ARRS_HUMAN
ID ARRS_HUMAN Reviewed; 405 AA.
AC P10523; A0FDN6; Q53SV3; Q99858;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 27-JUN-2006, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=S-arrestin;
DE AltName: Full=48 kDa protein;
DE AltName: Full=Retinal S-antigen {ECO:0000303|PubMed:3164688};
DE Short=S-AG;
DE AltName: Full=Rod photoreceptor arrestin;
GN Name=SAG;
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], AND VARIANT ALA-403.
RC TISSUE=Retina;
RX PubMed=3164688; DOI=10.1016/0014-5793(88)81298-5;
RA Yamaki K., Tsuda M., Shinohara T.;
RT "The sequence of human retinal S-antigen reveals similarities with alpha-
RT transducin.";
RL FEBS Lett. 234:39-43(1988).
RN [2]
RP ERRATUM OF PUBMED:3164688.
RA Yamaki K., Tsuda M., Shinohara T.;
RL FEBS Lett. 236:507-507(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-403.
RX PubMed=9020843; DOI=10.1038/ng0297-175;
RA Yamamoto S., Sippel K.C., Berson E.L., Dryja T.P.;
RT "Defects in the rhodopsin kinase gene in the Oguchi form of stationary
RT night blindness.";
RL Nat. Genet. 15:175-178(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-133.
RC TISSUE=Retina;
RX PubMed=17286855; DOI=10.1186/1471-2164-8-42;
RA Roni V., Carpio R., Wissinger B.;
RT "Mapping of transcription start sites of human retina expressed genes.";
RL BMC Genomics 8:42-42(2007).
RN [6]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=3720866; DOI=10.1016/0014-4835(86)90007-2;
RA McKechnie N.M., Al-Mahdawi S., Dutton G., Forrester J.V.;
RT "Ultrastructural localization of retinal S antigen in the human retina.";
RL Exp. Eye Res. 42:479-487(1986).
RN [7]
RP INVOLVEMENT IN CSNBO1, AND VARIANT VAL-76.
RX PubMed=7670478; DOI=10.1038/ng0795-360;
RA Fuchs S., Nakazawa M., Maw M., Tamai M., Oguchi Y., Gal A.;
RT "A homozygous 1-base pair deletion in the arrestin gene is a frequent cause
RT of Oguchi disease in Japanese.";
RL Nat. Genet. 10:360-362(1995).
RN [8]
RP INVOLVEMENT IN RP47, AND FUNCTION.
RX PubMed=9565049; DOI=10.1001/archopht.116.4.498;
RA Nakazawa M., Wada Y., Tamai M.;
RT "Arrestin gene mutations in autosomal recessive retinitis pigmentosa.";
RL Arch. Ophthalmol. 116:498-501(1998).
RN [9]
RP SUBUNIT.
RX PubMed=21288033; DOI=10.1021/bi1018607;
RA Kim M., Hanson S.M., Vishnivetskiy S.A., Song X., Cleghorn W.M.,
RA Hubbell W.L., Gurevich V.V.;
RT "Robust self-association is a common feature of mammalian visual arrestin-
RT 1.";
RL Biochemistry 50:2235-2242(2011).
RN [10]
RP INTERACTION WITH RHO.
RX PubMed=26200343; DOI=10.1038/nature14656;
RA Kang Y., Zhou X.E., Gao X., He Y., Liu W., Ishchenko A., Barty A.,
RA White T.A., Yefanov O., Han G.W., Xu Q., de Waal P.W., Ke J., Tan M.H.,
RA Zhang C., Moeller A., West G.M., Pascal B.D., Van Eps N., Caro L.N.,
RA Vishnivetskiy S.A., Lee R.J., Suino-Powell K.M., Gu X., Pal K., Ma J.,
RA Zhi X., Boutet S., Williams G.J., Messerschmidt M., Gati C., Zatsepin N.A.,
RA Wang D., James D., Basu S., Roy-Chowdhury S., Conrad C.E., Coe J., Liu H.,
RA Lisova S., Kupitz C., Grotjohann I., Fromme R., Jiang Y., Tan M., Yang H.,
RA Li J., Wang M., Zheng Z., Li D., Howe N., Zhao Y., Standfuss J.,
RA Diederichs K., Dong Y., Potter C.S., Carragher B., Caffrey M., Jiang H.,
RA Chapman H.N., Spence J.C., Fromme P., Weierstall U., Ernst O.P.,
RA Katritch V., Gurevich V.V., Griffin P.R., Hubbell W.L., Stevens R.C.,
RA Cherezov V., Melcher K., Xu H.E.;
RT "Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray
RT laser.";
RL Nature 523:561-567(2015).
