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Q16281

- CNGA3_HUMAN

UniProt

Q16281 - CNGA3_HUMAN

Protein

Cyclic nucleotide-gated cation channel alpha-3

Gene

CNGA3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 138 (01 Oct 2014)
      Sequence version 2 (04 May 2001)
      Previous versions | rss
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    Functioni

    Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors. Induced a flickering channel gating, weakened the outward rectification in the presence of extracellular calcium, increased sensitivity for L-cis diltiazem and enhanced the cAMP efficacy of the channel when coexpressed with CNGB3 By similarity. Essential for the generation of light-evoked electrical responses in the red-, green- and blue sensitive cones.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei549 – 5491cGMPSequence Analysis
    Binding sitei564 – 5641cGMPSequence Analysis

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi482 – 605124cGMPAdd
    BLAST

    GO - Molecular functioni

    1. cGMP binding Source: UniProt
    2. intracellular cAMP activated cation channel activity Source: RefGenome
    3. intracellular cGMP activated cation channel activity Source: UniProt
    4. ligand-gated ion channel activity Source: ProtInc
    5. voltage-gated potassium channel activity Source: RefGenome

    GO - Biological processi

    1. cation transport Source: UniProt
    2. phototransduction, visible light Source: RefGenome
    3. potassium ion transmembrane transport Source: RefGenome
    4. regulation of membrane potential Source: RefGenome
    5. response to cAMP Source: Ensembl
    6. response to corticosteroid Source: Ensembl
    7. response to magnesium ion Source: Ensembl
    8. retinal cone cell development Source: Ensembl
    9. signal transduction Source: ProtInc
    10. transport Source: ProtInc
    11. visual perception Source: ProtInc

    Keywords - Molecular functioni

    Ion channel, Ligand-gated ion channel

    Keywords - Biological processi

    Ion transport, Sensory transduction, Transport, Vision

    Keywords - Ligandi

    cGMP, cGMP-binding, Nucleotide-binding

    Protein family/group databases

    TCDBi1.A.1.5.12. the voltage-gated ion channel (vic) superfamily.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclic nucleotide-gated cation channel alpha-3
    Alternative name(s):
    Cone photoreceptor cGMP-gated channel subunit alpha
    Cyclic nucleotide-gated channel alpha-3
    Short name:
    CNG channel alpha-3
    Short name:
    CNG-3
    Short name:
    CNG3
    Gene namesi
    Name:CNGA3
    Synonyms:CNCG3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:2150. CNGA3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. dendrite Source: Ensembl
    3. integral component of plasma membrane Source: RefGenome
    4. perikaryon Source: Ensembl
    5. photoreceptor outer segment membrane Source: Ensembl
    6. transmembrane transporter complex Source: UniProt

