ID RIC3_HUMAN Reviewed; 369 AA. AC Q7Z5B4; B2RD25; Q6UX78; Q7Z5B3; Q86T94; Q8TBJ9; Q9HAH8; DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 05-OCT-2010, entry version 48. DE RecName: Full=Protein RIC-3; DE Flags: Precursor; GN Name=RIC3; ORFNames=UNQ720/PRO1385; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), ALTERNATIVE SPLICING RP (ISOFORMS 1; 2; 3 AND 4), TISSUE SPECIFICITY, AND FUNCTION. RX MEDLINE=22829964; PubMed=12821669; DOI=10.1074/jbc.M300170200; RA Halevi S., Yassin L., Eshel M., Sala F., Sala S., Criado M., RA Treinin M.; RT "Conservation within the RIC-3 gene family. Effectors of mammalian RT nicotinic acetylcholine receptor expression."; RL J. Biol. Chem. 278:34411-34417(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX MEDLINE=22887296; PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., RA Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale RT effort to identify novel human secreted and transmembrane proteins: a RT bioinformatics assessment."; RL Genome Res. 13:2265-2270(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain, and Embryo; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Spinal cord; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANT RP HIS-57. RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP FUNCTION, AND INTERACTION WITH CHRNA7. RX PubMed=15504725; DOI=10.1074/jbc.M410039200; RA Williams M.E., Burton B., Urrutia A., Shcherbatko A., RA Chavez-Noriega L.E., Cohen C.J., Aiyar J.; RT "Ric-3 promotes functional expression of the nicotinic acetylcholine RT receptor alpha7 subunit in mammalian cells."; RL J. Biol. Chem. 280:1257-1263(2005). RN [8] RP FUNCTION, INTERACTION WITH HTR3A, AND SUBCELLULAR LOCATION. RX PubMed=15809299; DOI=10.1074/jbc.M414341200; RA Cheng A., McDonald N.A., Connolly C.N.; RT "Cell surface expression of 5-hydroxytryptamine type 3 receptors is RT promoted by RIC-3."; RL J. Biol. Chem. 280:22502-22507(2005). RN [9] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15927954; DOI=10.1074/jbc.M503746200; RA Castillo M., Mulet J., Gutierrez L.M., Ortiz J.A., Castelan F., RA Gerber S., Sala S., Sala F., Criado M.; RT "Dual role of the RIC-3 protein in trafficking of serotonin and RT nicotinic acetylcholine receptors."; RL J. Biol. Chem. 280:27062-27068(2005). RN [10] RP FUNCTION, AND INTERACTION WITH CHRNA7; CHRNA3; CHRNA4; CHRNB2 AND RP CHRNB4. RX PubMed=16120769; DOI=10.1124/mol.105.017459; RA Lansdell S.J., Gee V.J., Harkness P.C., Doward A.I., Baker E.R., RA Gibb A.J., Millar N.S.; RT "RIC-3 enhances functional expression of multiple nicotinic RT acetylcholine receptor subtypes in mammalian cells."; RL Mol. Pharmacol. 68:1431-1438(2005). RN [11] RP SUBCELLULAR LOCATION, TOPOLOGY, AND FUNCTION. RX PubMed=17609200; DOI=10.1074/jbc.M703899200; RA Cheng A., Bollan K.A., Greenwood S.M., Irving A.J., Connolly C.N.; RT "Differential subcellular localization of RIC-3 isoforms and their RT role in determining 5-HT3 receptor composition."; RL J. Biol. Chem. 282:26158-26166(2007). RN [12] RP TISSUE SPECIFICITY. RX PubMed=17640815; DOI=10.1016/j.neuroscience.2007.06.008; RA Severance E.G., Yolken R.H.; RT "Lack of RIC-3 congruence with beta2 subunit-containing nicotinic RT acetylcholine receptors in bipolar disorder."; RL Neuroscience 148:454-460(2007). RN [13] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-202, AND MASS RP SPECTROMETRY. RC TISSUE=Mammary cancer; RX PubMed=17370265; DOI=10.1002/pmic.200600410; RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.; RT "Tryptic digestion of ubiquitin standards reveals an improved strategy RT for identifying ubiquitinated proteins by mass spectrometry."; RL Proteomics 7:868-874(2007). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-202, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [15] RP VARIANT [LARGE SCALE ANALYSIS] VAL-346. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Promotes functional expression of homomeric alpha-7 and CC alpha-8 nicotinic acetylcholine receptors at the cell surface. May CC also promote functional expression of homomeric serotoninergic 5- CC HT3 receptors, and of heteromeric acetylcholine receptors alpha- CC 3/beta-2, alpha-3/beta-4, alpha-4/beta-2 and alpha-4/beta-4. CC -!