RECO_HUMAN
ID RECO_HUMAN Reviewed; 200 AA.
AC P35243; Q53XL0;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Recoverin;
DE AltName: Full=Cancer-associated retinopathy protein;
DE Short=Protein CAR;
GN Name=RCVRN; Synonyms=RCV1;
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 [MRNA].
RC TISSUE=Retina;
RX PubMed=1387789; DOI=10.1016/s0006-291x(05)81483-4;
RA Murakami A., Yajima T., Inana G.;
RT "Isolation of human retinal genes: recoverin cDNA and gene.";
RL Biochem. Biophys. Res. Commun. 187:234-244(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RX PubMed=8500558; DOI=10.1006/exer.1993.1059;
RA Wiechmann A.F., Hammarback J.A.;
RT "Molecular cloning and nucleotide sequence of a cDNA encoding recoverin
RT from human retina.";
RL Exp. Eye Res. 56:463-470(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1388144;
RA Thirkill C.E., Tait R.C., Tyler N.K., Roth A.M., Keltner J.L.;
RT "The cancer-associated retinopathy antigen is a recoverin-like protein.";
RL Invest. Ophthalmol. Vis. Sci. 33:2768-2772(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8912538; DOI=10.1038/bjc.1996.558;
RA Matsubara S., Yamaji Y., Sato M., Fujita J., Takahara J.;
RT "Expression of a photoreceptor protein, recoverin, as a cancer-associated
RT retinopathy autoantigen in human lung cancer cell lines.";
RL Br. J. Cancer 74:1419-1422(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Subthalamic nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=21697133; DOI=10.1167/iovs.11-7479;
RA Oshikawa M., Tsutsui C., Ikegami T., Fuchida Y., Matsubara M., Toyama S.,
RA Usami R., Ohtoko K., Kato S.;
RT "Full-length transcriptome analysis of human retina-derived cell lines
RT ARPE-19 and Y79 using the vector-capping method.";
RL Invest. Ophthalmol. Vis. Sci. 52:6662-6670(2011).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=1999465; DOI=10.1083/jcb.112.5.981;
RA Polans A.S., Buczylko J., Crabb J., Palczewski K.;
RT "A photoreceptor calcium binding protein is recognized by autoantibodies
RT obtained from patients with cancer-associated retinopathy.";
RL J. Cell Biol. 112:981-989(1991).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RG RIKEN structural genomics initiative (RSGI);
RT "Crystal structure of human recoverin at 2.2 A resolution.";
RL Submitted (FEB-2007) to the PDB data bank.
CC -!- FUNCTION: Acts as a calcium sensor and regulates phototransduction of
CC cone and rod photoreceptor cells (By similarity). Modulates light
CC sensitivity of cone photoreceptor in dark and dim conditions (By
CC similarity). In response to high Ca(2+) levels induced by low light
CC levels, prolongs RHO/rhodopsin activation in rod photoreceptor cells by
CC binding to and inhibiting GRK1-mediated phosphorylation of
CC RHO/rhodopsin (By similarity). Plays a role in scotopic vision/enhances
CC vision in dim light by enhancing signal transfer between rod
CC photoreceptors and rod bipolar cells (By similarity). Improves rod
CC photoreceptor sensitivity in dim light and mediates response of rod
CC photoreceptors to facilitate detection of change and motion in bright
CC light (By similarity). {ECO:0000250|UniProtKB:P21457,
CC ECO:0000250|UniProtKB:P34057}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Homodimerization
CC is caused by prolonged intense illumination (By similarity). May form a
CC complex composed of RHO, GRK1 and RCVRN in a Ca(2+)-dependent manner;
CC RCVRN prevents the interaction between GRK1 and RHO (By similarity).
CC Interacts (via C-terminus) with GRK1 (via N-terminus); the interaction
CC is Ca(2+)-dependent (By similarity). {ECO:0000250|UniProtKB:P21457}.