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Achromatopsia 2 (ACHM2) [MIM:216900]: An ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus.5 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti162 – 1621D → V in ACHM2. 1 Publication
    VAR_047566
    Natural varianti163 – 1631P → L in ACHM2. 2 Publications
    VAR_010903
    Natural varianti181 – 1811Y → C in ACHM2. 1 Publication
    VAR_047567
    Natural varianti182 – 1821N → Y in ACHM2. 1 Publication
    VAR_047568
    Natural varianti186 – 1861L → F in ACHM2. 1 Publication
    VAR_047569
    Natural varianti191 – 1911C → Y in ACHM2. 1 Publication
    VAR_047570
    Natural varianti194 – 1941E → K in ACHM2. 1 Publication
    VAR_047571
    Natural varianti223 – 2231R → W in ACHM2. 3 Publications
    VAR_047572
    Natural varianti224 – 2241T → R in ACHM2. 1 Publication
    VAR_047573
    Natural varianti228 – 2281E → K in ACHM2; the dose-response relationship for cGMP-activation is not significantly different from that of wild-type CNGA3; the dose-response relationship of the mutant CNGA3 + CNGB3 is similar to that of the wild-type protein; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 1 Publication
    Corresponds to variant rs147415641 [ dbSNP | Ensembl ].
    VAR_047574
    Natural varianti249 – 2491F → S in ACHM2. 1 Publication
    VAR_047575
    Natural varianti260 – 2601D → N in ACHM2. 1 Publication
    VAR_047576
    Natural varianti263 – 2631Y → D in ACHM2. 1 Publication
    VAR_047577
    Natural varianti267 – 2671G → D in ACHM2. 1 Publication
    VAR_047578
    Natural varianti277 – 2771R → C in ACHM2. 3 Publications
    VAR_047579
    Natural varianti277 – 2771R → H in ACHM2; does not form functional homomeric or heteromeric channels; cell surface expression levels is significantly reduced. 1 Publication
    VAR_047580
    Natural varianti283 – 2831R → Q in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is not significantly different from that of wild-type CNGA3; the dose-response relationship of the mutant CNGA3 + CNGB3 is similar to that of the wild-type protein; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 3 Publications
    VAR_010904
    Natural varianti283 – 2831R → W in ACHM2. 2 Publications
    VAR_010905
    Natural varianti291 – 2911T → R in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the K(1/2) value is shifted toward a higher cGMP concentration by a factor of 1.8; no positive influence of the CNGB3 subunit in the cGMP sensitivity is observed; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 2 Publications
    VAR_010906
    Natural varianti312 – 3121Missing in ACHM2. 1 Publication
    VAR_047581
    Natural varianti341 – 3411S → P in ACHM2. 2 Publications
    VAR_047582
    Natural varianti369 – 3691T → S in ACHM2. 1 Publication
    VAR_047583
    Natural varianti372 – 3721P → S in ACHM2. 1 Publication
    VAR_047584
    Natural varianti380 – 3801F → S in ACHM2. 1 Publication
    VAR_047585
    Natural varianti401 – 4011S → P in ACHM2. 1 Publication
    VAR_047586
    Natural varianti406 – 4061M → T in ACHM2. 1 Publication
    VAR_047587
    Natural varianti410 – 4101R → W in ACHM2. 3 Publications
    VAR_010910
    Natural varianti427 – 4271R → C in ACHM2. 2 Publications
    Corresponds to variant rs141386891 [ dbSNP | Ensembl ].
    VAR_047588
    Natural varianti436 – 4361R → W in ACHM2. 3 Publications
    VAR_047589
    Natural varianti439 – 4391R → W in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; the dose-response relationship of the mutant CNGA3 + CNGB3 is similar to that of the wild-type protein; coexpression of the CNGB3 subunit compensate completely for the slightly higher apparent cGMP sensitivity of homomers; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 1 Publication
    VAR_047590
    Natural varianti469 – 4691A → T in ACHM2; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; the left shift in the dose-response relationship of the mutant CNGA3 is less distinctive than in homomeric channels with this mutation indicating a partial rescue effect of the CNGB3 subunit; is in large part located in the cell membrane at 37 and 27 degrees Celsius. 1 Publication
    Corresponds to variant rs117522010 [ dbSNP | Ensembl ].
    VAR_047591
    Natural varianti471 – 4711N → S in ACHM2; mutant CNGA3 alone or together with the CNGB3 subunit exhibit an increase in apparent affinity for cGMP and an increase in the relative agonist efficacy of cAMP compared with cGMP; cell surface expression levels is unchanged. 1 Publication
    VAR_047592
    Natural varianti485 – 4851D → V in ACHM2. 1 Publication
    VAR_047593
    Natural varianti510 – 5101C → S in ACHM2. 1 Publication
    VAR_047594
    Natural varianti513 – 5131G → E in ACHM2. 1 Publication
    VAR_047595
    Natural varianti516 – 5161G → E in ACHM2. 1 Publication
    VAR_047596
    Natural varianti522 – 5221I → T in ACHM2. 1 Publication
    VAR_047597
    Natural varianti525 – 5251G → D in ACHM2. 1 Publication
    VAR_047598
    Natural varianti529 – 5291V → M in ACHM2. 3 Publications
    VAR_010907
    Natural varianti547 – 5471F → L in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; is in large part located in the cell membrane at 37 and 27 degrees Celsius. 4 Publications
    VAR_010908
    Natural varianti548 – 5481G → R in ACHM2. 1 Publication
    VAR_047599
    Natural varianti557 – 5571G → R in ACHM2; the K(1/2) value is shifted toward a higher cGMP concentration by a factor of 3.0; no positive influence of the CNGB3 subunit in the cGMP sensitivity is observed; average cGMP maximum current is decreased to half of the mean wild-type value for the mutant CNGA3 + CNGB3. 3 Publications
    VAR_010909
    Natural varianti563 – 5631R → H in ACHM2; mutant CNGA3 alone or together with the CNGB3 subunit exhibit an increase in apparent affinity for cGMP and an increase in the relative agonist efficacy of cAMP compared with cGMP; cell surface expression levels is significantly reduced. 1 Publication
    VAR_047600
    Natural varianti565 – 5651T → M in ACHM2. 2 Publications
    VAR_047601
    Natural varianti569 – 5691R → H in ACHM2. 2 Publications
    VAR_047602
    Natural varianti573 – 5731Y → C in ACHM2. 1 Publication
    VAR_047603
    Natural varianti590 – 5901E → K in ACHM2; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration. 1 Publication
    VAR_047604
    Natural varianti593 – 5931E → K in ACHM2. 1 Publication
    VAR_047605
    Defects in CNGA3 may be a cause of Leber congenital amaurosis (LCA), a severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.

