RECO_BOVIN
ID RECO_BOVIN Reviewed; 202 AA.
AC P21457;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Recoverin;
DE AltName: Full=p26;
GN Name=RCVRN; Synonyms=RCV1;
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], PROTEIN SEQUENCE OF 6-195, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=1672047; DOI=10.1126/science.1672047;
RA Dizhoor A.M., Ray S., Kumar S., Niemi G., Spencer M., Brolley D.,
RA Walsh K.A., Philipov P.P., Hurley J.B., Stryer L.;
RT "Recoverin: a calcium sensitive activator of retinal rod guanylate
RT cyclase.";
RL Science 251:915-918(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=1959664; DOI=10.1016/0014-5793(91)81143-v;
RA Kutuzov M.A., Shmukler B.E., Suslov O.N., Dergachev A.E., Zargarov A.A.,
RA Abdulaev N.G.;
RT "P26-calcium binding protein from bovine retinal photoreceptor cells.";
RL FEBS Lett. 293:21-24(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=1385864; DOI=10.1073/pnas.89.13.5705;
RA Ray S., Zozulya S., Niemi G.A., Flaherty K.M., Brolley D., Dizhoor A.M.,
RA McKay D.B., Hurley J., Stryer L.;
RT "Cloning, expression, and crystallization of recoverin, a calcium sensor in
RT vision.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5705-5709(1992).
RN [4]
RP PROTEIN SEQUENCE OF 18-36, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=1672637; DOI=10.1002/j.1460-2075.1991.tb08011.x;
RA Lambrecht H.G., Koch K.W.;
RT "A 26 kd calcium binding protein from bovine rod outer segments as
RT modulator of photoreceptor guanylate cyclase.";
RL EMBO J. 10:793-798(1991).
RN [5]
RP MYRISTOYLATION AT GLY-2.
RX PubMed=1386601; DOI=10.1016/s0021-9258(18)41959-x;
RA Dizhoor A.M., Ericsson L.H., Johnson R.S., Kumar S., Olshevskaya E.,
RA Zozulya S., Neubert T.A., Stryer L., Hurley J.B., Walsh K.A.;
RT "The NH2 terminus of retinal recoverin is acylated by a small family of
RT fatty acids.";
RL J. Biol. Chem. 267:16033-16036(1992).
RN [6]
RP SUBCELLULAR LOCATION, AND MYRISTOYLATION AT GLY-2.
RX PubMed=1454850; DOI=10.1073/pnas.89.23.11569;
RA Zozulya S., Stryer L.;
RT "Calcium-myristoyl protein switch.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:11569-11573(1992).
RN [7]
RP ROLE OF MYRISTOYLATION.
RX PubMed=8430337; DOI=10.1126/science.8430337;
RA Dizhoor A.M., Chen C.-K., Olshevskaya E., Sinelnikova V.V., Phillipov P.,
RA Hurley J.B.;
RT "Role of the acylated amino terminus of recoverin in Ca(2+)-dependent
RT membrane interaction.";
RL Science 259:829-832(1993).
RN [8]
RP RETRACTION NOTICE OF PUBMED:8430337 ON ORIGINAL PROPOSED FUNCTION.
RX PubMed=8097896; DOI=10.1126/science.8097896;
RA Hurley J.B., Dizhoor A.M., Stryer L.;
RT "Recoverin's role: conclusion withdrawn.";
RL Science 260:740-740(1993).
RN [9]
RP FUNCTION.
RX PubMed=8392055; DOI=10.1016/s0021-9258(18)82369-9;
RA Kawamura S., Hisatomi O., Kayada S., Tokunaga F., Kuo C.-H.;
RT "Recoverin has S-modulin activity in frog rods.";
RL J. Biol. Chem. 268:14579-14582(1993).
RN [10]
RP FUNCTION, AND INTERACTION WITH GRK1.
RX PubMed=16675451; DOI=10.1074/jbc.m602203200;
RA Higgins M.K., Oprian D.D., Schertler G.F.;
RT "Recoverin binds exclusively to an amphipathic peptide at the N terminus of
RT rhodopsin kinase, inhibiting rhodopsin phosphorylation without affecting
RT catalytic activity of the kinase.";
RL J. Biol. Chem. 281:19426-19432(2006).
