MCTP_DROME
ID MCTP_DROME Reviewed; 912 AA.
AC A1ZBD6; A0A0B4KEZ6; A0A0C4DHG8; A0A126GUP9;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2017, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Multiple C2 and transmembrane domain-containing protein {ECO:0000305};
GN Name=Mctp {ECO:0000312|FlyBase:FBgn0034389}; ORFNames=CG15078;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP FUNCTION, COFACTOR, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=28485711; DOI=10.7554/elife.22904;
RA Genc O., Dickman D.K., Ma W., Tong A., Fetter R.D., Davis G.W.;
RT "MCTP is an ER-resident calcium sensor that stabilizes synaptic
RT transmission and homeostatic plasticity.";
RL Elife 6:0-0(2017).
CC -!- FUNCTION: Calcium sensor which is essential for the stabilization of
CC normal baseline neurotransmitter release and for the induction and
CC long-term maintenance of presynaptic homeostatic plasticity
CC (PubMed:28485711). {ECO:0000269|PubMed:28485711}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041,
CC ECO:0000269|PubMed:28485711};
CC Note=Binds Ca(2+) via the C2 domains in absence of phospholipids.
CC {ECO:0000269|PubMed:28485711};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:28485711}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=A1ZBD6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A1ZBD6-2; Sequence=VSP_059095;
CC Name=3;
CC IsoId=A1ZBD6-3; Sequence=VSP_059096;
CC -!- TISSUE SPECIFICITY: Motor neurons (at protein level).
CC {ECO:0000269|PubMed:28485711}.
CC -!- DISRUPTION PHENOTYPE: Mutant flies exhibit impaired homeostatic
CC modulation of presynaptic neurotransmitter release and altered baseline
CC neurotransmitter release transmission. {ECO:0000269|PubMed:28485711}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AGB93610.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE013599; AAO41353.3; -; Genomic_DNA.
DR EMBL; AE013599; AHN56385.1; -; Genomic_DNA.
DR EMBL; AE013599; AGB93610.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AE013599; ABI31105.2; -; Genomic_DNA.
DR EMBL; AE013599; ALI30186.1; -; Genomic_DNA.
DR RefSeq; NP_001036559.2; NM_001043094.2. [A1ZBD6-2]
DR RefSeq; NP_001261078.1; NM_001274149.1.
DR RefSeq; NP_001286590.1; NM_001299661.1. [A1ZBD6-3]
DR RefSeq; NP_001303357.1; NM_001316428.1. [A1ZBD6-1]
DR RefSeq; NP_611372.3; NM_137528.5. [A1ZBD6-3]
DR AlphaFoldDB; A1ZBD6; -.
DR STRING; 7227.FBpp0303040; -.
DR PRIDE; A1ZBD6; -.
DR DNASU; 37165; -.
DR EnsemblMetazoa; FBtr0110970; FBpp0110270; FBgn0034389. [A1ZBD6-3]
DR EnsemblMetazoa; FBtr0330004; FBpp0303039; FBgn0034389.
DR EnsemblMetazoa; FBtr0330005; FBpp0303040; FBgn0034389. [A1ZBD6-2]
DR EnsemblMetazoa; FBtr0345950; FBpp0311864; FBgn0034389. [A1ZBD6-3]
DR EnsemblMetazoa; FBtr0346955; FBpp0312419; FBgn0034389. [A1ZBD6-1]
DR GeneID; 37165; -.
DR KEGG; dme:Dmel_CG15078; -.
DR UCSC; CG15078-RA; d. melanogaster. [A1ZBD6-1]
DR CTD; 37165; -.
DR FlyBase; FBgn0034389; Mctp.
DR VEuPathDB; VectorBase:FBgn0034389; -.
DR eggNOG; KOG1030; Eukaryota.
DR GeneTree; ENSGT00940000169787; -.
DR HOGENOM; CLU_011170_2_0_1; -.
