MCTP1_RAT
ID MCTP1_RAT Reviewed; 946 AA.
AC D4ABL6; A0A1W2Q6L3;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2017, sequence version 4.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Multiple C2 and transmembrane domain-containing protein 1 {ECO:0000305};
GN Name=Mctp1 {ECO:0000312|RGD:1305199};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=26195140; DOI=10.1111/jnc.13251;
RA Qiu L., Yu H., Liang F.;
RT "Multiple C2 domains transmembrane protein 1 is expressed in CNS neurons
RT and possibly regulates cellular vesicle retrieval and oxidative stress.";
RL J. Neurochem. 135:492-507(2015).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
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 (By
CC similarity). Overexpression in cultured neurons significantly inhibits
CC neuronal transferrin endocytosis, secretory vesicle retrieval, cell
CC migration, and oxidative stress from glutamate toxicity
CC (PubMed:26195140). {ECO:0000250|UniProtKB:A1ZBD6,
CC ECO:0000269|PubMed:26195140}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds Ca(2+) via the C2 domains in absence of phospholipids.
CC {ECO:0000250|UniProtKB:Q6DN14};
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle, synaptic
CC vesicle membrane {ECO:0000269|PubMed:26195140}; Multi-pass membrane
CC protein {ECO:0000255}. Recycling endosome
CC {ECO:0000269|PubMed:26195140}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:A1ZBD6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=Mctp1L {ECO:0000303|PubMed:26195140};
CC IsoId=D4ABL6-1; Sequence=Displayed;
CC Name=2; Synonyms=Mctp1S {ECO:0000303|PubMed:26195140};
CC IsoId=D4ABL6-2; Sequence=VSP_059094;
CC -!- TISSUE SPECIFICITY: Expressed in the brain and central nervous system
CC (at protein level). Isoform 1 and isoform 2 are expressed in the brain,
CC kidney, liver, heart, lung, skeletal muscle, testis and spleen. Isoform
CC 2 shows a higher expression in the brain, heart and skeletal muscle.
CC {ECO:0000269|PubMed:26195140}.
CC -!- SIMILARITY: Belongs to the MCTP family. {ECO:0000305}.
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DR EMBL; AABR07007350; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07072675; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07072676; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07072677; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC097940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC103536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC120719; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC125565; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_017446641.1; XM_017591152.1.
DR RefSeq; XP_017449722.1; XM_017594233.1.
DR AlphaFoldDB; D4ABL6; -.
DR SMR; D4ABL6; -.
DR STRING; 10116.ENSRNOP00000017828; -.
DR PaxDb; D4ABL6; -.
DR PRIDE; D4ABL6; -.
DR Ensembl; ENSRNOT00000093593; ENSRNOP00000076318; ENSRNOG00000013282. [D4ABL6-1]
DR GeneID; 309928; -.
DR CTD; 79772; -.
DR RGD; 1305199; Mctp1.
DR eggNOG; KOG1030; Eukaryota.
DR GeneTree; ENSGT00940000156031; -.
DR HOGENOM; CLU_011170_0_1_1; -.
DR InParanoid; D4ABL6; -.
DR OrthoDB; 234298at2759; -.
DR TreeFam; TF323373; -.
DR PRO; PR:D4ABL6; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Bgee; ENSRNOG00000013282; Expressed in cerebellum and 15 other tissues.
DR ExpressionAtlas; D4ABL6; baseline and differential.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB.
DR GO; GO:0030672; C:synaptic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0045806; P:negative regulation of endocytosis; IDA:UniProtKB.
DR GO; GO:1902883; P:negative regulation of response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0046928; P:regulation of neurotransmitter secretion; ISS:UniProtKB.
DR Gene3D; 2.60.40.150; -; 3.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR Pfam; PF00168; C2; 3.
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; Cytoplasmic vesicle; Endoplasmic reticulum;
KW Endosome; Membrane; Metal-binding; Reference proteome; Repeat; Synapse;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..946
FT /note="Multiple C2 and transmembrane domain-containing
FT protein 1"
FT /id="PRO_0000441712"
FT TRANSMEM 758..778
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 861..881
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 235..353
FT /note="C2 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 399..516
FT /note="C2 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 550..671
FT /note="C2 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 28..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..229
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 61..75
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..166
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..186
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 270
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 270
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 276
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 323
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 325
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 331
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 433
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 439
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 486
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 486
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 488
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 488
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 494
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 589
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 589
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 595
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 641
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 641
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 643
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 643
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 649
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT VAR_SEQ 1..234
FT /note="MEPRGAAAGEPEPAVSPSFQARLWKNLQLGVGKGKGGGGGRAGGPERRTAAT
FT PTPSLPPPKTTQDVGSTGSRWSGFKKRKQVLDRVFSSSQPNLCCSSPEPLEPGGAGRAE
FT QGSTLRRRLREHLLPVAKGSSTAAGTVGVTPPGGRSPDSAPSSSASSSLSSSPQPPPRG
FT DRIRDEGTRRGSPEAHLCHQKSSSLPGTACLEQLLEPAPPPAEPARRPAEPQSLQKGEE
FT LDCSQ -> MLDSYRLKSFCNLPLVCHK (in isoform 2)"
FT /id="VSP_059094"
SQ SEQUENCE 946 AA; 106483 MW; D30F550693552232 CRC64;
MEPRGAAAGE PEPAVSPSFQ ARLWKNLQLG VGKGKGGGGG RAGGPERRTA ATPTPSLPPP
KTTQDVGSTG SRWSGFKKRK QVLDRVFSSS QPNLCCSSPE PLEPGGAGRA EQGSTLRRRL
REHLLPVAKG SSTAAGTVGV TPPGGRSPDS APSSSASSSL SSSPQPPPRG DRIRDEGTRR
GSPEAHLCHQ KSSSLPGTAC LEQLLEPAPP PAEPARRPAE PQSLQKGEEL DCSQKINPVE
TSNADVPLAD PGMYQLDITL RRGQSLAARD RGGTSDPYVK FKIGRKEVFR SKIIHKNLNP
VWEEKACVLI DHLREPLYIK VFDYDFGLQD DFMGSAFLDL TQLELNRPTD VTLTLKDPHY
PDHDLGIILL SVILTPKEGE PRDVTMLMRK SWKRSSKFQT QSLRLSDQHR KSHLWRGIVS
ITLIEGRDLK AMDSNGLSDP YVKFRLGHQK YKSKIMPKTL NPQWREQFDF HLYEERGGVM
DITAWDKDAG KRDDFIGRCQ VDLSSLSREQ THKLELQLEE GEGHLVLLVT LTASATVSIS
DLSVNSMEDH KEREEILKRY SPLRIFNNIK DVGFLQVKVI RAEGLMAADV TGKSDPFCVV
ELNNDRLLTH TVYKNLNPEW NKVFTFNIKD IHSVLEVTVY DEDRDRSADF LGRVAIPLLS
IQNGEQKAYV LKNKQLTGPT KGVIHLEIDV IFNAVKASLR TLIPKERKYI EEENRLSKQL
LLRNFIRTKR CVMVLVNAAY YVNSCFDWDS PPRSLAAFVL FLLVVWNFEL YMIPLLLLLL
LTWNYFLIIS GKDNRQRDTV VEDMLEDEEE EDDRDDKDGE KKGFINKIYA IQEVCVSVQN
ILDEAASLGE RVKNTFNWTV PFLSWLAIIA LCVFTAILYF IPLRYIVLVW GINKFTKKLR
SPYAIDNNEL LDFLSRVPSD VQVVQYQELK PDHSHSPYKR KKNNLG
