ID   ARRS_MOUSE              Reviewed;         403 AA.
AC   P20443; Q91W62;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 167.
DE   RecName: Full=S-arrestin;
DE   AltName: Full=48 kDa protein;
DE   AltName: Full=Retinal S-antigen;
DE            Short=S-AG;
DE   AltName: Full=Rod photoreceptor arrestin;
GN   Name=Sag;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=2977355; DOI=10.1016/0378-1119(88)90308-3;
RA   Tsuda M., Syed M., Bugra K., Whelan J.P., McGinnis J.F., Shinohara T.;
RT   "Structural analysis of mouse S-antigen.";
RL   Gene 73:11-20(1988).
RN   [2]
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   [3]
RP   DISRUPTION PHENOTYPE, FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=9333241; DOI=10.1038/39068;
RA   Xu J., Dodd R.L., Makino C.L., Simon M.I., Baylor D.A., Chen J.;
RT   "Prolonged photoresponses in transgenic mouse rods lacking arrestin.";
RL   Nature 389:505-509(1997).
RN   [4]
RP   DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=16421323; DOI=10.1523/jneurosci.3301-05.2006;
RA   Burns M.E., Mendez A., Chen C.K., Almuete A., Quillinan N., Simon M.I.,
RA   Baylor D.A., Chen J.;
RT   "Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin
RT   splice variants.";
RL   J. Neurosci. 26:1036-1044(2006).
RN   [5]
RP   SUBUNIT, AND MUTAGENESIS OF PHE-86; PHE-198 AND ALA-349.
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   [6] {ECO:0007744|PDB:4ZWJ}
RP   X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 10-392 IN COMPLEX WITH RHO, AND
RP   MUTAGENESIS OF 374-LEU--PHE-376.
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   [7] {ECO:0007744|PDB:5W0P}
RP   X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 10-392 IN COMPLEX 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).
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 (PubMed:9333241, PubMed:16421323). May play a role
CC       in preventing light-dependent degeneration of retinal photoreceptor
CC       cells (PubMed:16421323). {ECO:0000269|PubMed:16421323,
CC       ECO:0000269|PubMed:9333241}.
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   -!- SUBCELLULAR LOCATION: Cell projection, cilium, photoreceptor outer
CC       segment {ECO:0000269|PubMed:16421323}. Membrane
CC       {ECO:0000269|PubMed:16421323}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:16421323}. 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. {ECO:0000250|UniProtKB:P08168,
CC       ECO:0000250|UniProtKB:P10523}.
CC   -!- TISSUE SPECIFICITY: Detected in retina (at protein level).
CC       {ECO:0000269|PubMed:16421323, ECO:0000269|PubMed:9333241}.
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   -!- DISRUPTION PHENOTYPE: The morphology of the retina is not affected when
CC       mice are kept in constant darkness. When mice are exposed to
CC       alternating 12 hour light and dark cycles, the rod photoreceptor outer
CC       segments are about 25% shorter than in wild-type, and the photoreceptor
CC       outer segments appear somewhat disordered (PubMed:9333241). After one
CC       year exposure to alternating 12 hour light and dark cycles, there are
CC       clear signs of photoreceptor degeneration with about 50% reduction in
CC       the number of photoreceptor nuclei in the outer layer of the retina
CC       (PubMed:16421323). Rod photoreceptor cells show normal flash
CC       sensitivity, but display prolonged RHO signaling, due to a strongly
CC       decreased rate of deactivation (PubMed:9333241, PubMed:16421323).
CC       {ECO:0000269|PubMed:16421323, ECO:0000269|PubMed:9333241}.
CC   -!- SIMILARITY: Belongs to the arrestin family. {ECO:0000305}.
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DR   EMBL; M24086; AAA40090.1; -; mRNA.
DR   EMBL; BC016498; AAH16498.1; -; mRNA.
DR   CCDS; CCDS35656.1; -.
DR   PIR; JS0066; JS0066.
DR   RefSeq; NP_033144.1; NM_009118.2.
DR   PDB; 4ZWJ; X-ray; 3.30 A; A/B/C/D=10-392.
DR   PDB; 5DGY; X-ray; 7.70 A; A/B/C/D=10-392.
DR   PDB; 5W0P; X-ray; 3.01 A; A/B/C/D=10-392.
DR   PDBsum; 4ZWJ; -.
DR   PDBsum; 5DGY; -.
DR   PDBsum; 5W0P; -.
DR   AlphaFoldDB; P20443; -.
DR   SMR; P20443; -.
DR   BioGRID; 203065; 2.
DR   IntAct; P20443; 1.
DR   STRING; 10090.ENSMUSP00000076948; -.
DR   iPTMnet; P20443; -.
DR   PhosphoSitePlus; P20443; -.
DR   PaxDb; 10090-ENSMUSP00000076948; -.
DR   ProteomicsDB; 281805; -.
DR   Antibodypedia; 11899; 300 antibodies from 24 providers.
DR   DNASU; 20215; -.
DR   Ensembl; ENSMUST00000077772.12; ENSMUSP00000076948.6; ENSMUSG00000056055.15.
DR   GeneID; 20215; -.
DR   KEGG; mmu:20215; -.
DR   UCSC; uc007bxp.1; mouse.
DR   AGR; MGI:98227; -.
DR   CTD; 6295; -.
DR   MGI; MGI:98227; Sag.
