GUC1A_BOVIN
ID GUC1A_BOVIN Reviewed; 205 AA.
AC P46065;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Guanylyl cyclase-activating protein 1;
DE Short=GCAP 1;
DE AltName: Full=Guanylate cyclase activator 1A;
GN Name=GUCA1A; Synonyms=GCAP1, GUCA1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION BY MASS
RP SPECTROMETRY, CALCIUM-BINDING, AND MYRISTOYLATION AT GLY-2.
RC TISSUE=Retina;
RX PubMed=7520254; DOI=10.1016/0896-6273(94)90355-7;
RA Palczewski K., Subbaraya I., Gorczyca W.A., Helekar B.S., Ruiz C.C.,
RA Ohguro H., Huang J., Zhao X., Crabb J.W., Johnson R.S., Walsh K.A.,
RA Gray-Keller M.P., Detwiler P.B., Baehr W.;
RT "Molecular cloning and characterization of retinal photoreceptor guanylyl
RT cyclase-activating protein.";
RL Neuron 13:395-404(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=8626484; DOI=10.1074/jbc.271.14.8022;
RA Frins S., Boenigk W., Mueller F., Kellner R., Koch K.W.;
RT "Functional characterization of a guanylyl cyclase-activating protein from
RT vertebrate rods. Cloning, heterologous expression, and localization.";
RL J. Biol. Chem. 271:8022-8027(1996).
RN [3]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=9620085;
RA Cuenca N., Lopez S., Howes K., Kolb H.;
RT "The localization of guanylyl cyclase-activating proteins in the mammalian
RT retina.";
RL Invest. Ophthalmol. Vis. Sci. 39:1243-1250(1998).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=10821676; DOI=10.1021/bi9929960;
RA Venkataraman V., Nagele R., Duda T., Sharma R.K.;
RT "Rod outer segment membrane guanylate cyclase type 1-linked stimulatory and
RT inhibitory calcium signaling systems in the pineal gland: biochemical,
RT molecular, and immunohistochemical evidence.";
RL Biochemistry 39:6042-6052(2000).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF TYR-99.
RX PubMed=9651312; DOI=10.1074/jbc.273.28.17311;
RA Dizhoor A.M., Boikov S.G., Olshevskaya E.V.;
RT "Constitutive activation of photoreceptor guanylate cyclase by Y99C mutant
RT of GCAP-1. Possible role in causing human autosomal dominant cone
RT degeneration.";
RL J. Biol. Chem. 273:17311-17314(1998).
RN [6]
RP STRUCTURE BY NMR OF 2-205, CALCIUM-BINDING, FUNCTION, DOMAIN, AND
RP MUTAGENESIS OF VAL-77; ARG-172; SER-173 AND LEU-174.
RX PubMed=26703466; DOI=10.1074/jbc.m115.696161;
RA Lim S., Peshenko I.V., Olshevskaya E.V., Dizhoor A.M., Ames J.B.;
RT "Structure of guanylyl cyclase activator protein 1 (GCAP1) mutant V77E in a
RT Ca2+-free/Mg2+-bound activator state.";
RL J. Biol. Chem. 291:4429-4441(2016).
CC -!- FUNCTION: Stimulates retinal guanylyl cyclase when free calcium ions
CC concentration is low and inhibits guanylyl cyclase when free calcium
CC ions concentration is elevated (PubMed:7520254, PubMed:8626484,
CC PubMed:9651312, PubMed:26703466). This Ca(2+)-sensitive regulation of
CC retinal guanylyl cyclase is a key event in recovery of the dark state
CC of rod photoreceptors following light exposure (PubMed:7520254,
CC PubMed:8626484). May be involved in cone photoreceptor light response
CC and recovery of response in bright light (By similarity).
CC {ECO:0000250|UniProtKB:P43081, ECO:0000269|PubMed:7520254,
CC ECO:0000269|PubMed:8626484}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P43080}.
CC -!- INTERACTION:
CC P46065; P55203: GUCY2D; NbExp=2; IntAct=EBI-6943108, EBI-6943076;
CC P46065; P81948: TUBA4A; NbExp=2; IntAct=EBI-6943108, EBI-6943159;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor
CC {ECO:0000269|PubMed:7520254}. Photoreceptor inner segment
CC {ECO:0000269|PubMed:9620085}. Cell projection, cilium, photoreceptor
CC outer segment {ECO:0000269|PubMed:9620085}. Note=Subcellular location
CC is not affected by light or dark conditions.
CC {ECO:0000250|UniProtKB:P43081}.
CC -!- TISSUE SPECIFICITY: Detected in the retina (PubMed:7520254). Detected
CC in rod and cone photoreceptor cells (at protein level) (PubMed:8626484,
CC PubMed:9620085). Also present in certain pinealocytes
CC (PubMed:10821676). {ECO:0000269|PubMed:10821676,
CC ECO:0000269|PubMed:7520254, ECO:0000269|PubMed:8626484,
CC ECO:0000269|PubMed:9620085}.
CC -!- DOMAIN: Binds three calcium ions (via EF-hands 2, 3 and 4) when calcium
CC levels are high. Binds Mg(2+) when calcium levels are low.
CC {ECO:0000269|PubMed:26703466}.
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DR EMBL; S74247; AAB31698.2; -; Genomic_DNA.
