C2C2L_MOUSE
ID C2C2L_MOUSE Reviewed; 706 AA.
AC Q80X80; G5E8D9;
DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Phospholipid transfer protein C2CD2L {ECO:0000305};
DE AltName: Full=C2 domain-containing protein 2-like {ECO:0000312|MGI:MGI:1919014};
DE AltName: Full=Transmembrane protein 24 {ECO:0000303|PubMed:24012759};
GN Name=C2cd2l {ECO:0000312|MGI:MGI:1919014};
GN Synonyms=Tmem24 {ECO:0000303|PubMed:24012759};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-613 AND SER-619, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358; SER-374; SER-411;
RP THR-419; THR-428; SER-613; SER-619; THR-621; SER-623 AND SER-662, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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 [7]
RP FUNCTION.
RX PubMed=24012759; DOI=10.1016/j.celrep.2013.07.050;
RA Pottekat A., Becker S., Spencer K.R., Yates J.R. III, Manning G.,
RA Itkin-Ansari P., Balch W.E.;
RT "Insulin biosynthetic interaction network component, TMEM24, facilitates
RT insulin reserve pool release.";
RL Cell Rep. 4:921-930(2013).
CC -!- FUNCTION: Lipid-binding protein that transports phosphatidylinositol,
CC the precursor of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2),
CC from its site of synthesis in the endoplasmic reticulum to the cell
CC membrane (By similarity). It thereby maintains the pool of cell
CC membrane phosphoinositides, which are degraded during phospholipase C
CC (PLC) signaling (By similarity). Plays a key role in the coordination
CC of Ca(2+) and phosphoinositide signaling: localizes to sites of contact
CC between the endoplasmic reticulum and the cell membrane, where it
CC tethers the two bilayers (By similarity). In response to elevation of
CC cytosolic Ca(2+), it is phosphorylated at its C-terminus and
CC dissociates from the cell membrane, abolishing phosphatidylinositol
CC transport to the cell membrane (By similarity). Positively regulates
CC insulin secretion in response to glucose (PubMed:24012759).
CC Phosphatidylinositol transfer to the cell membrane allows replenishment
CC of PI(4,5)P2 pools and calcium channel opening, priming a new
CC population of insulin granules (By similarity).
CC {ECO:0000250|UniProtKB:O14523, ECO:0000269|PubMed:24012759}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:O14523}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O14523}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:O14523}. Cell membrane
CC {ECO:0000250|UniProtKB:O14523}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O14523}. Note=Localizes to sites of contact
CC between the endoplasmic reticulum and the cell membrane. Embedded into
CC the endoplasmic reticulum membrane via its N-terminal transmembrane
CC domain and associates with cell membrane via its C-terminus. In
CC response to elevation of cytosolic Ca(2+), it is phosphorylated at its
CC C-terminus and dissociates from the cell membrane and localizes to the
CC reticular endoplasmic reticulum. Reassociates with cell membrane upon
CC dephosphorylation. {ECO:0000250|UniProtKB:O14523}.
CC -!- DOMAIN: The SMP-LBD domain is a lipid transport module, which binds
CC glycerolipids with a preference for phosphatidylinositol (PI).
CC {ECO:0000250|UniProtKB:O14523}.
CC -!- PTM: Phosphorylation at the C-terminus acidifies the protein and leads
CC to disassociation from the acidic cell membrane. Reassociates with the
CC cell membrane upon dephosphorylation. {ECO:0000250|UniProtKB:O14523}.
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DR EMBL; AC124577; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466522; EDL25576.1; -; Genomic_DNA.
DR EMBL; BC049875; AAH49875.1; -; mRNA.
DR EMBL; BC060156; AAH60156.1; -; mRNA.
DR CCDS; CCDS23103.1; -.
DR RefSeq; NP_082185.2; NM_027909.2.
DR AlphaFoldDB; Q80X80; -.
DR SMR; Q80X80; -.
DR BioGRID; 214908; 2.
DR STRING; 10090.ENSMUSP00000065233; -.
DR iPTMnet; Q80X80; -.
DR PhosphoSitePlus; Q80X80; -.
DR SwissPalm; Q80X80; -.
DR EPD; Q80X80; -.
DR jPOST; Q80X80; -.
DR MaxQB; Q80X80; -.
DR PaxDb; Q80X80; -.
DR PeptideAtlas; Q80X80; -.
DR PRIDE; Q80X80; -.
DR ProteomicsDB; 265267; -.
