ID   CS13A_LEPWF             Reviewed;        1182 AA.
AC   U2PSH1;
DT   22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2013, sequence version 1.
DT   25-MAY-2022, entry version 21.
DE   RecName: Full=CRISPR-associated endoribonuclease Cas13a {ECO:0000303|PubMed:28475872};
DE            Short=EndoRNase;
DE            EC=3.1.-.-;
DE   AltName: Full=LwaCas13a {ECO:0000303|PubMed:28475872};
GN   Name=cas13a {ECO:0000303|PubMed:28475872}; ORFNames=HMPREF9015_00520;
OS   Leptotrichia wadei (strain F0279).
OC   Bacteria; Fusobacteria; Fusobacteriales; Leptotrichiaceae; Leptotrichia.
OX   NCBI_TaxID=888055;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=F0279;
RA   Weinstock G., Sodergren E., Lobos E.A., Fulton L., Fulton R., Courtney L.,
RA   Fronick C., O'Laughlin M., Godfrey J., Wilson R.M., Miner T., Farmer C.,
RA   Delehaunty K., Cordes M., Minx P., Tomlinson C., Chen J., Wollam A.,
RA   Pepin K.H., Bhonagiri V., Zhang X., Warren W., Mitreva M., Mardis E.R.,
RA   Wilson R.K.;
RL   Submitted (JUN-2013) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   FUNCTION IN CRRNA PROCESSING, FUNCTION IN TARGET SSRNA CLEAVAGE, FUNCTION
RP   AS AN ENDORIBONUCLEASE, AND ACTIVITY REGULATION.
RX   PubMed=28475872; DOI=10.1016/j.molcel.2017.04.008;
RA   East-Seletsky A., O'Connell M.R., Burstein D., Knott G.J., Doudna J.A.;
RT   "RNA targeting by functionally orthogonal type VI-A CRISPR-Cas enzymes.";
RL   Mol. Cell 66:373-383(2017).
RN   [3]
RP   FUNCTION IN TARGET SSRNA CLEAVAGE, FUNCTION AS AN ENDORIBONUCLEASE,
RP   ACTIVITY REGULATION, AND BIOTECHNOLOGY.
RX   PubMed=28408723; DOI=10.1126/science.aam9321;
RA   Gootenberg J.S., Abudayyeh O.O., Lee J.W., Essletzbichler P., Dy A.J.,
RA   Joung J., Verdine V., Donghia N., Daringer N.M., Freije C.A., Myhrvold C.,
RA   Bhattacharyya R.P., Livny J., Regev A., Koonin E.V., Hung D.T.,
RA   Sabeti P.C., Collins J.J., Zhang F.;
RT   "Nucleic acid detection with CRISPR-Cas13a/C2c2.";
RL   Science 356:438-442(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 sequences complementary to
CC       antecedent mobile elements and target invading nucleic acids. Unlike
CC       many single-component effectors, this CRISPR-Cas system targets RNA
CC       (PubMed:28475872). CRISPR clusters are transcribed from pre-CRISPR RNA
CC       (crRNA) and processed into crRNA by this protein (PubMed:28475872).
CC       Cleaves linear target ssRNA in a pre-crRNA-dependent fashion,
CC       preferentially before U residues (PubMed:28475872). Binding a viable
CC       target RNA target activates this protein for non-specific RNA
CC       degradation in vitro (called collateral RNA degradation), which is
CC       fairly sensitive as it requires picomolar levels of viable target RNA
CC       (PubMed:28475872, PubMed:28408723). {ECO:0000269|PubMed:28475872}.
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000250|UniProtKB:C7NBY4};
CC       Note=Pre-crRNA processing is metal independent, while crRNA-guided
CC       target RNA cleavage is dependent on divalent metal.
CC       {ECO:0000250|UniProtKB:C7NBY4};
CC   -!- ACTIVITY REGULATION: Target RNA acts as an activator for non-specific
CC       ssRNA degradation (PubMed:28475872, PubMed:28408723).
CC       {ECO:0000269|PubMed:28408723, ECO:0000269|PubMed:28475872}.
CC   -!- DOMAIN: The target ssRNase active sites are probably within the 2 HEPN-
CC       like folds, and the 2 folds interact in vivo.
CC       {ECO:0000250|UniProtKB:C7NBY4}.
CC   -!- BIOTECHNOLOGY: Can be used to detect RNA or DNA with atomolar
CC       sensitivity and single-base mismatch specificity when combined with
CC       isothermal amplification, allowing detection of virus, bacterial
CC       pathogens, to genotype DNA and to identify mutations in cell-free DNA.
CC       Additionally the reagents can be lyophilized and reconstituted on paper
CC       for field work (PubMed:28408723). {ECO:0000269|PubMed:28408723}.
