GUC1B_HUMAN
ID GUC1B_HUMAN Reviewed; 200 AA.
AC Q9UMX6; Q9NU15;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Guanylyl cyclase-activating protein 2;
DE Short=GCAP 2;
DE AltName: Full=Guanylate cyclase activator 1B;
GN Name=GUCA1B; Synonyms=GCAP2;
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].
RX PubMed=9119368; DOI=10.1006/geno.1996.4513;
RA Surguchov A., Bronson J.D., Banerjee P., Knowles J.A., Ruiz C.,
RA Subbaraya I., Palczewski K., Baehr W.;
RT "The human GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on
RT the short arm of chromosome 6 (p21.1).";
RL Genomics 39:312-322(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
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 VARIANT ASP-155.
RX PubMed=10507726;
RA Payne A.M., Downes S.M., Bessant D.A.R., Plant C., Moore T., Bird A.C.,
RA Bhattacharya S.S.;
RT "Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in
RT patients with autosomal dominant retinal dystrophies.";
RL J. Med. Genet. 36:691-693(1999).
RN [5]
RP VARIANT RP48 ARG-157.
RX PubMed=15452722; DOI=10.1007/s00417-004-1015-7;
RA Sato M., Nakazawa M., Usui T., Tanimoto N., Abe H., Ohguro H.;
RT "Mutations in the gene coding for guanylate cyclase-activating protein 2
RT (GUCA1B gene) in patients with autosomal dominant retinal dystrophies.";
RL Graefes Arch. Clin. Exp. Ophthalmol. 243:235-242(2005).
CC -!- FUNCTION: Stimulates two retinal guanylyl cyclases (GCs) GUCY2D and
CC GUCY2F when free calcium ions concentration is low, and inhibits GUCY2D
CC and GUCY2F when free calcium ions concentration is elevated (By
CC similarity). This Ca(2+)-sensitive regulation of GCs is a key event in
CC recovery of the dark state of rod photoreceptors following light
CC exposure (By similarity). May be involved in cone photoreceptor
CC response and recovery of response in bright light (By similarity).
CC {ECO:0000250|UniProtKB:P51177, ECO:0000250|UniProtKB:Q8VBV8}.
CC -!- INTERACTION:
CC Q9UMX6; P32243-2: OTX2; NbExp=3; IntAct=EBI-12896859, EBI-9087860;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P51177};
CC Lipid-anchor {ECO:0000250|UniProtKB:P51177}. Photoreceptor inner
CC segment {ECO:0000269|PubMed:9620085}. Cell projection, cilium,
CC photoreceptor outer segment {ECO:0000269|PubMed:9620085}.
CC Note=Subcellular location is not affected by light or dark conditions.
CC {ECO:0000250|UniProtKB:Q8VBV8}.
CC -!- TISSUE SPECIFICITY: In the retina, it is expressed in cone and rod
CC photoreceptor cells. {ECO:0000269|PubMed:9620085}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000250|UniProtKB:P51177}.
CC -!- DISEASE: Retinitis pigmentosa 48 (RP48) [MIM:613827]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:15452722}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Binds three calcium ions. {ECO:0000250}.
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DR EMBL; AF173229; AAD47279.1; -; Genomic_DNA.
DR EMBL; AF173227; AAD47279.1; JOINED; Genomic_DNA.
DR EMBL; AF173228; AAD47279.1; JOINED; Genomic_DNA.
DR EMBL; AL096814; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS4865.1; -.
DR RefSeq; NP_002089.4; NM_002098.5.
DR AlphaFoldDB; Q9UMX6; -.
DR SMR; Q9UMX6; -.
DR BioGRID; 109234; 10.
DR IntAct; Q9UMX6; 1.
DR STRING; 9606.ENSP00000230361; -.
DR TCDB; 8.A.82.2.9; the calmodulin calcium binding protein (calmodulin) family.
DR iPTMnet; Q9UMX6; -.
DR PhosphoSitePlus; Q9UMX6; -.
DR BioMuta; GUCA1B; -.
DR DMDM; 116242507; -.
DR MassIVE; Q9UMX6; -.
DR PaxDb; Q9UMX6; -.
DR PeptideAtlas; Q9UMX6; -.
