CSCL1_HUMAN
ID CSCL1_HUMAN Reviewed; 807 AA.
AC O94886; Q53GI7; Q5TE96; Q8N2U2;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 3.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=CSC1-like protein 1;
DE AltName: Full=Transmembrane protein 63A;
GN Name=TMEM63A; Synonyms=KIAA0489, KIAA0792;
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=9872452; DOI=10.1093/dnares/5.5.277;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XI. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:277-286(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Blood;
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 REVIEW, AND SUBCELLULAR LOCATION.
RX PubMed=20957757; DOI=10.1002/pmic.201000196;
RA Schroeder B.A., Wrocklage C., Hasilik A., Saftig P.;
RT "The proteome of lysosomes.";
RL Proteomics 10:4053-4076(2010).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [7]
RP FUNCTION.
RX PubMed=30382938; DOI=10.7554/elife.41844;
RA Murthy S.E., Dubin A.E., Whitwam T., Jojoa-Cruz S., Cahalan S.M.,
RA Mousavi S.A.R., Ward A.B., Patapoutian A.;
RT "OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically
RT Activated Ion Channels.";
RL Elife 7:0-0(2018).
RN [8]
RP VARIANTS HLD19 GLU-168; ASN-462 AND SER-567, CHARACTERIZATION OF VARIANTS
RP HLD19 GLU-168; ASN-462 AND SER-567, AND FUNCTION.
RX PubMed=31587869; DOI=10.1016/j.ajhg.2019.09.011;
RA Yan H., Helman G., Murthy S.E., Ji H., Crawford J., Kubisiak T., Bent S.J.,
RA Xiao J., Taft R.J., Coombs A., Wu Y., Pop A., Li D., de Vries L.S.,
RA Jiang Y., Salomons G.S., van der Knaap M.S., Patapoutian A., Simons C.,
RA Burmeister M., Wang J., Wolf N.I.;
RT "Heterozygous Variants in the Mechanosensitive Ion Channel TMEM63A Result
RT in Transient Hypomyelination during Infancy.";
RL Am. J. Hum. Genet. 105:996-1004(2019).
CC -!- FUNCTION: Acts as an osmosensitive calcium-permeable cation channel
CC (PubMed:30382938, PubMed:31587869). Mechanosensitive ion channel that
CC converts mechanical stimuli into a flow of ion (PubMed:30382938,
CC PubMed:31587869). {ECO:0000250|UniProtKB:Q91YT8,
CC ECO:0000269|PubMed:30382938, ECO:0000269|PubMed:31587869}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:20957757};
CC Multi-pass membrane protein {ECO:0000255}. Cell membrane
CC {ECO:0000250|UniProtKB:Q91YT8}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISEASE: Leukodystrophy, hypomyelinating, 19, transient infantile
CC (HLD19) [MIM:618688]: An autosomal dominant disorder characterized by
CC marked hypomyelination on brain imaging, congenital nystagmus, and
CC motor delay manifesting in early infancy. Both neurologic impairment
CC and abnormal brain imaging spontaneously resolve during childhood.
CC {ECO:0000269|PubMed:31587869}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the CSC1 (TC 1.A.17) family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA34512.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96654.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96664.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB018335; BAA34512.2; ALT_INIT; mRNA.
DR EMBL; AK222944; BAD96664.1; ALT_INIT; mRNA.
DR EMBL; AK222934; BAD96654.1; ALT_INIT; mRNA.
DR EMBL; AL117348; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591895; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030245; AAH30245.1; -; mRNA.
DR CCDS; CCDS31042.1; -.
DR RefSeq; NP_055513.2; NM_014698.2.
DR RefSeq; XP_011542630.1; XM_011544328.2.
DR RefSeq; XP_011542631.1; XM_011544329.2.
DR RefSeq; XP_011542632.1; XM_011544330.2.
DR AlphaFoldDB; O94886; -.
DR SMR; O94886; -.
DR BioGRID; 115074; 101.
DR IntAct; O94886; 41.
DR MINT; O94886; -.
DR STRING; 9606.ENSP00000355800; -.
DR TCDB; 1.A.17.5.21; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; O94886; 1 site.
DR iPTMnet; O94886; -.
DR PhosphoSitePlus; O94886; -.
DR SwissPalm; O94886; -.
DR BioMuta; TMEM63A; -.
DR EPD; O94886; -.
DR jPOST; O94886; -.
DR MassIVE; O94886; -.
DR MaxQB; O94886; -.
DR PaxDb; O94886; -.
DR PeptideAtlas; O94886; -.
DR PRIDE; O94886; -.
DR ProteomicsDB; 50523; -.
DR Antibodypedia; 34647; 76 antibodies from 16 providers.
DR DNASU; 9725; -.
DR Ensembl; ENST00000366835.8; ENSP00000355800.3; ENSG00000196187.12.
DR GeneID; 9725; -.
DR KEGG; hsa:9725; -.
