RGS16_HUMAN
ID RGS16_HUMAN Reviewed; 202 AA.
AC O15492; B2R4M4; Q5VYN9; Q99701;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Regulator of G-protein signaling 16;
DE Short=RGS16;
DE AltName: Full=A28-RGS14P;
DE AltName: Full=Retinal-specific RGS;
DE Short=RGS-r;
DE Short=hRGS-r;
DE AltName: Full=Retinally abundant regulator of G-protein signaling;
GN Name=RGS16; Synonyms=RGSR;
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 ARG-137.
RC TISSUE=Brain;
RX PubMed=9223279; DOI=10.1073/pnas.94.15.7868;
RA Buckbinder L., Velasco-Miguel S., Chen Y., Xu N., Talbott R., Gelbert L.,
RA Gao J., Seizinger B.R., Gutkind J.S., Kley N.;
RT "The p53 tumor suppressor targets a novel regulator of G protein
RT signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:7868-7872(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT ARG-137.
RC TISSUE=Retina;
RX PubMed=9469939; DOI=10.1016/s0378-1119(97)00593-3;
RA Snow B.E., Antonio L., Suggs S., Siderovski D.P.;
RT "Cloning of a retinally abundant regulator of G-protein signaling (RGS-
RT r/RGS16): genomic structure and chromosomal localization of the human
RT gene.";
RL Gene 206:247-253(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-137.
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-137.
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.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-137.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-137.
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-137.
RC TISSUE=Lung;
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 [9]
RP PHOSPHORYLATION AT TYR-168 BY EGFR, FUNCTION, PHOSPHORYLATION AT TYR-177,
RP AND MUTAGENESIS OF TYR-168 AND TYR-177.
RX PubMed=11602604; DOI=10.1074/jbc.m108862200;
RA Derrien A., Druey K.M.;
RT "RGS16 function is regulated by epidermal growth factor receptor-mediated
RT tyrosine phosphorylation.";
RL J. Biol. Chem. 276:48532-48538(2001).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 53-190 IN COMPLEX WITH GNAI1,
RP FUNCTION, AND INTERACTION WITH GNAI1 AND GNAQ.
RX PubMed=18434541; DOI=10.1073/pnas.0801508105;
RA Soundararajan M., Willard F.S., Kimple A.J., Turnbull A.P., Ball L.J.,
RA Schoch G.A., Gileadi C., Fedorov O.Y., Dowler E.F., Higman V.A.,
RA Hutsell S.Q., Sundstroem M., Doyle D.A., Siderovski D.P.;
RT "Structural diversity in the RGS domain and its interaction with
RT heterotrimeric G protein alpha-subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:6457-6462(2008).
CC -!- FUNCTION: Regulates G protein-coupled receptor signaling cascades.
CC Inhibits signal transduction by increasing the GTPase activity of G
CC protein alpha subunits, thereby driving them into their inactive GDP-
CC bound form (PubMed:11602604, PubMed:18434541). Plays an important role
CC in the phototransduction cascade by regulating the lifetime and
CC effective concentration of activated transducin alpha. May regulate
CC extra and intracellular mitogenic signals (By similarity).
CC {ECO:0000250|UniProtKB:P97428, ECO:0000269|PubMed:11602604,
CC ECO:0000269|PubMed:18434541}.
CC -!- SUBUNIT: Interacts with GNAI1 and GNAQ (PubMed:18434541). Interacts
CC with GNAI2, GNAI3 and GNAO1 (By similarity).
CC {ECO:0000250|UniProtKB:P97428, ECO:0000269|PubMed:18434541}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P97428}; Lipid-
CC anchor {ECO:0000250|UniProtKB:P97428}.
CC -!- TISSUE SPECIFICITY: Abundantly expressed in retina with lower levels of
CC expression in most other tissues.
CC -!- PTM: Palmitoylated on Cys-2 and/or Cys-12.
CC {ECO:0000250|UniProtKB:P97428}.
CC -!- PTM: Phosphorylated. Phosphorylation at Tyr-168 by EGFR enhances GTPase
CC accelerating (GAP) activity toward GNAI1.
CC {ECO:0000269|PubMed:11602604}.
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DR EMBL; U70426; AAC16912.1; -; mRNA.
DR EMBL; U94829; AAC52040.1; -; mRNA.
DR EMBL; AF009356; AAC39642.1; -; Genomic_DNA.
DR EMBL; AF493937; AAM12651.1; -; mRNA.
DR EMBL; BT006638; AAP35284.1; -; mRNA.
DR EMBL; AK311880; BAG34821.1; -; mRNA.
DR EMBL; AL353778; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471067; EAW91129.1; -; Genomic_DNA.
DR EMBL; BC006243; AAH06243.1; -; mRNA.
DR CCDS; CCDS1348.1; -.
DR RefSeq; NP_002919.3; NM_002928.3.
DR PDB; 2BT2; X-ray; 1.90 A; A/B/C/D/E=53-190.
DR PDB; 2IK8; X-ray; 2.71 A; B/D=53-190.
DR PDBsum; 2BT2; -.
DR PDBsum; 2IK8; -.
DR AlphaFoldDB; O15492; -.
DR SMR; O15492; -.
DR BioGRID; 111936; 14.
DR DIP; DIP-59094N; -.
DR IntAct; O15492; 3.
DR STRING; 9606.ENSP00000356529; -.
