Full text data of RIMS1
RIMS1
(KIAA0340, RAB3IP2, RIM1)
[Confidence: low (only semi-automatic identification from reviews)]
Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1; RIM 1; Rab-3-interacting protein 2)
Regulating synaptic membrane exocytosis protein 1 (Rab-3-interacting molecule 1; RIM 1; Rab-3-interacting protein 2)
UniProt
Q86UR5
ID RIMS1_HUMAN Reviewed; 1692 AA.
AC Q86UR5; A7MBN6; B7Z2M0; B7Z2Q9; B7Z3S3; B7Z6S2; E7EX08; E9PCB7;
read moreAC E9PCZ1; E9PF48; E9PHF5; E9PHR1; O15048; Q5JY21; Q5JY25; Q5SZK1;
AC Q8TDY9; Q8TDZ5; Q9HBA1; Q9HBA2; Q9HBA3; Q9HBA4; Q9HBA5; Q9HBA6;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Regulating synaptic membrane exocytosis protein 1;
DE AltName: Full=Rab-3-interacting molecule 1;
DE Short=RIM 1;
DE AltName: Full=Rab-3-interacting protein 2;
GN Name=RIMS1; Synonyms=KIAA0340, RAB3IP2, RIM1; ORFNames=Nbla00761;
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] (ISOFORM 1), ALTERNATIVE SPLICING, AND
RP VARIANT CORD7 HIS-820.
RX PubMed=12659814; DOI=10.1016/S0888-7543(03)00010-7;
RA Johnson S., Halford S., Morris A.G., Patel R.J., Wilkie S.E.,
RA Hardcastle A.J., Moore A.T., Zhang K., Hunt D.M.;
RT "Genomic organisation and alternative splicing of human RIM1, a gene
RT implicated in autosomal dominant cone-rod dystrophy (CORD7).";
RL Genomics 81:304-314(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Neuroblastoma;
RA Aoyama M., Asai K., Shishikura T., Ohira M., Inuzuka H., Morohashi A.,
RA Kato T., Nakagawara A.;
RT "Identification of the alternative form of human RIM.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 9; 10; 11; 12 AND
RP 13).
RC TISSUE=Brain, Small intestine, and Thalamus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 776-1692 (ISOFORMS 3; 4; 5; 6; 7 AND 8),
RP MUTAGENESIS OF 796-LYS-LYS-797 AND 1591-ARG-ARG-1592, AND INTERACTION
RP WITH SNAP25; SYT1 AND CACNA1B.
RC TISSUE=Brain;
RX PubMed=11438518; DOI=10.1074/jbc.M100929200;
RA Coppola T., Magnin-Luethi S., Perret-Menoud V., Gattesco S.,
RA Schiavo G., Regazzi R.;
RT "Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-
RT 25, and synaptotagmin.";
RL J. Biol. Chem. 276:32756-32762(2001).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1677; SER-1680; SER-1683
RP AND SER-1692, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP STRUCTURE BY NMR OF 585-694.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ domain of human KIAA0340 protein.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Rab effector involved in exocytosis. May act as scaffold
CC protein that regulates neurotransmitter release at the active
CC zone. Essential for maintaining normal probability of
CC neurotransmitter release and for regulating release during short-
CC term synaptic plasticity (By similarity).
CC -!- SUBUNIT: Binds RAB3A, RAB3B and RAB3D that have been activated by
CC GTP-binding. Interacts with RAB3C, RAB10, RAB26 AND RAB37. Binds
CC UNC13A. Interacts with BZRAP1/RIMBP1 and RIMBP2. Interacts with
CC PPFIA3 and PPFIA4. Interacts with ERC1 (By similarity). Binds
CC SNAP25, SYT1 and CACNA1B. Interaction with SYT1 is enhanced by
CC calcium ions. Interaction with SNAP25 is weaker in the presence of
CC calcium ions.
CC -!- INTERACTION:
CC P00519:ABL1; NbExp=2; IntAct=EBI-1043236, EBI-375543;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein
CC (By similarity). Cell junction, synapse (By similarity). Cell
CC junction, synapse, presynaptic cell membrane; Peripheral membrane
CC protein (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=13;
CC Comment=Additional isoforms seem to exist;
CC Name=1; Synonyms=RIM1 alpha;
CC IsoId=Q86UR5-1; Sequence=Displayed;
CC Name=2; Synonyms=RIM short form;
CC IsoId=Q86UR5-2; Sequence=VSP_008165;
CC Note=May be due to intron retention;
CC Name=3; Synonyms=RIM long form, Rab3 interacting protein variant
CC 2;
CC IsoId=Q86UR5-3; Sequence=VSP_008164, VSP_008167, VSP_008171;
CC Name=4; Synonyms=Rab3 interacting protein variant 1;
CC IsoId=Q86UR5-4; Sequence=VSP_008166, VSP_008167;
CC Name=5; Synonyms=Rab3 interacting protein variant 3;
CC IsoId=Q86UR5-5; Sequence=VSP_008161, VSP_008163, VSP_008170;
CC Name=6; Synonyms=Rab3 interacting protein variant 4;
CC IsoId=Q86UR5-6; Sequence=VSP_008164, VSP_008168, VSP_008169;
CC Name=7; Synonyms=Rab3 interacting protein variant 5;
CC IsoId=Q86UR5-7; Sequence=VSP_008161, VSP_008164, VSP_008167,
CC VSP_008169;
CC Name=8; Synonyms=Rab3 interacting protein variant 6;
CC IsoId=Q86UR5-8; Sequence=VSP_008161, VSP_008162, VSP_008169;
CC Name=9;
CC IsoId=Q86UR5-9; Sequence=VSP_043177, VSP_043178, VSP_008164,
CC VSP_043179, VSP_043180, VSP_008169;
CC Note=No experimental confirmation available;
CC Name=10;
CC IsoId=Q86UR5-10; Sequence=VSP_045486, VSP_008164, VSP_043179,
CC VSP_043180, VSP_008169;
CC Note=No experimental confirmation available;
CC Name=11;
CC IsoId=Q86UR5-11; Sequence=VSP_045485;
CC Note=No experimental confirmation available;
CC Name=12;
CC IsoId=Q86UR5-12; Sequence=VSP_046796, VSP_008161, VSP_008164,
CC VSP_043179, VSP_043180;
CC Name=13;
CC IsoId=Q86UR5-13; Sequence=VSP_046796, VSP_008164, VSP_008167,
CC VSP_008169;
CC -!- TISSUE SPECIFICITY: Detected in brain and retina.
CC -!- PTM: Phosphorylated by BRSK1 (By similarity).
CC -!- DISEASE: Cone-rod dystrophy 7 (CORD7) [MIM:603649]: An inherited
CC retinal dystrophy characterized by retinal pigment deposits
CC visible on fundus examination, predominantly in the macular
CC region, and initial loss of cone photoreceptors followed by rod
CC degeneration. This leads to decreased visual acuity and
CC sensitivity in the central visual field, followed by loss of
CC peripheral vision. Severe loss of vision occurs earlier than in
CC retinitis pigmentosa. Note=The disease may be caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 2 C2 domains.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 PDZ (DHR) domain.
CC -!- SIMILARITY: Contains 1 RabBD (Rab-binding) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20798.1; Type=Erroneous initiation;
CC Sequence=CAI39600.1; Type=Erroneous gene model prediction;
CC Sequence=CAI42135.1; Type=Erroneous gene model prediction;
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DR EMBL; AY190519; AAO38848.1; -; mRNA.
DR EMBL; AB045726; BAB87121.1; -; mRNA.
DR EMBL; AB051866; BAB87242.1; -; mRNA.
DR EMBL; AB002338; BAA20798.1; ALT_INIT; mRNA.
DR EMBL; AK296303; BAH12309.1; -; mRNA.
DR EMBL; AK294868; BAH11906.1; -; mRNA.
DR EMBL; AK295001; BAH11945.1; -; mRNA.
DR EMBL; AK300853; BAH13358.1; -; mRNA.
DR EMBL; AK309185; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL160405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590011; CAI16961.1; -; Genomic_DNA.
DR EMBL; AL034373; CAI16961.1; JOINED; Genomic_DNA.
DR EMBL; AL390056; CAI16961.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI16961.1; JOINED; Genomic_DNA.
DR EMBL; AL034373; CAI20558.1; -; Genomic_DNA.
DR EMBL; AL390056; CAI20558.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI20558.1; JOINED; Genomic_DNA.
DR EMBL; AL590011; CAI20558.1; JOINED; Genomic_DNA.
DR EMBL; AL390056; CAI21554.1; -; Genomic_DNA.
DR EMBL; AL034373; CAI21554.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI21554.1; JOINED; Genomic_DNA.
DR EMBL; AL590011; CAI21554.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI39598.1; -; Genomic_DNA.
DR EMBL; AL034373; CAI39598.1; JOINED; Genomic_DNA.
DR EMBL; AL390056; CAI39598.1; JOINED; Genomic_DNA.
DR EMBL; AL590011; CAI39598.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI39600.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL035633; CAI39600.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI39604.1; -; Genomic_DNA.
DR EMBL; AL035633; CAI39604.1; JOINED; Genomic_DNA.
DR EMBL; AL035633; CAI42135.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL445256; CAI42135.1; JOINED; Genomic_DNA.
DR EMBL; AL035633; CAI42139.1; -; Genomic_DNA.
DR EMBL; AL445256; CAI42139.1; JOINED; Genomic_DNA.
DR EMBL; BC151853; AAI51854.1; -; mRNA.
DR EMBL; BC152435; AAI52436.1; -; mRNA.
DR EMBL; AF263305; AAG23162.1; -; mRNA.
DR EMBL; AF263306; AAG23163.1; -; mRNA.
DR EMBL; AF263307; AAG23164.1; -; mRNA.
DR EMBL; AF263308; AAG23165.1; -; mRNA.
DR EMBL; AF263309; AAG23166.1; -; mRNA.
DR EMBL; AF263310; AAG23167.1; -; mRNA.
DR RefSeq; NP_001161879.1; NM_001168407.1.
DR RefSeq; NP_001161880.1; NM_001168408.1.
DR RefSeq; NP_001161881.1; NM_001168409.1.
DR RefSeq; NP_001161882.1; NM_001168410.1.
DR RefSeq; NP_001161883.1; NM_001168411.1.
DR RefSeq; NP_055804.2; NM_014989.5.
DR RefSeq; XP_005248749.1; XM_005248692.1.
DR UniGene; Hs.485729; -.
DR PDB; 2CSS; NMR; -; A=585-692.
DR PDBsum; 2CSS; -.
DR ProteinModelPortal; Q86UR5; -.
DR SMR; Q86UR5; 113-170, 583-691, 745-871, 1524-1671.
DR IntAct; Q86UR5; 5.
DR MINT; MINT-2808819; -.
DR PhosphoSite; Q86UR5; -.
DR DMDM; 34395763; -.
DR PaxDb; Q86UR5; -.
DR PRIDE; Q86UR5; -.