DR Antibodypedia; 32613; 61 antibodies from 17 providers.
DR DNASU; 71764; -.
DR Ensembl; ENSMUST00000065080; ENSMUSP00000065233; ENSMUSG00000032120.
DR GeneID; 71764; -.
DR KEGG; mmu:71764; -.
DR UCSC; uc009pct.1; mouse.
DR CTD; 9854; -.
DR MGI; MGI:1919014; C2cd2l.
DR VEuPathDB; HostDB:ENSMUSG00000032120; -.
DR eggNOG; ENOG502QRBG; Eukaryota.
DR GeneTree; ENSGT00530000063764; -.
DR HOGENOM; CLU_024872_1_0_1; -.
DR InParanoid; Q80X80; -.
DR OMA; ISHVTCT; -.
DR OrthoDB; 307984at2759; -.
DR PhylomeDB; Q80X80; -.
DR TreeFam; TF331604; -.
DR BioGRID-ORCS; 71764; 5 hits in 71 CRISPR screens.
DR ChiTaRS; C2cd2l; mouse.
DR PRO; PR:Q80X80; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q80X80; protein.
DR Bgee; ENSMUSG00000032120; Expressed in retinal neural layer and 237 other tissues.
DR ExpressionAtlas; Q80X80; baseline and differential.
DR Genevisible; Q80X80; MM.
DR GO; GO:0032541; C:cortical endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0098592; C:cytoplasmic side of apical plasma membrane; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0140268; C:endoplasmic reticulum-plasma membrane contact site; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043559; F:insulin binding; IDA:MGI.
DR GO; GO:0035091; F:phosphatidylinositol binding; ISS:UniProtKB.
DR GO; GO:0008526; F:phosphatidylinositol transfer activity; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:MGI.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR039934; C2CD2/C2CD2L.
DR InterPro; IPR040885; SMP_C2CD2L.
DR PANTHER; PTHR21119; PTHR21119; 1.
DR Pfam; PF18696; SMP_C2CD2L; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Endoplasmic reticulum; Lipid transport; Lipid-binding;
KW Membrane; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..706
FT /note="Phospholipid transfer protein C2CD2L"
FT /id="PRO_0000072597"
FT TOPO_DOM 1..9
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 10..30
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 31..706
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 76..260
FT /note="SMP-LBD"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT DOMAIN 268..389
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 408..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 452..503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 564..682
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 412..428
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..502
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 585..602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 603..617
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 661..677
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 59
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 358
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 411
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 417
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 419
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 428
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 464
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 470
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 613
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 621
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 638
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14523"
FT CONFLICT 550
FT /note="A -> V (in Ref. 3; AAH60156)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 706 AA; 76329 MW; 719B7D32897068F0 CRC64;
MDPDWGQRDV GWAALLVLFA ASLITVLGWM LQYARGLWLS RADGGRDSRP ASAAEPGGSL
RELGVWRSLL RLRATRTSTP EEAGVRGLLA SLFAFKSFRE NWQRAWVRAL NEQACRDGSS
IQIAFEEIPQ LPPRASISHV TCVDQSERTM VLHCQLSAEE VRFPISVTQQ SPAAVSMETY
HVTLTLPPTQ LEVSLEEIPD EGLLVSWAFT DRPELSLKVL PKLQTRERDE EQPELSTVEE
LIKDAIVSTQ PAMMVNLRAC SAPGGLVPSE KPPTMSQAQP SIPRPTRLFL RQLRASHLGS
ELGGTEELCC AAELDNPMQQ KWTKPMRAGP EVEWTEDLAL DLGPQSRELT LKVLRSSSCG
DAELLGQATL PVGSPSRPMS RRQVCPLTPG PGKSLSPAAT VTAELHYEQG SPRNLGTPTS
STPRPSITPT KKIELDRTIM PDGTVVTTVT TVQSRPRVDG KLDSPSRSPS KVEVTEKMTT
VLSESSGPSN ASHSSSRESH LSNGLDPVAE TAIRQLTEPS GRAAKKTPTK RSTLIISGVS
KVPIAQDELA LSLGYAASLE ASMQDDAGTS GGPSSPPSDP SATSPGPVDA LSSPTSVQEA
DETTRSDISE RPSVDDVESE TGSTGALETR SLKDHKVSFL RSGTKLIFRR RPRQKEAGLS
QSHDDLSNTT ATPSVRKKAG SFSRRLIKRF SFKSKPKANG NPSPQL