    Keywords - Diseasei

    Disease mutation, Leber congenital amaurosis

    Organism-specific databases

    MIMi216900. phenotype.
    Orphaneti49382. Achromatopsia.
    PharmGKBiPA26660.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 694694Cyclic nucleotide-gated cation channel alpha-3PRO_0000219317Add
    BLAST

    Proteomic databases

    PaxDbiQ16281.
    PRIDEiQ16281.

    PTM databases

    PhosphoSiteiQ16281.

    Expressioni

    Tissue specificityi

    Prominently expressed in retina.

    Gene expression databases

    ArrayExpressiQ16281.
    BgeeiQ16281.
    CleanExiHS_CNGA3.
    GenevestigatoriQ16281.

    Interactioni

    Subunit structurei

    Tetramer formed of three CNGA3 and one CNGB3 modulatory subunits.3 Publications

    Protein-protein interaction databases

    BioGridi107661. 1 interaction.
    IntActiQ16281. 1 interaction.
    STRINGi9606.ENSP00000272602.

    Structurei

    Secondary structure

    1
    694
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi626 – 66843

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3SWYX-ray1.90A/B/C626-669[»]
    ProteinModelPortaliQ16281.
    SMRiQ16281. Positions 351-669.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei171 – 19222HelicalSequence AnalysisAdd
    BLAST
    Transmembranei305 – 32521HelicalSequence AnalysisAdd
    BLAST
    Transmembranei378 – 39720HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili626 – 66944Add
    BLAST

    Domaini

    The C-terminal coiled-coil domain mediates homotrimerization of CNGA subunits.

    Sequence similaritiesi

    Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG300025.
    HOGENOMiHOG000007898.
    HOVERGENiHBG000281.
    KOiK04950.
    OrthoDBiEOG771268.
    PhylomeDBiQ16281.
    TreeFamiTF319048.

