CYA1_MYCTU
ID CYA1_MYCTU Reviewed; 443 AA.
AC P9WQ35; L0TA06; O06142; O30820; P0A4Y0;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Adenylate cyclase;
DE EC=4.6.1.1 {ECO:0000269|PubMed:11431477, ECO:0000269|PubMed:11447108, ECO:0000269|PubMed:16403515, ECO:0000269|PubMed:25295175};
DE AltName: Full=ATP pyrophosphate-lyase;
DE AltName: Full=Adenylyl cyclase;
GN Name=cya; OrderedLocusNames=Rv1625c; ORFNames=MTCY01B2.17c;
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 [GENOMIC DNA], CHARACTERIZATION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-43 AND ARG-44.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11431477; DOI=10.1074/jbc.m104108200;
RA Reddy S.K., Kamireddi M., Dhanireddy K., Young L., Davis A., Reddy P.T.;
RT "Eukaryotic-like adenylyl cyclases in Mycobacterium tuberculosis H37Rv:
RT cloning and characterization.";
RL J. Biol. Chem. 276:35141-35149(2001).
RN [2]
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 [3]
RP CHARACTERIZATION, SUBUNIT, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR
RP LOCATION, TOPOLOGY, AND MUTAGENESIS OF ASP-256; LYS-296; ASP-300; ASP-365
RP AND ARG-376.
RX PubMed=11447108; DOI=10.1093/emboj/20.14.3667;
RA Guo Y.L., Seebacher T., Kurz U., Linder J.U., Schultz J.E.;
RT "Adenylyl cyclase Rv1625c of Mycobacterium tuberculosis: a progenitor of
RT mammalian adenylyl cyclases.";
RL EMBO J. 20:3667-3675(2001).
RN [4]
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 [5]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 240-443 OF INACTIVE CONFORMATION,
RP CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF LYS-296; PHE-363 AND
RP ASP-365.
RX PubMed=16403515; DOI=10.1016/j.jmb.2005.12.017;
RA Ketkar A.D., Shenoy A.R., Ramagopal U.A., Visweswariah S.S., Suguna K.;
RT "A structural basis for the role of nucleotide specifying residues in
RT regulating the oligomerization of the Rv1625c adenylyl cyclase from M.
RT tuberculosis.";
RL J. Mol. Biol. 356:904-916(2006).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 212-443 OF INACTIVE CONFORMATION
RP OF MUTANT ARG-363 IN COMPLEX WITH MAGNESIUM, CATALYTIC ACTIVITY, SUBUNIT,
RP AND MUTAGENESIS OF PHE-363.
RX PubMed=25295175; DOI=10.1107/s2052252514016741;
RA Barathy D., Mattoo R., Visweswariah S., Suguna K.;
RT "New structural forms of a mycobacterial adenylyl cyclase Rv1625c.";
RL IUCrJ 1:338-348(2014).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000269|PubMed:11431477, ECO:0000269|PubMed:11447108,
CC ECO:0000269|PubMed:16403515, ECO:0000269|PubMed:25295175};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11431477, ECO:0000269|PubMed:11447108};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11431477, ECO:0000269|PubMed:11447108};
CC Note=Binds 1 Mg(2+) ion per subunit (PubMed:25295175). Is also active
CC with manganese ions (in vitro) (PubMed:11431477, PubMed:11447108).
CC {ECO:0000269|PubMed:11431477, ECO:0000269|PubMed:11447108,
CC ECO:0000269|PubMed:25295175};
CC -!- SUBUNIT: Homodimer (PubMed:11447108, PubMed:16403515, PubMed:25295175).
CC Can also exist as monomer (PubMed:16403515, PubMed:25295175).
CC {ECO:0000269|PubMed:11447108, ECO:0000269|PubMed:16403515,
CC ECO:0000269|PubMed:25295175}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11431477,
CC ECO:0000269|PubMed:11447108}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- CAUTION: The structures described in PubMed:16403515 and
CC PubMed:25295175 corresponds to an inactive form, and displays a
CC conformation that alters the position and orientation of the residues
CC that are expected to bind the substrate and the catalytic metal ions.
CC {ECO:0000305|PubMed:16403515, ECO:0000305|PubMed:25295175}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF017731; AAB70274.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP44389.1; -; Genomic_DNA.
DR PIR; G70558; G70558.
DR RefSeq; NP_216141.2; NC_000962.3.
DR RefSeq; WP_003408035.1; NZ_NVQJ01000016.1.
DR PDB; 1YK9; X-ray; 2.70 A; A=240-443.
DR PDB; 4P2F; X-ray; 2.05 A; A=212-443.
DR PDB; 4P2M; X-ray; 2.70 A; A/B=212-443.
DR PDB; 4P2X; X-ray; 2.40 A; A/B=212-443.
DR PDBsum; 1YK9; -.
DR PDBsum; 4P2F; -.
DR PDBsum; 4P2M; -.
