TLCD1_HUMAN
ID TLCD1_HUMAN Reviewed; 247 AA.
AC Q96CP7; A8MYP9;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=TLC domain-containing protein 1;
DE AltName: Full=Calfacilitin;
DE Flags: Precursor;
GN Name=TLCD1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2011) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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, AND SUBCELLULAR LOCATION.
RX PubMed=30509349; DOI=10.7554/elife.40686;
RA Ruiz M., Bodhicharla R., Svensk E., Devkota R., Busayavalasa K.,
RA Palmgren H., Staahlman M., Boren J., Pilon M.;
RT "Membrane fluidity is regulated by the C. elegans transmembrane protein
RT FLD-1 and its human homologs TLCD1/2.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Regulates the composition and fluidity of the plasma membrane
CC (PubMed:30509349). Inhibits the incorporation of membrane-fluidizing
CC phospholipids containing omega-3 long-chain polyunsaturated fatty acids
CC (LCPUFA) and thereby promotes membrane rigidity (PubMed:30509349). Does
CC not appear to have any effect on LCPUFA synthesis (PubMed:30509349).
CC {ECO:0000269|PubMed:30509349}.
CC -!- INTERACTION:
CC Q96CP7; Q13520: AQP6; NbExp=3; IntAct=EBI-11337932, EBI-13059134;
CC Q96CP7; P25942: CD40; NbExp=3; IntAct=EBI-11337932, EBI-525714;
CC Q96CP7; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-11337932, EBI-6942903;
CC Q96CP7; Q15125: EBP; NbExp=3; IntAct=EBI-11337932, EBI-3915253;
CC Q96CP7; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-11337932, EBI-12175685;
CC Q96CP7; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-11337932, EBI-17280858;
CC Q96CP7; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-11337932, EBI-8638294;
CC Q96CP7; Q96HE8: TMEM80; NbExp=3; IntAct=EBI-11337932, EBI-11742770;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:30509349};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:F1NZP5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96CP7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96CP7-2; Sequence=VSP_055726;
CC -!- CAUTION: Was originally proposed to be a calcium channel facilitator
CC (By similarity). However, a more recent study shows that this protein
CC regulates membrane phospholipid homeostasis (PubMed:30509349).
CC Therefore, any effects on calcium flux are most likely a secondary
CC consequence of defects in membrane composition or fluidity
CC (PubMed:30509349). {ECO:0000250|UniProtKB:F1NZP5,
CC ECO:0000269|PubMed:30509349}.
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DR EMBL; AC010761; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471159; EAW51134.1; -; Genomic_DNA.
DR EMBL; BC014072; AAH14072.1; -; mRNA.
DR CCDS; CCDS11242.1; -. [Q96CP7-1]
DR CCDS; CCDS54102.1; -. [Q96CP7-2]
DR RefSeq; NP_001153879.1; NM_001160407.1. [Q96CP7-2]
DR RefSeq; NP_612472.1; NM_138463.3. [Q96CP7-1]
DR AlphaFoldDB; Q96CP7; -.
DR BioGRID; 125493; 22.
DR IntAct; Q96CP7; 16.
DR STRING; 9606.ENSP00000292090; -.
DR iPTMnet; Q96CP7; -.
DR PhosphoSitePlus; Q96CP7; -.
DR SwissPalm; Q96CP7; -.
DR BioMuta; TLCD1; -.
DR DMDM; 74731368; -.
DR EPD; Q96CP7; -.
DR jPOST; Q96CP7; -.
DR MassIVE; Q96CP7; -.
DR MaxQB; Q96CP7; -.
DR PaxDb; Q96CP7; -.
DR PeptideAtlas; Q96CP7; -.
DR PRIDE; Q96CP7; -.
DR ProteomicsDB; 2417; -.
DR ProteomicsDB; 76206; -. [Q96CP7-1]
DR Antibodypedia; 51370; 72 antibodies from 14 providers.
DR DNASU; 116238; -.