    Family and domain databases

    Gene3Di2.60.120.10. 1 hit.
    InterProiIPR018490. cNMP-bd-like.
    IPR018488. cNMP-bd_CS.
    IPR000595. cNMP-bd_dom.
    IPR005821. Ion_trans_dom.
    IPR014710. RmlC-like_jellyroll.
    [Graphical view]
    PfamiPF00027. cNMP_binding. 1 hit.
    PF00520. Ion_trans. 1 hit.
    [Graphical view]
    SMARTiSM00100. cNMP. 1 hit.
    [Graphical view]
    SUPFAMiSSF51206. SSF51206. 1 hit.
    PROSITEiPS00888. CNMP_BINDING_1. 1 hit.
    PS00889. CNMP_BINDING_2. 1 hit.
    PS50042. CNMP_BINDING_3. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q16281-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAKINTQYSH PSRTHLKVKT SDRDLNRAEN GLSRAHSSSE ETSSVLQPGI    50
    AMETRGLADS GQGSFTGQGI ARLSRLIFLL RRWAARHVHH QDQGPDSFPD 100
    RFRGAELKEV SSQESNAQAN VGSQEPADRG RSAWPLAKCN TNTSNNTEEE 150
    KKTKKKDAIV VDPSSNLYYR WLTAIALPVF YNWYLLICRA CFDELQSEYL 200
    MLWLVLDYSA DVLYVLDVLV RARTGFLEQG LMVSDTNRLW QHYKTTTQFK 250
    LDVLSLVPTD LAYLKVGTNY PEVRFNRLLK FSRLFEFFDR TETRTNYPNM 300
    FRIGNLVLYI LIIIHWNACI YFAISKFIGF GTDSWVYPNI SIPEHGRLSR 350
    KYIYSLYWST LTLTTIGETP PPVKDEEYLF VVVDFLVGVL IFATIVGNVG 400
    SMISNMNASR AEFQAKIDSI KQYMQFRKVT KDLETRVIRW FDYLWANKKT 450
    VDEKEVLKSL PDKLKAEIAI NVHLDTLKKV RIFQDCEAGL LVELVLKLRP 500
    TVFSPGDYIC KKGDIGKEMY IINEGKLAVV ADDGVTQFVV LSDGSYFGEI 550
    SILNIKGSKS GNRRTANIRS IGYSDLFCLS KDDLMEALTE YPEAKKALEE 600
    KGRQILMKDN LIDEELARAG ADPKDLEEKV EQLGSSLDTL QTRFARLLAE 650
    YNATQMKMKQ RLSQLESQVK GGGDKPLADG EVPGDATKTE DKQQ 694
    Length:694
    Mass (Da):78,838
    Last modified:May 4, 2001 - v2
    Checksum:iAE00B4EE760D70A0
    GO
    Isoform 2 (identifier: Q16281-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         132-150: SAWPLAKCNTNTSNNTEEE → R

    Note: No experimental confirmation available.