RN [11]
RP INTERACTION WITH RHO.
RX PubMed=28753425; DOI=10.1016/j.cell.2017.07.002;
RA Zhou X.E., He Y., de Waal P.W., Gao X., Kang Y., Van Eps N., Yin Y.,
RA Pal K., Goswami D., White T.A., Barty A., Latorraca N.R., Chapman H.N.,
RA Hubbell W.L., Dror R.O., Stevens R.C., Cherezov V., Gurevich V.V.,
RA Griffin P.R., Ernst O.P., Melcher K., Xu H.E.;
RT "Identification of Phosphorylation Codes for Arrestin Recruitment by G
RT Protein-Coupled Receptors.";
RL Cell 170:457-469(2017).
RN [12]
RP VARIANTS VAL-76; CYS-84; MET-125; LEU-364; ILE-378 AND CYS-384.
RX PubMed=9501883;
RA Sippel K.C., DeStefano J.D., Berson E.L., Dryja T.P.;
RT "Evaluation of the human arrestin gene in patients with retinitis
RT pigmentosa and stationary night blindness.";
RL Invest. Ophthalmol. Vis. Sci. 39:665-670(1998).
CC -!- FUNCTION: Binds to photoactivated, phosphorylated RHO and terminates
CC RHO signaling via G-proteins by competing with G-proteins for the same
CC binding site on RHO (By similarity). May play a role in preventing
CC light-dependent degeneration of retinal photoreceptor cells
CC (PubMed:9565049). {ECO:0000250|UniProtKB:P08168,
CC ECO:0000305|PubMed:9565049}.
CC -!- SUBUNIT: Monomer. Homodimer. Homotetramer (PubMed:21288033). Interacts
CC with RHO (via the phosphorylated C-terminus) (PubMed:26200343,
CC PubMed:28753425). {ECO:0000269|PubMed:21288033,
CC ECO:0000269|PubMed:26200343, ECO:0000269|PubMed:28753425}.
CC -!- INTERACTION:
CC P10523; P49761: CLK3; NbExp=3; IntAct=EBI-1642180, EBI-745579;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium, photoreceptor outer
CC segment {ECO:0000269|PubMed:3720866}. Membrane
CC {ECO:0000250|UniProtKB:P20443}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P20443}. Note=Highly expressed in photoreceptor
CC outer segments in light-exposed retina. Evenly distributed throughout
CC rod photoreceptor cells in dark-adapted retina (By similarity).
CC Predominantly dectected at the proximal region of photoreceptor outer
CC segments, near disk membranes (PubMed:3720866).
CC {ECO:0000250|UniProtKB:P08168, ECO:0000269|PubMed:3720866}.
CC -!- TISSUE SPECIFICITY: Detected in retina, in the proximal portion of the
CC outer segment of rod photoreceptor cells (at protein level).
CC {ECO:0000269|PubMed:3720866}.
CC -!- DOMAIN: The C-terminus interferes with binding to non-phosphorylated
CC RHO. Interaction with phosphorylated RHO triggers displacement of the
CC C-terminus and leads to a conformation change that mediates high-
CC affinity RHO binding. {ECO:0000250|UniProtKB:P08168}.
CC -!- DISEASE: Night blindness, congenital stationary, Oguchi type 1 (CSNBO1)
CC [MIM:258100]: A non-progressive retinal disorder characterized by
CC impaired night vision, often associated with nystagmus and myopia.
CC Congenital stationary night blindness Oguchi type is an autosomal
CC recessive form associated with fundus discoloration and abnormally slow
CC dark adaptation. {ECO:0000269|PubMed:7670478}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Retinitis pigmentosa 47 (RP47) [MIM:613758]: 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:9565049}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the SAG gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/sagmut.htm";
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DR EMBL; X12453; CAA30984.1; -; mRNA.
DR EMBL; U70976; AAC50992.1; -; Genomic_DNA.