DR PDBsum; 4P2X; -.
DR AlphaFoldDB; P9WQ35; -.
DR SMR; P9WQ35; -.
DR STRING; 83332.Rv1625c; -.
DR PaxDb; P9WQ35; -.
DR DNASU; 888538; -.
DR GeneID; 45425593; -.
DR GeneID; 888538; -.
DR KEGG; mtu:Rv1625c; -.
DR TubercuList; Rv1625c; -.
DR eggNOG; COG2114; Bacteria.
DR OMA; IPRLCPL; -.
DR PhylomeDB; P9WQ35; -.
DR BRENDA; 4.6.1.1; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:MTBBASE.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:MTBBASE.
DR GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; cAMP biosynthesis; Cell membrane; Lyase;
KW Magnesium; Manganese; Membrane; Metal-binding; Nucleotide-binding;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..443
FT /note="Adenylate cyclase"
FT /id="PRO_0000195727"
FT TRANSMEM 47..69
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..93
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..167
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 180..202
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 203..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:11447108"
FT DOMAIN 251..378
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 256
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:11447108"
FT BINDING 300
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000305|PubMed:11447108"
FT MUTAGEN 43
FT /note="R->A,G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11431477"
FT MUTAGEN 43
FT /note="R->K: Almost no loss of activity."
FT /evidence="ECO:0000269|PubMed:11431477"
FT MUTAGEN 44
FT /note="R->A,G: Loss of activity."
FT /evidence="ECO:0000269|PubMed:11431477"
FT MUTAGEN 44
FT /note="R->K: Almost no loss of activity."
FT /evidence="ECO:0000269|PubMed:11431477"
FT MUTAGEN 256
FT /note="D->A: Almost complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:11447108"
FT MUTAGEN 296
FT /note="K->A: Decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:11447108"
FT MUTAGEN 296
FT /note="K->E: Strongly decreased enzyme activity. Abolishes
FT homodimerization and strongly decreases enzyme activity;
FT when associated with R-363 and C-365."
FT /evidence="ECO:0000269|PubMed:16403515,
FT ECO:0000269|PubMed:25295175"
FT MUTAGEN 300
FT /note="D->A: Almost complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:11447108"
FT MUTAGEN 363
FT /note="F->R: Promotes formation of a domain-swapped dimer.
FT Abolishes homodimerization and strongly decreases enzyme
FT activity; when associated with E-296 and C-365."
FT /evidence="ECO:0000269|PubMed:16403515,
FT ECO:0000269|PubMed:25295175"
FT MUTAGEN 365
FT /note="D->A: Almost complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:11447108"
FT MUTAGEN 365
FT /note="D->C: Abolishes homodimerization and strongly
FT decreases enzyme activitywhen associated with E-296 and R-
FT 363."
FT /evidence="ECO:0000269|PubMed:16403515"
FT MUTAGEN 376
FT /note="R->A: Almost complete loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:11447108"
FT STRAND 240..257
FT /evidence="ECO:0007829|PDB:4P2F"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:4P2F"
FT HELIX 269..290
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 302..310
FT /evidence="ECO:0007829|PDB:4P2F"
FT HELIX 315..330
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:1YK9"
FT STRAND 343..368
FT /evidence="ECO:0007829|PDB:4P2F"
FT HELIX 369..379
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 385..389
FT /evidence="ECO:0007829|PDB:4P2F"
FT HELIX 390..396
FT /evidence="ECO:0007829|PDB:4P2F"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 400..410
FT /evidence="ECO:0007829|PDB:4P2F"
FT TURN 411..413
FT /evidence="ECO:0007829|PDB:4P2F"
FT STRAND 414..424
FT /evidence="ECO:0007829|PDB:4P2F"
SQ SEQUENCE 443 AA; 47370 MW; 64B13168B4B792E2 CRC64;
MAARKCGAPP IAADGSTRRP DCVTAVRTQA RAPTQHYAES VARRQRVLTI TAWLAVVVTG
SFALMQLATG AGGWYIALIN VFTAVTFAIV PLLHRFGGLV APLTFIGTAY VAIFAIGWDV
GTDAGAQFFF LVAAALVVLL VGIEHTALAV GLAAVAAGLV IALEFLVPPD TGLQPPWAMS
VSFVLTTVSA CGVAVATVWF ALRDTARAEA VMEAEHDRSE ALLANMLPAS IAERLKEPER
NIIADKYDEA SVLFADIVGF TERASSTAPA DLVRFLDRLY SAFDELVDQH GLEKIKVSGD
SYMVVSGVPR PRPDHTQALA DFALDMTNVA AQLKDPRGNP VPLRVGLATG PVVAGVVGSR
RFFYDVWGDA VNVASRMEST DSVGQIQVPD EVYERLKDDF VLRERGHINV KGKGVMRTWY
LIGRKVAADP GEVRGAEPRT AGV