    Show »
    Length:676
    Mass (Da):76,903
    Checksum:iC6FB264BE7EB3D8D
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti48 – 481P → L.1 Publication
    Corresponds to variant rs62156348 [ dbSNP | Ensembl ].
    VAR_047565
    Natural varianti153 – 1531T → M.2 Publications
    Corresponds to variant rs34314205 [ dbSNP | Ensembl ].
    VAR_010902
    Natural varianti162 – 1621D → V in ACHM2. 1 Publication
    VAR_047566
    Natural varianti163 – 1631P → L in ACHM2. 2 Publications
    VAR_010903
    Natural varianti181 – 1811Y → C in ACHM2. 1 Publication
    VAR_047567
    Natural varianti182 – 1821N → Y in ACHM2. 1 Publication
    VAR_047568
    Natural varianti186 – 1861L → F in ACHM2. 1 Publication
    VAR_047569
    Natural varianti191 – 1911C → Y in ACHM2. 1 Publication
    VAR_047570
    Natural varianti194 – 1941E → K in ACHM2. 1 Publication
    VAR_047571
    Natural varianti198 – 1981E → K.
    Corresponds to variant rs2271041 [ dbSNP | Ensembl ].
    VAR_021963
    Natural varianti223 – 2231R → W in ACHM2. 3 Publications
    VAR_047572
    Natural varianti224 – 2241T → R in ACHM2. 1 Publication
    VAR_047573
    Natural varianti228 – 2281E → K in ACHM2; the dose-response relationship for cGMP-activation is not significantly different from that of wild-type CNGA3; the dose-response relationship of the mutant CNGA3 + CNGB3 is similar to that of the wild-type protein; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 1 Publication
    Corresponds to variant rs147415641 [ dbSNP | Ensembl ].
    VAR_047574
    Natural varianti249 – 2491F → S in ACHM2. 1 Publication
    VAR_047575
    Natural varianti260 – 2601D → N in ACHM2. 1 Publication
    VAR_047576
    Natural varianti263 – 2631Y → D in ACHM2. 1 Publication
    VAR_047577
    Natural varianti267 – 2671G → D in ACHM2. 1 Publication
    VAR_047578
    Natural varianti277 – 2771R → C in ACHM2. 3 Publications
    VAR_047579
    Natural varianti277 – 2771R → H in ACHM2; does not form functional homomeric or heteromeric channels; cell surface expression levels is significantly reduced. 1 Publication
    VAR_047580
    Natural varianti283 – 2831R → Q in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is not significantly different from that of wild-type CNGA3; the dose-response relationship of the mutant CNGA3 + CNGB3 is similar to that of the wild-type protein; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 3 Publications
    VAR_010904
    Natural varianti283 – 2831R → W in ACHM2. 2 Publications
    VAR_010905
    Natural varianti291 – 2911T → R in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the K(1/2) value is shifted toward a higher cGMP concentration by a factor of 1.8; no positive influence of the CNGB3 subunit in the cGMP sensitivity is observed; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 2 Publications
    VAR_010906
    Natural varianti312 – 3121Missing in ACHM2. 1 Publication
    VAR_047581
    Natural varianti335 – 3351W → C.1 Publication
    VAR_069398
    Natural varianti341 – 3411S → P in ACHM2. 2 Publications
    VAR_047582
    Natural varianti369 – 3691T → S in ACHM2. 1 Publication
    VAR_047583
    Natural varianti372 – 3721P → S in ACHM2. 1 Publication
    VAR_047584
    Natural varianti380 – 3801F → S in ACHM2. 1 Publication
    VAR_047585
    Natural varianti401 – 4011S → P in ACHM2. 1 Publication
    VAR_047586
    Natural varianti406 – 4061M → T in ACHM2. 1 Publication
    VAR_047587
    Natural varianti410 – 4101R → W in ACHM2. 3 Publications
    VAR_010910
    Natural varianti427 – 4271R → C in ACHM2. 2 Publications
    Corresponds to variant rs141386891 [ dbSNP | Ensembl ].
    VAR_047588
    Natural varianti436 – 4361R → W in ACHM2. 3 Publications
    VAR_047589
    Natural varianti439 – 4391R → W in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; the dose-response relationship of the mutant CNGA3 + CNGB3 is similar to that of the wild-type protein; coexpression of the CNGB3 subunit compensate completely for the slightly higher apparent cGMP sensitivity of homomers; the channel density into the cell membrane is considerably improved by decreasing the cultivation temparature. 1 Publication
    VAR_047590
    Natural varianti469 – 4691A → T in ACHM2; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; the left shift in the dose-response relationship of the mutant CNGA3 is less distinctive than in homomeric channels with this mutation indicating a partial rescue effect of the CNGB3 subunit; is in large part located in the cell membrane at 37 and 27 degrees Celsius. 1 Publication
    Corresponds to variant rs117522010 [ dbSNP | Ensembl ].
    VAR_047591
    Natural varianti471 – 4711N → S in ACHM2; mutant CNGA3 alone or together with the CNGB3 subunit exhibit an increase in apparent affinity for cGMP and an increase in the relative agonist efficacy of cAMP compared with cGMP; cell surface expression levels is unchanged. 1 Publication
    VAR_047592
    Natural varianti485 – 4851D → V in ACHM2. 1 Publication
    VAR_047593
    Natural varianti510 – 5101C → S in ACHM2. 1 Publication
    VAR_047594
    Natural varianti513 – 5131G → E in ACHM2. 1 Publication
    VAR_047595
    Natural varianti516 – 5161G → E in ACHM2. 1 Publication
    VAR_047596
    Natural varianti522 – 5221I → T in ACHM2. 1 Publication
    VAR_047597
    Natural varianti525 – 5251G → D in ACHM2. 1 Publication
    VAR_047598
    Natural varianti527 – 5271L → M in LCA. 1 Publication
    VAR_066860
    Natural varianti529 – 5291V → M in ACHM2. 3 Publications
    VAR_010907
    Natural varianti547 – 5471F → L in ACHM2; does not reveal any detectable calcium influx upon agonist application at 37 degrees Celsius; the channel function could be restored by incubating the transfected cells at 27 degrees Celsius; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration; a substantial reduction of macroscopic cGMP maximum current to only one-third of the mean value for wild-type CNGA3 + CNGB3 is observed for the mutant CNGA3 + CNGB3; is in large part located in the cell membrane at 37 and 27 degrees Celsius. 4 Publications
    VAR_010908
    Natural varianti548 – 5481G → R in ACHM2. 1 Publication
    VAR_047599
    Natural varianti557 – 5571G → R in ACHM2; the K(1/2) value is shifted toward a higher cGMP concentration by a factor of 3.0; no positive influence of the CNGB3 subunit in the cGMP sensitivity is observed; average cGMP maximum current is decreased to half of the mean wild-type value for the mutant CNGA3 + CNGB3. 3 Publications
    VAR_010909
    Natural varianti563 – 5631R → H in ACHM2; mutant CNGA3 alone or together with the CNGB3 subunit exhibit an increase in apparent affinity for cGMP and an increase in the relative agonist efficacy of cAMP compared with cGMP; cell surface expression levels is significantly reduced. 1 Publication
    VAR_047600
    Natural varianti565 – 5651T → M in ACHM2. 2 Publications
    VAR_047601
    Natural varianti569 – 5691R → H in ACHM2. 2 Publications
    VAR_047602
    Natural varianti573 – 5731Y → C in ACHM2. 1 Publication
    VAR_047603
    Natural varianti590 – 5901E → K in ACHM2; the dose-response relationship for cGMP-activation is shifted toward a lower cGMP concentration. 1 Publication
    VAR_047604
    Natural varianti593 – 5931E → K in ACHM2. 1 Publication
    VAR_047605