CC -!- SUBCELLULAR LOCATION: Photoreceptor inner segment
CC {ECO:0000250|UniProtKB:P34057}. Cell projection, cilium, photoreceptor
CC outer segment {ECO:0000250|UniProtKB:P34057}. Photoreceptor outer
CC segment membrane {ECO:0000250|UniProtKB:P21457}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P21457}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P21457}. 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 (By similarity).
CC {ECO:0000250|UniProtKB:P21457, ECO:0000250|UniProtKB:P34057}.
CC -!- TISSUE SPECIFICITY: Retina and pineal gland.
CC -!- DOMAIN: EF-hand 2 and EF-hand 3 domains are the low-affinity and the
CC high-affinity calcium binding sites, respectively. EF-hand 1 and EF-
CC hand 4 domains do not bind calcium due to substitutions that disrupt
CC their respective Ca(2+) binding loops. The cooperative binding of
CC calcium to the EF-hand 2 domain following EF-hand 3 domain calcium
CC binding requires myristoylation (By similarity). Calcium binding to the
CC 2 EF-hand domains induces exposure of the myristoyl group through a
CC protein conformation change, this process known as the calcium-
CC myristoyl switch facilitates binding to photoreceptor cell membranes
CC (By similarity). {ECO:0000250|UniProtKB:P21457}.
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 (By similarity). The Ca(2+)
CC induced exposure of the myristoyl group, known as the calcium-myristoyl
CC switch, promotes RCVRN binding to the photoreceptor cell membranes only
CC when intracellular Ca(2+) concentration is high (By similarity).
CC {ECO:0000250|UniProtKB:P21457}.
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:0000250|UniProtKB:P21457}.
CC -!- SIMILARITY: Belongs to the recoverin family. {ECO:0000305}.
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DR EMBL; S43855; AAB23163.1; -; mRNA.
DR EMBL; S45545; AAB23392.1; -; mRNA.
DR EMBL; S62028; AAB26894.1; -; mRNA.
DR EMBL; AB001838; BAA19460.1; -; mRNA.
DR EMBL; BT009838; AAP88840.1; -; mRNA.
DR EMBL; AK314129; BAG36819.1; -; mRNA.
DR EMBL; AB593156; BAJ84088.1; -; mRNA.
DR EMBL; CH471108; EAW90014.1; -; Genomic_DNA.
DR EMBL; BC001720; AAH01720.1; -; mRNA.
DR CCDS; CCDS11151.1; -.
DR PIR; JC1227; JC1227.
DR RefSeq; NP_002894.1; NM_002903.2.
DR PDB; 2D8N; X-ray; 2.20 A; A=1-200.
DR PDBsum; 2D8N; -.
DR AlphaFoldDB; P35243; -.
DR SMR; P35243; -.
DR BioGRID; 111890; 18.
DR IntAct; P35243; 9.
DR STRING; 9606.ENSP00000226193; -.
DR DrugBank; DB08231; Myristic acid.
DR TCDB; 8.A.82.2.7; the calmodulin calcium binding protein (calmodulin) family.
DR iPTMnet; P35243; -.
DR PhosphoSitePlus; P35243; -.
DR BioMuta; RCVRN; -.
DR DMDM; 464600; -.
DR MassIVE; P35243; -.
DR PaxDb; P35243; -.
DR PeptideAtlas; P35243; -.
DR PRIDE; P35243; -.
DR ProteomicsDB; 55010; -.
DR Antibodypedia; 12699; 509 antibodies from 33 providers.
DR DNASU; 5957; -.
DR Ensembl; ENST00000226193.6; ENSP00000226193.5; ENSG00000109047.8.
DR GeneID; 5957; -.
DR KEGG; hsa:5957; -.
DR MANE-Select; ENST00000226193.6; ENSP00000226193.5; NM_002903.3; NP_002894.1.
DR UCSC; uc002gme.2; human.