DR Ensembl; ENST00000264839; ENSP00000264839; ENSG00000079841.
DR Ensembl; ENST00000370420; ENSP00000359448; ENSG00000079841.
DR Ensembl; ENST00000401910; ENSP00000385649; ENSG00000079841.
DR Ensembl; ENST00000414192; ENSP00000402273; ENSG00000079841.
DR Ensembl; ENST00000425662; ENSP00000411235; ENSG00000079841.
DR Ensembl; ENST00000491071; ENSP00000430101; ENSG00000079841.
DR Ensembl; ENST00000517827; ENSP00000428367; ENSG00000079841.
DR Ensembl; ENST00000517960; ENSP00000429959; ENSG00000079841.
DR Ensembl; ENST00000518273; ENSP00000430408; ENSG00000079841.
DR Ensembl; ENST00000520567; ENSP00000430502; ENSG00000079841.
DR Ensembl; ENST00000521978; ENSP00000428417; ENSG00000079841.
DR Ensembl; ENST00000522291; ENSP00000430932; ENSG00000079841.
DR Ensembl; ENST00000523963; ENSP00000428328; ENSG00000079841.
DR GeneID; 22999; -.
DR KEGG; hsa:22999; -.
DR UCSC; uc010kar.3; human.
DR CTD; 22999; -.
DR GeneCards; GC06P072653; -.
DR HGNC; HGNC:17282; RIMS1.
DR HPA; HPA039297; -.
DR MIM; 603649; phenotype.
DR MIM; 606629; gene.
DR neXtProt; NX_Q86UR5; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR PharmGKB; PA38220; -.
DR eggNOG; NOG286957; -.
DR HOGENOM; HOG000082403; -.
DR HOVERGEN; HBG058147; -.
DR InParanoid; Q86UR5; -.
DR KO; K15291; -.
DR OMA; ERKKTPG; -.
DR OrthoDB; EOG7BGHJV; -.
DR Reactome; REACT_13685; Neuronal System.
DR ChiTaRS; RIMS1; human.
DR EvolutionaryTrace; Q86UR5; -.
DR GeneWiki; RIMS1; -.
DR GenomeRNAi; 22999; -.
DR NextBio; 43896; -.
DR PRO; PR:Q86UR5; -.
DR ArrayExpress; Q86UR5; -.
DR Bgee; Q86UR5; -.
DR Genevestigator; Q86UR5; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005083; F:small GTPase regulator activity; TAS:UniProtKB.
DR GO; GO:0017156; P:calcium ion-dependent exocytosis; TAS:UniProtKB.
DR GO; GO:0048791; P:calcium ion-dependent exocytosis of neurotransmitter; IEA:Ensembl.
DR GO; GO:0014047; P:glutamate secretion; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0061025; P:membrane fusion; NAS:UniProtKB.
DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB.
DR GO; GO:0045055; P:regulated secretory pathway; NAS:UniProtKB.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0042391; P:regulation of membrane potential; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR010911; Znf_FYVE-typ.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF02318; FYVE_2; 1.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00239; C2; 2.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF57903; SSF57903; 2.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50916; RABBD; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Complete proteome; Cone-rod dystrophy; Disease mutation; Exocytosis;
KW Membrane; Metal-binding; Neurotransmitter transport; Phosphoprotein;
KW Reference proteome; Repeat; Sensory transduction; Synapse; Transport;
KW Vision; Zinc; Zinc-finger.
FT CHAIN 1 1692 Regulating synaptic membrane exocytosis
FT protein 1.
FT /FTId=PRO_0000190198.
FT DOMAIN 22 182 RabBD.
FT DOMAIN 605 691 PDZ.
FT DOMAIN 744 850 C2 1.
FT DOMAIN 1538 1640 C2 2.
FT ZN_FING 110 170 FYVE-type.
FT COMPBIAS 1336 1402 Ser-rich.
FT MOD_RES 1677 1677 Phosphoserine.
FT MOD_RES 1680 1680 Phosphoserine.
FT MOD_RES 1683 1683 Phosphoserine.
FT MOD_RES 1692 1692 Phosphoserine.
FT VAR_SEQ 1 1473 Missing (in isoform 11).
FT /FTId=VSP_045485.
FT VAR_SEQ 1 607 Missing (in isoform 10).
FT /FTId=VSP_045486.
FT VAR_SEQ 1 559 MSSAVGPRGPRPPTVPPPMQELPDLSHLTEEERNIIMAVMD
FT RQKEEEEKEEAMLKCVVRDMAKPAACKTPRNAENQPHQPSP
FT RLHQQFESYKEQVRKIGEEARRYQGEHKDDAPTCGICHKTK
FT FADGCGHLCSYCRTKFCARCGGRVSLRSNNEDKVVMWVCNL
FT CRKQQEILTKSGAWFFGSGPQQTSQDGTLSDTATGAGSEVP
FT REKKARLQERSRSQTPLSTAAASSQDAAPPSAPPDRSKGAE
FT PSQQALGPEQKQASSRSRSEPPRERKKTPGLSEQNGKGALK
FT SERKRVPKTSAQPVEGAVEERERKERRESRRLEKGRSQDYP
FT DTPEKRDEGKAADEEKQRKEEDYQTRYRSDPNLARYPVKPP
FT PEEQQMRMHARVSRARHERRHSDVALPRTEAGAALPEGKAG
FT KRAPAAARASPPDSPRAYSAERTAETRAPGAKQLTNHSPPA
FT PRHGPVPAEAPELKAQEPLRKQSRLDPSSAVLMRKAKREKV
FT ETMLRNDSLSSDQSESVRPSPPKPHRSKRGGKKRQMSVSSS
FT EEEGVSTPEYTSCEDVELESESVSEK -> MCAPGIHVSSE
FT GWEEVRSVDSEEGTIEARRAVA (in isoform 12 and
FT isoform 13).
FT /FTId=VSP_046796.
FT VAR_SEQ 1 18 MSSAVGPRGPRPPTVPPP -> MFAGFLQFLLLHTLHSGT
FT (in isoform 9).
FT /FTId=VSP_043177.
FT VAR_SEQ 19 559 Missing (in isoform 9).
FT /FTId=VSP_043178.
FT VAR_SEQ 924 924 Missing (in isoform 5, isoform 7, isoform
FT 8 and isoform 12).
FT /FTId=VSP_008161.
FT VAR_SEQ 1018 1245 Missing (in isoform 8).
FT /FTId=VSP_008162.
FT VAR_SEQ 1038 1244 Missing (in isoform 5).
FT /FTId=VSP_008163.
FT VAR_SEQ 1039 1102 Missing (in isoform 3, isoform 6, isoform
FT 7, isoform 9, isoform 10, isoform 12 and
FT isoform 13).
FT /FTId=VSP_008164.
FT VAR_SEQ 1040 1692 Missing (in isoform 2).
FT /FTId=VSP_008165.
FT VAR_SEQ 1065 1102 Missing (in isoform 4).
FT /FTId=VSP_008166.
FT VAR_SEQ 1133 1245 Missing (in isoform 3, isoform 4, isoform
FT 7 and isoform 13).
FT /FTId=VSP_008167.
FT VAR_SEQ 1133 1160 Missing (in isoform 9, isoform 10 and
FT isoform 12).
FT /FTId=VSP_043179.
FT VAR_SEQ 1161 1245 Missing (in isoform 6).
FT /FTId=VSP_008168.
FT VAR_SEQ 1185 1245 Missing (in isoform 9, isoform 10 and
FT isoform 12).
FT /FTId=VSP_043180.
FT VAR_SEQ 1284 1455 Missing (in isoform 6, isoform 7, isoform
FT 8, isoform 9, isoform 10 and isoform 13).
FT /FTId=VSP_008169.
FT VAR_SEQ 1377 1385 Missing (in isoform 5).
FT /FTId=VSP_008170.
FT VAR_SEQ 1540 1573 Missing (in isoform 3).
FT /FTId=VSP_008171.
FT VARIANT 820 820 R -> H (in CORD7).
FT /FTId=VAR_016804.
FT MUTAGEN 796 797 RR->AA: Abolishes interaction with SYT1
FT and CACNA1B.
FT MUTAGEN 1591 1592 KK->AA: Abolishes interaction with SYT1
FT and CACNA1B.
FT CONFLICT 157 157 V -> Y (in Ref. 5; CAI16961).
FT CONFLICT 484 494 Missing (in Ref. 2; BAB87121/BAB87242, 3;
FT BAA20798 and 6; AAI51854/AAI52436).
FT CONFLICT 1272 1272 P -> S (in Ref. 4; BAH11945).
FT CONFLICT 1606 1606 Q -> R (in Ref. 4; BAH11906).
FT CONFLICT 1609 1609 V -> A (in Ref. 4; BAH13358).
FT CONFLICT 1662 1662 S -> P (in Ref. 4; AK309185).
