GUC1C_HUMAN
ID GUC1C_HUMAN Reviewed; 209 AA.
AC O95843; O95844; Q9UNM0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Guanylyl cyclase-activating protein 3;
DE Short=GCAP 3;
DE AltName: Full=Guanylate cyclase activator 1C;
GN Name=GUCA1C; Synonyms=GCAP3;
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 [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2),
RP CHARACTERIZATION, MYRISTOYLATION AT GLY-2, AND VARIANT ILE-72.
RC TISSUE=Retina;
RX PubMed=10037746; DOI=10.1074/jbc.274.10.6526;
RA Haeseleer F., Sokal I., Li N., Pettenati M.J., Rao N., Bronson J.D.,
RA Wechter R., Baehr W., Palczewski K.;
RT "Molecular characterization of a third member of the guanylyl cyclase-
RT activating protein subfamily.";
RL J. Biol. Chem. 274:6526-6535(1999).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) IN COMPLEX WITH CALCIUM IONS.
RX PubMed=16626734; DOI=10.1016/j.jmb.2006.03.042;
RA Stephen R., Palczewski K., Sousa M.C.;
RT "The crystal structure of GCAP3 suggests molecular mechanism of GCAP-linked
RT cone dystrophies.";
RL J. Mol. Biol. 359:266-275(2006).
CC -!- FUNCTION: Stimulates guanylyl cyclase 1 (GC1) and GC2 when free calcium
CC ions concentration is low and inhibits guanylyl cyclases when free
CC calcium ions concentration is elevated. This Ca(2+)-sensitive
CC regulation of guanylyl cyclase (GC) is a key event in recovery of the
CC dark state of rod photoreceptors following light exposure.
CC -!- INTERACTION:
CC O95843; O14964: HGS; NbExp=3; IntAct=EBI-23668738, EBI-740220;
CC O95843; Q9UIG4: PSORS1C2; NbExp=3; IntAct=EBI-23668738, EBI-11974061;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O95843-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95843-2; Sequence=VSP_000736;
CC -!- TISSUE SPECIFICITY: Retina.
CC -!- DOMAIN: Binds three calcium ions (via EF-hand 2, 3 and 4).
CC {ECO:0000269|PubMed:16626734}.
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; AF110001; AAD19943.1; -; Genomic_DNA.
DR EMBL; AF109998; AAD19943.1; JOINED; Genomic_DNA.
DR EMBL; AF109999; AAD19943.1; JOINED; Genomic_DNA.
DR EMBL; AF110000; AAD19943.1; JOINED; Genomic_DNA.
DR EMBL; AF110002; AAD19944.1; -; mRNA.
DR EMBL; AF110003; AAD19945.1; -; mRNA.
DR CCDS; CCDS2954.1; -. [O95843-1]
DR CCDS; CCDS87118.1; -. [O95843-2]
DR RefSeq; NP_005450.3; NM_005459.3. [O95843-1]
DR PDB; 2GGZ; X-ray; 3.00 A; A/B=1-209.
DR PDBsum; 2GGZ; -.
DR AlphaFoldDB; O95843; -.
DR SMR; O95843; -.
DR BioGRID; 114985; 3.
DR IntAct; O95843; 2.
DR STRING; 9606.ENSP00000261047; -.
DR iPTMnet; O95843; -.
DR BioMuta; GUCA1C; -.
DR PaxDb; O95843; -.
DR PeptideAtlas; O95843; -.
DR PRIDE; O95843; -.
DR Antibodypedia; 32403; 141 antibodies from 19 providers.
DR DNASU; 9626; -.
DR Ensembl; ENST00000261047.8; ENSP00000261047.3; ENSG00000138472.11. [O95843-1]
DR GeneID; 9626; -.
DR KEGG; hsa:9626; -.
DR MANE-Select; ENST00000261047.8; ENSP00000261047.3; NM_005459.4; NP_005450.3.
DR UCSC; uc003dxj.3; human. [O95843-1]
DR CTD; 9626; -.
DR DisGeNET; 9626; -.
DR GeneCards; GUCA1C; -.
DR HGNC; HGNC:4680; GUCA1C.
DR HPA; ENSG00000138472; Tissue enriched (retina).
DR MIM; 605128; gene.
DR neXtProt; NX_O95843; -.
DR OpenTargets; ENSG00000138472; -.
DR PharmGKB; PA29064; -.
DR VEuPathDB; HostDB:ENSG00000138472; -.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000162847; -.