DR EMBL; U70962; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70963; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70964; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70965; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70966; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70967; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70968; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70969; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70970; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70971; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70972; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70973; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70974; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; U70975; AAC50992.1; JOINED; Genomic_DNA.
DR EMBL; AC013726; AAY14861.1; -; Genomic_DNA.
DR EMBL; DQ980620; ABJ97141.1; -; mRNA.
DR CCDS; CCDS46545.1; -.
DR PIR; A30357; A30357.
DR RefSeq; NP_000532.2; NM_000541.4.
DR AlphaFoldDB; P10523; -.
DR SMR; P10523; -.
DR BioGRID; 112202; 22.
DR IntAct; P10523; 3.
DR STRING; 9606.ENSP00000386444; -.
DR iPTMnet; P10523; -.
DR PhosphoSitePlus; P10523; -.
DR BioMuta; SAG; -.
DR DMDM; 109940055; -.
DR jPOST; P10523; -.
DR MassIVE; P10523; -.
DR PaxDb; P10523; -.
DR PeptideAtlas; P10523; -.
DR PRIDE; P10523; -.
DR ProteomicsDB; 52611; -.
DR Antibodypedia; 11899; 271 antibodies from 24 providers.
DR DNASU; 6295; -.
DR Ensembl; ENST00000409110.6; ENSP00000386444.1; ENSG00000130561.17.
DR Ensembl; ENST00000631149.3; ENSP00000486571.1; ENSG00000281857.3.
DR GeneID; 6295; -.
DR KEGG; hsa:6295; -.
DR MANE-Select; ENST00000409110.6; ENSP00000386444.1; NM_000541.5; NP_000532.2.
DR UCSC; uc002vuh.3; human.
DR CTD; 6295; -.
DR DisGeNET; 6295; -.
DR GeneCards; SAG; -.
DR GeneReviews; SAG; -.
DR HGNC; HGNC:10521; SAG.
DR HPA; ENSG00000130561; Tissue enriched (retina).
DR MalaCards; SAG; -.
DR MIM; 181031; gene.
DR MIM; 258100; phenotype.
DR MIM; 613758; phenotype.
DR neXtProt; NX_P10523; -.
DR OpenTargets; ENSG00000130561; -.
DR Orphanet; 215; Congenital stationary night blindness.
DR Orphanet; 75382; Oguchi disease.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA34929; -.
DR VEuPathDB; HostDB:ENSG00000130561; -.
DR eggNOG; KOG3865; Eukaryota.
DR GeneTree; ENSGT00950000182887; -.
DR HOGENOM; CLU_033484_1_1_1; -.
DR InParanoid; P10523; -.
DR OMA; GHYQDAN; -.
DR OrthoDB; 783081at2759; -.
DR PhylomeDB; P10523; -.
DR TreeFam; TF314260; -.
DR PathwayCommons; P10523; -.
DR Reactome; R-HSA-2485179; Activation of the phototransduction cascade.
DR Reactome; R-HSA-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR SignaLink; P10523; -.
DR BioGRID-ORCS; 6295; 8 hits in 1060 CRISPR screens.
DR ChiTaRS; SAG; human.
DR GeneWiki; SAG_(gene); -.
DR GenomeRNAi; 6295; -.
DR Pharos; P10523; Tbio.
DR PRO; PR:P10523; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P10523; protein.
DR Bgee; ENSG00000130561; Expressed in nucleus accumbens and 77 other tissues.
DR ExpressionAtlas; P10523; baseline and differential.
DR Genevisible; P10523; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0001917; C:photoreceptor inner segment; IBA:GO_Central.
DR GO; GO:0001750; C:photoreceptor outer segment; IDA:UniProtKB.
DR GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR GO; GO:0002046; F:opsin binding; IEA:Ensembl.
DR GO; GO:0051219; F:phosphoprotein binding; IEA:Ensembl.
DR GO; GO:0004864; F:protein phosphatase inhibitor activity; TAS:ProtInc.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0002031; P:G protein-coupled receptor internalization; IBA:GO_Central.
DR GO; GO:0016056; P:rhodopsin mediated signaling pathway; TAS:ProtInc.
DR Gene3D; 2.60.40.640; -; 1.
DR Gene3D; 2.60.40.840; -; 1.