FT STRAND 585 589
FT STRAND 591 602
FT STRAND 609 611
FT STRAND 616 625
FT STRAND 629 638
FT HELIX 643 646
FT STRAND 655 661
FT HELIX 669 678
FT HELIX 679 681
FT STRAND 685 691
SQ SEQUENCE 1692 AA; 189073 MW; 0A96642DC832C15E CRC64;
MSSAVGPRGP RPPTVPPPMQ ELPDLSHLTE EERNIIMAVM DRQKEEEEKE EAMLKCVVRD
MAKPAACKTP RNAENQPHQP SPRLHQQFES YKEQVRKIGE EARRYQGEHK DDAPTCGICH
KTKFADGCGH LCSYCRTKFC ARCGGRVSLR SNNEDKVVMW VCNLCRKQQE ILTKSGAWFF
GSGPQQTSQD GTLSDTATGA GSEVPREKKA RLQERSRSQT PLSTAAASSQ DAAPPSAPPD
RSKGAEPSQQ ALGPEQKQAS SRSRSEPPRE RKKTPGLSEQ NGKGALKSER KRVPKTSAQP
VEGAVEERER KERRESRRLE KGRSQDYPDT PEKRDEGKAA DEEKQRKEED YQTRYRSDPN
LARYPVKPPP EEQQMRMHAR VSRARHERRH SDVALPRTEA GAALPEGKAG KRAPAAARAS
PPDSPRAYSA ERTAETRAPG AKQLTNHSPP APRHGPVPAE APELKAQEPL RKQSRLDPSS
AVLMRKAKRE KVETMLRNDS LSSDQSESVR PSPPKPHRSK RGGKKRQMSV SSSEEEGVST
PEYTSCEDVE LESESVSEKG DLDYYWLDPA TWHSRETSPI SSHPVTWQPS KEGDRLIGRV
ILNKRTTMPK DSGALLGLKV VGGKMTDLGR LGAFITKVKK GSLADVVGHL RAGDEVLEWN
GKPLPGATNE EVYNIILESK SEPQVEIIVS RPIGDIPRIP ESSHPPLESS SSSFESQKME
RPSISVISPT SPGALKDAPQ VLPGQLSVKL WYDKVGHQLI VNVLQATDLP ARVDGRPRNP
YVKMYFLPDR SDKSKRRTKT VKKILEPKWN QTFVYSHVHR RDFRERMLEI TVWDQPRVQE
EESEFLGEIL IELETALLDD EPHWYKLQTH DESSLPLPQP SPFMPRRHIH GESSSKKLQR
SQRISDSDIS DYEVDDGIGV VPPVGYRSSA RESKSTTLTV PEQQRTTHHR SRSVSPHRGN
DQGKPRSRLP NVPLQRSLDE IHPTRRSRSP TRHHDASRSP VDHRTRDVDS QYLSEQDSEL
LMLPRAKRGR SAECLHTTRH LVRHYKTLPP KMPLLQSSSH WNIYSSILPA HTKTKSVTRQ
DISLHHECFN STVLRFTDEI LVSELQPFLD RARSASTNCL RPDTSLHSPE RERGRWSPSL
DRRRPPSPRI QIQHASPEND RHSRKSERSS IQKQTRKGTA SDAERVLPTC LSRRGHAAPR
ATDQPVIRGK HPARSRSSEH SSIRTLCSMH HLVPGGSAPP SPLLTRMHRQ RSPTQSPPAD
TSFSSRRGRQ LPQVPVRSGS IEQASLVVEE RTRQMKMKVH RFKQTTGSGS SQELDREQYS
KYNIHKDQYR SCDNVSAKSS DSDVSDVSAI SRTSSASRLS STSFMSEQSE RPRGRISSFT
PKMQGRRMGT SGRSIMKSTS VSGEMYTLEH NDGSQSDTAV GTVGAGGKKR RSSLSAKVVA
IVSRRSRSTS QLSQTESGHK KLKSTIQRST ETGMAAEMRK MVRQPSREST DGSINSYSSE
GNLIFPGVRL GADSQFSDFL DGLGPAQLVG RQTLATPAMG DIQIGMEDKK GQLEVEVIRA
RSLTQKPGSK STPAPYVKVY LLENGACIAK KKTRIARKTL DPLYQQSLVF DESPQGKVLQ
VIVWGDYGRM DHKCFMGVAQ ILLEELDLSS MVIGWYKLFP PSSLVDPTLT PLTRRASQSS
LESSTGPPCI RS
//
ID RIMS1_HUMAN Reviewed; 1692 AA.
AC Q86UR5; A7MBN6; B7Z2M0; B7Z2Q9; B7Z3S3; B7Z6S2; E7EX08; E9PCB7;
read moreAC E9PCZ1; E9PF48; E9PHF5; E9PHR1; O15048; Q5JY21; Q5JY25; Q5SZK1;
AC Q8TDY9; Q8TDZ5; Q9HBA1; Q9HBA2; Q9HBA3; Q9HBA4; Q9HBA5; Q9HBA6;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 22-JAN-2014, entry version 123.
DE RecName: Full=Regulating synaptic membrane exocytosis protein 1;
DE AltName: Full=Rab-3-interacting molecule 1;
DE Short=RIM 1;
DE AltName: Full=Rab-3-interacting protein 2;
GN Name=RIMS1; Synonyms=KIAA0340, RAB3IP2, RIM1; ORFNames=Nbla00761;
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] (ISOFORM 1), ALTERNATIVE SPLICING, AND
RP VARIANT CORD7 HIS-820.
RX PubMed=12659814; DOI=10.1016/S0888-7543(03)00010-7;
RA Johnson S., Halford S., Morris A.G., Patel R.J., Wilkie S.E.,
RA Hardcastle A.J., Moore A.T., Zhang K., Hunt D.M.;
RT "Genomic organisation and alternative splicing of human RIM1, a gene
RT implicated in autosomal dominant cone-rod dystrophy (CORD7).";
RL Genomics 81:304-314(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Neuroblastoma;
RA Aoyama M., Asai K., Shishikura T., Ohira M., Inuzuka H., Morohashi A.,
RA Kato T., Nakagawara A.;
RT "Identification of the alternative form of human RIM.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII.
RT The complete sequences of 100 new cDNA clones from brain which can
RT code for large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 9; 10; 11; 12 AND
RP 13).
RC TISSUE=Brain, Small intestine, and Thalamus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 NUCLEOTIDE SEQUENCE [MRNA] OF 776-1692 (ISOFORMS 3; 4; 5; 6; 7 AND 8),
RP MUTAGENESIS OF 796-LYS-LYS-797 AND 1591-ARG-ARG-1592, AND INTERACTION
RP WITH SNAP25; SYT1 AND CACNA1B.
RC TISSUE=Brain;
RX PubMed=11438518; DOI=10.1074/jbc.M100929200;
RA Coppola T., Magnin-Luethi S., Perret-Menoud V., Gattesco S.,
RA Schiavo G., Regazzi R.;
RT "Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-
RT 25, and synaptotagmin.";
RL J. Biol. Chem. 276:32756-32762(2001).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1677; SER-1680; SER-1683
RP AND SER-1692, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP STRUCTURE BY NMR OF 585-694.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ domain of human KIAA0340 protein.";
RL Submitted (NOV-2005) to the PDB data bank.
CC -!- FUNCTION: Rab effector involved in exocytosis. May act as scaffold
CC protein that regulates neurotransmitter release at the active
CC zone. Essential for maintaining normal probability of
CC neurotransmitter release and for regulating release during short-
CC term synaptic plasticity (By similarity).
CC -!- SUBUNIT: Binds RAB3A, RAB3B and RAB3D that have been activated by
CC GTP-binding. Interacts with RAB3C, RAB10, RAB26 AND RAB37. Binds
CC UNC13A. Interacts with BZRAP1/RIMBP1 and RIMBP2. Interacts with
CC PPFIA3 and PPFIA4. Interacts with ERC1 (By similarity). Binds
CC SNAP25, SYT1 and CACNA1B. Interaction with SYT1 is enhanced by
CC calcium ions. Interaction with SNAP25 is weaker in the presence of
CC calcium ions.
CC -!- INTERACTION:
CC P00519:ABL1; NbExp=2; IntAct=EBI-1043236, EBI-375543;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Peripheral membrane protein
CC (By similarity). Cell junction, synapse (By similarity). Cell
CC junction, synapse, presynaptic cell membrane; Peripheral membrane
CC protein (By similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=13;
CC Comment=Additional isoforms seem to exist;
CC Name=1; Synonyms=RIM1 alpha;
CC IsoId=Q86UR5-1; Sequence=Displayed;
CC Name=2; Synonyms=RIM short form;
CC IsoId=Q86UR5-2; Sequence=VSP_008165;
CC Note=May be due to intron retention;
CC Name=3; Synonyms=RIM long form, Rab3 interacting protein variant
CC 2;
CC IsoId=Q86UR5-3; Sequence=VSP_008164, VSP_008167, VSP_008171;
CC Name=4; Synonyms=Rab3 interacting protein variant 1;
CC IsoId=Q86UR5-4; Sequence=VSP_008166, VSP_008167;
CC Name=5; Synonyms=Rab3 interacting protein variant 3;
CC IsoId=Q86UR5-5; Sequence=VSP_008161, VSP_008163, VSP_008170;
CC Name=6; Synonyms=Rab3 interacting protein variant 4;
CC IsoId=Q86UR5-6; Sequence=VSP_008164, VSP_008168, VSP_008169;
CC Name=7; Synonyms=Rab3 interacting protein variant 5;
CC IsoId=Q86UR5-7; Sequence=VSP_008161, VSP_008164, VSP_008167,
CC VSP_008169;
CC Name=8; Synonyms=Rab3 interacting protein variant 6;
CC IsoId=Q86UR5-8; Sequence=VSP_008161, VSP_008162, VSP_008169;
CC Name=9;
CC IsoId=Q86UR5-9; Sequence=VSP_043177, VSP_043178, VSP_008164,
CC VSP_043179, VSP_043180, VSP_008169;
CC Note=No experimental confirmation available;
CC Name=10;
CC IsoId=Q86UR5-10; Sequence=VSP_045486, VSP_008164, VSP_043179,
CC VSP_043180, VSP_008169;
CC Note=No experimental confirmation available;
CC Name=11;
CC IsoId=Q86UR5-11; Sequence=VSP_045485;
CC Note=No experimental confirmation available;
CC Name=12;
CC IsoId=Q86UR5-12; Sequence=VSP_046796, VSP_008161, VSP_008164,
CC VSP_043179, VSP_043180;
CC Name=13;
CC IsoId=Q86UR5-13; Sequence=VSP_046796, VSP_008164, VSP_008167,
CC VSP_008169;
CC -!- TISSUE SPECIFICITY: Detected in brain and retina.
CC -!- PTM: Phosphorylated by BRSK1 (By similarity).
CC -!- DISEASE: Cone-rod dystrophy 7 (CORD7) [MIM:603649]: An inherited
CC retinal dystrophy characterized by retinal pigment deposits
CC visible on fundus examination, predominantly in the macular
CC region, and initial loss of cone photoreceptors followed by rod
CC degeneration. This leads to decreased visual acuity and
CC sensitivity in the central visual field, followed by loss of
CC peripheral vision. Severe loss of vision occurs earlier than in
CC retinitis pigmentosa. Note=The disease may be caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 2 C2 domains.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 PDZ (DHR) domain.
CC -!- SIMILARITY: Contains 1 RabBD (Rab-binding) domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA20798.1; Type=Erroneous initiation;
CC Sequence=CAI39600.1; Type=Erroneous gene model prediction;
CC Sequence=CAI42135.1; Type=Erroneous gene model prediction;
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DR EMBL; AY190519; AAO38848.1; -; mRNA.
DR EMBL; AB045726; BAB87121.1; -; mRNA.
DR EMBL; AB051866; BAB87242.1; -; mRNA.
DR EMBL; AB002338; BAA20798.1; ALT_INIT; mRNA.
DR EMBL; AK296303; BAH12309.1; -; mRNA.
DR EMBL; AK294868; BAH11906.1; -; mRNA.
DR EMBL; AK295001; BAH11945.1; -; mRNA.
DR EMBL; AK300853; BAH13358.1; -; mRNA.
DR EMBL; AK309185; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL160405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590011; CAI16961.1; -; Genomic_DNA.
DR EMBL; AL034373; CAI16961.1; JOINED; Genomic_DNA.
DR EMBL; AL390056; CAI16961.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI16961.1; JOINED; Genomic_DNA.
DR EMBL; AL034373; CAI20558.1; -; Genomic_DNA.
DR EMBL; AL390056; CAI20558.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI20558.1; JOINED; Genomic_DNA.
DR EMBL; AL590011; CAI20558.1; JOINED; Genomic_DNA.
DR EMBL; AL390056; CAI21554.1; -; Genomic_DNA.
DR EMBL; AL034373; CAI21554.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI21554.1; JOINED; Genomic_DNA.
DR EMBL; AL590011; CAI21554.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI39598.1; -; Genomic_DNA.
DR EMBL; AL034373; CAI39598.1; JOINED; Genomic_DNA.
