CPLX3_MOUSE
ID CPLX3_MOUSE Reviewed; 158 AA.
AC Q8R1B5; Q96AW7;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Complexin-3;
DE AltName: Full=Complexin III;
DE Short=CPX III;
DE Flags: Precursor;
GN Name=Cplx3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, ISOPRENYLATION AT CYS-155, AND
RP METHYLATION AT CYS-155.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=15911881; DOI=10.1083/jcb.200502115;
RA Reim K., Wegmeyer H., Brandstaetter J.H., Xue M., Rosenmund C.,
RA Dresbach T., Hofmann K., Brose N.;
RT "Structurally and functionally unique complexins at retinal ribbon
RT synapses.";
RL J. Cell Biol. 169:669-680(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19386896; DOI=10.1242/jcs.045401;
RA Reim K., Regus-Leidig H., Ammermueller J., El-Kordi A., Radyushkin K.,
RA Ehrenreich H., Brandstaetter J.H., Brose N.;
RT "Aberrant function and structure of retinal ribbon synapses in the absence
RT of complexin 3 and complexin 4.";
RL J. Cell Sci. 122:1352-1361(2009).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=22694764; DOI=10.1111/j.1460-9568.2012.08149.x;
RA Landgraf I., Muehlhans J., Dedek K., Reim K., Brandstaetter J.H.,
RA Ammermueller J.;
RT "The absence of Complexin 3 and Complexin 4 differentially impacts the ON
RT and OFF pathways in mouse retina.";
RL Eur. J. Neurosci. 36:2470-2481(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27335398; DOI=10.1523/jneurosci.4335-15.2016;
RA Babai N., Sendelbeck A., Regus-Leidig H., Fuchs M., Mertins J., Reim K.,
RA Brose N., Feigenspan A., Brandstaetter J.H.;
RT "Functional Roles of Complexin 3 and Complexin 4 at Mouse Photoreceptor
RT Ribbon Synapses.";
RL J. Neurosci. 36:6651-6667(2016).
CC -!- FUNCTION: Complexin that regulates SNARE protein complex-mediated
CC synaptic vesicle fusion (PubMed:19386896). Required for the maintenance
CC of synaptic ultrastructure in the adult retina (PubMed:19386896).
CC Positively regulates synaptic transmission through synaptic vesicle
CC availability and exocytosis of neurotransmitters at photoreceptor
CC ribbon synapses in the retina (PubMed:15911881, PubMed:19386896,
CC PubMed:27335398). Suppresses tonic photoreceptor activity and baseline
CC 'noise' by suppression of Ca(2+) vesicle tonic release and the
CC facilitation of evoked synchronous and asynchronous Ca(2+) vesicle
CC release (PubMed:22694764, PubMed:27335398).
CC {ECO:0000269|PubMed:15911881, ECO:0000269|PubMed:19386896,
CC ECO:0000269|PubMed:22694764, ECO:0000269|PubMed:27335398}.
CC -!- SUBUNIT: Binds to the SNARE core complex containing SNAP25, VAMP2 and
CC STX1A. {ECO:0000269|PubMed:15911881}.
CC -!- SUBCELLULAR LOCATION: Synapse {ECO:0000269|PubMed:15911881,
CC ECO:0000269|PubMed:22694764}. Cell membrane
CC {ECO:0000269|PubMed:15911881}; Lipid-anchor
CC {ECO:0000269|PubMed:15911881}. Note=Enriched at the synaptic terminal
CC (PubMed:15911881). Localized at glycinergic synaptic contacts of AII
CC amacrine cells with OFF cone bipolar cells in the OFF sublamina of the
CC retina inner nuclear layer (PubMed:22694764).
CC {ECO:0000269|PubMed:15911881, ECO:0000269|PubMed:22694764}.
CC -!- TISSUE SPECIFICITY: Present in many brain regions, including
CC hippocampus and cerebellum (at protein level) (PubMed:15911881).
CC Expressed in the retina (at protein level) (PubMed:15911881,
CC PubMed:19386896). Expressed in retinal amacrine cells (at protein
CC level) (PubMed:19386896, PubMed:22694764). Expressed in retinal
CC photoreceptor ribbon synapses (PubMed:19386896). Expressed in the
CC retinal inner nuclear layer, at bipolar cells (at protein level)
CC (PubMed:22694764). Expressed in cone photoreceptor synaptic terminals
CC (at protein level) (PubMed:22694764). {ECO:0000269|PubMed:15911881,
CC ECO:0000269|PubMed:19386896, ECO:0000269|PubMed:22694764}.
CC -!- DEVELOPMENTAL STAGE: In the brain, expression starts at P6 and
CC increases to reach a plateau at P20. {ECO:0000269|PubMed:15911881}.
CC -!- PTM: Farnesylation mediates presynaptic targeting.
CC {ECO:0000269|PubMed:15911881}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are generally phenotypically
CC normal, viable, and fertile (PubMed:19386896). Normal overall retina
CC structure and morphology of the outer plexiform layer (OPL) and inner
CC plexiform layer (IPL) (PubMed:19386896). Abundance and distribution of
CC synaptic proteins remain consistent (PubMed:19386896). Reduced retinal
CC synaptic transmission and inner retinal processing (PubMed:19386896).
