CAP4_ACIS2
ID CAP4_ACIS2 Reviewed; 462 AA.
AC C0VHC9;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 1.
DT 03-AUG-2022, entry version 31.
DE RecName: Full=CD-NTase-associated protein 4 {ECO:0000303|PubMed:32544385};
DE Short=Cap4 {ECO:0000303|PubMed:32544385};
DE EC=3.1.-.- {ECO:0000269|PubMed:32544385};
DE AltName: Full=Endodeoxyribonuclease Cap4 {ECO:0000305};
GN Name=cap4 {ECO:0000303|PubMed:32544385};
GN ORFNames=HMPREF0023_0548 {ECO:0000312|EMBL:EEH69891.1};
OS Acinetobacter sp. (strain ATCC 27244 / 9458).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Moraxellales; Moraxellaceae;
OC Acinetobacter.
OX NCBI_TaxID=525244;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27244 / 9458;
RA Qin X., Bachman B., Battles P., Bell A., Bess C., Bickham C., Chaboub L.,
RA Chen D., Coyle M., Deiros D.R., Dinh H., Forbes L., Fowler G.,
RA Francisco L., Fu Q., Gubbala S., Hale W., Han Y., Hemphill L.,
RA Highlander S.K., Hirani K., Hogues M., Jackson L., Jakkamsetti A.,
RA Javaid M., Jiang H., Korchina V., Kovar C., Lara F., Lee S., Mata R.,
RA Mathew T., Moen C., Morales K., Munidasa M., Nazareth L., Ngo R.,
RA Nguyen L., Okwuonu G., Ongeri F., Patil S., Petrosino J., Pham C., Pham P.,
RA Pu L.-L., Puazo M., Raj R., Reid J., Rouhana J., Saada N., Shang Y.,
RA Simmons D., Thornton R., Warren J., Weissenberger G., Zhang J., Zhang L.,
RA Zhou C., Zhu D., Muzny D., Worley K., Gibbs R.;
RL Submitted (OCT-2008) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP CLASSIFICATION AND NOMENCLATURE.
RX PubMed=32839535; DOI=10.1038/s41564-020-0777-y;
RA Millman A., Melamed S., Amitai G., Sorek R.;
RT "Diversity and classification of cyclic-oligonucleotide-based anti-phage
RT signalling systems.";
RL Nat. Microbiol. 5:1608-1615(2020).
RN [3] {ECO:0007744|PDB:6VM6, ECO:0007744|PDB:6WAM, ECO:0007744|PDB:6WAN}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 2-462 ALONE AND IN COMPLEX WITH
RP CYCLIC NUCLEOTIDES, FUNCTION AS AN ENDONUCLEASE, COFACTOR, ACTIVITY
RP REGULATION, SUBUNIT, NUCLEOTIDE-BINDING, DNA-BINDING, OPERON STRUCTURE,
RP DOMAIN, AND MUTAGENESIS OF 1-MET--VAL-18; LYS-69; LYS-299; ARG-301;
RP HIS-324; ASN-325; LYS-425 AND TRP-449.
RC STRAIN=ATCC 27244 / 9458;
RX PubMed=32544385; DOI=10.1016/j.cell.2020.05.019;
RA Lowey B., Whiteley A.T., Keszei A.F.A., Morehouse B.R., Antine S.P.,
RA Cabrera V.J., Kashin D., Schwede F., Mekalanos J.J., Shao S., Lee A.S.Y.,
RA Kranzusch P.J.;
RT "CBASS immunity uses CARF-related effectors to sense 3'-5' and 2'-5'-linked
RT cyclic oligonucleotide signals and protect bacteria from phage infection.";
RL Cell 182:38-49(2020).
CC -!- FUNCTION: CBASS (cyclic oligonucleotide-based antiphage signaling
CC system) provides immunity against bacteriophage. The CD-NTase protein
CC synthesizes cyclic nucleotides in response to infection; these serve as
CC specific second messenger signals. The signals activate a diverse range
CC of effectors, leading to bacterial cell death and thus abortive phage
CC infection. A type II-C(AAAA) CBASS system (PubMed:32839535).
CC {ECO:0000303|PubMed:32839535, ECO:0000305|PubMed:32544385}.
CC -!- FUNCTION: Binds cyclic nucleotide second messengers (synthesized by
CC CdnD, the cognate CD-NTase in the CBASS operon). Ligand binding
CC activates it to endonucleolytically degrade dsDNA to approximately 6 bp
CC length fragments, with a preference for 5'-C or 5'-G cleavage site. The
CC minor product of CdnD is the activating nucleotide; also binds the
CC major product (2',3',3'-cyclic AMP-AMP-AMP) but is not activated by it.
CC Only binds DNA in the presence of ligand. Is not activated by c-di-AMP,
CC c-di-GMP, 3'3'-cyclic GMP-AMP (3'3'-cGAMP) or 3',3',3'-cyclic AMP-AMP-
CC GMP. {ECO:0000269|PubMed:32544385}.
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:32544385};
CC -!- ACTIVITY REGULATION: DNase activity is activated upon ligand binding.
CC Inhibited by EDTA. {ECO:0000269|PubMed:32544385}.
CC -!- SUBUNIT: A monomer in the absence of ligand, in its presence it forms
CC oligomers. {ECO:0000269|PubMed:32544385}.