DR EMBL; AL390056; CAI39598.1; JOINED; Genomic_DNA.
DR EMBL; AL590011; CAI39598.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI39600.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL035633; CAI39600.1; JOINED; Genomic_DNA.
DR EMBL; AL445256; CAI39604.1; -; Genomic_DNA.
DR EMBL; AL035633; CAI39604.1; JOINED; Genomic_DNA.
DR EMBL; AL035633; CAI42135.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AL445256; CAI42135.1; JOINED; Genomic_DNA.
DR EMBL; AL035633; CAI42139.1; -; Genomic_DNA.
DR EMBL; AL445256; CAI42139.1; JOINED; Genomic_DNA.
DR EMBL; BC151853; AAI51854.1; -; mRNA.
DR EMBL; BC152435; AAI52436.1; -; mRNA.
DR EMBL; AF263305; AAG23162.1; -; mRNA.
DR EMBL; AF263306; AAG23163.1; -; mRNA.
DR EMBL; AF263307; AAG23164.1; -; mRNA.
DR EMBL; AF263308; AAG23165.1; -; mRNA.
DR EMBL; AF263309; AAG23166.1; -; mRNA.
DR EMBL; AF263310; AAG23167.1; -; mRNA.
DR RefSeq; NP_001161879.1; NM_001168407.1.
DR RefSeq; NP_001161880.1; NM_001168408.1.
DR RefSeq; NP_001161881.1; NM_001168409.1.
DR RefSeq; NP_001161882.1; NM_001168410.1.
DR RefSeq; NP_001161883.1; NM_001168411.1.
DR RefSeq; NP_055804.2; NM_014989.5.
DR RefSeq; XP_005248749.1; XM_005248692.1.
DR UniGene; Hs.485729; -.
DR PDB; 2CSS; NMR; -; A=585-692.
DR PDBsum; 2CSS; -.
DR ProteinModelPortal; Q86UR5; -.
DR SMR; Q86UR5; 113-170, 583-691, 745-871, 1524-1671.
DR IntAct; Q86UR5; 5.
DR MINT; MINT-2808819; -.
DR PhosphoSite; Q86UR5; -.
DR DMDM; 34395763; -.
DR PaxDb; Q86UR5; -.
DR PRIDE; Q86UR5; -.
DR Ensembl; ENST00000264839; ENSP00000264839; ENSG00000079841.
DR Ensembl; ENST00000370420; ENSP00000359448; ENSG00000079841.
DR Ensembl; ENST00000401910; ENSP00000385649; ENSG00000079841.
DR Ensembl; ENST00000414192; ENSP00000402273; ENSG00000079841.
DR Ensembl; ENST00000425662; ENSP00000411235; ENSG00000079841.
DR Ensembl; ENST00000491071; ENSP00000430101; ENSG00000079841.
DR Ensembl; ENST00000517827; ENSP00000428367; ENSG00000079841.
DR Ensembl; ENST00000517960; ENSP00000429959; ENSG00000079841.
DR Ensembl; ENST00000518273; ENSP00000430408; ENSG00000079841.
DR Ensembl; ENST00000520567; ENSP00000430502; ENSG00000079841.
DR Ensembl; ENST00000521978; ENSP00000428417; ENSG00000079841.
DR Ensembl; ENST00000522291; ENSP00000430932; ENSG00000079841.
DR Ensembl; ENST00000523963; ENSP00000428328; ENSG00000079841.
DR GeneID; 22999; -.
DR KEGG; hsa:22999; -.
DR UCSC; uc010kar.3; human.
DR CTD; 22999; -.
DR GeneCards; GC06P072653; -.
DR HGNC; HGNC:17282; RIMS1.
DR HPA; HPA039297; -.
DR MIM; 603649; phenotype.
DR MIM; 606629; gene.
DR neXtProt; NX_Q86UR5; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR PharmGKB; PA38220; -.
DR eggNOG; NOG286957; -.
DR HOGENOM; HOG000082403; -.
DR HOVERGEN; HBG058147; -.
DR InParanoid; Q86UR5; -.
DR KO; K15291; -.
DR OMA; ERKKTPG; -.
DR OrthoDB; EOG7BGHJV; -.
DR Reactome; REACT_13685; Neuronal System.
DR ChiTaRS; RIMS1; human.
DR EvolutionaryTrace; Q86UR5; -.
DR GeneWiki; RIMS1; -.
DR GenomeRNAi; 22999; -.
DR NextBio; 43896; -.
DR PRO; PR:Q86UR5; -.
DR ArrayExpress; Q86UR5; -.
DR Bgee; Q86UR5; -.
DR Genevestigator; Q86UR5; -.
DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005083; F:small GTPase regulator activity; TAS:UniProtKB.
DR GO; GO:0017156; P:calcium ion-dependent exocytosis; TAS:UniProtKB.
DR GO; GO:0048791; P:calcium ion-dependent exocytosis of neurotransmitter; IEA:Ensembl.
DR GO; GO:0014047; P:glutamate secretion; TAS:Reactome.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0061025; P:membrane fusion; NAS:UniProtKB.
DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB.
DR GO; GO:0045055; P:regulated secretory pathway; NAS:UniProtKB.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0042391; P:regulation of membrane potential; IEA:Ensembl.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR017455; Znf_FYVE-rel.
DR InterPro; IPR010911; Znf_FYVE-typ.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF00168; C2; 2.
DR Pfam; PF02318; FYVE_2; 1.
DR Pfam; PF00595; PDZ; 1.
DR SMART; SM00239; C2; 2.
DR SMART; SM00228; PDZ; 1.
DR SUPFAM; SSF49562; SSF49562; 2.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF57903; SSF57903; 2.
DR PROSITE; PS50004; C2; 2.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50916; RABBD; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell junction; Cell membrane;
KW Complete proteome; Cone-rod dystrophy; Disease mutation; Exocytosis;
KW Membrane; Metal-binding; Neurotransmitter transport; Phosphoprotein;
KW Reference proteome; Repeat; Sensory transduction; Synapse; Transport;
KW Vision; Zinc; Zinc-finger.
FT CHAIN 1 1692 Regulating synaptic membrane exocytosis
FT protein 1.
FT /FTId=PRO_0000190198.
FT DOMAIN 22 182 RabBD.
FT DOMAIN 605 691 PDZ.
FT DOMAIN 744 850 C2 1.
FT DOMAIN 1538 1640 C2 2.
FT ZN_FING 110 170 FYVE-type.
FT COMPBIAS 1336 1402 Ser-rich.
FT MOD_RES 1677 1677 Phosphoserine.
FT MOD_RES 1680 1680 Phosphoserine.
FT MOD_RES 1683 1683 Phosphoserine.
FT MOD_RES 1692 1692 Phosphoserine.
FT VAR_SEQ 1 1473 Missing (in isoform 11).
FT /FTId=VSP_045485.
FT VAR_SEQ 1 607 Missing (in isoform 10).
FT /FTId=VSP_045486.
FT VAR_SEQ 1 559 MSSAVGPRGPRPPTVPPPMQELPDLSHLTEEERNIIMAVMD
FT RQKEEEEKEEAMLKCVVRDMAKPAACKTPRNAENQPHQPSP
FT RLHQQFESYKEQVRKIGEEARRYQGEHKDDAPTCGICHKTK
FT FADGCGHLCSYCRTKFCARCGGRVSLRSNNEDKVVMWVCNL
FT CRKQQEILTKSGAWFFGSGPQQTSQDGTLSDTATGAGSEVP
FT REKKARLQERSRSQTPLSTAAASSQDAAPPSAPPDRSKGAE
FT PSQQALGPEQKQASSRSRSEPPRERKKTPGLSEQNGKGALK
FT SERKRVPKTSAQPVEGAVEERERKERRESRRLEKGRSQDYP
FT DTPEKRDEGKAADEEKQRKEEDYQTRYRSDPNLARYPVKPP
FT PEEQQMRMHARVSRARHERRHSDVALPRTEAGAALPEGKAG
FT KRAPAAARASPPDSPRAYSAERTAETRAPGAKQLTNHSPPA
FT PRHGPVPAEAPELKAQEPLRKQSRLDPSSAVLMRKAKREKV
FT ETMLRNDSLSSDQSESVRPSPPKPHRSKRGGKKRQMSVSSS
FT EEEGVSTPEYTSCEDVELESESVSEK -> MCAPGIHVSSE
FT GWEEVRSVDSEEGTIEARRAVA (in isoform 12 and
FT isoform 13).
FT /FTId=VSP_046796.
FT VAR_SEQ 1 18 MSSAVGPRGPRPPTVPPP -> MFAGFLQFLLLHTLHSGT
FT (in isoform 9).
FT /FTId=VSP_043177.
FT VAR_SEQ 19 559 Missing (in isoform 9).
FT /FTId=VSP_043178.
FT VAR_SEQ 924 924 Missing (in isoform 5, isoform 7, isoform
FT 8 and isoform 12).
FT /FTId=VSP_008161.
FT VAR_SEQ 1018 1245 Missing (in isoform 8).
FT /FTId=VSP_008162.
FT VAR_SEQ 1038 1244 Missing (in isoform 5).
FT /FTId=VSP_008163.
FT VAR_SEQ 1039 1102 Missing (in isoform 3, isoform 6, isoform
FT 7, isoform 9, isoform 10, isoform 12 and
FT isoform 13).
FT /FTId=VSP_008164.
FT VAR_SEQ 1040 1692 Missing (in isoform 2).
FT /FTId=VSP_008165.
FT VAR_SEQ 1065 1102 Missing (in isoform 4).
FT /FTId=VSP_008166.
FT VAR_SEQ 1133 1245 Missing (in isoform 3, isoform 4, isoform
FT 7 and isoform 13).
FT /FTId=VSP_008167.
FT VAR_SEQ 1133 1160 Missing (in isoform 9, isoform 10 and
FT isoform 12).
FT /FTId=VSP_043179.
FT VAR_SEQ 1161 1245 Missing (in isoform 6).
FT /FTId=VSP_008168.
FT VAR_SEQ 1185 1245 Missing (in isoform 9, isoform 10 and
FT isoform 12).
FT /FTId=VSP_043180.
FT VAR_SEQ 1284 1455 Missing (in isoform 6, isoform 7, isoform
FT 8, isoform 9, isoform 10 and isoform 13).
FT /FTId=VSP_008169.
FT VAR_SEQ 1377 1385 Missing (in isoform 5).
FT /FTId=VSP_008170.
FT VAR_SEQ 1540 1573 Missing (in isoform 3).
FT /FTId=VSP_008171.
FT VARIANT 820 820 R -> H (in CORD7).
FT /FTId=VAR_016804.
FT MUTAGEN 796 797 RR->AA: Abolishes interaction with SYT1
FT and CACNA1B.
FT MUTAGEN 1591 1592 KK->AA: Abolishes interaction with SYT1
FT and CACNA1B.
FT CONFLICT 157 157 V -> Y (in Ref. 5; CAI16961).