RN [11]
RP FUNCTION, INTERACTION WITH GRK1, AND MUTAGENESIS OF PRO-190; GLN-191;
RP LYS-192; VAL-193; 185-LEU--LYS-202; 187-GLN--LYS-202; 188-PHE--LYS-202;
RP 189-GLU--LYS-202; 191-GLN--LYS-202; 193-VAL--LYS-202 AND 197-LEU--LYS-202.
RX PubMed=21299498; DOI=10.1042/bj20110013;
RA Zernii E.Y., Komolov K.E., Permyakov S.E., Kolpakova T., Dell'orco D.,
RA Poetzsch A., Knyazeva E.L., Grigoriev I.I., Permyakov E.A., Senin I.I.,
RA Philippov P.P., Koch K.W.;
RT "Involvement of the recoverin C-terminal segment in recognition of the
RT target enzyme rhodopsin kinase.";
RL Biochem. J. 435:441-450(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBUNIT, TISSUE SPECIFICITY, AND
RP OXIDATION.
RX PubMed=25772009; DOI=10.1016/j.freeradbiomed.2015.03.001;
RA Zernii E.Y., Nazipova A.A., Gancharova O.S., Kazakov A.S.,
RA Serebryakova M.V., Zinchenko D.V., Tikhomirova N.K., Senin I.I.,
RA Philippov P.P., Permyakov E.A., Permyakov S.E.;
RT "Light-induced disulfide dimerization of recoverin under ex vivo and in
RT vivo conditions.";
RL Free Radic. Biol. Med. 83:283-295(2015).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 2-202 IN COMPLEX WITH CALCIUM,
RP AND DOMAIN.
RX PubMed=8242744; DOI=10.1016/0092-8674(93)90491-8;
RA Flaherty K.M., Zozulya S., Stryer L., McKay D.B.;
RT "Three-dimensional structure of recoverin, a calcium sensor in vision.";
RL Cell 75:709-716(1993).
RN [14]
RP STRUCTURE BY NMR OF 2-202 IN COMPLEX WITH CALCIUM, DOMAIN, AND
RP MYRISTOYLATION AT GLY-2.
RX PubMed=7630423; DOI=10.1038/376444a0;
RA Tanaka T., Ames J.B., Harvey T.S., Stryer L., Ikura M.;
RT "Sequestration of the membrane-targeting myristoyl group of recoverin in
RT the calcium-free state.";
RL Nature 376:444-446(1995).
RN [15] {ECO:0007744|PDB:1JSA}
RP STRUCTURE BY NMR OF 2-202.
RX PubMed=9296500; DOI=10.1038/38310;
RA Ames J.B., Ishima R., Tanaka T., Gordon J.I., Stryer L., Ikura M.;
RT "Molecular mechanics of calcium-myristoyl switches.";
RL Nature 389:198-202(1997).
RN [16] {ECO:0007744|PDB:1LA3}
RP STRUCTURE BY NMR OF 2-202 IN COMPLEX WITH CALCIUM, DOMAIN, MYRISTOYLATION,
RP AND MUTAGENESIS OF GLU-85.
RX PubMed=11980481; DOI=10.1021/bi012153k;
RA Ames J.B., Hamasaki N., Molchanova T.;
RT "Structure and calcium-binding studies of a recoverin mutant (E85Q) in an
RT allosteric intermediate state.";
RL Biochemistry 41:5776-5787(2002).
RN [17] {ECO:0007744|PDB:1OMR, ECO:0007744|PDB:1OMV}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 2-202 IN COMPLEX WITH CALCIUM,
RP FUNCTION, DOMAIN, MYRISTOYLATION, AND MUTAGENESIS OF GLU-85.
RX PubMed=12686556; DOI=10.1074/jbc.m300447200;
RA Weiergraeber O.H., Senin I.I., Philippov P.P., Granzin J., Koch K.W.;
RT "Impact of N-terminal myristoylation on the Ca2+-dependent conformational
RT transition in recoverin.";
RL J. Biol. Chem. 278:22972-22979(2003).
RN [18] {ECO:0007744|PDB:2I94}
RP STRUCTURE BY NMR IN COMPLEX WITH CALCIUM AND GRK1 PEPTIDE, AND INTERACTION
RP WITH RHO.