DR BindingDB; O15492; -.
DR ChEMBL; CHEMBL3707469; -.
DR iPTMnet; O15492; -.
DR PhosphoSitePlus; O15492; -.
DR SwissPalm; O15492; -.
DR BioMuta; RGS16; -.
DR MassIVE; O15492; -.
DR PaxDb; O15492; -.
DR PeptideAtlas; O15492; -.
DR PRIDE; O15492; -.
DR ProteomicsDB; 48695; -.
DR Antibodypedia; 34439; 360 antibodies from 25 providers.
DR DNASU; 6004; -.
DR Ensembl; ENST00000367558.6; ENSP00000356529.5; ENSG00000143333.7.
DR GeneID; 6004; -.
DR KEGG; hsa:6004; -.
DR MANE-Select; ENST00000367558.6; ENSP00000356529.5; NM_002928.4; NP_002919.3.
DR UCSC; uc001gpl.5; human.
DR CTD; 6004; -.
DR DisGeNET; 6004; -.
DR GeneCards; RGS16; -.
DR HGNC; HGNC:9997; RGS16.
DR HPA; ENSG00000143333; Tissue enhanced (brain, thyroid gland).
DR MIM; 602514; gene.
DR neXtProt; NX_O15492; -.
DR OpenTargets; ENSG00000143333; -.
DR PharmGKB; PA34367; -.
DR VEuPathDB; HostDB:ENSG00000143333; -.
DR eggNOG; KOG3589; Eukaryota.
DR GeneTree; ENSGT00940000154304; -.
DR HOGENOM; CLU_059863_3_0_1; -.
DR InParanoid; O15492; -.
DR OMA; KSPAYQD; -.
DR OrthoDB; 1296189at2759; -.
DR PhylomeDB; O15492; -.
DR TreeFam; TF315837; -.
DR PathwayCommons; O15492; -.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR SignaLink; O15492; -.
DR SIGNOR; O15492; -.
DR BioGRID-ORCS; 6004; 9 hits in 1073 CRISPR screens.
DR EvolutionaryTrace; O15492; -.
DR GeneWiki; RGS16; -.
DR GenomeRNAi; 6004; -.
DR Pharos; O15492; Tbio.
DR PRO; PR:O15492; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O15492; protein.
DR Bgee; ENSG00000143333; Expressed in lateral nuclear group of thalamus and 153 other tissues.
DR Genevisible; O15492; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0031224; C:intrinsic component of membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005516; F:calmodulin binding; TAS:ProtInc.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; TAS:Reactome.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0009968; P:negative regulation of signal transduction; IEA:UniProtKB-KW.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 1.10.167.10; -; 1.
DR Gene3D; 1.10.196.10; -; 2.
DR IDEAL; IID00607; -.
DR InterPro; IPR016137; RGS.
DR InterPro; IPR036305; RGS_sf.
DR InterPro; IPR024066; RGS_subdom1/3.
DR InterPro; IPR044926; RGS_subdomain_2.
DR Pfam; PF00615; RGS; 1.
DR PRINTS; PR01301; RGSPROTEIN.
DR SMART; SM00315; RGS; 1.
DR SUPFAM; SSF48097; SSF48097; 1.
DR PROSITE; PS50132; RGS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; GTPase activation; Lipoprotein; Membrane; Palmitate;
KW Phosphoprotein; Reference proteome; Signal transduction inhibitor.
FT CHAIN 1..202
FT /note="Regulator of G-protein signaling 16"
FT /id="PRO_0000204221"
FT DOMAIN 65..181
FT /note="RGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00171"
FT MOD_RES 168
FT /note="Phosphotyrosine; by EGFR"
FT /evidence="ECO:0000269|PubMed:11602604"
FT MOD_RES 177
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:11602604"
FT LIPID 2
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P97428"
FT LIPID 12
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P97428"
FT VARIANT 137
FT /note="H -> R (in dbSNP:rs1144566)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9223279,
FT ECO:0000269|PubMed:9469939, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.4, ECO:0000269|Ref.7"
FT /id="VAR_046528"
FT MUTAGEN 168
FT /note="Y->F: 30% decrease in GAP activity."
FT /evidence="ECO:0000269|PubMed:11602604"
FT MUTAGEN 177
FT /note="Y->F: No effect on GAP activity."
FT /evidence="ECO:0000269|PubMed:11602604"
FT CONFLICT 42
FT /note="F -> S (in Ref. 1; AAC16912)"
FT /evidence="ECO:0000305"
FT HELIX 53..62
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 66..70
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 73..85
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 89..101
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 107..121
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 134..143
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2BT2"
FT TURN 149..152
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 153..165
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 167..173
FT /evidence="ECO:0007829|PDB:2BT2"
FT HELIX 175..186
FT /evidence="ECO:0007829|PDB:2BT2"
SQ SEQUENCE 202 AA; 22749 MW; 19B384E935F3E5D1 CRC64;
MCRTLAAFPT TCLERAKEFK TRLGIFLHKS ELGCDTGSTG KFEWGSKHSK ENRNFSEDVL
GWRESFDLLL SSKNGVAAFH AFLKTEFSEE NLEFWLACEE FKKIRSATKL ASRAHQIFEE
FICSEAPKEV NIDHETHELT RMNLQTATAT CFDAAQGKTR TLMEKDSYPR FLKSPAYRDL
AAQASAASAT LSSCSLDEPS HT