FT CONFLICT 484 494 Missing (in Ref. 2; BAB87121/BAB87242, 3;
FT BAA20798 and 6; AAI51854/AAI52436).
FT CONFLICT 1272 1272 P -> S (in Ref. 4; BAH11945).
FT CONFLICT 1606 1606 Q -> R (in Ref. 4; BAH11906).
FT CONFLICT 1609 1609 V -> A (in Ref. 4; BAH13358).
FT CONFLICT 1662 1662 S -> P (in Ref. 4; AK309185).
FT STRAND 585 589
FT STRAND 591 602
FT STRAND 609 611
FT STRAND 616 625
FT STRAND 629 638
FT HELIX 643 646
FT STRAND 655 661
FT HELIX 669 678
FT HELIX 679 681
FT STRAND 685 691
SQ SEQUENCE 1692 AA; 189073 MW; 0A96642DC832C15E CRC64;
MSSAVGPRGP RPPTVPPPMQ ELPDLSHLTE EERNIIMAVM DRQKEEEEKE EAMLKCVVRD
MAKPAACKTP RNAENQPHQP SPRLHQQFES YKEQVRKIGE EARRYQGEHK DDAPTCGICH
KTKFADGCGH LCSYCRTKFC ARCGGRVSLR SNNEDKVVMW VCNLCRKQQE ILTKSGAWFF
GSGPQQTSQD GTLSDTATGA GSEVPREKKA RLQERSRSQT PLSTAAASSQ DAAPPSAPPD
RSKGAEPSQQ ALGPEQKQAS SRSRSEPPRE RKKTPGLSEQ NGKGALKSER KRVPKTSAQP
VEGAVEERER KERRESRRLE KGRSQDYPDT PEKRDEGKAA DEEKQRKEED YQTRYRSDPN
LARYPVKPPP EEQQMRMHAR VSRARHERRH SDVALPRTEA GAALPEGKAG KRAPAAARAS
PPDSPRAYSA ERTAETRAPG AKQLTNHSPP APRHGPVPAE APELKAQEPL RKQSRLDPSS
AVLMRKAKRE KVETMLRNDS LSSDQSESVR PSPPKPHRSK RGGKKRQMSV SSSEEEGVST
PEYTSCEDVE LESESVSEKG DLDYYWLDPA TWHSRETSPI SSHPVTWQPS KEGDRLIGRV
ILNKRTTMPK DSGALLGLKV VGGKMTDLGR LGAFITKVKK GSLADVVGHL RAGDEVLEWN
GKPLPGATNE EVYNIILESK SEPQVEIIVS RPIGDIPRIP ESSHPPLESS SSSFESQKME
RPSISVISPT SPGALKDAPQ VLPGQLSVKL WYDKVGHQLI VNVLQATDLP ARVDGRPRNP
YVKMYFLPDR SDKSKRRTKT VKKILEPKWN QTFVYSHVHR RDFRERMLEI TVWDQPRVQE
EESEFLGEIL IELETALLDD EPHWYKLQTH DESSLPLPQP SPFMPRRHIH GESSSKKLQR
SQRISDSDIS DYEVDDGIGV VPPVGYRSSA RESKSTTLTV PEQQRTTHHR SRSVSPHRGN
DQGKPRSRLP NVPLQRSLDE IHPTRRSRSP TRHHDASRSP VDHRTRDVDS QYLSEQDSEL
LMLPRAKRGR SAECLHTTRH LVRHYKTLPP KMPLLQSSSH WNIYSSILPA HTKTKSVTRQ
DISLHHECFN STVLRFTDEI LVSELQPFLD RARSASTNCL RPDTSLHSPE RERGRWSPSL
DRRRPPSPRI QIQHASPEND RHSRKSERSS IQKQTRKGTA SDAERVLPTC LSRRGHAAPR
ATDQPVIRGK HPARSRSSEH SSIRTLCSMH HLVPGGSAPP SPLLTRMHRQ RSPTQSPPAD
TSFSSRRGRQ LPQVPVRSGS IEQASLVVEE RTRQMKMKVH RFKQTTGSGS SQELDREQYS
KYNIHKDQYR SCDNVSAKSS DSDVSDVSAI SRTSSASRLS STSFMSEQSE RPRGRISSFT
PKMQGRRMGT SGRSIMKSTS VSGEMYTLEH NDGSQSDTAV GTVGAGGKKR RSSLSAKVVA
IVSRRSRSTS QLSQTESGHK KLKSTIQRST ETGMAAEMRK MVRQPSREST DGSINSYSSE
GNLIFPGVRL GADSQFSDFL DGLGPAQLVG RQTLATPAMG DIQIGMEDKK GQLEVEVIRA
RSLTQKPGSK STPAPYVKVY LLENGACIAK KKTRIARKTL DPLYQQSLVF DESPQGKVLQ
VIVWGDYGRM DHKCFMGVAQ ILLEELDLSS MVIGWYKLFP PSSLVDPTLT PLTRRASQSS
LESSTGPPCI RS
//
MIM
603649
*RECORD*
*FIELD* NO
603649
*FIELD* TI
#603649 CONE-ROD DYSTROPHY 7; CORD7
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read morecone-rod dystrophy-7 (CORD7) is caused by mutation in the RIMS1 gene
(606629).
For a general phenotypic description and a discussion of genetic
heterogeneity of cone-rod dystrophy, see 120970.
CLINICAL FEATURES
Kelsell et al. (1998) described a 4-generation British family with
autosomal dominant cone-rod dystrophy. Affected members first became
aware of reduced color vision and visual acuity between the ages of 20
and 40 years. As the disorder progressed, they reported difficulty
seeing in bright light. At the onset of symptoms, retinal pigmentary
changes were already present around the fovea, simulating a bull's eye
dystrophy, and progressed to macular atrophy.
Kniazeva et al. (1999) examined 10 members of a 4-generation family
segregating an autosomal dominant form of macular dystrophy and
identified 5 individuals with characteristic features of cone-rod
dystrophy and Stargardt disease; a sixth family member (deceased) was
classified as affected by history. Most affected individuals had gradual
onset of decreased visual acuity during the fourth decade, bilateral
macular atrophy, diffusely abnormal ERG responses, and markedly reduced
color vision. In addition, several affected individuals demonstrated
features highly suggestive of Stargardt-like disease (see 248200), such
as yellow 'flavimaculatus flecks' in the retinal pigment epithelium and
a 'dark choroid' pattern on fluorescein angiography.
MAPPING
Kelsell et al. (1998) mapped a form of autosomal dominant cone-rod
dystrophy to chromosome 6q in a 4-generation British family. Two-point
linkage data for the family excluded the 6p12 region occupied by the
gene encoding peripherin/RDS (PRPH2; 179605) and the 6q14-q16.2 region
occupied by the genes for North Carolina macular dystrophy (MCDR1;
136550) and progressive bifocal chorioretinal atrophy (PBCRA; 600790).
Haplotype analysis localized the disease-causing locus, designated
CORD7, between D6S430 and D6S1625, a region estimated to be 7 cM. The
IMPG1 gene (602870), a good functional candidate for retinal
dystrophies, maps to the same region of chromosome 6 but was shown by
Kelsell et al. (1998) to map telomeric to CORD7. An autosomal dominant
Stargardt-like disease (STGD3; 600110) maps to the same region of
chromosome 6 but is clinically distinct.
In a 4-generation family segregating autosomal dominant cone-rod
dystrophy with features of Stargardt disease, Kniazeva et al. (1999)
performed linkage analysis using DNA markers linked to known loci for
cone-rod dystrophy and dominant Stargardt disease and obtained a maximum
lod score of 3.3 (theta = 0.010) at marker D6S280 on chromosome 6q14. A
recombination event in the family defined marker D6S284 as the telomeric
marker for the genetic interval.
MOLECULAR GENETICS
In 6 affected members of the 4-generation British family with CORD7,
previously described by Kelsell et al. (1998), Johnson et al. (2003)
identified heterozygosity for a missense mutation in the RIMS1 gene
(606629.0001). The mutation was not found in 3 unaffected members of the
family or in 115 ethnically matched controls. The authors stated that
this was the first example of a mutation in a protein with a defined
role in synaptic function giving rise to a retinal disease.
*FIELD* RF
1. Johnson, S.; Halford, S.; Morris, A. G.; Patel, R. J.; Wilkie,
S. E.; Hardcastle, A. J.; Moore, A. T.; Zhang, K.; Hunt, D. M.: Genomic
organisation and alternative splicing of human RIM1, a gene implicated
in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81: 304-314,
2003.
2. Kelsell, R. E.; Gregory-Evans, K.; Gregory-Evans, C. Y.; Holder,
G. E.; Jay, M. R.; Weber, B. H. F.; Moore, A. T.; Bird, A. C.; Hunt,
D. M.: Localization of a gene (CORD7) for a dominant cone-rod dystrophy
to chromosome 6q. (Letter) Am. J. Hum. Genet. 63: 274-279, 1998.
3. Kniazeva, M.; Chiang, M. F.; Cutting, G. R.; Zack, D. J.; Han,
M.; Zhang, K.: Clinical and genetic studies of an autosomal dominant
cone-rod dystrophy with features of Stargardt disease. Ophthal. Genet. 20:
71-81, 1999.
*FIELD* CN
Marla J. F. O'Neill - updated: 3/6/2009
Marla J. F. O'Neill - updated: 9/14/2007
*FIELD* CD
Victor A. McKusick: 3/16/1999
*FIELD* ED
carol: 03/06/2009
terry: 3/6/2009
carol: 10/30/2008
carol: 7/21/2008
wwang: 9/19/2007
terry: 9/14/2007
wwang: 12/13/2006
mgross: 3/18/2004
carol: 3/16/1999
*RECORD*
*FIELD* NO
603649
*FIELD* TI
#603649 CONE-ROD DYSTROPHY 7; CORD7
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read morecone-rod dystrophy-7 (CORD7) is caused by mutation in the RIMS1 gene
(606629).
For a general phenotypic description and a discussion of genetic
heterogeneity of cone-rod dystrophy, see 120970.
CLINICAL FEATURES
Kelsell et al. (1998) described a 4-generation British family with
autosomal dominant cone-rod dystrophy. Affected members first became
aware of reduced color vision and visual acuity between the ages of 20
and 40 years. As the disorder progressed, they reported difficulty
seeing in bright light. At the onset of symptoms, retinal pigmentary
changes were already present around the fovea, simulating a bull's eye
dystrophy, and progressed to macular atrophy.
Kniazeva et al. (1999) examined 10 members of a 4-generation family
segregating an autosomal dominant form of macular dystrophy and
identified 5 individuals with characteristic features of cone-rod
dystrophy and Stargardt disease; a sixth family member (deceased) was
classified as affected by history. Most affected individuals had gradual
onset of decreased visual acuity during the fourth decade, bilateral
macular atrophy, diffusely abnormal ERG responses, and markedly reduced
color vision. In addition, several affected individuals demonstrated
features highly suggestive of Stargardt-like disease (see 248200), such
as yellow 'flavimaculatus flecks' in the retinal pigment epithelium and
a 'dark choroid' pattern on fluorescein angiography.