RX PubMed=17020884; DOI=10.1074/jbc.m606913200;
RA Ames J.B., Levay K., Wingard J.N., Lusin J.D., Slepak V.Z.;
RT "Structural basis for calcium-induced inhibition of rhodopsin kinase by
RT recoverin.";
RL J. Biol. Chem. 281:37237-37245(2006).
RN [19] {ECO:0007744|PDB:2HET}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-190 IN COMPLEX WITH CALCIUM,
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 191-GLN--LEU-202.
RX PubMed=17015448; DOI=10.1074/jbc.m603700200;
RA Weiergraber O.H., Senin I.I., Zernii E.Y., Churumova V.A., Kovaleva N.A.,
RA Nazipova A.A., Permyakov S.E., Permyakov E.A., Philippov P.P., Granzin J.,
RA Koch K.W.;
RT "Tuning of a neuronal calcium sensor.";
RL J. Biol. Chem. 281:37594-37602(2006).
RN [20] {ECO:0007744|PDB:4M2O, ECO:0007744|PDB:4M2P, ECO:0007744|PDB:4M2Q, ECO:0007744|PDB:4MLW}
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 2-202 IN COMPLEX WITH CALCIUM,
RP INTERACTION WITH GRK1, DOMAIN, OXIDATION AT CYS-39, AND MUTAGENESIS OF
RP CYS-39 AND PRO-40.
RX PubMed=24189072; DOI=10.1074/jbc.m113.524355;
RA Ranaghan M.J., Kumar R.P., Chakrabarti K.S., Buosi V., Kern D.,
RA Oprian D.D.;
RT "A highly conserved cysteine of neuronal calcium-sensing proteins controls
RT cooperative binding of Ca2+ to recoverin.";
RL J. Biol. Chem. 288:36160-36167(2013).
RN [21] {ECO:0007744|PDB:4YI8, ECO:0007744|PDB:4YI9}
RP X-RAY CRYSTALLOGRAPHY (1.20 ANGSTROMS) OF 2-202 IN COMPLEX WITH CALCIUM,
RP INTERACTION WITH GRK1, DOMAIN, AND MUTAGENESIS OF GLU-153.
RX PubMed=26584024; DOI=10.1021/acs.biochem.5b01160;
RA Kumar R.P., Ranaghan M.J., Ganjei A.Y., Oprian D.D.;
RT "Crystal Structure of Recoverin with Calcium Ions Bound to Both Functional
RT EF Hands.";
RL Biochemistry 54:7222-7228(2015).
CC -!- FUNCTION: Acts as a calcium sensor and regulates phototransduction of
CC cone and rod photoreceptor cells (PubMed:1672047, PubMed:1672637).
CC Modulates light sensitivity of cone photoreceptor in dark and dim
CC conditions (By similarity). In response to high Ca(2+) levels induced
CC by low light levels, prolongs RHO/rhodopsin activation in rod
CC photoreceptor cells by binding to and inhibiting GRK1-mediated
CC phosphorylation of RHO/rhodopsin (PubMed:1672047, PubMed:1672637,
CC PubMed:8392055, PubMed:16675451, PubMed:21299498, PubMed:12686556,
CC PubMed:17015448). Plays a role in scotopic vision/enhances vision in
CC dim light by enhancing signal transfer between rod photoreceptors and
CC rod bipolar cells (By similarity). Improves rod photoreceptor
CC sensitivity in dim light and mediates response of rod photoreceptors to
CC facilitate detection of change and motion in bright light (By
CC similarity). {ECO:0000250|UniProtKB:P34057,
CC ECO:0000269|PubMed:12686556, ECO:0000269|PubMed:16675451,
CC ECO:0000269|PubMed:1672047, ECO:0000269|PubMed:1672637,
CC ECO:0000269|PubMed:17015448, ECO:0000269|PubMed:21299498,
CC ECO:0000269|PubMed:8392055}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:25772009).
CC Homodimerization is caused by prolonged intense illumination
CC (PubMed:25772009). May form a complex composed of RHO, GRK1 and RCVRN
CC in a Ca(2+)-dependent manner; RCVRN prevents the interaction between
CC GRK1 and RHO (PubMed:17020884). Interacts (via C-terminus) with GRK1
CC (via N-terminus); the interaction is Ca(2+)-dependent (PubMed:16675451,
CC PubMed:21299498, PubMed:24189072, PubMed:26584024).
