GUC2D_BOVIN
ID GUC2D_BOVIN Reviewed; 1110 AA.
AC P55203; O02809;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Retinal guanylyl cyclase 1;
DE Short=RETGC-1;
DE EC=4.6.1.2 {ECO:0000269|PubMed:8102054};
DE AltName: Full=Guanylate cyclase 2D, retinal;
DE AltName: Full=Guanylate cyclase E;
DE Short=GC-E;
DE AltName: Full=Rod outer segment membrane guanylate cyclase {ECO:0000303|PubMed:7916565};
DE Short=ROS-GC {ECO:0000303|PubMed:7916565};
DE Flags: Precursor;
GN Name=GUCY2D; Synonyms=GUC2D;
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 [MRNA].
RC TISSUE=Retina;
RX PubMed=7916565; DOI=10.1042/bj3020455;
RA Goraczniak R.M., Duda T., Sitaramayya A., Sharma R.K.;
RT "Structural and functional characterization of the rod outer segment
RT membrane guanylate cyclase.";
RL Biochem. J. 302:455-461(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RA Duda T., Venkataraman V., Sharma R.K.;
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=Holstein; TISSUE=Retina;
RX PubMed=9256080; DOI=10.1016/s0378-1119(97)00125-x;
RA Johnston J.P., Farhangfar F., Aparicio J.G., Nam S.H., Applebury M.L.;
RT "The bovine guanylate cyclase GC-E gene and 5' flanking region.";
RL Gene 193:219-227(1997).
RN [4]
RP PROTEIN SEQUENCE OF 57-71; 163-178; 702-713 AND 749-763, TISSUE
RP SPECIFICITY, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND FUNCTION.
RC TISSUE=Retina;
RX PubMed=8102054; DOI=10.1006/bbrc.1993.1900;
RA Margulis A., Goraczniak R.M., Duda T., Sharma R.K., Sitaramayya A.;
RT "Structural and biochemical identity of retinal rod outer segment membrane
RT guanylate cyclase.";
RL Biochem. Biophys. Res. Commun. 194:855-861(1993).
CC -!- FUNCTION: Catalyzes the synthesis of cyclic GMP (cGMP) in rods and
CC cones of photoreceptors. Plays an essential role in phototransduction,
CC by mediating cGMP replenishment (PubMed:8102054). May also participate
CC in the trafficking of membrane-asociated proteins to the photoreceptor
CC outer segment membrane (By similarity). {ECO:0000250|UniProtKB:P52785,
CC ECO:0000269|PubMed:8102054}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC Evidence={ECO:0000269|PubMed:8102054};
CC -!- ACTIVITY REGULATION: Activated by GUCA1A when free calcium ions
CC concentration is low, and inhibited by GUCA1A when free calcium ions
CC concentration is high (By similarity). Negatively regulated by RD3;
CC inhibits the basal and GUCA1A-stimulated guanylate cyclase activity (By
CC similarity). {ECO:0000250|UniProtKB:P52785,
CC ECO:0000250|UniProtKB:Q02846}.
CC -!- SUBUNIT: Homodimer; requires homodimerization for guanylyl cyclase
CC activity (By similarity). Interacts (via C-terminus) with RD3 (via C-
CC terminus); promotes the exit of GUCY2D from the endoplasmic reticulum
CC and its trafficking to the photoreceptor outer segments (By
CC similarity). Interaction with RD3 negatively regulates GUCY2D guanylate
CC cyclase activity (By similarity). {ECO:0000250|UniProtKB:P51840,
CC ECO:0000250|UniProtKB:Q02846}.
CC -!- INTERACTION:
CC P55203; Q28181: CNGB1; NbExp=5; IntAct=EBI-6943076, EBI-6979031;
CC P55203; P46065: GUCA1A; NbExp=2; IntAct=EBI-6943076, EBI-6943108;
CC -!- SUBCELLULAR LOCATION: Photoreceptor outer segment membrane
CC {ECO:0000269|PubMed:8102054}; Single-pass type I membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q02846}; Single-pass type I membrane protein
CC {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina in rod outer segment.
CC {ECO:0000269|PubMed:8102054}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; L37089; AAA50790.1; -; mRNA.
DR EMBL; AF027203; AAB86385.1; -; Genomic_DNA.
DR EMBL; AF027200; AAB86385.1; JOINED; Genomic_DNA.
DR EMBL; AF027201; AAB86385.1; JOINED; Genomic_DNA.
DR EMBL; AF027202; AAB86385.1; JOINED; Genomic_DNA.
DR EMBL; U77095; AAC48734.1; -; mRNA.
DR EMBL; U77103; AAD12319.1; -; Genomic_DNA.
DR EMBL; U77096; AAD12319.1; JOINED; Genomic_DNA.
DR EMBL; U77097; AAD12319.1; JOINED; Genomic_DNA.
