PYCC_PSEAI
ID PYCC_PSEAI Reviewed; 514 AA.
AC P0DV40;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 1.
DT 03-AUG-2022, entry version 2.
DE RecName: Full=Uridylate cyclase {ECO:0000303|PubMed:34644530};
DE EC=4.6.1.- {ECO:0000269|PubMed:34644530};
DE AltName: Full=Adenylyl cyclase-like protein {ECO:0000303|PubMed:32454240};
DE Short=PaAClp {ECO:0000303|PubMed:32454240};
DE AltName: Full=Cyclic UMP synthase;
DE Short=cUMP synthase {ECO:0000303|PubMed:34644530};
DE AltName: Full=PaPycC {ECO:0000303|PubMed:34644530};
GN Name=pycC {ECO:0000303|PubMed:34644530}; ORFNames=Ga0130373_10433;
OS Pseudomonas aeruginosa.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=287;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=RW93;
RA Weiser R.;
RL Submitted (MAR-2015) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND CLASSIFICATION.
RC STRAIN=RW93;
RX PubMed=34644530; DOI=10.1016/j.cell.2021.09.031;
RA Tal N., Morehouse B.R., Millman A., Stokar-Avihail A., Avraham C.,
RA Fedorenko T., Yirmiya E., Herbst E., Brandis A., Mehlman T.,
RA Oppenheimer-Shaanan Y., Keszei A.F.A., Shao S., Amitai G., Kranzusch P.J.,
RA Sorek R.;
RT "Cyclic CMP and cyclic UMP mediate bacterial immunity against phages.";
RL Cell 0:0-0(2021).
RN [3] {ECO:0007744|PDB:6YII}
RP X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) IN COMPLEX WITH NTP; MANGANESE AND
RP CALCIUM, COFACTOR, SUBUNIT, DOMAIN, AND NUCLEOTIDE-BINDING.
RX PubMed=32454240; DOI=10.1016/j.jsb.2020.107534;
RA Linder J., Hupfeld E., Weyand M., Steegborn C., Moniot S.;
RT "Crystal structure of a class III adenylyl cyclase-like ATP-binding protein
RT from Pseudomonas aeruginosa.";
RL J. Struct. Biol. 211:107534-107534(2020).
CC -!- FUNCTION: Pycsar (pyrimidine cyclase system for antiphage resistance)
CC provides immunity against bacteriophage. The pyrimidine cyclase (PycC)
CC synthesizes cyclic nucleotides in response to infection; these serve as
CC specific second messenger signals. The signals activate the adjacent
CC effector, leading to bacterial cell death and abortive phage infection.
CC A clade A Pycsar system. {ECO:0000305|PubMed:34644530}.
CC -!- FUNCTION: The pyrimidine cyclase gene of a two-gene Pycsar system,
CC generates cyclic UMP (cUMP) from UTP, has little to no activity on ATP,
CC CTP or GTP (PubMed:34644530). Expression of this and adjacent effector
CC PaPycTIR (AC P0DV41) probably confers resistance to bacteriophage. The
CC genes are probably only expressed in response to bacteriophage
CC infection (Probable). Does not have adenylyl or guanylyl cyclase
CC activity (PubMed:32454240). {ECO:0000269|PubMed:32454240,
CC ECO:0000269|PubMed:34644530, ECO:0000305|PubMed:34644530}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=UTP = 3',5'-cyclic UMP + diphosphate; Xref=Rhea:RHEA:69603,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:46398, ChEBI:CHEBI:184387;
CC Evidence={ECO:0000269|PubMed:34644530};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:32454240};
CC Note=When crystallized with (non-physiological) ATP it binds both
CC Ca(2+) and Mn(2+) (PubMed:32454240). The enzyme assay showing cUMP
CC synthase activity has Mn(2+) and Mg(2+) (PubMed:34644530).
CC {ECO:0000269|PubMed:32454240, ECO:0000269|PubMed:34644530,
CC ECO:0007744|PDB:6YII};
CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:32454240}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DOMAIN: The 2 guanylate cyclase domains fold into a pseudo-dimeric
CC structure; the second domain binds metal while the first provides most
CC of the nucleotide-binding residues. {ECO:0000269|PubMed:32454240}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. Pyrimidine cyclase subfamily. {ECO:0000305|PubMed:34644530}.
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DR EMBL; CUYG01000043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 6YII; X-ray; 1.44 A; A=1-514.
DR PDBsum; 6YII; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; 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 Gene3D; 3.30.70.1230; -; 2.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR SUPFAM; SSF55073; SSF55073; 2.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Calcium; Cytoplasm; Lyase; Manganese;
KW Metal-binding; Nucleotide-binding; Repeat.
FT CHAIN 1..514
FT /note="Uridylate cyclase"
FT /id="PRO_0000455225"
FT DOMAIN 49..190
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 286..428
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 495..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 500..514
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 52
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0000305|PubMed:34644530, ECO:0007744|PDB:6YII"
FT BINDING 105
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0000305|PubMed:34644530, ECO:0007744|PDB:6YII"
FT BINDING 178
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
FT BINDING 184..188
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
FT BINDING 291..296
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
FT BINDING 291
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
FT BINDING 291
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
FT BINDING 339
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:32454240,
FT ECO:0007744|PDB:6YII"
SQ SEQUENCE 514 AA; 56580 MW; 8F4E16194466EBE5 CRC64;
MSKSWNHDRA AKHIDQKIAD VEEITIKDYV RDMSLESIPT STAYRVDGVH MYADIMNLED
MLNITAVEGT ECHKRTLRFL DQHYRAVKRI LNKVDARRVD FHSQRLHSLF TKPYNTESGA
ETKRVQRAVA TAQLIIDVLA ETGDDDEQIP AAKVRIGIDT GLALAVNNGR SGYREPLFLG
DPANHAAKLA SNNKARGIYL TNNARKAIGL AESDEPEKSA LTAIEIKACQ DAAKLDVTSD
EIVEEWREDL KKNPIGGYQF SRQTPPLRDM DIYSLTPANS KRQEMVSLYA DIDGFTAYVA
DHINEKTDDV VRTLHVIRSE LERVVTSDFE GRRVRFIGDC VQALSCDGTA HTTDEEKSVS
EATRLAGALR SSFNLAIERL NAEGIETGDL GLAIGFDLGP IAVTRLGAKG NRVRCAIGRS
VIESEKRQCA CSGVETAIGQ VAYDAASKAV QNLFGKSRKT SHLDYNEATE ALADDGDASA
KQARSEAYAG SAAIIRADER QVQPHSRQKV DGSR