CC {ECO:0000269|PubMed:16675451, ECO:0000269|PubMed:17020884,
CC ECO:0000269|PubMed:21299498, ECO:0000269|PubMed:24189072,
CC ECO:0000269|PubMed:25772009, ECO:0000269|PubMed:26584024}.
CC -!- INTERACTION:
CC P21457; P28327: GRK1; NbExp=2; IntAct=EBI-8592784, EBI-7865560;
CC -!- SUBCELLULAR LOCATION: Photoreceptor inner segment
CC {ECO:0000269|PubMed:1672047}. Cell projection, cilium, photoreceptor
CC outer segment {ECO:0000269|PubMed:1454850, ECO:0000269|PubMed:1672047,
CC ECO:0000269|PubMed:1672637, ECO:0000269|PubMed:17015448}. Photoreceptor
CC outer segment membrane {ECO:0000269|PubMed:1454850}; Lipid-anchor
CC {ECO:0000269|PubMed:1454850}; Cytoplasmic side
CC {ECO:0000269|PubMed:1454850}. Perikaryon
CC {ECO:0000250|UniProtKB:P34057}. Note=Primarily expressed in the inner
CC segments of light-adapted rod photoreceptors, approximately 10% of
CC which translocates from photoreceptor outer segments upon light
CC stimulation (By similarity). Targeting of myristoylated protein to rod
CC photoreceptor outer segments is calcium dependent (PubMed:17015448).
CC {ECO:0000250|UniProtKB:P34057, ECO:0000269|PubMed:17015448}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina (at protein level)
CC (PubMed:1672047, PubMed:1672637, PubMed:25772009). Expressed in the
CC pineal gland (at protein level) (PubMed:1672047).
CC {ECO:0000269|PubMed:1672047, ECO:0000269|PubMed:1672637,
CC ECO:0000269|PubMed:25772009}.
CC -!- DOMAIN: EF-hand 2 and EF-hand 3 domains are the low-affinity and the
CC high-affinity calcium binding sites, respectively (PubMed:11980481,
CC PubMed:26584024). EF-hand 1 and EF-hand 4 domains do not bind calcium
CC due to substitutions that disrupt their respective Ca(2+) binding loops
CC (Probable). The cooperative binding of calcium to the EF-hand 2 domain
CC following EF-hand 3 domain calcium binding requires myristoylation
CC (PubMed:12686556, PubMed:24189072). Calcium binding to the 2 EF-hand
CC domains induces exposure of the myristoyl group through a protein
CC conformation change, this process known as the calcium-myristoyl switch
CC facilitates binding to photoreceptor cell membranes (PubMed:7630423).
CC {ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
CC ECO:0000269|PubMed:24189072, ECO:0000269|PubMed:26584024,
CC ECO:0000269|PubMed:7630423, ECO:0000305|PubMed:26584024,
CC ECO:0000305|PubMed:8242744}.
CC -!- PTM: The N-terminal glycine is linked to one of four different types of
CC acyl groups. The most abundant is myristoleate (14:1), but 14:0, 14:2,
CC and 12:0 acyl residues are also present (PubMed:1386601,
CC PubMed:1454850, PubMed:11980481, PubMed:12686556). The Ca(2+) induced
CC exposure of the myristoyl group, known as the calcium-myristoyl switch,
CC promotes RCVRN binding to the photoreceptor cell membranes only when
CC intracellular Ca(2+) concentration is high (PubMed:7630423).
CC {ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
CC ECO:0000269|PubMed:1386601, ECO:0000269|PubMed:1454850,
CC ECO:0000269|PubMed:7630423}.
CC -!- PTM: Oxidation on Cys-39 occurs in response to prolonged intense
CC illumination and results in the formation of disulfide homodimers, and
CC to a lesser extent disulfide-linked heterodimers.
CC {ECO:0000269|PubMed:25772009}.
CC -!- SIMILARITY: Belongs to the recoverin family. {ECO:0000305}.
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DR EMBL; M95858; AAB59256.1; -; mRNA.