DR EMBL; U77098; AAD12319.1; JOINED; Genomic_DNA.
DR EMBL; U77099; AAD12319.1; JOINED; Genomic_DNA.
DR EMBL; U77100; AAD12319.1; JOINED; Genomic_DNA.
DR EMBL; U77101; AAD12319.1; JOINED; Genomic_DNA.
DR EMBL; U77102; AAD12319.1; JOINED; Genomic_DNA.
DR PIR; S55279; S55279.
DR AlphaFoldDB; P55203; -.
DR SMR; P55203; -.
DR IntAct; P55203; 2.
DR MINT; P55203; -.
DR STRING; 9913.ENSBTAP00000011564; -.
DR PaxDb; P55203; -.
DR PRIDE; P55203; -.
DR eggNOG; KOG1023; Eukaryota.
DR InParanoid; P55203; -.
DR OrthoDB; 229634at2759; -.
DR BRENDA; 4.6.1.2; 908.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0120200; C:rod photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR011645; HNOB_dom_associated.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR028082; Peripla_BP_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07701; HNOBA; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Cell projection; cGMP biosynthesis; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; GTP-binding; Lyase;
KW Membrane; Nucleotide-binding; Reference proteome; Sensory transduction;
KW Signal; Transmembrane; Transmembrane helix; Vision.
FT SIGNAL 1..56
FT /evidence="ECO:0000269|PubMed:8102054"
FT CHAIN 57..1110
FT /note="Retinal guanylyl cyclase 1"
FT /id="PRO_0000012379"
FT TOPO_DOM 57..467
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 468..492
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..1110
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 493..813
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 885..1015
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT REGION 1070..1110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1089..1103
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 302
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 454
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT DISULFID 462
FT /note="Interchain"
FT /evidence="ECO:0000305"
FT CONFLICT 18
FT /note="G -> A (in Ref. 3; AAC48734/AAD12319)"
FT /evidence="ECO:0000305"
FT CONFLICT 1013
FT /note="A -> R (in Ref. 3; AAC48734/AAD12319)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1110 AA; 120369 MW; 016502A2EDBF27B2 CRC64;
MTACTFLAGG LRDPGLCGPT RWAPSPPGLP PIPPRPRLRL RPPLLLLLLL PRSVLSAVFT
VGVLGPWACD PIFARARPDL AARLAASRLN HAAALEGGPR FEVALLPEPC RTPGSLGAVS
SALTRVSGLV GPVNPAACRP AELLAQEAGV ALVPWGCPGT RAAGTTAPVV TPAADALYAL
LRAFRWAHVA LVTAPQDLWV EAGHALSTAL RARGLPVALV TSMEPSDLSG AREALRRVQD
GPRVRAVIMV MHSVLLGGEE QRCLLEAAEE LGLADGSLVF LPFDTLHYAL SPGPDALAVL
ANSSQLRKAH DAVLTLTRHC PLGGSVRDSL RRAQEHRELP LDLNLQQVSP LFGTIYDSVF
LLAGGVARAR VAAGGGWVSG AAVARHIRDA RVPGFCGALG GAEEPSFVLL DTDATGDQLF
ATYVLDPTQG FFHSAGTPVH FPKGGRGPGP DPSCWFDPDT ICNGGVEPSV VFIGFLLVVG
MGLAGAFLAH YCRHRLLHIQ MVSGPNKIIL TLDDITFLHP HGGNSRKVAQ GSRTSLAARS
ISDVRSIHSQ LPDYTNIGLY EGDWVWLKKF PGDRHIAIRP ATKMAFSKIR ELRHENVALY
LGLFLAGGAG GPAAPGEGVL AVVSEHCARG SLQDLLAQRD IKLDWMFKSS LLLDLIKGIR
YLHHRGVAHG RLKSRNCVVD GRFVLKVTDH GHGRLLEAQR VLPEPPSAED QLWTAPELLR
DPVLERRGTL AGDVFSLGII MQEVVCRSAP YAMLELTPEE VVKRVQSPPP LCRPSVSIDQ
APMECIQLMK QCWAEQPELR PSMDRTFELF KSINKGRKMN IIDSMLRMLE QYSSNLEDLI
RERTEELELE KQKTDRLLTQ MLPPSVAEAL KMGTPVEPEY FEEVTLYFSD IVGFTTISAM
SEPIEVVDLL NDLYTLFDAI IGSHDVYKVE TIGDAYMVAS GLPQRNGHRH AAEIANMALD
ILSAVGTFRM RHMPEVPVRI RIGLHSGPCV AGVVGLTMPR YCLFGDTVNT ASAMESTGLP
YRIHVNRSTV QILSALNEGF LTEVRGRTEL KGKGAEETYW LVGRRGFNKP IPKPPDLQPG
ASNHGISLHE IPPDRRQKLE KARPGQFSGK