CC Cplx3 and Cplx4 double knockout mice are generally phenotypically
CC normal, viable, and fertile, however show disordered morphology of the
CC OPL and vision perturbation when compared to single knockout mice
CC (PubMed:19386896). Cplx3 and Cplx4 double knockout mice show evidence
CC of mild vision perturbation, with a reduction in the number of
CC morphologically normal anchored presynaptic ribbon synapses and a
CC decrease in controlled neurotransmitter release at photoreceptor ribbon
CC synapses (PubMed:19386896). Cplx3 and Cplx4 double knockout mice show
CC reduced response and sensitivity of ON and OFF ganglion cell response
CC as a result of disrupted synaptic transmission (PubMed:22694764). Cplx3
CC and Cplx4 double knockout mice show a greater variance in photoreceptor
CC activity response and a decrease in sustained response, this is caused
CC by an increase in release and fusion of synaptic vesicles in an
CC asynchronous manner, this is particularly evident following multiple
CC stimuli (PubMed:27335398). {ECO:0000269|PubMed:19386896,
CC ECO:0000269|PubMed:22694764, ECO:0000269|PubMed:27335398}.
CC -!- SIMILARITY: Belongs to the complexin/synaphin family. {ECO:0000305}.
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DR EMBL; AY264290; AAP22133.1; -; mRNA.
DR EMBL; AK044211; BAC31818.1; -; mRNA.
DR EMBL; BC016632; AAH16632.1; -; mRNA.
DR EMBL; BC024854; AAH24854.1; -; mRNA.
DR EMBL; BC033343; AAH33343.1; -; mRNA.
DR CCDS; CCDS23226.1; -.
DR RefSeq; NP_666335.1; NM_146223.3.
DR AlphaFoldDB; Q8R1B5; -.
DR SMR; Q8R1B5; -.
DR BioGRID; 231656; 4.
DR CORUM; Q8R1B5; -.
DR STRING; 10090.ENSMUSP00000046748; -.
DR PhosphoSitePlus; Q8R1B5; -.
DR MaxQB; Q8R1B5; -.
DR PaxDb; Q8R1B5; -.
DR PeptideAtlas; Q8R1B5; -.
DR PRIDE; Q8R1B5; -.
DR ProteomicsDB; 283936; -.
DR Antibodypedia; 43203; 142 antibodies from 22 providers.
DR Ensembl; ENSMUST00000045068; ENSMUSP00000046748; ENSMUSG00000039714.
DR GeneID; 235415; -.
DR KEGG; mmu:235415; -.
DR UCSC; uc009pvg.2; mouse.
DR CTD; 594855; -.
DR MGI; MGI:2384571; Cplx3.
DR VEuPathDB; HostDB:ENSMUSG00000039714; -.
DR eggNOG; ENOG502QZ0D; Eukaryota.
DR GeneTree; ENSGT00950000182938; -.
DR HOGENOM; CLU_141096_0_0_1; -.
DR InParanoid; Q8R1B5; -.
DR OMA; QSAEKCY; -.
DR OrthoDB; 1441014at2759; -.
DR PhylomeDB; Q8R1B5; -.
DR TreeFam; TF331867; -.
DR BioGRID-ORCS; 235415; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Cplx3; mouse.
DR PRO; PR:Q8R1B5; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8R1B5; protein.
DR Bgee; ENSMUSG00000039714; Expressed in retinal neural layer and 21 other tissues.
DR ExpressionAtlas; Q8R1B5; baseline and differential.
DR Genevisible; Q8R1B5; MM.
DR GO; GO:0099029; C:anchored component of presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IDA:SynGO.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0098684; C:photoreceptor ribbon synapse; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0031201; C:SNARE complex; IBA:GO_Central.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0043195; C:terminal bouton; IBA:GO_Central.
DR GO; GO:0005326; F:neurotransmitter transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0000149; F:SNARE binding; IDA:MGI.
DR GO; GO:0019905; F:syntaxin binding; IEA:InterPro.
DR GO; GO:0030073; P:insulin secretion; IMP:UniProtKB.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IDA:MGI.
DR GO; GO:0031630; P:regulation of synaptic vesicle fusion to presynaptic active zone membrane; IDA:SynGO.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IMP:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
DR InterPro; IPR008849; Synaphin.
DR PANTHER; PTHR16705; PTHR16705; 1.
DR Pfam; PF05835; Synaphin; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Coiled coil; Exocytosis; Lipoprotein; Membrane; Methylation;
KW Neurotransmitter transport; Prenylation; Reference proteome;
KW Sensory transduction; Synapse; Transport; Vision.
FT CHAIN 1..155
FT /note="Complexin-3"
FT /id="PRO_0000239273"
FT PROPEP 156..158
FT /note="Removed in mature form"
FT /id="PRO_0000240234"
FT REGION 14..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 39..74
FT /evidence="ECO:0000255"
FT COMPBIAS 24..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 155
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000269|PubMed:15911881"
FT LIPID 155
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:15911881"
SQ SEQUENCE 158 AA; 17586 MW; E452E829DC019A70 CRC64;
MAFMVKSMVG GQLKNLTGSL GGGEDKGDGD KSAAEAQGMS REEYEEYQKQ LVEEKMERDA
QFTQRKAERA TLRSHFRDKY RLPKNETDES QIQLAGGDVE LPRELAKMIE EDTEEEEDKA
SVLGQLASLP GLDLSSLKDK AQTTLGDLKQ SAEKCHIM