DR EMBL; X63322; CAA44928.1; -; mRNA.
DR PIR; A46129; A46129.
DR RefSeq; NP_776590.1; NM_174165.2.
DR PDB; 1IKU; NMR; -; A=2-202.
DR PDB; 1JSA; NMR; -; A=2-202.
DR PDB; 1LA3; NMR; -; A=2-202.
DR PDB; 1OMR; X-ray; 1.50 A; A=2-202.
DR PDB; 1OMV; X-ray; 1.90 A; A=2-202.
DR PDB; 1REC; X-ray; 1.90 A; A=2-202.
DR PDB; 2HET; X-ray; 3.00 A; A/B/C/D=2-190.
DR PDB; 2I94; NMR; -; A=1-202.
DR PDB; 4M2O; X-ray; 1.50 A; A=2-197.
DR PDB; 4M2P; X-ray; 1.45 A; A=2-202.
DR PDB; 4M2Q; X-ray; 1.90 A; A=2-202.
DR PDB; 4MLW; X-ray; 1.45 A; A=2-202.
DR PDB; 4YI8; X-ray; 1.20 A; A=2-202.
DR PDB; 4YI9; X-ray; 1.35 A; A=2-202.
DR PDBsum; 1IKU; -.
DR PDBsum; 1JSA; -.
DR PDBsum; 1LA3; -.
DR PDBsum; 1OMR; -.
DR PDBsum; 1OMV; -.
DR PDBsum; 1REC; -.
DR PDBsum; 2HET; -.
DR PDBsum; 2I94; -.
DR PDBsum; 4M2O; -.
DR PDBsum; 4M2P; -.
DR PDBsum; 4M2Q; -.
DR PDBsum; 4MLW; -.
DR PDBsum; 4YI8; -.
DR PDBsum; 4YI9; -.
DR AlphaFoldDB; P21457; -.
DR BMRB; P21457; -.
DR SMR; P21457; -.
DR ELM; P21457; -.
DR IntAct; P21457; 4.
DR MINT; P21457; -.
DR STRING; 9913.ENSBTAP00000034949; -.
DR iPTMnet; P21457; -.
DR PaxDb; P21457; -.
DR Ensembl; ENSBTAT00000035069; ENSBTAP00000034949; ENSBTAG00000025088.
DR GeneID; 281447; -.
DR KEGG; bta:281447; -.
DR CTD; 5957; -.
DR VEuPathDB; HostDB:ENSBTAG00000025088; -.
DR VGNC; VGNC:33838; RCVRN.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000159441; -.
DR HOGENOM; CLU_072366_1_0_1; -.
DR InParanoid; P21457; -.
DR OMA; WEFFGKK; -.
DR OrthoDB; 1271942at2759; -.
DR TreeFam; TF300009; -.
DR EvolutionaryTrace; P21457; -.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000025088; Expressed in retina and 36 other tissues.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0001917; C:photoreceptor inner segment; IEA:UniProtKB-SubCell.
DR GO; GO:0001750; C:photoreceptor outer segment; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR GO; GO:0007602; P:phototransduction; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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; IPR028846; Recoverin.
