ID   CNGA2_HUMAN             Reviewed;         664 AA.
AC   Q16280; A0AVD0;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   12-DEC-2006, sequence version 2.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=Cyclic nucleotide-gated olfactory channel;
DE   AltName: Full=Cyclic nucleotide-gated cation channel 2;
DE   AltName: Full=Cyclic nucleotide-gated channel alpha-2;
DE            Short=CNG channel alpha-2;
DE            Short=CNG-2;
DE            Short=CNG2;
GN   Name=CNGA2; Synonyms=CNCA, CNCA1, CNCG2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 292-552.
RX   PubMed=7532814; DOI=10.1016/0028-3908(94)90027-2;
RA   Distler M., Biel M., Flockerzi V., Hofmann F.;
RT   "Expression of cyclic nucleotide-gated cation channels in non-sensory
RT   tissues and cells.";
RL   Neuropharmacology 33:1275-1282(1994).
RN   [3]
RP   VARIANTS [LARGE SCALE ANALYSIS] HIS-97 AND GLN-399.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Odorant signal transduction is probably mediated by a G-
CC       protein coupled cascade using cAMP as second messenger. The olfactory
CC       channel can be shown to be activated by cyclic nucleotides which leads
CC       to a depolarization of olfactory sensory neurons.
CC   -!- SUBUNIT: Heterotetramer composed of two subunits of CNGA2, one of CNGA4
CC       and one of CNGB1b. The complex forms the cyclic nucleotide-gated (CNG)
CC       channel of olfactory sensory neurons (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- DOMAIN: The C-terminal coiled-coil domain mediates trimerization of
CC       CNGA subunits. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the cyclic nucleotide-gated cation channel
CC       (TC 1.A.1.5) family. CNGA2 subfamily. {ECO:0000305}.
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DR   EMBL; BC126302; AAI26303.1; -; mRNA.
DR   EMBL; BC126304; AAI26305.1; -; mRNA.
DR   EMBL; S76067; AAD14207.1; -; Genomic_DNA.
DR   CCDS; CCDS14701.1; -.
DR   PIR; I78559; I78559.
DR   RefSeq; NP_005131.1; NM_005140.1.
DR   AlphaFoldDB; Q16280; -.
DR   SMR; Q16280; -.
DR   STRING; 9606.ENSP00000328478; -.
DR   DrugCentral; Q16280; -.
DR   GuidetoPHARMACOLOGY; 395; -.
DR   GlyCosmos; Q16280; 1 site, No reported glycans.
DR   GlyGen; Q16280; 2 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q16280; -.
DR   PhosphoSitePlus; Q16280; -.
DR   BioMuta; CNGA2; -.
DR   DMDM; 119370323; -.
DR   MassIVE; Q16280; -.
DR   PaxDb; 9606-ENSP00000328478; -.
DR   PeptideAtlas; Q16280; -.
DR   ProteomicsDB; 60847; -.
DR   Antibodypedia; 17043; 299 antibodies from 31 providers.
DR   DNASU; 1260; -.
DR   Ensembl; ENST00000329903.5; ENSP00000328478.4; ENSG00000183862.6.
DR   GeneID; 1260; -.
DR   KEGG; hsa:1260; -.
DR   MANE-Select; ENST00000329903.5; ENSP00000328478.4; NM_005140.3; NP_005131.1.
DR   UCSC; uc065bqd.1; human.
DR   AGR; HGNC:2149; -.
DR   CTD; 1260; -.
DR   DisGeNET; 1260; -.
DR   GeneCards; CNGA2; -.
DR   HGNC; HGNC:2149; CNGA2.
DR   HPA; ENSG00000183862; Not detected.
DR   MalaCards; CNGA2; -.
DR   MIM; 300338; gene.
DR   neXtProt; NX_Q16280; -.
DR   OpenTargets; ENSG00000183862; -.
DR   Orphanet; 88620; Isolated congenital anosmia.
DR   PharmGKB; PA26659; -.
DR   VEuPathDB; HostDB:ENSG00000183862; -.
DR   eggNOG; KOG0500; Eukaryota.
DR   GeneTree; ENSGT00940000155374; -.
DR   HOGENOM; CLU_005746_12_0_1; -.
DR   InParanoid; Q16280; -.
DR   OMA; DWYYHWL; -.
DR   OrthoDB; 74296at2759; -.
DR   PhylomeDB; Q16280; -.
DR   TreeFam; TF319048; -.
DR   PathwayCommons; Q16280; -.
DR   Reactome; R-HSA-381753; Olfactory Signaling Pathway.
DR   Reactome; R-HSA-5620916; VxPx cargo-targeting to cilium.
DR   SignaLink; Q16280; -.
DR   BioGRID-ORCS; 1260; 11 hits in 762 CRISPR screens.
DR   GeneWiki; Cyclic_nucleotide-gated_channel_alpha_2; -.
DR   GenomeRNAi; 1260; -.
DR   Pharos; Q16280; Tchem.
DR   PRO; PR:Q16280; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q16280; Protein.
DR   Bgee; ENSG00000183862; Expressed in testis and 1 other cell type or tissue.
DR   GO; GO:0060170; C:ciliary membrane; ISS:ARUK-UCL.
DR   GO; GO:0030660; C:Golgi-associated vesicle membrane; TAS:Reactome.
DR   GO; GO:0017071; C:intracellular cyclic nucleotide activated cation channel complex; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030553; F:cGMP binding; IBA:GO_Central.
DR   GO; GO:0005222; F:intracellular cAMP-activated cation channel activity; IBA:GO_Central.
