CSC1_HUMAN
ID CSC1_HUMAN Reviewed; 806 AA.
AC Q9P1W3; B2RN22; B3KWJ5; Q86TS3; Q86TS4; Q9NSQ4; Q9P1W1;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Calcium permeable stress-gated cation channel 1;
DE AltName: Full=Transmembrane protein 63C;
GN Name=TMEM63C; Synonyms=C14orf171, CSC1;
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 MRNA].
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 139-274 AND 148-360.
RC TISSUE=Fetal brain;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 613-806.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=24503647; DOI=10.1038/cr.2014.14;
RA Hou C., Tian W., Kleist T., He K., Garcia V., Bai F., Hao Y., Luan S.,
RA Li L.;
RT "DUF221 proteins are a family of osmosensitive calcium-permeable cation
RT channels conserved across eukaryotes.";
RL Cell Res. 24:632-635(2014).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=30900988; DOI=10.7554/elife.42068;
RA Schulz A., Mueller N.V., van de Lest N.A., Eisenreich A., Schmidbauer M.,
RA Barysenka A., Purfuerst B., Sporbert A., Lorenzen T., Meyer A.M.,
RA Herlan L., Witten A., Ruehle F., Zhou W., de Heer E., Scharpfenecker M.,
RA Panakova D., Stoll M., Kreutz R.;
RT "Analysis of the genomic architecture of a complex trait locus in
RT hypertensive rat models links Tmem63c to kidney damage.";
RL Elife 8:0-0(2019).
CC -!- FUNCTION: Acts as an osmosensitive calcium-permeable cation channel
CC (PubMed:24503647). Required for the functional integrity of the kidney
CC glomerular filtration barrier (By similarity).
CC {ECO:0000250|UniProtKB:D3ZNF5, ECO:0000269|PubMed:24503647}.
CC -!- ACTIVITY REGULATION: Activated by hyperosmotic shock after mannitol
CC treatment. {ECO:0000269|PubMed:24503647}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q8CBX0};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in podocytes of kidney glomeruli
CC (PubMed:30900988). Significantly reduced expression in patients with
CC focal segmental glomerulosclerosis (PubMed:30900988).
CC {ECO:0000269|PubMed:30900988}.
CC -!- SIMILARITY: Belongs to the CSC1 (TC 1.A.17) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF62556.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK125159; BAG54157.1; -; mRNA.
DR EMBL; AC007375; AAF63182.1; -; Genomic_DNA.
DR EMBL; AC007954; AAF62556.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471061; EAW81272.1; -; Genomic_DNA.
DR EMBL; BC136613; AAI36614.1; -; mRNA.
DR EMBL; BC136614; AAI36615.1; -; mRNA.
DR EMBL; BX248756; CAD66563.1; -; mRNA.
DR EMBL; BX248759; CAD66566.1; -; mRNA.
DR EMBL; AL157492; CAB75676.1; -; mRNA.
DR CCDS; CCDS45141.1; -.
DR PIR; T46920; T46920.
DR RefSeq; NP_065164.2; NM_020431.3.
DR AlphaFoldDB; Q9P1W3; -.
DR SMR; Q9P1W3; -.
DR BioGRID; 121412; 44.
DR STRING; 9606.ENSP00000298351; -.
DR TCDB; 1.A.17.5.12; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; Q9P1W3; 1 site.
DR iPTMnet; Q9P1W3; -.
DR PhosphoSitePlus; Q9P1W3; -.
DR BioMuta; TMEM63C; -.
DR DMDM; 74719955; -.
DR EPD; Q9P1W3; -.
DR jPOST; Q9P1W3; -.
DR MassIVE; Q9P1W3; -.
DR PaxDb; Q9P1W3; -.
DR PeptideAtlas; Q9P1W3; -.
DR PRIDE; Q9P1W3; -.
DR ProteomicsDB; 83671; -.
DR Antibodypedia; 25977; 25 antibodies from 14 providers.
DR DNASU; 57156; -.
DR Ensembl; ENST00000298351.5; ENSP00000298351.4; ENSG00000165548.11.
DR GeneID; 57156; -.
DR KEGG; hsa:57156; -.
DR MANE-Select; ENST00000298351.5; ENSP00000298351.4; NM_020431.4; NP_065164.2.
DR UCSC; uc001xtf.3; human.
DR CTD; 57156; -.
DR DisGeNET; 57156; -.
DR GeneCards; TMEM63C; -.
DR HGNC; HGNC:23787; TMEM63C.
DR HPA; ENSG00000165548; Tissue enhanced (brain, pituitary gland).
DR neXtProt; NX_Q9P1W3; -.
DR OpenTargets; ENSG00000165548; -.