DR PANTHER; PTHR23055; PTHR23055; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR Pfam; PF13833; EF-hand_8; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell projection; Direct protein sequencing;
KW Disulfide bond; Lipoprotein; Membrane; Metal-binding; Myristate; Oxidation;
KW Redox-active center; Reference proteome; Repeat; Sensory transduction;
KW Vision.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:11980481,
FT ECO:0000269|PubMed:12686556, ECO:0000269|PubMed:1386601,
FT ECO:0000269|PubMed:1454850, ECO:0000269|PubMed:7630423"
FT CHAIN 2..202
FT /note="Recoverin"
FT /id="PRO_0000073758"
FT DOMAIN 24..59
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 61..96
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 97..132
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 147..182
FT /note="EF-hand 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 189..192
FT /note="Interaction with GRK1"
FT /evidence="ECO:0000269|PubMed:21299498"
FT REGION 191..202
FT /note="Modulates EF-hand 3 domain calcium binding affinity"
FT /evidence="ECO:0000269|PubMed:17015448"
FT BINDING 74
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0007744|PDB:4YI8"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0007744|PDB:4YI8"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0007744|PDB:4YI8"
FT BINDING 80
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0007744|PDB:4YI8"
FT BINDING 85
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /ligand_note="low affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0007744|PDB:4YI8"
FT BINDING 110
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
FT ECO:0000269|PubMed:17015448, ECO:0000269|PubMed:17020884,
FT ECO:0000269|PubMed:24189072, ECO:0000269|PubMed:26584024,
FT ECO:0000269|PubMed:7630423, ECO:0000269|PubMed:8242744,
FT ECO:0007744|PDB:1OMR, ECO:0007744|PDB:1OMV,
FT ECO:0007744|PDB:1REC, ECO:0007744|PDB:2HET,
FT ECO:0007744|PDB:2I94, ECO:0007744|PDB:4M2O,
FT ECO:0007744|PDB:4M2P, ECO:0007744|PDB:4M2Q,
FT ECO:0007744|PDB:4MLW, ECO:0007744|PDB:4YI8,
FT ECO:0007744|PDB:4YI9"
FT BINDING 112
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
FT ECO:0000269|PubMed:17015448, ECO:0000269|PubMed:17020884,
FT ECO:0000269|PubMed:24189072, ECO:0000269|PubMed:26584024,
FT ECO:0000269|PubMed:7630423, ECO:0000269|PubMed:8242744,
FT ECO:0007744|PDB:1OMV, ECO:0007744|PDB:1REC,
FT ECO:0007744|PDB:2HET, ECO:0007744|PDB:2I94,
FT ECO:0007744|PDB:4M2O, ECO:0007744|PDB:4M2P,
FT ECO:0007744|PDB:4M2Q, ECO:0007744|PDB:4MLW,
FT ECO:0007744|PDB:4YI8, ECO:0007744|PDB:4YI9"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
FT ECO:0000269|PubMed:17020884, ECO:0000269|PubMed:24189072,
FT ECO:0000269|PubMed:26584024, ECO:0000269|PubMed:7630423,
FT ECO:0000269|PubMed:8242744, ECO:0007744|PDB:1OMR,
FT ECO:0007744|PDB:1OMV, ECO:0007744|PDB:1REC,
FT ECO:0007744|PDB:2I94, ECO:0007744|PDB:4M2O,
FT ECO:0007744|PDB:4M2P, ECO:0007744|PDB:4M2Q,
FT ECO:0007744|PDB:4MLW, ECO:0007744|PDB:4YI8,
FT ECO:0007744|PDB:4YI9"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
FT ECO:0000269|PubMed:17015448, ECO:0000269|PubMed:17020884,
FT ECO:0000269|PubMed:24189072, ECO:0000269|PubMed:26584024,
FT ECO:0000269|PubMed:7630423, ECO:0000269|PubMed:8242744,
FT ECO:0007744|PDB:1OMR, ECO:0007744|PDB:1OMV,
FT ECO:0007744|PDB:1REC, ECO:0007744|PDB:2HET,
FT ECO:0007744|PDB:2I94, ECO:0007744|PDB:4M2O,
FT ECO:0007744|PDB:4M2P, ECO:0007744|PDB:4MLW,
FT ECO:0007744|PDB:4YI8, ECO:0007744|PDB:4YI9"
FT BINDING 121
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11980481, ECO:0000269|PubMed:12686556,
FT ECO:0000269|PubMed:17015448, ECO:0000269|PubMed:17020884,
FT ECO:0000269|PubMed:24189072, ECO:0000269|PubMed:26584024,
FT ECO:0000269|PubMed:7630423, ECO:0007744|PDB:1OMR,
FT ECO:0007744|PDB:1OMV, ECO:0007744|PDB:2HET,
FT ECO:0007744|PDB:2I94, ECO:0007744|PDB:4M2O,
FT ECO:0007744|PDB:4M2P, ECO:0007744|PDB:4M2Q,
FT ECO:0007744|PDB:4MLW, ECO:0007744|PDB:4YI8"
FT SITE 192
FT /note="Interaction with GRK1"
FT /evidence="ECO:0000269|PubMed:21299498"
FT MOD_RES 39
FT /note="Cysteine sulfenic acid (-SOH)"
FT /evidence="ECO:0000269|PubMed:24189072,
FT ECO:0000269|PubMed:25772009"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000269|PubMed:11980481,
FT ECO:0000269|PubMed:1386601, ECO:0000269|PubMed:7630423"
FT DISULFID 39
FT /note="Interchain, redox-active"
FT /evidence="ECO:0000269|PubMed:25772009"
FT MUTAGEN 39
FT /note="C->A: Increases calcium binding affinity at EF-hand
FT 3 domain; induces co-operative calcium binding in non-
FT myristoylated protein."