MAPPING
Kelsell et al. (1998) mapped a form of autosomal dominant cone-rod
dystrophy to chromosome 6q in a 4-generation British family. Two-point
linkage data for the family excluded the 6p12 region occupied by the
gene encoding peripherin/RDS (PRPH2; 179605) and the 6q14-q16.2 region
occupied by the genes for North Carolina macular dystrophy (MCDR1;
136550) and progressive bifocal chorioretinal atrophy (PBCRA; 600790).
Haplotype analysis localized the disease-causing locus, designated
CORD7, between D6S430 and D6S1625, a region estimated to be 7 cM. The
IMPG1 gene (602870), a good functional candidate for retinal
dystrophies, maps to the same region of chromosome 6 but was shown by
Kelsell et al. (1998) to map telomeric to CORD7. An autosomal dominant
Stargardt-like disease (STGD3; 600110) maps to the same region of
chromosome 6 but is clinically distinct.
In a 4-generation family segregating autosomal dominant cone-rod
dystrophy with features of Stargardt disease, Kniazeva et al. (1999)
performed linkage analysis using DNA markers linked to known loci for
cone-rod dystrophy and dominant Stargardt disease and obtained a maximum
lod score of 3.3 (theta = 0.010) at marker D6S280 on chromosome 6q14. A
recombination event in the family defined marker D6S284 as the telomeric
marker for the genetic interval.
MOLECULAR GENETICS
In 6 affected members of the 4-generation British family with CORD7,
previously described by Kelsell et al. (1998), Johnson et al. (2003)
identified heterozygosity for a missense mutation in the RIMS1 gene
(606629.0001). The mutation was not found in 3 unaffected members of the
family or in 115 ethnically matched controls. The authors stated that
this was the first example of a mutation in a protein with a defined
role in synaptic function giving rise to a retinal disease.
*FIELD* RF
1. Johnson, S.; Halford, S.; Morris, A. G.; Patel, R. J.; Wilkie,
S. E.; Hardcastle, A. J.; Moore, A. T.; Zhang, K.; Hunt, D. M.: Genomic
organisation and alternative splicing of human RIM1, a gene implicated
in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81: 304-314,
2003.
2. Kelsell, R. E.; Gregory-Evans, K.; Gregory-Evans, C. Y.; Holder,
G. E.; Jay, M. R.; Weber, B. H. F.; Moore, A. T.; Bird, A. C.; Hunt,
D. M.: Localization of a gene (CORD7) for a dominant cone-rod dystrophy
to chromosome 6q. (Letter) Am. J. Hum. Genet. 63: 274-279, 1998.
3. Kniazeva, M.; Chiang, M. F.; Cutting, G. R.; Zack, D. J.; Han,
M.; Zhang, K.: Clinical and genetic studies of an autosomal dominant
cone-rod dystrophy with features of Stargardt disease. Ophthal. Genet. 20:
71-81, 1999.
*FIELD* CN
Marla J. F. O'Neill - updated: 3/6/2009
Marla J. F. O'Neill - updated: 9/14/2007
*FIELD* CD
Victor A. McKusick: 3/16/1999
*FIELD* ED
carol: 03/06/2009
terry: 3/6/2009
carol: 10/30/2008
carol: 7/21/2008
wwang: 9/19/2007
terry: 9/14/2007
wwang: 12/13/2006
mgross: 3/18/2004
carol: 3/16/1999
MIM
606629
*RECORD*
*FIELD* NO
606629
*FIELD* TI
*606629 PROTEIN REGULATING SYNAPTIC MEMBRANE EXOCYTOSIS 1; RIMS1
;;RAB3A-INTERACTING MOLECULE 1; RIM1;;
read moreRIM;;
KIAA0340
*FIELD* TX
DESCRIPTION
RAB3A (179490), a member of the RAS gene superfamily, is a synaptic
vesicle protein that regulates synaptic vesicle exocytosis. MUNC13
(UNC13; 605836) and its isoforms are required for priming synaptic
vesicles for exocytosis. The RIM family of active zone proteins likely
function as protein scaffolds that help regulate vesicle exocytosis
during short-term plasticity.
CLONING
By screening for cDNAs with the potential to encode large proteins
expressed in brain, Nagase et al. (1997) identified a cDNA encoding
RIM1, which they called KIAA0340. The deduced 1,053-amino acid protein
was predicted to be weakly homologous to mouse rabphilin-3A (612159) and
to be involved in cell signaling/communication. RT-PCR analysis detected
expression of KIAA0340 only in brain and testis.
Coppola et al. (2001) obtained 6 isoforms of human RIM that differ from
each other in the distance between their 2 C2 domains. Binding analysis
showed that the C2 domains of RIM interact in a calcium-independent
manner with N-type calcium channels. They also interact weakly with
SNAP25 (600322) and strongly with synaptotagmin-1 (SYT1; 185605). In the
presence of calcium, the interaction with SYT1 increases and that with
SNAP25 decreases. Coppola et al. (2001) concluded that RIM1 is a
scaffold protein that interacts with multiple binding partners and
coordinates different stages of the secretory process.
Johnson et al. (2003) stated that the 1,693-amino acid RIMS1 protein
contains an N-terminal RAB3A (179490)-GTP-binding site, followed by a
pair of C4-type zinc fingers, a PDZ domain, and 2 C-terminal C2 domains
separated by an SH3-binding domain. By PCR of retina and brain cDNA
libraries, followed by screening an adult retinal cDNA library, they
cloned several RIMS1 variants. PCR analysis of normal human tissues
detected RIMS1 only in retina and brain.
GENE FUNCTION
Wang et al. (2000) showed that Rim1 and Rim2 bound to Rab3a and to the
Rim-binding proteins Rimbp1 (BZRAP1; 610764) and Rimbp2 (611602) in rat.
Betz et al. (2001) demonstrated an interaction between the N-terminal
zinc finger of Rim1 and Munc13 in rat.
GENE STRUCTURE
Johnson et al. (2003) determined that the RIMS1 gene contains 34 exons
and spans about 577 kb.
MAPPING
Using radiation hybrid analysis, Nagase et al. (1997) mapped the RIMS1
gene to chromosome 6. By genomic sequence analysis, Wang and Sudhof
(2003) mapped the RIMS1 gene to human chromosome 6q14 and to mouse
chromosome 1A3.
MOLECULAR GENETICS
Johnson et al. (2003) identified a missense mutation in the RIMS1 gene
(606629.0001) in a 4-generation British family with autosomal dominant
cone-rod dystrophy mapping to chromosome 6q (CORD7; 603649), previously
described by Kelsell et al. (1998). The authors stated that this was the
first example of a mutation in a protein with a defined role in synaptic
function giving rise to a retinal disease.
ANIMAL MODEL
By targeted deletion of exon 1 of the Rim1 gene, Schoch et al. (2002)
abolished expression of the largest and most-abundant Rim1 isoform,
Rim1-alpha, in mice. The mutant mice were fertile and viable but had a
deficit in maternal behavior and a decrease in expression of Munc13-1,
but in not other Munc isoforms. A moderate increase in postsynaptic
density proteins was observed, but it did not lead to overall remodeling
of synapses. Homozygous Rim1-deficient mice and Rab3a-deficient mice had
increased PPF (paired-pulse facilitation, which is the enhancement of
transmitter release in response to 2 closely spaced stimuli) at short
interstimulus intervals (ISIs), while heterozygous Munc13-deficient mice
had no change in PPF at short ISIs. Overall electrophysiologic analyses
determined that Rim1 performs a multifaceted role in synapses that can
be divided into Rab3a-dependent and Rab3a-independent components. Using
yeast 2-hybrid and GST pull-down binding analyses, Schoch et al. (2002)
showed that Rim1 interacts not only with Rab3a, Munc13, and Syt1, but
also with alpha-liprins (see 603143), adaptor proteins that bind to
receptor tyrosine phosphatases and are essential for the presynaptic
active zone in C. elegans. Schoch et al. (2002) proposed that RIM1, and
by extension the less-abundant RIM2 (606630), function at the active
zone to integrate the actions of several molecules with diverse roles in
neurotransmitter release. Specifically, they suggested that RIMs form a
complex through interactions with 3 active zone proteins (MUNC13,
RIMBPs, and alpha-liprins) and 2 synaptic vesicle proteins (RAB3A and
SYT1).
Long-term potentiation (LTP) is involved in learning and memory. One
form of LTP requires activation of postsynaptic NMDA receptors (e.g.,
GRIN2B; 138252), while another form, mossy fiber LTP (mfLTP), occurs in
the presynaptic areas and requires Rab3a and activation of protein
kinase A (PKA; see 176911). RIM1 is a PKA substrate. Castillo et al.
(2002) showed that in Rim1-deficient mice, mfLTP was abolished in the
hippocampus and cerebellum. They localized the expression of mfLTP to
the interface between synaptic vesicles and the active zone and showed
that the vesicle protein Rab3a and the active zone protein Rim1 are
required.
Corticoamygdala LTP and late-phase LTP at hippocampal synapses are 2
forms of LTP that require both postsynaptic NMDA receptor activation and
presynaptic PKA activation. By in vitro analysis of transverse slices
from the hippocampus and lateral amygdala of Rab3a (179490)-null mice,
Huang et al. (2005) found that Rab3a was necessary for both forms of
synaptic plasticity. Rim1-alpha was also required for hippocampal
late-phase LTP. The findings indicated that presynaptic proteins also
play a role in plasticity that is dependent on postsynaptic activity,
thus adding a layer of complexity to synaptic interactions.
Lonart et al. (2003) determined that PKA directly phosphorylated rat
RIM1 at ser413 and was required for cerebellar LTP in the mouse.
Simsek-Duran et al. (2004) found that phosphorylated ser413 Rim1 bound a
14-3-3 protein from brain lysate (see 113508), whereas
nonphosphorylatable Rim1 mutants did not. Presynaptic transfection with
a dominant-negative 14-3-3-eta mutant protein, which showed reduced
binding to Rim1, inhibited mouse cerebellar LTP. The authors concluded
that 14-3-3 is a necessary downstream component of the ser413-Rim1
pathway involved in presynaptic LTP.
Powell et al. (2004) found that Rim1-alpha knockout mice exhibited
impaired associative learning and memory, as measured by the fear
conditioning and Morris water maze tests. In contrast, Rab3A knockout
mice, which have impaired long-term potentiation, and mice with an
inactivating Syt1 mutation, which have decreased neurotransmitter
release, did not demonstrate the same learning deficits. Powell et al.
(2004) concluded that Rim1 modulates multiple presynaptic plasticity
mechanisms and suggested that selective deficits in cognitive function
result when multiple presynaptic functions are disrupted.