DR PharmGKB; PA134993950; -.
DR VEuPathDB; HostDB:ENSG00000165548; -.
DR eggNOG; KOG1134; Eukaryota.
DR GeneTree; ENSGT00940000159072; -.
DR HOGENOM; CLU_015647_0_0_1; -.
DR InParanoid; Q9P1W3; -.
DR OMA; PPLMMFF; -.
DR OrthoDB; 395194at2759; -.
DR PhylomeDB; Q9P1W3; -.
DR TreeFam; TF324300; -.
DR PathwayCommons; Q9P1W3; -.
DR BioGRID-ORCS; 57156; 15 hits in 1072 CRISPR screens.
DR ChiTaRS; TMEM63C; human.
DR GenomeRNAi; 57156; -.
DR Pharos; Q9P1W3; Tdark.
DR PRO; PR:Q9P1W3; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9P1W3; protein.
DR Bgee; ENSG00000165548; Expressed in cerebellar cortex and 144 other tissues.
DR ExpressionAtlas; Q9P1W3; baseline and differential.
DR Genevisible; Q9P1W3; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005227; F:calcium activated cation channel activity; IDA:UniProtKB.
DR GO; GO:1990760; F:osmolarity-sensing cation channel activity; ISS:UniProtKB.
DR GO; GO:0006812; P:cation transport; IDA:UniProtKB.
DR GO; GO:0003094; P:glomerular filtration; ISS:UniProtKB.
DR InterPro; IPR045122; Csc1-like.
DR InterPro; IPR032880; Csc1_N.
DR InterPro; IPR027815; PHM7_cyt.
DR InterPro; IPR003864; RSN1_7TM.
DR PANTHER; PTHR13018; PTHR13018; 1.
DR Pfam; PF14703; PHM7_cyt; 1.
DR Pfam; PF02714; RSN1_7TM; 1.
DR Pfam; PF13967; RSN1_TM; 1.
PE 2: Evidence at transcript level;
KW Calcium; Cell membrane; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..806
FT /note="Calcium permeable stress-gated cation channel 1"
FT /id="PRO_0000280730"
FT TRANSMEM 35..55
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 410..430
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 457..477
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 496..516
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 542..562
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 606..626
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 657..677
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 687..707
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 755..781
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 755..774
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBX0"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CBX0"
FT VARIANT 654
FT /note="M -> V (in dbSNP:rs2287384)"
FT /id="VAR_031193"
FT CONFLICT 7
FT /note="D -> N (in Ref. 1; BAG54157)"
FT /evidence="ECO:0000305"
FT CONFLICT 23
FT /note="F -> L (in Ref. 1; BAG54157)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 806 AA; 93317 MW; 99BEE7EE687D300C CRC64;
MSASPDDLST GGRLQNMTVD ECFQSRNTVL QGQPFGGVPT VLCLNIALWV LVLVVYSFLR
KAAWDYGRLA LLIHNDSLTS LIYGEQSEKT SPSETSLEME RRDKGFCSWF FNSITMKDED
LINKCGDDAR IYIVFQYHLI IFVLIICIPS LGIILPINYT GSVLDWSSHF ARTTIVNVST
ESKLLWLHSL LSFFYFITNF MFMAHHCLGF APRNSQKVTR TLMITYVPKD IEDPELIIKH
FHEAYPGSVV TRVHFCYDVR NLIDLDDQRR HAMRGRLFYT AKAKKTGKVM IRIHPCARLC
FCKCWTCFKE VDAEQYYSEL EEQLTDEFNA ELNRVPLKRL DLIFVTFQDS RMAKRVRKDY
KYVQCGVQPQ QSSVTTIVKS YYWRVTMAPH PKDIIWKHLS VRRFFWWARF IAINTFLFFL
FFFLTTPAII MNTIDMYNVT RPIEKLQNPI VTQFFPSVML WGFTVILPLI VYFSAFLEAH
WTRSSQNLVM VHKCYIFLVF MVVILPSMGL TSLDVFLRWL FDIYYLEQAS IRFQCVFLPD
NGAFFVNYVI TAALLGTGME LLRLGSLFCY STRLFFSRSE PERVNIRKNQ AIDFQFGREY
AWMMNVFSVV MAYSITCPII VPFGLLYLCM KHLTDRYNMY YSFAPTKLNE QIHMAAVSQA
IFAPLLGLFW MLFFSILRLG SLHAITIFSL STLLIAMVIA FVGIFLGKLR MVADYEPEEE
EIQTVFDMEP SSTSSTPTSL LYVATVLQEP ELNLTPASSP ARHTYGTMNN QPEEGEEESG
LRGFARELDS AQFQEGLELE GQNQYH