FT /evidence="ECO:0000269|PubMed:24189072"
FT MUTAGEN 39
FT /note="C->D: Reduces binding affinity for calcium at both
FT EF-hand 2 and EF-hand 3 domains. Abolishes interaction with
FT GRK1."
FT /evidence="ECO:0000269|PubMed:24189072"
FT MUTAGEN 40
FT /note="P->A: Reduces calcium binding affinity."
FT /evidence="ECO:0000269|PubMed:24189072"
FT MUTAGEN 85
FT /note="E->Q: Abolishes binding of calcium to EF-hand 2
FT domain. Abolishes calcium-dependent inhibition of GRK1."
FT /evidence="ECO:0000269|PubMed:11980481,
FT ECO:0000269|PubMed:12686556"
FT MUTAGEN 153
FT /note="E->A: No effect on calcium binding to EF-hand 2 and
FT EF-hand 3 domains. No effect on interaction with GRK1."
FT /evidence="ECO:0000269|PubMed:26584024"
FT MUTAGEN 185..202
FT /note="Missing: Decrease in thermostability."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 187..202
FT /note="Missing: Decrease in thermostability."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 188..202
FT /note="Missing: Decrease in thermostability."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 189..202
FT /note="Missing: Reduces calcium binding affinity. Reduces
FT interaction with GRK1. Reduces inhibition of GRK1
FT activity."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 190
FT /note="P->G: Reduces interaction with GRK1."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 191..202
FT /note="Missing: Reduces calcium binding affinity to EF-hand
FT 3 domain. Reduces interaction with GRK1."
FT /evidence="ECO:0000269|PubMed:17015448,
FT ECO:0000269|PubMed:21299498"
FT MUTAGEN 191
FT /note="Q->A: Reduces inhibition of GRK1 activity."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 192
FT /note="K->A: Reduces interaction with GRK1. Reduces
FT inhibition of GRK1 activity."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 193..202
FT /note="Missing: Reduces calcium binding affinity. Reduces
FT interaction with GRK1."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 193
FT /note="V->G: Reduces interaction with GRK1."
FT /evidence="ECO:0000269|PubMed:21299498"
FT MUTAGEN 197..202
FT /note="Missing: Reduces interaction with GRK1."
FT /evidence="ECO:0000269|PubMed:21299498"
FT CONFLICT 19
FT /note="L -> Q (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="T -> N (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 11..20
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:4YI8"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:4YI9"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:4YI8"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:1JSA"
FT HELIX 63..73
FT /evidence="ECO:0007829|PDB:4YI8"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 83..94
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 98..100
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 102..109
FT /evidence="ECO:0007829|PDB:4YI8"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 135..138
FT /evidence="ECO:0007829|PDB:4YI8"
FT STRAND 139..141
FT /evidence="ECO:0007829|PDB:2HET"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 148..158
FT /evidence="ECO:0007829|PDB:4YI8"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:1IKU"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:1JSA"
FT HELIX 169..178
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 180..186
FT /evidence="ECO:0007829|PDB:4YI8"
FT HELIX 190..196
FT /evidence="ECO:0007829|PDB:4YI8"
SQ SEQUENCE 202 AA; 23333 MW; 75504DEBE8288BA8 CRC64;
MGNSKSGALS KEILEELQLN TKFTEEELSS WYQSFLKECP SGRITRQEFQ TIYSKFFPEA
DPKAYAQHVF RSFDANSDGT LDFKEYVIAL HMTSAGKTNQ KLEWAFSLYD VDGNGTISKN
EVLEIVTAIF KMISPEDTKH LPEDENTPEK RAEKIWGFFG KKDDDKLTEK EFIEGTLANK
EILRLIQFEP QKVKEKLKEK KL