CC   -!- MISCELLANEOUS: Part of a type VI-A uridine-prefering CRISPR-Cas system.
CC       {ECO:0000305|PubMed:28475872}.
CC   -!- SIMILARITY: Belongs to the CRISPR-associated endoribonuclease Cas13a
CC       family. {ECO:0000305}.
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DR   EMBL; AWVM01000026; ERK53440.1; -; Genomic_DNA.
DR   AlphaFoldDB; U2PSH1; -.
DR   SMR; U2PSH1; -.
DR   STRING; 888055.HMPREF9015_00520; -.
DR   EnsemblBacteria; ERK53440; ERK53440; HMPREF9015_00520.
DR   PATRIC; fig|888055.3.peg.499; -.
DR   HOGENOM; CLU_008486_0_0_0; -.
DR   Proteomes; UP000016626; Unassembled WGS sequence.
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.
PE   1: Evidence at protein level;
KW   Antiviral defense; Coiled coil; Endonuclease; Hydrolase; Nuclease; Repeat;
KW   RNA-binding.
FT   CHAIN           1..1182
FT                   /note="CRISPR-associated endoribonuclease Cas13a"
FT                   /id="PRO_0000442269"
FT   REGION          366..508
FT                   /note="HEPN-like fold 1"
FT                   /evidence="ECO:0000250|UniProtKB:C7NBY4"
FT   REGION          965..1120
FT                   /note="HEPN-like fold 2"
FT                   /evidence="ECO:0000250|UniProtKB:C7NBY4"
FT   COILED          132..279
FT                   /evidence="ECO:0000255"
FT   COILED          896..955
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   1182 AA;  143747 MW;  546FF11AA5516E81 CRC64;
     MYMKITKIDG VSHYKKQDKG ILKKKWKDLD ERKQREKIEA RYNKQIESKI YKEFFRLKNK
     KRIEKEEDQN IKSLYFFIKE LYLNEKNEEW ELKNINLEIL DDKERVIKGY KFKEDVYFFK
     EGYKEYYLRI LFNNLIEKVQ NENREKVRKN KEFLDLKEIF KKYKNRKIDL LLKSINNNKI
     NLEYKKENVN EEIYGINPTN DREMTFYELL KEIIEKKDEQ KSILEEKLDN FDITNFLENI
     EKIFNEETEI NIIKGKVLNE LREYIKEKEE NNSDNKLKQI YNLELKKYIE NNFSYKKQKS
     KSKNGKNDYL YLNFLKKIMF IEEVDEKKEI NKEKFKNKIN SNFKNLFVQH ILDYGKLLYY
     KENDEYIKNT GQLETKDLEY IKTKETLIRK MAVLVSFAAN SYYNLFGRVS GDILGTEVVK
     SSKTNVIKVG SHIFKEKMLN YFFDFEIFDA NKIVEILESI SYSIYNVRNG VGHFNKLILG
     KYKKKDINTN KRIEEDLNNN EEIKGYFIKK RGEIERKVKE KFLSNNLQYY YSKEKIENYF
     EVYEFEILKR KIPFAPNFKR IIKKGEDLFN NKNNKKYEYF KNFDKNSAEE KKEFLKTRNF
     LLKELYYNNF YKEFLSKKEE FEKIVLEVKE EKKSRGNINN KKSGVSFQSI DDYDTKINIS
     DYIASIHKKE MERVEKYNEE KQKDTAKYIR DFVEEIFLTG FINYLEKDKR LHFLKEEFSI
     LCNNNNNVVD FNININEEKI KEFLKENDSK TLNLYLFFNM IDSKRISEFR NELVKYKQFT
     KKRLDEEKEF LGIKIELYET LIEFVILTRE KLDTKKSEEI DAWLVDKLYV KDSNEYKEYE
     EILKLFVDEK ILSSKEAPYY ATDNKTPILL SNFEKTRKYG TQSFLSEIQS NYKYSKVEKE
     NIEDYNKKEE IEQKKKSNIE KLQDLKVELH KKWEQNKITE KEIEKYNNTT RKINEYNYLK
     NKEELQNVYL LHEMLSDLLA RNVAFFNKWE RDFKFIVIAI KQFLRENDKE KVNEFLNPPD
     NSKGKKVYFS VSKYKNTVEN IDGIHKNFMN LIFLNNKFMN RKIDKMNCAI WVYFRNYIAH
     FLHLHTKNEK ISLISQMNLL IKLFSYDKKV QNHILKSTKT LLEKYNIQIN FEISNDKNEV
     FKYKIKNRLY SKKGKMLGKN NKFEILENEF LENVKAMLEY SE