DR CTD; 5957; -.
DR DisGeNET; 5957; -.
DR GeneCards; RCVRN; -.
DR HGNC; HGNC:9937; RCVRN.
DR HPA; ENSG00000109047; Tissue enriched (retina).
DR MIM; 179618; gene.
DR neXtProt; NX_P35243; -.
DR OpenTargets; ENSG00000109047; -.
DR PharmGKB; PA162400987; -.
DR VEuPathDB; HostDB:ENSG00000109047; -.
DR eggNOG; KOG0044; Eukaryota.
DR GeneTree; ENSGT00940000159441; -.
DR HOGENOM; CLU_072366_1_0_1; -.
DR InParanoid; P35243; -.
DR OMA; WEFFGKK; -.
DR OrthoDB; 1271942at2759; -.
DR PhylomeDB; P35243; -.
DR TreeFam; TF300009; -.
DR PathwayCommons; P35243; -.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR SignaLink; P35243; -.
DR BioGRID-ORCS; 5957; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; RCVRN; human.
DR EvolutionaryTrace; P35243; -.
DR GenomeRNAi; 5957; -.
DR Pharos; P35243; Tbio.
DR PRO; PR:P35243; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P35243; protein.
DR Bgee; ENSG00000109047; Expressed in eyeball of camera-type eye and 115 other tissues.
DR Genevisible; P35243; HS.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
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; TAS:ProtInc.
DR GO; GO:0008048; F:calcium sensitive guanylate cyclase activator activity; TAS:ProtInc.
DR GO; GO:0007602; P:phototransduction; IEA:Ensembl.
DR GO; GO:0051924; P:regulation of calcium ion transport; IEA:Ensembl.
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; 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; 3.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 3.
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:0000250|UniProtKB:P21457"
FT CHAIN 2..200
FT /note="Recoverin"
FT /id="PRO_0000073759"
FT DOMAIN 25..60
FT /note="EF-hand 1"
FT /evidence="ECO:0000305"
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:0000250|UniProtKB:P21457"
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:0000250|UniProtKB:P21457"
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:0000250|UniProtKB:P21457"
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:0000250|UniProtKB:P21457"
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:0000250|UniProtKB:P21457"
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:0000250|UniProtKB:P21457"
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 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 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 BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="high affinity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 SITE 192
FT /note="Interaction with GRK1"
FT /evidence="ECO:0000250|UniProtKB:P21457"
FT MOD_RES 39
FT /note="Cysteine sulfenic acid (-SOH)"
FT /evidence="ECO:0000250|UniProtKB:P21457"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT DISULFID 39
FT /note="Interchain, redox-active"
FT /evidence="ECO:0000250|UniProtKB:P21457"
FT HELIX 11..20
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:2D8N"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 46..55
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 63..73
FT /evidence="ECO:0007829|PDB:2D8N"
FT STRAND 79..82
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 83..93
FT /evidence="ECO:0007829|PDB:2D8N"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 102..109
FT /evidence="ECO:0007829|PDB:2D8N"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 119..132
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 135..139
FT /evidence="ECO:0007829|PDB:2D8N"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 148..158
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 169..178
FT /evidence="ECO:0007829|PDB:2D8N"
FT HELIX 180..186
FT /evidence="ECO:0007829|PDB:2D8N"
SQ SEQUENCE 200 AA; 23130 MW; 7B1FA91EF19E6122 CRC64;
MGNSKSGALS KEILEELQLN TKFSEEELCS WYQSFLKDCP TGRITQQQFQ SIYAKFFPDT
DPKAYAQHVF RSFDSNLDGT LDFKEYVIAL HMTTAGKTNQ KLEWAFSLYD VDGNGTISKN
EVLEIVMAIF KMITPEDVKL LPDDENTPEK RAEKIWKYFG KNDDDKLTEK EFIEGTLANK
EILRLIQFEP QKVKEKMKNA