DR PRIDE; Q9UMX6; -.
DR ProteomicsDB; 85223; -.
DR Antibodypedia; 30141; 145 antibodies from 22 providers.
DR DNASU; 2979; -.
DR Ensembl; ENST00000230361.4; ENSP00000230361.3; ENSG00000112599.9.
DR GeneID; 2979; -.
DR KEGG; hsa:2979; -.
DR MANE-Select; ENST00000230361.4; ENSP00000230361.3; NM_002098.6; NP_002089.4.
DR UCSC; uc003orz.4; human.
DR CTD; 2979; -.
DR DisGeNET; 2979; -.
DR GeneCards; GUCA1B; -.
DR GeneReviews; GUCA1B; -.
DR HGNC; HGNC:4679; GUCA1B.
DR HPA; ENSG00000112599; Tissue enriched (retina).
DR MalaCards; GUCA1B; -.
DR MIM; 602275; gene.
DR MIM; 613827; phenotype.
DR neXtProt; NX_Q9UMX6; -.
DR OpenTargets; ENSG00000112599; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA29063; -.
DR VEuPathDB; HostDB:ENSG00000112599; -.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000157530; -.
DR HOGENOM; CLU_072366_4_0_1; -.
DR InParanoid; Q9UMX6; -.
DR OMA; HEFKGFF; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; Q9UMX6; -.
DR TreeFam; TF333971; -.
DR PathwayCommons; Q9UMX6; -.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR SignaLink; Q9UMX6; -.
DR BioGRID-ORCS; 2979; 9 hits in 1072 CRISPR screens.
DR GeneWiki; GUCA1B; -.
DR GenomeRNAi; 2979; -.
DR Pharos; Q9UMX6; Tbio.
DR PRO; PR:Q9UMX6; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q9UMX6; protein.
DR Bgee; ENSG00000112599; Expressed in cerebellar hemisphere and 121 other tissues.
DR Genevisible; Q9UMX6; HS.
DR GO; GO:0120199; C:cone photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0097381; C:photoreceptor disc membrane; TAS:Reactome.
DR GO; GO:0001917; C:photoreceptor inner segment; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0007589; P:body fluid secretion; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; TAS:ProtInc.
DR GO; GO:0031282; P:regulation of guanylate cyclase activity; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IBA:GO_Central.
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; IPR015756; GCAP-2.
DR InterPro; IPR028846; Recoverin.
DR PANTHER; PTHR23055; PTHR23055; 1.
DR PANTHER; PTHR23055:SF11; PTHR23055:SF11; 1.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13499; EF-hand_7; 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 Calcium; Cell membrane; Cell projection; Disease variant; Lipoprotein;
KW Membrane; Metal-binding; Myristate; Reference proteome; Repeat;
KW Retinitis pigmentosa; Sensory transduction; Vision.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..200
FT /note="Guanylyl cyclase-activating protein 2"
FT /id="PRO_0000073808"
FT DOMAIN 14..31
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 53..88
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 89..124
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 141..176
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 BINDING 72
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 77
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 BINDING 104
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 BINDING 108
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 113
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 BINDING 156
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 158
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 160
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VARIANT 155
FT /note="E -> D (in dbSNP:rs139923590)"
FT /evidence="ECO:0000269|PubMed:10507726"
FT /id="VAR_009127"
FT VARIANT 157
FT /note="G -> R (in RP48; dbSNP:rs121909124)"
FT /evidence="ECO:0000269|PubMed:15452722"
FT /id="VAR_065355"
FT CONFLICT 137
FT /note="G -> D (in Ref. 1; AAD47279)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 200 AA; 23420 MW; 79B898868BA35768 CRC64;
MGQEFSWEEA EAAGEIDVAE LQEWYKKFVM ECPSGTLFMH EFKRFFKVTD DEEASQYVEG
MFRAFDKNGD NTIDFLEYVA ALNLVLRGTL EHKLKWTFKI YDKDGNGCID RLELLNIVEG
IYQLKKACRR ELQTEQGQLL TPEEVVDRIF LLVDENGDGQ LSLNEFVEGA RRDKWVMKML
QMDMNPSSWL AQQRRKSAMF