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei132 – 15019SAWPL…NTEEE → R in isoform 2. 1 PublicationVSP_042525Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF065314 mRNA. Translation: AAC17440.1.
    AC092675 Genomic DNA. Translation: AAY24181.1.
    BC096298 mRNA. Translation: AAH96298.1.
    BC096299 mRNA. Translation: AAH96299.1.
    BC096300 mRNA. Translation: AAH96300.1.
    S76069 Genomic DNA. Translation: AAD14208.1.
    CCDSiCCDS2034.1. [Q16281-1]
    CCDS42719.1. [Q16281-2]
    PIRiI78560.
    S74179.
    RefSeqiNP_001073347.1. NM_001079878.1. [Q16281-2]
    NP_001289.1. NM_001298.2. [Q16281-1]
    UniGeneiHs.234785.

    Genome annotation databases

    EnsembliENST00000272602; ENSP00000272602; ENSG00000144191. [Q16281-1]
    ENST00000393504; ENSP00000377140; ENSG00000144191. [Q16281-1]
    ENST00000436404; ENSP00000410070; ENSG00000144191. [Q16281-2]
    GeneIDi1261.
    KEGGihsa:1261.
    UCSCiuc002syt.3. human. [Q16281-1]
    uc002syu.3. human. [Q16281-2]

    Polymorphism databases

    DMDMi13959682.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Mutations of the CNGA3 gene

