CPLX4_MOUSE
ID CPLX4_MOUSE Reviewed; 160 AA.
AC Q80WM3; Q8C8Y0; Q91WE5;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Complexin-4;
DE AltName: Full=Complexin IV;
DE Short=CPX IV;
DE Flags: Precursor;
GN Name=Cplx4;
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, ISOPRENYLATION AT CYS-157, AND METHYLATION AT CYS-157.
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 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 [6]
RP FUNCTION, TISSUE SPECIFICITY, 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: Weakly binds to the SNARE core complex containing SNAP25,
CC VAMP2 and 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 {ECO:0000269|PubMed:15911881}.
CC -!- TISSUE SPECIFICITY: Present specifically in the retina (at protein
CC level) (PubMed:15911881, PubMed:19386896, PubMed:22694764,
CC PubMed:27335398). Expressed in the outer nuclear layer of the retina
CC (at protein level) (PubMed:22694764). Strongly expressed at rod
CC photoreceptor ribbon synapses (at protein level) (PubMed:15911881,
CC PubMed:22694764). Not expressed at conventional amacrine cell synapses,
CC nor at cone photoreceptor ribbon synapses (at protein level)
CC (PubMed:15911881). Weakly expressed at cone photoreceptor synaptic
CC terminals (at protein level) (PubMed:22694764). Not expressed in the
CC brain (at protein level) (PubMed:19386896).
CC {ECO:0000269|PubMed:15911881, ECO:0000269|PubMed:19386896,
CC ECO:0000269|PubMed:22694764, ECO:0000269|PubMed:27335398}.
CC -!- PTM: Farnesylation mediates presynaptic targeting and is important for
CC function in neurotransmitter release. {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 inner
CC retinal processing and retinal synaptic transmission at low light
CC intensities (PubMed:19386896). Cplx3 and Cplx4 double knockout mice are
CC generally phenotypically normal, viable, and fertile, however show
CC disordered morphology of the OPL and vision perturbation when compared
CC to single knockout mice (PubMed:19386896). Cplx3 and Cplx4 double
CC knockout mice show evidence of mild vision perturbation, with a
CC reduction in the number of morphologically normal anchored presynaptic
CC ribbon synapses and a decrease in controlled neurotransmitter release
CC at photoreceptor ribbon synapses (PubMed:19386896). Cplx3 and Cplx4
CC double knockout mice show a reduced response and sensitivity of ON and
CC OFF ganglion cell response as a result of disrupted synaptic
CC transmission (PubMed:22694764). Cplx3 and Cplx4 double knockout mice
CC show a greater variance in photoreceptor activity response and a
CC decrease in sustained response, this is caused by an increase in
CC release and fusion of synaptic vesicles in an asynchronous manner, this
CC is particularly evident following multiple stimuli (PubMed:27335398).
CC {ECO:0000269|PubMed:19386896, ECO:0000269|PubMed:22694764,
CC ECO:0000269|PubMed:27335398}.
CC -!- SIMILARITY: Belongs to the complexin/synaphin family. {ECO:0000305}.
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DR EMBL; AY264291; AAP22134.1; -; mRNA.
DR EMBL; AK044262; BAC31843.1; -; mRNA.
DR EMBL; BC016082; AAH16082.1; -; mRNA.
DR EMBL; BC029011; AAH29011.1; -; mRNA.
DR CCDS; CCDS29312.1; -.
DR RefSeq; NP_663468.1; NM_145493.1.
DR AlphaFoldDB; Q80WM3; -.
DR SMR; Q80WM3; -.
DR CORUM; Q80WM3; -.
DR STRING; 10090.ENSMUSP00000025397; -.
DR iPTMnet; Q80WM3; -.
DR PhosphoSitePlus; Q80WM3; -.
DR MaxQB; Q80WM3; -.
DR PaxDb; Q80WM3; -.
DR PeptideAtlas; Q80WM3; -.
DR PRIDE; Q80WM3; -.
DR ProteomicsDB; 284001; -.
DR Antibodypedia; 42122; 72 antibodies from 15 providers.
DR Ensembl; ENSMUST00000025397; ENSMUSP00000025397; ENSMUSG00000024519.
DR GeneID; 225644; -.
DR KEGG; mmu:225644; -.
DR UCSC; uc008ffm.1; mouse.
DR CTD; 339302; -.
DR MGI; MGI:2685803; Cplx4.
DR VEuPathDB; HostDB:ENSMUSG00000024519; -.
DR eggNOG; ENOG502RY7Q; Eukaryota.
DR GeneTree; ENSGT00950000182938; -.
DR HOGENOM; CLU_141096_0_0_1; -.
DR InParanoid; Q80WM3; -.
DR OMA; MGQFQNL; -.
DR OrthoDB; 1441014at2759; -.
DR PhylomeDB; Q80WM3; -.
DR TreeFam; TF331867; -.
DR BioGRID-ORCS; 225644; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Cplx4; mouse.
DR PRO; PR:Q80WM3; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; Q80WM3; protein.
DR Bgee; ENSMUSG00000024519; Expressed in retinal neural layer and 11 other tissues.
DR Genevisible; Q80WM3; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0000149; F:SNARE binding; IDA:MGI.
DR GO; GO:0019905; F:syntaxin binding; IEA:InterPro.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IDA:MGI.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IBA:GO_Central.
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; Exocytosis; Lipoprotein; Membrane; Methylation;
KW Neurotransmitter transport; Prenylation; Reference proteome;
KW Sensory transduction; Synapse; Transport; Vision.
FT CHAIN 1..157
FT /note="Complexin-4"
FT /id="PRO_0000240237"
FT PROPEP 158..160
FT /note="Removed in mature form"
FT /id="PRO_0000240238"
FT REGION 14..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 157
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000269|PubMed:15911881"
FT LIPID 157
FT /note="S-farnesyl cysteine"
FT /evidence="ECO:0000269|PubMed:15911881"
FT CONFLICT 136
FT /note="D -> G (in Ref. 2; BAC31843)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="T -> P (in Ref. 1; AAP22134)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 160 AA; 18351 MW; C3FEDB58F25FAE44 CRC64;
MAFFVKNMIS NQVKNLGFGG GSEEKKEEGG TSDPAAAKGM TREEYEEYQK QMIEEKMERD
AAFTQKKAER ACLRVHLRDK YRLPKSEMDE TQIQLAGDDV DLPEDLRKMV DEDQDEEEEK
DSILGQLQNL QNMDLDTIKE KAQATFTEIK QSAEQKCSVM