CC -!- INDUCTION: Part of the CBASS operon consisting of cdnD-cap2-cap3-cap4.
CC {ECO:0000305|PubMed:32544385}.
CC -!- DOMAIN: The cyclic nucleotide ligand binds in the C-terminal SAVED
CC domain. DNA binding requires the extreme N-terminus.
CC {ECO:0000269|PubMed:32544385}.
CC -!- SIMILARITY: Belongs to the Cap4 nuclease family.
CC {ECO:0000305|PubMed:32544385}.
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DR EMBL; ABYN01000046; EEH69891.1; -; Genomic_DNA.
DR RefSeq; WP_008942236.1; NZ_GG665962.1.
DR PDB; 6VM6; X-ray; 2.10 A; A/B/C/D/E/F=2-462.
DR PDB; 6WAM; X-ray; 2.60 A; A/B/C/D/E/F=2-462.
DR PDB; 6WAN; X-ray; 2.40 A; A/B/C/D/E/F=2-462.
DR PDBsum; 6VM6; -.
DR PDBsum; 6WAM; -.
DR PDBsum; 6WAN; -.
DR AlphaFoldDB; C0VHC9; -.
DR SMR; C0VHC9; -.
DR STRING; 525244.HMPREF0023_0548; -.
DR EnsemblBacteria; EEH69891; EEH69891; HMPREF0023_0548.
DR eggNOG; ENOG50330SX; Bacteria.
DR HOGENOM; CLU_044448_0_0_6; -.
DR Proteomes; UP000012347; Unassembled WGS sequence.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR InterPro; IPR040836; SAVED.
DR Pfam; PF18145; SAVED; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; DNA-binding; Endonuclease; Hydrolase;
KW Nuclease; Nucleotide-binding.
FT CHAIN 1..462
FT /note="CD-NTase-associated protein 4"
FT /id="PRO_0000451850"
FT REGION 1..226
FT /note="N-terminal endonuclease domain"
FT /evidence="ECO:0000305|PubMed:32544385"
FT REGION 235..462
FT /note="C-terminal SAVED domain"
FT /evidence="ECO:0000305|PubMed:32544385"
FT BINDING 299..301
FT /ligand="2',3',3'-c-tri-AMP"
FT /ligand_id="ChEBI:CHEBI:156512"
FT /evidence="ECO:0000269|PubMed:32544385"
FT BINDING 449
FT /ligand="2',3',3'-c-tri-AMP"
FT /ligand_id="ChEBI:CHEBI:156512"
FT /evidence="ECO:0000269|PubMed:32544385"
FT BINDING 454
FT /ligand="2',3',3'-c-tri-AMP"
FT /ligand_id="ChEBI:CHEBI:156512"
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 1..18
FT /note="Missing: Required for nuclease activity, still binds
FT ligand."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 69
FT /note="K->A: Loss of nuclease activity, still binds
FT ligand."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 299
FT /note="K->A: Greatly reduced DNase activity."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 301
FT /note="R->A: Greatly reduced DNase activity."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 324
FT /note="H->A: Greatly reduced DNase activity."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 325
FT /note="N->A: Greatly reduced DNase activity."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 425
FT /note="K->A: Greatly reduced DNase activity."
FT /evidence="ECO:0000269|PubMed:32544385"
FT MUTAGEN 449
FT /note="W->A: Greatly reduced DNase activity."
FT /evidence="ECO:0000269|PubMed:32544385"
FT HELIX 21..35
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 40..44
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 62..68
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 75..91
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:6VM6"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 111..120
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 134..147
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 152..161
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 162..166
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 172..184
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 190..204
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 205..209
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 214..225
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 229..233
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 268..288
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 293..297
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 302..311
FT /evidence="ECO:0007829|PDB:6VM6"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 319..324
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 343..348
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 354..361
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 367..372
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 375..378
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 382..386
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 394..415
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 418..426
FT /evidence="ECO:0007829|PDB:6VM6"
FT HELIX 428..436
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 443..450
FT /evidence="ECO:0007829|PDB:6VM6"
FT STRAND 453..460
FT /evidence="ECO:0007829|PDB:6VM6"
SQ SEQUENCE 462 AA; 52196 MW; 5B1D76CB9E476BA9 CRC64;
MSASLLEKQS TGGAIARVGF GYQDAFVLRS LPLWLSQSAF SHIVSEALSD IEVCYFSSEK
SLHVMYEAKN HSLTATEFWD EIRRFKSLFD THPKNFIWFN LVCPSYNTAI SPLISKIDRL
RGVGSSYDDD SSVSVNGRSE YLDWCVGKKI DFSLAEFALD YVGFITFNSE NSESIFLSEI
QDTINIELLR SQVKQLKDQF KNLISRSSFG PIYRKDFENF ICHALEEDRS QWLLDPIKIN
LSASSSQYQD LNLDISDFNG PDRAQKTSSD WNSLIKKAVS IGDFIHNSGD RRTLLIDGKQ
RMSTACMLGY VFSATRNFLL EIEHNGLIYR TDDHKQKEGQ FFTKIEAVEP QGETEAIVAI
GFPTAIGKDI DSTINEVKSL PRLNLESSHA IDNMETLNLA VREAKSALVS FKSENKLSKL
HLFIKAPSVF AMVLGHRLNG ICDIQLYDWV DGQYIPTAEL NL