    Retina International's Scientific Newsletter

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF065314 mRNA. Translation: AAC17440.1 .
    AC092675 Genomic DNA. Translation: AAY24181.1 .
    BC096298 mRNA. Translation: AAH96298.1 .
    BC096299 mRNA. Translation: AAH96299.1 .
    BC096300 mRNA. Translation: AAH96300.1 .
    S76069 Genomic DNA. Translation: AAD14208.1 .
    CCDSi CCDS2034.1. [Q16281-1 ]
    CCDS42719.1. [Q16281-2 ]
    PIRi I78560.
    S74179.
    RefSeqi NP_001073347.1. NM_001079878.1. [Q16281-2 ]
    NP_001289.1. NM_001298.2. [Q16281-1 ]
    UniGenei Hs.234785.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3SWY X-ray 1.90 A/B/C 626-669 [» ]
    ProteinModelPortali Q16281.
    SMRi Q16281. Positions 351-669.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107661. 1 interaction.
    IntActi Q16281. 1 interaction.
    STRINGi 9606.ENSP00000272602.

    Chemistry

    ChEMBLi CHEMBL1628463.
    GuidetoPHARMACOLOGYi 396.

    Protein family/group databases

    TCDBi 1.A.1.5.12. the voltage-gated ion channel (vic) superfamily.

    PTM databases

    PhosphoSitei Q16281.

    Polymorphism databases

    DMDMi 13959682.

    Proteomic databases

    PaxDbi Q16281.
    PRIDEi Q16281.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000272602 ; ENSP00000272602 ; ENSG00000144191 . [Q16281-1 ]
    ENST00000393504 ; ENSP00000377140 ; ENSG00000144191 . [Q16281-1 ]
    ENST00000436404 ; ENSP00000410070 ; ENSG00000144191 . [Q16281-2 ]
    GeneIDi 1261.
    KEGGi hsa:1261.
    UCSCi uc002syt.3. human. [Q16281-1 ]
    uc002syu.3. human. [Q16281-2 ]

    Organism-specific databases

    CTDi 1261.
    GeneCardsi GC02P098962.
    GeneReviewsi CNGA3.
    HGNCi HGNC:2150. CNGA3.
    MIMi 216900. phenotype.
    600053. gene.
    neXtProti NX_Q16281.
    Orphaneti 49382. Achromatopsia.
    PharmGKBi PA26660.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG300025.
    HOGENOMi HOG000007898.
    HOVERGENi HBG000281.
    KOi K04950.
    OrthoDBi EOG771268.
    PhylomeDBi Q16281.
    TreeFami TF319048.

    Miscellaneous databases

    GeneWikii Cyclic_nucleotide-gated_channel_alpha_3.
    GenomeRNAii 1261.
    NextBioi 5101.
    PROi Q16281.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q16281.
    Bgeei Q16281.
    CleanExi HS_CNGA3.
    Genevestigatori Q16281.