DR InParanoid; A1ZBD6; -.
DR OMA; DCGPTLE; -.
DR PhylomeDB; A1ZBD6; -.
DR BioGRID-ORCS; 37165; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 37165; -.
DR PRO; PR:A1ZBD6; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034389; Expressed in crop (Drosophila) and 19 other tissues.
DR ExpressionAtlas; A1ZBD6; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:FlyBase.
DR GO; GO:0030672; C:synaptic vesicle membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:UniProtKB.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; IMP:UniProtKB.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR013583; PRibTrfase_C.
DR Pfam; PF00168; C2; 3.
DR Pfam; PF08372; PRT_C; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR SMART; SM00239; C2; 3.
DR SUPFAM; SSF49562; SSF49562; 3.
DR PROSITE; PS50004; C2; 3.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Endoplasmic reticulum; Membrane;
KW Metal-binding; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..912
FT /note="Multiple C2 and transmembrane domain-containing
FT protein"
FT /id="PRO_0000441713"
FT TRANSMEM 729..749
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 826..846
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 218..337
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 371..493
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 522..637
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 1..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 887..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 258
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 305
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 305
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 307
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 307
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 313
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 553
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 559
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 605
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 607
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1..2
FT /note="MS -> MLAGIGHVMQPLHLANSFKSSKNSERPQASVLCHRINKIFPVTA
FT (in isoform 2)"
FT /id="VSP_059095"
FT VAR_SEQ 218..236
FT /note="Missing (in isoform 3)"
FT /id="VSP_059096"
SQ SEQUENCE 912 AA; 103506 MW; DEFD111068739693 CRC64;
MSRIQYVDQV DQVELDQQQQ PGSSSTVSGS TPPLQISPHG SPSLQQSQRL GKHLSKSASE
LNGHDCHLSE SPHISPKRAK SAVAQQLAGV SSGGVASGVG VLQKTHGFFN NLRHRWSRAK
SKDRLGRKSP SDFLEESTDY AADYSSEGSS VTHSPRHRST TIGGSPLARE FRATAKMAQV
IQRFGGSMEG RIDEHPENGS AGCSPPELST QQQLEALQAN ELRRKREAQL RQFVFFQLRV
HLKSGSDLVA MDKNGLSDPY VKFKVGGRLL HKSRTIHRDL NPVWDEVFIV PIEDPFQPII
VKVFDYDWGL QDDFMGSAKL DLTQLELGKA EDIHLQLCDS SGNGGSGLGE ILINLTLWPR
SQEDKEMHFQ RNSKLAESSK RLKSQIWSSV VTILLVKAKD LPLAEDGSKL NDTHFKFRLG
NEKYKSKSSW TERWLEQFDL HLFDEDQNLE IALWNRNTLY GKAIIDLSVF QRENTHGIWK
PLEDCPGEVH LMLTISGTTA LETISDLKAF KEDPREAQLL RERYKFLRCL QNLRDVGHLT
VKVFGATGLA AADIGGKSDP FCVLELGNAR LQTQTEYKTL TPNWNKIFTF NVKDITQVLE
ITVFDEDRDH RVEFLGKLVI PLLRIKSGVK RWYTLKDKNL CVRAKGNSPQ IQLELTVVWS
EIRAVCRALQ PKEEKLIQQE AKFKRQLFLR NVNRLKEIIM DILDAARYVQ SCFEWESPVR
SSIAFVFWIV ACVYGDLETV PLVLLLIILK NWLVRLITGT TDAAAHYDYE YDEDDDDDKE
KEEKKSIKER LQAIQEVSQT VQNTIGYLAS LGESTINTFN FSVPELTWLA VVLLLGAILV
LHFVPLRWLL LFWGLMKFSR RLLRPNTIPN NELLDFLSRV PDNEEINQYR ELPPSAPTDQ
TRNNPKKKLK GS