DR   GO; GO:0005223; F:intracellular cGMP-activated cation channel activity; IBA:GO_Central.
DR   GO; GO:0044877; F:protein-containing complex binding; IBA:GO_Central.
DR   GO; GO:0098655; P:monoatomic cation transmembrane transport; IBA:GO_Central.
DR   GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR   GO; GO:0007608; P:sensory perception of smell; IEA:UniProtKB-KW.
DR   CDD; cd00038; CAP_ED; 1.
DR   Gene3D; 1.10.287.70; -; 1.
DR   Gene3D; 1.20.5.300; -; 1.
DR   Gene3D; 1.10.287.630; Helix hairpin bin; 1.
DR   Gene3D; 2.60.120.10; Jelly Rolls; 1.
DR   InterPro; IPR032406; CLZ_dom.
DR   InterPro; IPR018488; cNMP-bd_CS.
DR   InterPro; IPR000595; cNMP-bd_dom.
DR   InterPro; IPR018490; cNMP-bd_dom_sf.
DR   InterPro; IPR005821; Ion_trans_dom.
DR   InterPro; IPR014710; RmlC-like_jellyroll.
DR   PANTHER; PTHR45638; CYCLIC NUCLEOTIDE-GATED CATION CHANNEL SUBUNIT A; 1.
DR   PANTHER; PTHR45638:SF3; CYCLIC NUCLEOTIDE-GATED OLFACTORY CHANNEL; 1.
DR   Pfam; PF16526; CLZ; 1.
DR   Pfam; PF00027; cNMP_binding; 1.
DR   Pfam; PF00520; Ion_trans; 1.
DR   SMART; SM00100; cNMP; 1.
DR   SUPFAM; SSF51206; cAMP-binding domain-like; 1.
DR   SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR   PROSITE; PS00888; CNMP_BINDING_1; 1.
DR   PROSITE; PS00889; CNMP_BINDING_2; 1.
DR   PROSITE; PS50042; CNMP_BINDING_3; 1.
PE   2: Evidence at transcript level;
KW   Calmodulin-binding; cAMP; cAMP-binding; Coiled coil; Glycoprotein;
KW   Ion channel; Ion transport; Ligand-gated ion channel; Membrane;
KW   Nucleotide-binding; Olfaction; Reference proteome; Sensory transduction;
KW   Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..664
FT                   /note="Cyclic nucleotide-gated olfactory channel"
FT                   /id="PRO_0000219312"
FT   TOPO_DOM        1..138
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        139..159
FT                   /note="Helical; Name=H1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        160..171
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        172..192
FT                   /note="Helical; Name=H2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        193..224
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        225..245
FT                   /note="Helical; Name=H3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        246..274
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        275..295
FT                   /note="Helical; Name=H4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        296..350
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        351..371
FT                   /note="Helical; Name=H5"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        372..453
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        454..474
FT                   /note="Helical; Name=H6"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        475..662
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..49
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          641..664
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          597..640
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        1..17
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        23..49
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         454..577
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /evidence="ECO:0000250"
FT   BINDING         521
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /evidence="ECO:0000250"
FT   BINDING         536
FT                   /ligand="3',5'-cyclic AMP"
FT                   /ligand_id="ChEBI:CHEBI:58165"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        379
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VARIANT         97
FT                   /note="R -> H (in a breast cancer sample; somatic mutation;
FT                   dbSNP:rs561786347)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036603"
FT   VARIANT         118
FT                   /note="D -> H (in dbSNP:rs6627455)"
FT                   /id="VAR_048748"
FT   VARIANT         139
FT                   /note="W -> L (in dbSNP:rs35350051)"
FT                   /id="VAR_061107"
FT   VARIANT         399
FT                   /note="R -> Q (in a breast cancer sample; somatic mutation;
FT                   dbSNP:rs150539917)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036604"
FT   VARIANT         663
FT                   /note="E -> K (in dbSNP:rs714147)"
FT                   /id="VAR_048749"
SQ   SEQUENCE   664 AA;  76048 MW;  E8FB934468429CE5 CRC64;
     MTEKTNGVKS SPANNHNHHA PPAIKANGKD DHRTSSRPHS AADDDTSSEL QRLADVDAPQ
     QGRSGFRRIV RLVGIIREWA NKNFREEEPR PDSFLERFRG PELQTVTTQE GDGKGDKDGE
     DKGTKKKFEL FVLDPAGDWY YCWLFVIAMP VLYNWCLLVA RACFSDLQKG YYLVWLVLDY
     VSDVVYIADL FIRLRTGFLE QGLLVKDTKK LRDNYIHTLQ FKLDVASIIP TDLIYFAVDI
     HSPEVRFNRL LHFARMFEFF DRTETRTNYP NIFRISNLVL YILVIIHWNA CIYYAISKSI
     GFGVDTWVYP NITDPEYGYL AREYIYCLYW STLTLTTIGE TPPPVKDEEY LFVIFDFLIG
     VLIFATIVGN VGSMISNMNA TRAEFQAKID AVKHYMQFRK VSKGMEAKVI RWFDYLWTNK
     KTVDEREILK NLPAKLRAEI AINVHLSTLK KVRIFHDCEA GLLVELVLKL RPQVFSPGDY
     ICRKGDIGKE MYIIKEGKLA VVADDGVTQY ALLSAGSCFG EISILNIKGS KMGNRRTANI
     RSLGYSDLFC LSKDDLMEAV TEYPDAKKVL EERGREILMK EGLLDENEVA TSMEVDVQEK
     LGQLETNMET LYTRFGRLLA EYTGAQQKLK QRITVLETKM KQNNEDDYLS DGMNSPELAA
     ADEP
//