DR   VEuPathDB; HostDB:ENSMUSG00000056055; -.
DR   eggNOG; KOG3865; Eukaryota.
DR   GeneTree; ENSGT00950000182887; -.
DR   HOGENOM; CLU_033484_0_0_1; -.
DR   InParanoid; P20443; -.
DR   OMA; QPAPQDM; -.
DR   OrthoDB; 3059077at2759; -.
DR   PhylomeDB; P20443; -.
DR   TreeFam; TF314260; -.
DR   Reactome; R-MMU-2514859; Inactivation, recovery and regulation of the phototransduction cascade.
DR   BioGRID-ORCS; 20215; 2 hits in 78 CRISPR screens.
DR   ChiTaRS; Sag; mouse.
DR   PRO; PR:P20443; -.
DR   Proteomes; UP000000589; Chromosome 1.
DR   RNAct; P20443; Protein.
DR   Bgee; ENSMUSG00000056055; Expressed in retinal neural layer and 55 other cell types or tissues.
DR   ExpressionAtlas; P20443; baseline and differential.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0001917; C:photoreceptor inner segment; IDA:MGI.
DR   GO; GO:0001750; C:photoreceptor outer segment; IDA:MGI.
DR   GO; GO:0001664; F:G protein-coupled receptor binding; IBA:GO_Central.
DR   GO; GO:0002046; F:opsin binding; IDA:MGI.
DR   GO; GO:0051219; F:phosphoprotein binding; IDA:MGI.
DR   GO; GO:0030507; F:spectrin binding; ISO:MGI.
DR   GO; GO:0002031; P:G protein-coupled receptor internalization; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
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; ARRESTIN; 1.
DR   PANTHER; PTHR11792:SF15; S-ARRESTIN; 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; E set domains; 2.
DR   PROSITE; PS00295; ARRESTINS; 1.
DR   Genevisible; P20443; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Cell projection; Membrane; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..403
FT                   /note="S-arrestin"
FT                   /id="PRO_0000205187"
FT   REGION          11..19
FT                   /note="Interaction with RHO"
FT                   /evidence="ECO:0000269|PubMed:28753425"
FT   REGION          381..403
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         231
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:P15887"
FT   MUTAGEN         86
FT                   /note="F->A: Abrogates tetramerization, reduces
FT                   dimerization, does not affect binding to microtubules and
FT                   to phosphorylated light-activated rhodopsin; when
FT                   associated with A-198, or with A-198 and V-349."
FT                   /evidence="ECO:0000269|PubMed:21288033"
FT   MUTAGEN         198
FT                   /note="F->A: Abrogates tetramerization, reduces
FT                   dimerization, does not affect binding to microtubules and
FT                   to phosphorylated light-activated rhodopsin; when
FT                   associated with A-86, or with A-86 and V-349."
FT                   /evidence="ECO:0000269|PubMed:21288033"
FT   MUTAGEN         349
FT                   /note="A->V: Abrogates tetramerization, reduces
FT                   dimerization, does not affect binding to microtubules and
FT                   to phosphorylated light-activated rhodopsin; when
FT                   associated with A-86 and A-198."
FT                   /evidence="ECO:0000269|PubMed:21288033"
FT   MUTAGEN         374..376
FT                   /note="LVF->AAA: Strongly increases affinity for RHO."
FT                   /evidence="ECO:0000269|PubMed:26200343"
FT   CONFLICT        391
FT                   /note="T -> P (in Ref. 2; AAH16498)"
FT                   /evidence="ECO:0000305"
FT   STRAND          13..17
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          19..28
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          30..34
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          36..39
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          42..48
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   TURN            50..52
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          53..55
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          57..69
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   HELIX           71..76
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          83..93
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   HELIX           103..111
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          116..121
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          131..133
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          144..157
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   TURN            159..162
FT                   /evidence="ECO:0007829|PDB:4ZWJ"
FT   TURN            167..169
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          171..178
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          190..195
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          204..211
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          213..216
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          221..229
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          231..233
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          235..265
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          273..281
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   HELIX           285..288
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          295..297
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          300..302
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          323..337
FT                   /evidence="ECO:0007829|PDB:5W0P"
FT   STRAND          345..358
FT                   /evidence="ECO:0007829|PDB:5W0P"
SQ   SEQUENCE   403 AA;  44930 MW;  2D4CFEAF81C5FC6D CRC64;
     MAACGKTNKS HVIFKKVSRD KSVTIYLGKR DYVDHVSQVE PVDGVVLVDP ELVKGKKVYV
     TLTCAFRYGQ EDIDVMGLTF RRDLYFSRVQ VYPPVGAMSV LTQLQESLLK KLGDNTYPFL
     LTFPDYLPCS VMLQPAPQDV GKSCGVDFEV KAFASDITDP EEDKIPKKSS VRLLIRKVQH
     APPEMGPQPS AEASWQFFMS DKPLNLSVSL SKEIYFHGEP IPVTVTVTNN TDKVVKKIKV
     SVEQIANVVL YSSDYYVKPV ASEETQEKVQ PNSTLTKTLV LVPLLANNRE RRGIALDGKI
     KHEDTNLASS TIIKEGIDRT VMGILVSYHI KVKLTVSGFL GELTSSEVAT EVPFRLMHPQ
     PEDPAKESVQ DENLVFEEFA RQNLKDTGEN TEGKKDEDAG QDE
//