RASEGDYEGE GNRQRFDKRA PLASIFNVVN
SETKGLANYT YSFEKEQVYR YPTDAKKEYT SSQYAALVNK MTDDLSNKLK VGPDSFSSLL
QWTESLWSYI PSSTDTNQVM DVSLYDHSKI TCAIASCIYD YLTEMNCVNY RKELFSPYEK
TKQFYQEDVF LLVSLDMSGI QDFIYNISGS KALKSLRSRS FYLETMLESL VDDLLSDLEL
SRANLLYTGG GHAYLLLPNT ERARDVLASF EGEMKEWFIK IFKTDLSVAI AYKACTGEDL
MNSNGTYSDL WQTVSRKLSD KKAHKYSLNE IKLFNSTIHA GTQECKECLR SDIDISEDSL
CKICEGIIAI SNDLRDYSFF VVSPEGKVPL PRNRYLSVEN QDGAERKIKM NKETRIYSKN
QPFVGKQLVT NLWMCDYDFS TLNPETKKQG IASYVNREVG IPRLGVLRAD IDNLGTTFIK
GIPEQYRSIS RTATLSRQLS MFFKFELSNI LKGARISVIY SGGDDLFLIG AWDDVISKAL
VLRKAFTRFS AGKLTFSAGI GMYPVKYPIS KMASETGVLE DLAKRGEKNQ VALWNDSKVF
GWSQLEEQIL KEKMIPLQEA LTNSQEHGKS FLYKMLELLR NEDQINIARL AYLLARSSLS
EELTQSIFAW SQNKQQKVEL ITAIEYLVYQ IREAD