- SUBUNIT: Interacts with CHRNA7, CHRNA3, CHRNA4, CHRNB2, CHRNB4 and CC HTR3A. CC -!- SUBCELLULAR LOCATION: Isoform 1: Endoplasmic reticulum membrane; CC Single-pass membrane protein. CC -!- SUBCELLULAR LOCATION: Isoform 2: Endoplasmic reticulum membrane; CC Single-pass membrane protein. Golgi apparatus membrane; Single- CC pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=a; CC IsoId=Q7Z5B4-1; Sequence=Displayed; CC Name=2; Synonyms=d; CC IsoId=Q7Z5B4-2; Sequence=VSP_027940, VSP_027941; CC Note=Ref.1 (AAP92163) sequence is in conflict in position: CC 124:I->T; CC Name=3; CC IsoId=Q7Z5B4-3; Sequence=VSP_027939; CC Note=No experimental confirmation available; CC Name=4; CC IsoId=Q7Z5B4-5; Sequence=VSP_027943; CC -!- TISSUE SPECIFICITY: Broadly expressed, with high levels in muscle, CC brain and heart. Over-expressed in brains from patients with CC bipolar disease or schizophrenia. CC -!- SIMILARITY: Belongs to the ric-3 family. CC -!- SEQUENCE CAUTION: CC Sequence=BAB13871.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AY326435; AAP92162.1; -; mRNA. DR EMBL; AY326436; AAP92163.1; -; mRNA. DR EMBL; AY358475; AAQ88839.1; -; mRNA. DR EMBL; AK021670; BAB13871.1; ALT_SEQ; mRNA. DR EMBL; AK315379; BAG37772.1; -; mRNA. DR EMBL; AL832601; CAD89943.1; -; mRNA. DR EMBL; CH471064; EAW68628.1; -; Genomic_DNA. DR EMBL; BC022455; AAH22455.1; -; mRNA. DR IPI; IPI00152216; -. DR IPI; IPI00384049; -. DR IPI; IPI00432408; -. DR IPI; IPI00855702; -. DR RefSeq; NP_001128581.1; -. DR RefSeq; NP_078833.3; -. DR UniGene; Hs.231850; -. DR ProteinModelPortal; Q7Z5B4; -. DR STRING; Q7Z5B4; -. DR PhosphoSite; Q7Z5B4; -. DR PRIDE; Q7Z5B4; -. DR Ensembl; ENST00000309737; ENSP00000308820; ENSG00000166405. DR GeneID; 79608; -. DR KEGG; hsa:79608; -. DR UCSC; uc001mgb.1; human. DR UCSC; uc001mgc.1; human. DR UCSC; uc001mgd.1; human. DR UCSC; uc001mge.1; human. DR UCSC; uc001mgf.2; human. DR CTD; 79608; -. DR GeneCards; GC11M008084; -. DR HGNC; HGNC:30338; RIC3. DR MIM; 610509; gene. DR PharmGKB; PA142671066; -. DR eggNOG; prNOG09590; -. DR HOGENOM; HBG281575; -. DR HOVERGEN; HBG106009; -. DR InParanoid; Q7Z5B4; -. DR OMA; AEDRKCS; -. DR OrthoDB; EOG9TF35P; -. DR NextBio; 68650; -. DR ArrayExpress; Q7Z5B4; -. DR Bgee; Q7Z5B4; -. DR CleanEx; HS_RIC3; -. DR Genevestigator; Q7Z5B4; -. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Coiled coil; Complete proteome; KW Endoplasmic reticulum; Golgi apparatus; Isopeptide bond; Membrane; KW Polymorphism; Signal; Transmembrane; Transmembrane helix; KW Ubl conjugation. FT SIGNAL 1 28 Potential. FT CHAIN 29 369 Protein RIC-3. FT /FTId=PRO_0000302731. FT TOPO_DOM 29 95 Lumenal (Potential). FT TRANSMEM 96 116 Helical; (Potential). FT TOPO_DOM 117 369 Cytoplasmic (Potential). FT COILED 140 169 Potential. FT COMPBIAS 81 94 Poly-Gly. FT COMPBIAS 269 272 Poly-Glu. FT MOD_RES 202 202 N6-acetyllysine. FT CROSSLNK 202 202 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT VAR_SEQ 41 222 Missing (in isoform 3). FT /FTId=VSP_027939. FT VAR_SEQ 118 128 LSKGKTTAEDG -> VSRIILIILHQ (in isoform FT 2). FT /FTId=VSP_027940. FT VAR_SEQ 129 369 Missing (in isoform 2). FT /FTId=VSP_027941. FT VAR_SEQ 174 174 Missing (in isoform 4). FT /FTId=VSP_027943. FT VARIANT 57 57 P -> H (in dbSNP:rs17855498). FT /FTId=VAR_034943. FT VARIANT 130 130 C -> Y (in dbSNP:rs55990541). FT /FTId=VAR_062208. FT VARIANT 346 346 G -> V (in a colorectal cancer sample; FT somatic mutation). FT /FTId=VAR_036391. FT CONFLICT 23 23 Missing (in Ref. 1; AAP92163). FT CONFLICT 165 165 I -> F (in Ref. 6; AAH22455). SQ SEQUENCE 369 AA; 41092 MW; 15FD70384070345D CRC64; MAYSTVQRVA LASGLVLALS LLLPKAFLSR GKRQEPPPTP EGKLGRFPPM MHHHQAPSDG QTPGARFQRS HLAEAFAKAK GSGGGAGGGG SGRGLMGQII PIYGFGIFLY ILYILFKLSK GKTTAEDGKC YTAMPGNTHR KITSFELAQL QEKLKETEAA MEKLINRVGP NGESRAQTVT SDQEKRLLHQ LREITRVMKE GKFIDRFSPE KEAEEAPYME DWEGYPEETY PIYDLSDCIK RRQETILVDY PDPKELSAEE IAERMGMIEE EESDHLGWES LPTDPRAQED NSVTSCDPKP ETCSCCFHED EDPAVLAENA GFSADSYPEQ EETTKEEWSQ DFKDEGLGIS TDKAYTGSML RKRNPQGLE //