DR HOGENOM; CLU_072366_4_1_1; -.
DR InParanoid; O95843; -.
DR OMA; HYYSKFM; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; O95843; -.
DR TreeFam; TF333971; -.
DR PathwayCommons; O95843; -.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR SignaLink; O95843; -.
DR BioGRID-ORCS; 9626; 10 hits in 1055 CRISPR screens.
DR EvolutionaryTrace; O95843; -.
DR GenomeRNAi; 9626; -.
DR Pharos; O95843; Tdark.
DR PRO; PR:O95843; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O95843; protein.
DR Bgee; ENSG00000138472; Expressed in body of pancreas and 58 other tissues.
DR ExpressionAtlas; O95843; baseline and differential.
DR Genevisible; O95843; HS.
DR GO; GO:0097381; C:photoreceptor disc membrane; TAS:Reactome.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0008048; F:calcium sensitive guanylate cyclase activator activity; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR CDD; cd00051; EFh; 2.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR032992; GUCA1C.
DR InterPro; IPR028846; Recoverin.
DR PANTHER; PTHR23055; PTHR23055; 1.
DR PANTHER; PTHR23055:SF80; PTHR23055:SF80; 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; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Lipoprotein; Metal-binding;
KW Myristate; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..209
FT /note="Guanylyl cyclase-activating protein 3"
FT /id="PRO_0000073812"
FT DOMAIN 15..50
FT /note="EF-hand 1"
FT /evidence="ECO:0000269|PubMed:16626734"
FT DOMAIN 52..87
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:16626734"
FT DOMAIN 88..123
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:16626734"
FT DOMAIN 130..165
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 187..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 192..209
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 65
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:16626734"
FT BINDING 67
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:16626734"
FT BINDING 69
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:16626734"
FT BINDING 76
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:16626734"
FT BINDING 101
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:16626734"
FT BINDING 103
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:16626734"
FT BINDING 105
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:16626734"
FT BINDING 107
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:16626734"
FT BINDING 112
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:16626734"
FT BINDING 143
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:16626734"
FT BINDING 145
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:16626734"
FT BINDING 147
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:16626734"
FT BINDING 149
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:16626734"
FT BINDING 154
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:16626734"
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:10037746"
FT VAR_SEQ 149..209
FT /note="ELTLEEFINGMAKDQDLLEIVYKSFDFSNVLRVICNGKQPDMETDSSKSPDK
FT AGLGKVKMK -> NGATLYWITFPTKGIDFRRIYQWHGKRSGSPGDCSQELRLLQCAES
FT NL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10037746"
FT /id="VSP_000736"
FT VARIANT 72
FT /note="V -> I (in dbSNP:rs2715687)"
FT /evidence="ECO:0000269|PubMed:10037746"
FT /id="VAR_055632"
FT VARIANT 85
FT /note="M -> V (in dbSNP:rs6804162)"
FT /id="VAR_055633"
FT VARIANT 119
FT /note="A -> V (in dbSNP:rs11917716)"
FT /id="VAR_055634"
FT VARIANT 159
FT /note="M -> V (in dbSNP:rs16854916)"
FT /id="VAR_055635"
FT HELIX 26..29
FT /evidence="ECO:0007829|PDB:2GGZ"
FT STRAND 33..36
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 37..43
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 51..64
FT /evidence="ECO:0007829|PDB:2GGZ"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 74..84
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 89..100
FT /evidence="ECO:0007829|PDB:2GGZ"
FT STRAND 105..108
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 110..120
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 131..142
FT /evidence="ECO:0007829|PDB:2GGZ"
FT STRAND 147..150
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 152..160
FT /evidence="ECO:0007829|PDB:2GGZ"
FT TURN 161..165
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 166..172
FT /evidence="ECO:0007829|PDB:2GGZ"
FT HELIX 177..185
FT /evidence="ECO:0007829|PDB:2GGZ"
SQ SEQUENCE 209 AA; 23822 MW; A407E7D4AEBBAED3 CRC64;
MGNGKSIAGD QKAVPTQETH VWYRTFMMEY PSGLQTLHEF KTLLGLQGLN QKANKHIDQV
YNTFDTNKDG FVDFLEFIAA VNLIMQEKME QKLKWYFKLY DADGNGSIDK NELLDMFMAV
QALNGQQTLS PEEFINLVFH KIDINNDGEL TLEEFINGMA KDQDLLEIVY KSFDFSNVLR
VICNGKQPDM ETDSSKSPDK AGLGKVKMK