In mouse hippocampal and amygdala slices, Chevaleyre et al. (2007) found
that Rim1-alpha is a key mediator of cannabinoid receptor (see, e.g.,
CNR1; 114610)-mediated suppression of neurotransmitter release at
presynaptic synapses. Studies manipulating cAMP and protein kinase A
(PRKAR1A; 188830) levels showed that the presynaptic cAMP/PKA pathway is
required for downstream activation of Cnr1-induced long-term, but not
short-term, plasticity. Brief activation of Cnr1 leads to short-term
depression by blocking presynaptic voltage-gated calcium channels or
altered G-protein signaling, resulting in a transient effect. In
contrast, long-term depression triggers a PKA and Rim1-dependent
modification in the release machinery. The overall findings demonstrated
that short and long-term presynaptic plasticity at inhibitory synapses
in these brain regions work via different pathways, and that Rim1-alpha
is a mediator of long-term plasticity.
*FIELD* AV
.0001
CONE-ROD DYSTROPHY 7
RIMS1, ARG820HIS
In 6 affected members of a 4-generation British family with autosomal
dominant CORD7 (603649), previously described by Kelsell et al. (1998),
Johnson et al. (2003) identified heterozygosity for a G-to-A transition
in the second position of codon 820 of the RIMS1 gene, resulting in an
arg820-to-his (R820H) substitution at a conserved residue in the C2A
domain. The authors termed the mutation ARG844HIS (R844H) based on
numbering that included exon 3 of the rat Rims1 gene and other indels in
the rat and human sequences, and they noted that exon 3 is rat-specific
and would appear to be invariably spliced out of the human transcript.
The mutation was not found in 3 unaffected members of the family or in
115 ethnically matched controls.
*FIELD* SA
Wang et al. (2000)
*FIELD* RF
1. Betz, A.; Thakur, P.; Junge, H. J.; Ashery, U.; Rhee, J.-S.; Scheuss,
V.; Rosenmund, C.; Rettig, J.; Brose, N.: Functional interaction
of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle
priming. Neuron 30: 183-196, 2001.
2. Castillo, P. E.; Schoch, S.; Schmitz, F.; Sudhof, T. C.; Malenka,
R. C.: RIM1-alpha is required for presynaptic long-term potentiation. Nature 415:
327-330, 2002.
3. Chevaleyre, V.; Heifets, B. D.; Kaeser, P. S.; Sudhof, T. C.; Castillo,
P. E.: Endocannabinoid-mediated long-term plasticity requires cAMP/PKA
signaling and RIM1-alpha. Neuron 54: 801-812, 2007. Note: Erratum:
Neuron 55: 169 only, 2007.
4. Coppola, T.; Magnin-Luthi, S.; Perret-Menoud, V.; Gattesco, S.;
Schiavo, G.; Regazzi, R.: Direct interaction of the Rab3 effector
RIM with Ca(2+) channels, SNAP-25, and synaptotagmin. J. Biol. Chem. 276:
32756-32762, 2001.
5. Huang, Y.-Y.; Zakharenko, S. S.; Schoch, S.; Kaeser, P. S.; Janz,
R.; Sudhof, T. C.; Siegelbaum, S. A.; Kandel, E. R.: Genetic evidence
for a protein-kinase-A-mediated presynaptic component in NMDA-receptor-dependent
forms of long-term synaptic potentiation. Proc. Nat. Acad. Sci. 102:
9365-9370, 2005.
6. Johnson, S.; Halford, S.; Morris, A. G.; Patel, R. J.; Wilkie,
S. E.; Hardcastle, A. J.; Moore, A. T.; Zhang, K.; Hunt, D. M.: Genomic
organisation and alternative splicing of human RIM1, a gene implicated
in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81: 304-314,
2003.
7. Kelsell, R. E.; Gregory-Evans, K.; Gregory-Evans, C. Y.; Holder,
G. E.; Jay, M. R.; Weber, B. H. F.; Moore, A. T.; Bird, A. C.; Hunt,
D. M.: Localization of a gene (CORD7) for a dominant cone-rod dystrophy
to chromosome 6q. (Letter) Am. J. Hum. Genet. 63: 274-279, 1998.
8. Lonart, G.; Schoch, S.; Kaeser, P. S.; Larkin, C. J.; Sudhof, T.
C.; Linden, D. J.: Phosphorylation of RIM1-alpha by PKA triggers
presynaptic long-term potentiation at cerebellar parallel fiber synapses. Cell 115:
49-60, 2003.
9. Nagase, T.; Ishikawa, K.; Nakajima, D.; Ohira, M.; Seki, N.; Miyajima,
N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O.: Prediction of
the coding sequences of unidentified human genes. VII. The complete
sequences of 100 new cDNA clones from brain which can code for large
proteins in vitro. DNA Res. 4: 141-150, 1997.
10. Powell, C. M.; Schoch, S.; Monteggia, L.; Barrot, M.; Matos, M.
F.; Feldmann, N.; Sudhof, T. C.; Nestler, E. J.: The presynaptic
active zone protein RIM1-alpha is critical for normal learning and
memory. Neuron 42: 143-153, 2004.
11. Schoch, S.; Castillo, P. E.; Jo, T.; Mukherjee, K.; Geppert, M.;
Wang, Y.; Schmitz, F.; Malenka, R. C.; Sudhof, T. C.: RIM1-alpha
forms a protein scaffold for regulating neurotransmitter release at
the active zone. Nature 415: 321-326, 2002.
12. Simsek-Duran, F.; Linden, D. J.; Lonart, G.: Adapter protein
14-3-3 is required for a presynaptic form of LTP in the cerebellum. Nature
Neurosci. 7: 1296-1298, 2004.
13. Wang, Y.; Sudhof, T. C.: Genomic definition of RIM proteins:
evolutionary amplification of a family of synaptic regulatory proteins. Genomics 81:
126-137, 2003.
14. Wang, Y.; Sugita, S.; Sudhof, T. C.: The RIM/NIM family of neuronal
C2 domain proteins: interactions with Rab3 and a new class of Src
homology 3 domain proteins. J. Biol. Chem. 275: 20033-20044, 2000.
15. Wang, Y.; Sugita, S.; Sudhof, T. C.: The RIM/NIM family of neuronal
C-2 domain proteins: interactions with Rab3 and a new class of Src
homology 3 domain proteins. J. Biol. Chem. 275: 20033-20044, 2000.
*FIELD* CN
Cassandra L. Kniffin - updated: 11/10/2009
Patricia A. Hartz - updated: 11/9/2007
Patricia A. Hartz - updated: 9/20/2007
Marla J. F. O'Neill - updated: 9/14/2007
Cassandra L. Kniffin - updated: 7/12/2005
Cassandra L. Kniffin - updated: 6/27/2005
Cassandra L. Kniffin - updated: 2/8/2005
*FIELD* CD
Paul J. Converse: 1/23/2002
*FIELD* ED
carol: 06/07/2012
wwang: 12/8/2009
ckniffin: 11/10/2009
wwang: 7/2/2008
mgross: 11/19/2007
terry: 11/9/2007
wwang: 9/20/2007
wwang: 9/19/2007
terry: 9/14/2007
wwang: 8/5/2005
wwang: 7/28/2005
ckniffin: 7/12/2005
wwang: 6/30/2005
ckniffin: 6/27/2005
tkritzer: 2/22/2005
ckniffin: 2/8/2005
mgross: 7/22/2002
mgross: 1/23/2002
*RECORD*
*FIELD* NO
606629
*FIELD* TI
*606629 PROTEIN REGULATING SYNAPTIC MEMBRANE EXOCYTOSIS 1; RIMS1
;;RAB3A-INTERACTING MOLECULE 1; RIM1;;
read moreRIM;;
KIAA0340
*FIELD* TX
DESCRIPTION
RAB3A (179490), a member of the RAS gene superfamily, is a synaptic
vesicle protein that regulates synaptic vesicle exocytosis. MUNC13
(UNC13; 605836) and its isoforms are required for priming synaptic
vesicles for exocytosis. The RIM family of active zone proteins likely
function as protein scaffolds that help regulate vesicle exocytosis
during short-term plasticity.
CLONING
By screening for cDNAs with the potential to encode large proteins
expressed in brain, Nagase et al. (1997) identified a cDNA encoding
RIM1, which they called KIAA0340. The deduced 1,053-amino acid protein
was predicted to be weakly homologous to mouse rabphilin-3A (612159) and
to be involved in cell signaling/communication. RT-PCR analysis detected
expression of KIAA0340 only in brain and testis.
Coppola et al. (2001) obtained 6 isoforms of human RIM that differ from
each other in the distance between their 2 C2 domains. Binding analysis
showed that the C2 domains of RIM interact in a calcium-independent
manner with N-type calcium channels. They also interact weakly with
SNAP25 (600322) and strongly with synaptotagmin-1 (SYT1; 185605). In the
presence of calcium, the interaction with SYT1 increases and that with
SNAP25 decreases. Coppola et al. (2001) concluded that RIM1 is a
scaffold protein that interacts with multiple binding partners and
coordinates different stages of the secretory process.
Johnson et al. (2003) stated that the 1,693-amino acid RIMS1 protein
contains an N-terminal RAB3A (179490)-GTP-binding site, followed by a
pair of C4-type zinc fingers, a PDZ domain, and 2 C-terminal C2 domains
separated by an SH3-binding domain. By PCR of retina and brain cDNA
libraries, followed by screening an adult retinal cDNA library, they
cloned several RIMS1 variants. PCR analysis of normal human tissues
detected RIMS1 only in retina and brain.
GENE FUNCTION
Wang et al. (2000) showed that Rim1 and Rim2 bound to Rab3a and to the
Rim-binding proteins Rimbp1 (BZRAP1; 610764) and Rimbp2 (611602) in rat.
Betz et al. (2001) demonstrated an interaction between the N-terminal
zinc finger of Rim1 and Munc13 in rat.
GENE STRUCTURE
Johnson et al. (2003) determined that the RIMS1 gene contains 34 exons
and spans about 577 kb.
MAPPING
Using radiation hybrid analysis, Nagase et al. (1997) mapped the RIMS1
gene to chromosome 6. By genomic sequence analysis, Wang and Sudhof
(2003) mapped the RIMS1 gene to human chromosome 6q14 and to mouse
chromosome 1A3.
MOLECULAR GENETICS
Johnson et al. (2003) identified a missense mutation in the RIMS1 gene
(606629.0001) in a 4-generation British family with autosomal dominant
cone-rod dystrophy mapping to chromosome 6q (CORD7; 603649), previously
described by Kelsell et al. (1998). The authors stated that this was the
first example of a mutation in a protein with a defined role in synaptic
function giving rise to a retinal disease.