DR Ensembl; ENST00000292090.8; ENSP00000292090.3; ENSG00000160606.11. [Q96CP7-1]
DR Ensembl; ENST00000394933.7; ENSP00000378391.3; ENSG00000160606.11. [Q96CP7-2]
DR GeneID; 116238; -.
DR KEGG; hsa:116238; -.
DR MANE-Select; ENST00000292090.8; ENSP00000292090.3; NM_138463.4; NP_612472.1.
DR UCSC; uc002hco.4; human. [Q96CP7-1]
DR CTD; 116238; -.
DR DisGeNET; 116238; -.
DR GeneCards; TLCD1; -.
DR HGNC; HGNC:25177; TLCD1.
DR HPA; ENSG00000160606; Low tissue specificity.
DR neXtProt; NX_Q96CP7; -.
DR OpenTargets; ENSG00000160606; -.
DR PharmGKB; PA142670807; -.
DR VEuPathDB; HostDB:ENSG00000160606; -.
DR eggNOG; KOG4474; Eukaryota.
DR GeneTree; ENSGT01010000222313; -.
DR HOGENOM; CLU_056440_2_1_1; -.
DR InParanoid; Q96CP7; -.
DR OMA; CAGQNGM; -.
DR OrthoDB; 1113854at2759; -.
DR PhylomeDB; Q96CP7; -.
DR TreeFam; TF315115; -.
DR PathwayCommons; Q96CP7; -.
DR SignaLink; Q96CP7; -.
DR BioGRID-ORCS; 116238; 97 hits in 1081 CRISPR screens.
DR ChiTaRS; TLCD1; human.
DR GenomeRNAi; 116238; -.
DR Pharos; Q96CP7; Tdark.
DR PRO; PR:Q96CP7; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q96CP7; protein.
DR Bgee; ENSG00000160606; Expressed in right uterine tube and 122 other tissues.
DR ExpressionAtlas; Q96CP7; baseline and differential.
DR Genevisible; Q96CP7; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; IBA:GO_Central.
DR GO; GO:0071709; P:membrane assembly; IMP:UniProtKB.
DR GO; GO:0055091; P:phospholipid homeostasis; IMP:UniProtKB.
DR GO; GO:0007009; P:plasma membrane organization; IMP:UniProtKB.
DR GO; GO:0097035; P:regulation of membrane lipid distribution; IMP:UniProtKB.
DR InterPro; IPR006634; TLC-dom.
DR Pfam; PF03798; TRAM_LAG1_CLN8; 1.
DR SMART; SM00724; TLC; 1.
DR PROSITE; PS50922; TLC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Membrane; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..35
FT /evidence="ECO:0000255"
FT CHAIN 36..247
FT /note="TLC domain-containing protein 1"
FT /id="PRO_0000285677"
FT TOPO_DOM 36..46
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NZP5"
FT TRANSMEM 47..67
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..83
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NZP5"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 105..123
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NZP5"
FT INTRAMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 145..173
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NZP5"
FT TRANSMEM 174..194
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 195..201
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:F1NZP5"
FT TRANSMEM 202..222
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 223..247
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:F1NZP5"
FT DOMAIN 40..234
FT /note="TLC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00205"
FT VAR_SEQ 1..65
FT /note="MPRLLHPALPLLLGATLTFRALRRALCRLPLPVHVRADPLRTWRWHNLLVSF
FT AHSIVSGIWALLC -> MGYSAVPKCPPRGRGRDS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055726"
SQ SEQUENCE 247 AA; 28548 MW; D23777D955BAB447 CRC64;
MPRLLHPALP LLLGATLTFR ALRRALCRLP LPVHVRADPL RTWRWHNLLV SFAHSIVSGI
WALLCVWQTP DMLVEIETAW SLSGYLLVCF SAGYFIHDTV DIVASGQTRA SWEYLVHHVM
AMGAFFSGIF WSSFVGGGVL TLLVEVSNIF LTIRMMMKIS NAQDHLLYRV NKYVNLVMYF
LFRLAPQAYL THFFLRYVNQ RTLGTFLLGI LLMLDVMIII YFSRLLRSDF CPEHVPKKQH
KDKFLTE