DR EMBL; X95352; CAA64642.1; -; mRNA.
DR RefSeq; NP_776971.1; NM_174546.2.
DR PDB; 2NA0; NMR; -; A=2-205.
DR PDBsum; 2NA0; -.
DR AlphaFoldDB; P46065; -.
DR BMRB; P46065; -.
DR SMR; P46065; -.
DR IntAct; P46065; 2.
DR MINT; P46065; -.
DR STRING; 9913.ENSBTAP00000017036; -.
DR iPTMnet; P46065; -.
DR PaxDb; P46065; -.
DR PRIDE; P46065; -.
DR Ensembl; ENSBTAT00000087322; ENSBTAP00000057125; ENSBTAG00000051956.
DR GeneID; 282243; -.
DR KEGG; bta:282243; -.
DR CTD; 2978; -.
DR VEuPathDB; HostDB:ENSBTAG00000051956; -.
DR VGNC; VGNC:29714; GUCA1A.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000160607; -.
DR HOGENOM; CLU_072366_4_1_1; -.
DR InParanoid; P46065; -.
DR OMA; IRTINPC; -.
DR OrthoDB; 1271942at2759; -.
DR TreeFam; TF333971; -.
DR Reactome; R-BTA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR Proteomes; UP000009136; Chromosome 23.
DR Bgee; ENSBTAG00000051956; Expressed in retina and 43 other tissues.
DR GO; GO:0120199; C:cone photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0008048; F:calcium sensitive guanylate cyclase activator activity; IDA:UniProtKB.
DR GO; GO:0030249; F:guanylate cyclase regulator activity; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB.
DR GO; GO:0007602; P:phototransduction; ISS:AgBase.
DR GO; GO:0031284; P:positive regulation of guanylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0031282; P:regulation of guanylate cyclase activity; ISS:AgBase.
DR GO; GO:0007601; P:visual perception; ISS:AgBase.
DR CDD; cd00051; EFh; 2.
DR DisProt; DP00840; -.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR033022; GUCA1A.
DR InterPro; IPR028846; Recoverin.
DR PANTHER; PTHR23055; PTHR23055; 1.
DR PANTHER; PTHR23055:SF13; PTHR23055:SF13; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 3.
DR PROSITE; PS50222; EF_HAND_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell projection; Direct protein sequencing;
KW Lipoprotein; Membrane; Metal-binding; Myristate; Reference proteome;
KW Repeat; Sensory transduction; Vision.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000255"
FT CHAIN 2..205
FT /note="Guanylyl cyclase-activating protein 1"
FT /id="PRO_0000073802"
FT DOMAIN 14..49
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT DOMAIN 51..86
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT DOMAIN 87..122
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT DOMAIN 131..166
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT REGION 185..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 70
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 100
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 102
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 104
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 106
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 111
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 144
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 146
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 148
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 150
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:26703466"
FT MOD_RES 3
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000255"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:7520254"
FT MUTAGEN 77
FT /note="V->E: Decreases affinity for calcium and promotes
FT magnesium binding at EF-hand 2."
FT /evidence="ECO:0000269|PubMed:26703466"
FT MUTAGEN 99
FT /note="Y->C: Constitutively activates GUCY2D."
FT /evidence="ECO:0000269|PubMed:9651312"
FT MUTAGEN 172
FT /note="Missing: Nearly abolishes activation of GUCY2D."
FT /evidence="ECO:0000269|PubMed:26703466"
FT MUTAGEN 173
FT /note="S->SG: Abolishes activation of GUCY2D."
FT /evidence="ECO:0000269|PubMed:26703466"
FT MUTAGEN 173
FT /note="Missing: Nearly abolishes activation of GUCY2D."
FT /evidence="ECO:0000269|PubMed:26703466"
FT MUTAGEN 174
FT /note="Missing: Nearly abolishes activation of GUCY2D."
FT /evidence="ECO:0000269|PubMed:26703466"
FT CONFLICT 108
FT /note="D -> I (in Ref. 1; AAB31698)"
FT /evidence="ECO:0000305"
FT HELIX 8..14
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 17..28
FT /evidence="ECO:0007829|PDB:2NA0"
FT STRAND 31..35
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 36..43
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 51..64
FT /evidence="ECO:0007829|PDB:2NA0"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 73..83
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 88..99
FT /evidence="ECO:0007829|PDB:2NA0"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 109..119
FT /evidence="ECO:0007829|PDB:2NA0"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 133..143
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 154..161
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 164..173
FT /evidence="ECO:0007829|PDB:2NA0"
FT HELIX 179..184
FT /evidence="ECO:0007829|PDB:2NA0"
SQ SEQUENCE 205 AA; 23510 MW; 027B54ADB79EC0E1 CRC64;
MGNIMDGKSV EELSSTECHQ WYKKFMTECP SGQLTLYEFR QFFGLKNLSP WASQYVEQMF
ETFDFNKDGY IDFMEYVAAL SLVLKGKVEQ KLRWYFKLYD VDGNGCIDRD ELLTIIRAIR
AINPCSDSTM TAEEFTDTVF SKIDVNGDGE LSLEEFMEGV QKDQMLLDTL TRSLDLTRIV
RRLQNGEQDE EGASGRETEA AEADG