ANIMAL MODEL
By targeted deletion of exon 1 of the Rim1 gene, Schoch et al. (2002)
abolished expression of the largest and most-abundant Rim1 isoform,
Rim1-alpha, in mice. The mutant mice were fertile and viable but had a
deficit in maternal behavior and a decrease in expression of Munc13-1,
but in not other Munc isoforms. A moderate increase in postsynaptic
density proteins was observed, but it did not lead to overall remodeling
of synapses. Homozygous Rim1-deficient mice and Rab3a-deficient mice had
increased PPF (paired-pulse facilitation, which is the enhancement of
transmitter release in response to 2 closely spaced stimuli) at short
interstimulus intervals (ISIs), while heterozygous Munc13-deficient mice
had no change in PPF at short ISIs. Overall electrophysiologic analyses
determined that Rim1 performs a multifaceted role in synapses that can
be divided into Rab3a-dependent and Rab3a-independent components. Using
yeast 2-hybrid and GST pull-down binding analyses, Schoch et al. (2002)
showed that Rim1 interacts not only with Rab3a, Munc13, and Syt1, but
also with alpha-liprins (see 603143), adaptor proteins that bind to
receptor tyrosine phosphatases and are essential for the presynaptic
active zone in C. elegans. Schoch et al. (2002) proposed that RIM1, and
by extension the less-abundant RIM2 (606630), function at the active
zone to integrate the actions of several molecules with diverse roles in
neurotransmitter release. Specifically, they suggested that RIMs form a
complex through interactions with 3 active zone proteins (MUNC13,
RIMBPs, and alpha-liprins) and 2 synaptic vesicle proteins (RAB3A and
SYT1).
Long-term potentiation (LTP) is involved in learning and memory. One
form of LTP requires activation of postsynaptic NMDA receptors (e.g.,
GRIN2B; 138252), while another form, mossy fiber LTP (mfLTP), occurs in
the presynaptic areas and requires Rab3a and activation of protein
kinase A (PKA; see 176911). RIM1 is a PKA substrate. Castillo et al.
(2002) showed that in Rim1-deficient mice, mfLTP was abolished in the
hippocampus and cerebellum. They localized the expression of mfLTP to
the interface between synaptic vesicles and the active zone and showed
that the vesicle protein Rab3a and the active zone protein Rim1 are
required.
Corticoamygdala LTP and late-phase LTP at hippocampal synapses are 2
forms of LTP that require both postsynaptic NMDA receptor activation and
presynaptic PKA activation. By in vitro analysis of transverse slices
from the hippocampus and lateral amygdala of Rab3a (179490)-null mice,
Huang et al. (2005) found that Rab3a was necessary for both forms of
synaptic plasticity. Rim1-alpha was also required for hippocampal
late-phase LTP. The findings indicated that presynaptic proteins also
play a role in plasticity that is dependent on postsynaptic activity,
thus adding a layer of complexity to synaptic interactions.
Lonart et al. (2003) determined that PKA directly phosphorylated rat
RIM1 at ser413 and was required for cerebellar LTP in the mouse.
Simsek-Duran et al. (2004) found that phosphorylated ser413 Rim1 bound a
14-3-3 protein from brain lysate (see 113508), whereas
nonphosphorylatable Rim1 mutants did not. Presynaptic transfection with
a dominant-negative 14-3-3-eta mutant protein, which showed reduced
binding to Rim1, inhibited mouse cerebellar LTP. The authors concluded
that 14-3-3 is a necessary downstream component of the ser413-Rim1
pathway involved in presynaptic LTP.
Powell et al. (2004) found that Rim1-alpha knockout mice exhibited
impaired associative learning and memory, as measured by the fear
conditioning and Morris water maze tests. In contrast, Rab3A knockout
mice, which have impaired long-term potentiation, and mice with an
inactivating Syt1 mutation, which have decreased neurotransmitter
release, did not demonstrate the same learning deficits. Powell et al.
(2004) concluded that Rim1 modulates multiple presynaptic plasticity
mechanisms and suggested that selective deficits in cognitive function
result when multiple presynaptic functions are disrupted.
In mouse hippocampal and amygdala slices, Chevaleyre et al. (2007) found
that Rim1-alpha is a key mediator of cannabinoid receptor (see, e.g.,
CNR1; 114610)-mediated suppression of neurotransmitter release at
presynaptic synapses. Studies manipulating cAMP and protein kinase A
(PRKAR1A; 188830) levels showed that the presynaptic cAMP/PKA pathway is
required for downstream activation of Cnr1-induced long-term, but not
short-term, plasticity. Brief activation of Cnr1 leads to short-term
depression by blocking presynaptic voltage-gated calcium channels or
altered G-protein signaling, resulting in a transient effect. In
contrast, long-term depression triggers a PKA and Rim1-dependent
modification in the release machinery. The overall findings demonstrated
that short and long-term presynaptic plasticity at inhibitory synapses
in these brain regions work via different pathways, and that Rim1-alpha
is a mediator of long-term plasticity.
*FIELD* AV
.0001
CONE-ROD DYSTROPHY 7
RIMS1, ARG820HIS
In 6 affected members of a 4-generation British family with autosomal
dominant CORD7 (603649), previously described by Kelsell et al. (1998),
Johnson et al. (2003) identified heterozygosity for a G-to-A transition
in the second position of codon 820 of the RIMS1 gene, resulting in an
arg820-to-his (R820H) substitution at a conserved residue in the C2A
domain. The authors termed the mutation ARG844HIS (R844H) based on
numbering that included exon 3 of the rat Rims1 gene and other indels in
the rat and human sequences, and they noted that exon 3 is rat-specific
and would appear to be invariably spliced out of the human transcript.
The mutation was not found in 3 unaffected members of the family or in
115 ethnically matched controls.
*FIELD* SA
Wang et al. (2000)
*FIELD* RF
1. Betz, A.; Thakur, P.; Junge, H. J.; Ashery, U.; Rhee, J.-S.; Scheuss,
V.; Rosenmund, C.; Rettig, J.; Brose, N.: Functional interaction
of the active zone proteins Munc13-1 and RIM1 in synaptic vesicle
priming. Neuron 30: 183-196, 2001.
2. Castillo, P. E.; Schoch, S.; Schmitz, F.; Sudhof, T. C.; Malenka,
R. C.: RIM1-alpha is required for presynaptic long-term potentiation. Nature 415:
327-330, 2002.
3. Chevaleyre, V.; Heifets, B. D.; Kaeser, P. S.; Sudhof, T. C.; Castillo,
P. E.: Endocannabinoid-mediated long-term plasticity requires cAMP/PKA
signaling and RIM1-alpha. Neuron 54: 801-812, 2007. Note: Erratum:
Neuron 55: 169 only, 2007.
4. Coppola, T.; Magnin-Luthi, S.; Perret-Menoud, V.; Gattesco, S.;
Schiavo, G.; Regazzi, R.: Direct interaction of the Rab3 effector
RIM with Ca(2+) channels, SNAP-25, and synaptotagmin. J. Biol. Chem. 276:
32756-32762, 2001.
5. Huang, Y.-Y.; Zakharenko, S. S.; Schoch, S.; Kaeser, P. S.; Janz,
R.; Sudhof, T. C.; Siegelbaum, S. A.; Kandel, E. R.: Genetic evidence
for a protein-kinase-A-mediated presynaptic component in NMDA-receptor-dependent
forms of long-term synaptic potentiation. Proc. Nat. Acad. Sci. 102:
9365-9370, 2005.
6. Johnson, S.; Halford, S.; Morris, A. G.; Patel, R. J.; Wilkie,
S. E.; Hardcastle, A. J.; Moore, A. T.; Zhang, K.; Hunt, D. M.: Genomic
organisation and alternative splicing of human RIM1, a gene implicated
in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81: 304-314,
2003.
7. Kelsell, R. E.; Gregory-Evans, K.; Gregory-Evans, C. Y.; Holder,
G. E.; Jay, M. R.; Weber, B. H. F.; Moore, A. T.; Bird, A. C.; Hunt,
D. M.: Localization of a gene (CORD7) for a dominant cone-rod dystrophy
to chromosome 6q. (Letter) Am. J. Hum. Genet. 63: 274-279, 1998.
8. Lonart, G.; Schoch, S.; Kaeser, P. S.; Larkin, C. J.; Sudhof, T.
C.; Linden, D. J.: Phosphorylation of RIM1-alpha by PKA triggers
presynaptic long-term potentiation at cerebellar parallel fiber synapses. Cell 115:
49-60, 2003.
9. Nagase, T.; Ishikawa, K.; Nakajima, D.; Ohira, M.; Seki, N.; Miyajima,
N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O.: Prediction of
the coding sequences of unidentified human genes. VII. The complete
sequences of 100 new cDNA clones from brain which can code for large
proteins in vitro. DNA Res. 4: 141-150, 1997.
10. Powell, C. M.; Schoch, S.; Monteggia, L.; Barrot, M.; Matos, M.
F.; Feldmann, N.; Sudhof, T. C.; Nestler, E. J.: The presynaptic
active zone protein RIM1-alpha is critical for normal learning and
memory. Neuron 42: 143-153, 2004.
11. Schoch, S.; Castillo, P. E.; Jo, T.; Mukherjee, K.; Geppert, M.;
Wang, Y.; Schmitz, F.; Malenka, R. C.; Sudhof, T. C.: RIM1-alpha
forms a protein scaffold for regulating neurotransmitter release at
the active zone. Nature 415: 321-326, 2002.
12. Simsek-Duran, F.; Linden, D. J.; Lonart, G.: Adapter protein
14-3-3 is required for a presynaptic form of LTP in the cerebellum. Nature
Neurosci. 7: 1296-1298, 2004.
13. Wang, Y.; Sudhof, T. C.: Genomic definition of RIM proteins:
evolutionary amplification of a family of synaptic regulatory proteins. Genomics 81:
126-137, 2003.
14. Wang, Y.; Sugita, S.; Sudhof, T. C.: The RIM/NIM family of neuronal
C2 domain proteins: interactions with Rab3 and a new class of Src
homology 3 domain proteins. J. Biol. Chem. 275: 20033-20044, 2000.
15. Wang, Y.; Sugita, S.; Sudhof, T. C.: The RIM/NIM family of neuronal
C-2 domain proteins: interactions with Rab3 and a new class of Src
homology 3 domain proteins. J. Biol. Chem. 275: 20033-20044, 2000.
*FIELD* CN
Cassandra L. Kniffin - updated: 11/10/2009
Patricia A. Hartz - updated: 11/9/2007
Patricia A. Hartz - updated: 9/20/2007
Marla J. F. O'Neill - updated: 9/14/2007
Cassandra L. Kniffin - updated: 7/12/2005
Cassandra L. Kniffin - updated: 6/27/2005
Cassandra L. Kniffin - updated: 2/8/2005
*FIELD* CD
Paul J. Converse: 1/23/2002
*FIELD* ED
carol: 06/07/2012
wwang: 12/8/2009
ckniffin: 11/10/2009
wwang: 7/2/2008
mgross: 11/19/2007
terry: 11/9/2007
wwang: 9/20/2007
wwang: 9/19/2007
terry: 9/14/2007
wwang: 8/5/2005
wwang: 7/28/2005
ckniffin: 7/12/2005
wwang: 6/30/2005
ckniffin: 6/27/2005
tkritzer: 2/22/2005
ckniffin: 2/8/2005
mgross: 7/22/2002
mgross: 1/23/2002