DR InterPro; IPR000698; Arrestin.
DR InterPro; IPR014752; Arrestin-like_C.
DR InterPro; IPR011021; Arrestin-like_N.
DR InterPro; IPR011022; Arrestin_C-like.
DR InterPro; IPR017864; Arrestin_CS.
DR InterPro; IPR014753; Arrestin_N.
DR InterPro; IPR014756; Ig_E-set.
DR PANTHER; PTHR11792; PTHR11792; 1.
DR Pfam; PF02752; Arrestin_C; 1.
DR Pfam; PF00339; Arrestin_N; 1.
DR PRINTS; PR00309; ARRESTIN.
DR SMART; SM01017; Arrestin_C; 1.
DR SUPFAM; SSF81296; SSF81296; 2.
DR PROSITE; PS00295; ARRESTINS; 1.
PE 1: Evidence at protein level;
KW Cell projection; Congenital stationary night blindness; Membrane;
KW Phosphoprotein; Reference proteome; Retinitis pigmentosa.
FT CHAIN 1..405
FT /note="S-arrestin"
FT /id="PRO_0000205186"
FT MOD_RES 234
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P15887"
FT VARIANT 76
FT /note="I -> V (in dbSNP:rs7565275)"
FT /evidence="ECO:0000269|PubMed:7670478,
FT ECO:0000269|PubMed:9501883"
FT /id="VAR_008263"
FT VARIANT 84
FT /note="R -> C (in dbSNP:rs115857633)"
FT /evidence="ECO:0000269|PubMed:9501883"
FT /id="VAR_008264"
FT VARIANT 125
FT /note="T -> M (in dbSNP:rs137886124)"
FT /evidence="ECO:0000269|PubMed:9501883"
FT /id="VAR_008265"
FT VARIANT 364
FT /note="P -> L (in dbSNP:rs112613526)"
FT /evidence="ECO:0000269|PubMed:9501883"
FT /id="VAR_008266"
FT VARIANT 378
FT /note="V -> I (in dbSNP:rs200602069)"
FT /evidence="ECO:0000269|PubMed:9501883"
FT /id="VAR_008267"
FT VARIANT 384
FT /note="R -> C (in dbSNP:rs1427707173)"
FT /evidence="ECO:0000269|PubMed:9501883"
FT /id="VAR_008268"
FT VARIANT 403
FT /note="V -> A (in dbSNP:rs1046976)"
FT /evidence="ECO:0000269|PubMed:3164688,
FT ECO:0000269|PubMed:9020843"
FT /id="VAR_048333"
FT VARIANT 403
FT /note="V -> I (in dbSNP:rs1046974)"
FT /id="VAR_033524"
FT CONFLICT 176
FT /note="L -> Y (in Ref. 1; CAA30984)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="K -> S (in Ref. 1; CAA30984)"
FT /evidence="ECO:0000305"
FT CONFLICT 197
FT /note="A -> T (in Ref. 1; CAA30984)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="K -> R (in Ref. 1; CAA30984)"
FT /evidence="ECO:0000305"
FT CONFLICT 244
FT /note="F -> C (in Ref. 1; CAA30984)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="Y -> I (in Ref. 1; CAA30984)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 405 AA; 45120 MW; CBBF65845A5F891E CRC64;
MAASGKTSKS EPNHVIFKKI SRDKSVTIYL GNRDYIDHVS QVQPVDGVVL VDPDLVKGKK
VYVTLTCAFR YGQEDIDVIG LTFRRDLYFS RVQVYPPVGA ASTPTKLQES LLKKLGSNTY
PFLLTFPDYL PCSVMLQPAP QDSGKSCGVD FEVKAFATDS TDAEEDKIPK KSSVRLLIRK
VQHAPLEMGP QPRAEAAWQF FMSDKPLHLA VSLNKEIYFH GEPIPVTVTV TNNTEKTVKK
IKAFVEQVAN VVLYSSDYYV KPVAMEEAQE KVPPNSTLTK TLTLLPLLAN NRERRGIALD
GKIKHEDTNL ASSTIIKEGI DRTVLGILVS YQIKVKLTVS GFLGELTSSE VATEVPFRLM
HPQPEDPAKE SYQDANLVFE EFARHNLKDA GEAEEGKRDK NDVDE