    Family and domain databases

    Gene3Di 2.60.120.10. 1 hit.
    InterProi IPR018490. cNMP-bd-like.
    IPR018488. cNMP-bd_CS.
    IPR000595. cNMP-bd_dom.
    IPR005821. Ion_trans_dom.
    IPR014710. RmlC-like_jellyroll.
    [Graphical view ]
    Pfami PF00027. cNMP_binding. 1 hit.
    PF00520. Ion_trans. 1 hit.
    [Graphical view ]
    SMARTi SM00100. cNMP. 1 hit.
    [Graphical view ]
    SUPFAMi SSF51206. SSF51206. 1 hit.
    PROSITEi PS00888. CNMP_BINDING_1. 1 hit.
    PS00889. CNMP_BINDING_2. 1 hit.
    PS50042. CNMP_BINDING_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning, chromosomal localization and functional expression of the gene encoding the alpha-subunit of the cGMP-gated channel in human cone photoreceptors."
      Wissinger B., Mueller F., Weyand I., Schuffenhauer S., Thanos S., Kaupp U.B., Zrenner E.
      Eur. J. Neurosci. 9:2512-2521(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    4. "Expression of cyclic nucleotide-gated cation channels in non-sensory tissues and cells."
      Distler M., Biel M., Flockerzi V., Hofmann F.
      Neuropharmacology 33:1275-1282(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 320-580.
    5. "Genetic basis of total colourblindness among the Pingelapese islanders."
      Sundin O.H., Yang J.-M., Li Y., Zhu D., Hurd J.N., Mitchell T.N., Silva E.D., Maumenee I.H.
      Nat. Genet. 25:289-293(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBUNIT.
    6. "Subunit configuration of heteromeric cone cyclic nucleotide-gated channels."
      Peng C., Rich E.D., Varnum M.D.
      Neuron 42:401-410(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT.
    7. "Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated ion channels."
      Shuart N.G., Haitin Y., Camp S.S., Black K.D., Zagotta W.N.
      Nat. Commun. 2:457-457(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 626-669, SUBUNIT STOICHIOMETRY.
    8. "Total colourblindness is caused by mutations in the gene encoding the alpha-subunit of the cone photoreceptor cGMP-gated cation channel."
      Kohl S., Marx T., Giddings I., Jaegle H., Jacobson S.G., Apfelstedt-Sylla E., Zrenner E., Sharpe L.T., Wissinger B.
      Nat. Genet. 19:257-259(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ACHM2 LEU-163; GLN-283; TRP-283; ARG-291; TRP-410; MET-529; LEU-547 AND ARG-557, VARIANT MET-153.
    9. Cited for: VARIANTS ACHM2 VAL-162; LEU-163; CYS-181; TYR-182; PHE-186; TYR-191; LYS-194; TRP-223; ARG-224; ASN-260; ASP-267; CYS-277; HIS-277; TRP-283; GLN-283; ARG-291; ILE-312 DEL; PRO-341; SER-369; SER-372; SER-380; THR-406; TRP-410; CYS-427; TRP-436; SER-471; VAL-485; SER-510; GLU-513; GLU-516; THR-522; ASP-525; MET-529; LEU-547; ARG-557; HIS-563; MET-565; HIS-569; CYS-573 AND LYS-593.
    10. Cited for: VARIANTS ACHM2 TRP-223; TRP-436; LEU-547; ARG-548 AND HIS-569.
    11. "Functional consequences of progressive cone dystrophy-associated mutations in the human cone photoreceptor cyclic nucleotide-gated channel CNGA3 subunit."
      Liu C., Varnum M.D.
      Am. J. Physiol. 289:C187-C198(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS ACHM2 CYS-277; SER-471 AND HIS-563.
    12. "Cone cGMP-gated channel mutations and clinical findings in patients with achromatopsia, macular degeneration, and other hereditary cone diseases."
      Nishiguchi K.M., Sandberg M.A., Gorji N., Berson E.L., Dryja T.P.
      Hum. Mutat. 25:248-258(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ACHM2 TRP-223; SER-249; ASP-263; CYS-277; PRO-341; PRO-401; TRP-410; CYS-427; TRP-436; MET-529; MET-565 AND LYS-590, VARIANTS LEU-48 AND MET-153.
    13. "Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia."
      Achromatopsia clinical study group
      Reuter P., Koeppen K., Ladewig T., Kohl S., Baumann B., Wissinger B.
      Hum. Mutat. 29:1228-1236(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS ACHM2 LYS-228; CYS-277; GLN-283; TRP-439; THR-469; LEU-547 AND ARG-557, CHARACTERIZATION OF VARIANTS ACHM2 LYS-228; GLN-283; ARG-291; TRP-439; THR-469; LEU-547; ARG-557 AND LYS-590.
    14. "Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in patients with Leber congenital amaurosis."
      Wang X., Wang H., Cao M., Li Z., Chen X., Patenia C., Gore A., Abboud E.B., Al-Rajhi A.A., Lewis A.R., Lupski J.R., Mardon G., Zhang K., Muzny D., Gibbs R.A., Chen R.
      Hum. Mutat. 32:1450-1459(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LCA MET-527.
    15. Cited for: VARIANT CYS-335.

    Entry informationi

    Entry nameiCNGA3_HUMAN
    AccessioniPrimary (citable) accession number: Q16281
    Secondary accession number(s): Q4VAP7, Q53RD2, Q9UP64
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: May 4, 2001
    Last modified: October 1, 2014
    This is version 138 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3