DR MANE-Select; ENST00000366835.8; ENSP00000355800.3; NM_014698.3; NP_055513.2.
DR UCSC; uc001hpm.3; human.
DR CTD; 9725; -.
DR DisGeNET; 9725; -.
DR GeneCards; TMEM63A; -.
DR HGNC; HGNC:29118; TMEM63A.
DR HPA; ENSG00000196187; Group enriched (brain, salivary gland).
DR MalaCards; TMEM63A; -.
DR MIM; 618685; gene.
DR MIM; 618688; phenotype.
DR neXtProt; NX_O94886; -.
DR OpenTargets; ENSG00000196187; -.
DR PharmGKB; PA142670776; -.
DR VEuPathDB; HostDB:ENSG00000196187; -.
DR eggNOG; KOG1134; Eukaryota.
DR GeneTree; ENSGT00940000159576; -.
DR HOGENOM; CLU_015647_2_0_1; -.
DR InParanoid; O94886; -.
DR OMA; TQVIWSN; -.
DR OrthoDB; 395194at2759; -.
DR PhylomeDB; O94886; -.
DR TreeFam; TF324300; -.
DR PathwayCommons; O94886; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; O94886; -.
DR BioGRID-ORCS; 9725; 10 hits in 1080 CRISPR screens.
DR ChiTaRS; TMEM63A; human.
DR GeneWiki; TMEM63A; -.
DR GenomeRNAi; 9725; -.
DR Pharos; O94886; Tdark.
DR PRO; PR:O94886; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O94886; protein.
DR Bgee; ENSG00000196187; Expressed in C1 segment of cervical spinal cord and 192 other tissues.
DR ExpressionAtlas; O94886; baseline and differential.
DR Genevisible; O94886; HS.
DR GO; GO:0034451; C:centriolar satellite; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome.
DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome.
DR GO; GO:0005227; F:calcium activated cation channel activity; IBA:GO_Central.
DR GO; GO:0008381; F:mechanosensitive ion channel activity; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:1990760; F:osmolarity-sensing cation channel activity; ISS:UniProtKB.
DR Gene3D; 3.30.70.330; -; 1.
DR InterPro; IPR045122; Csc1-like.
DR InterPro; IPR032880; Csc1_N.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR InterPro; IPR027815; PHM7_cyt.
DR InterPro; IPR035979; RBD_domain_sf.
DR InterPro; IPR003864; RSN1_7TM.
DR InterPro; IPR026957; TMEM63A.
DR PANTHER; PTHR13018; PTHR13018; 1.
DR PANTHER; PTHR13018:SF24; PTHR13018:SF24; 1.
DR Pfam; PF14703; PHM7_cyt; 1.
DR Pfam; PF02714; RSN1_7TM; 1.
DR Pfam; PF13967; RSN1_TM; 1.
DR SUPFAM; SSF54928; SSF54928; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Disease variant; Ion channel; Ion transport;
KW Leukodystrophy; Lysosome; Membrane; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..807
FT /note="CSC1-like protein 1"
FT /id="PRO_0000280725"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 191..211
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 423..443
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 462..482
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 508..528
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 553..573
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 620..640
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 665..685
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 698..718
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 739
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YT8"
FT VARIANT 121
FT /note="F -> I (in dbSNP:rs57306966)"
FT /id="VAR_061813"
FT VARIANT 168
FT /note="G -> E (in HLD19; loss of mechanosensitive ion
FT channel activity; dbSNP:rs1576101665)"
FT /evidence="ECO:0000269|PubMed:31587869"
FT /id="VAR_083043"
FT VARIANT 462
FT /note="I -> N (in HLD19; loss of mechanosensitive ion
FT channel activity; dbSNP:rs1576080546)"
FT /evidence="ECO:0000269|PubMed:31587869"
FT /id="VAR_083044"
FT VARIANT 567
FT /note="G -> S (in HLD19; loss of mechanosensitive ion
FT channel activity; dbSNP:rs1576074651)"
FT /evidence="ECO:0000269|PubMed:31587869"
FT /id="VAR_083045"
FT VARIANT 622
FT /note="V -> M (in dbSNP:rs1009668)"
FT /id="VAR_031191"
FT CONFLICT 5
FT /note="P -> L (in Ref. 2; BAD96654/BAD96664)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="L -> F (in Ref. 1; BAA34512)"
FT /evidence="ECO:0000305"
FT CONFLICT 547
FT /note="V -> I (in Ref. 2; BAD96654/BAD96664)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 807 AA; 92126 MW; D7C32A11F7FEDF63 CRC64;
MMDSPFLELW QSKAVSIREQ LGLGDRPNDS YCYNSAKNST VLQGVTFGGI PTVLLIDVSC
FLFLILVFSI IRRRFWDYGR IALVSEADSE SRFQRLSSTS SSGQQDFENE LGCCPWLTAI
FRLHDDQILE WCGEDAIHYL SFQRHIIFLL VVVSFLSLCV ILPVNLSGDL LDKDPYSFGR
TTIANLQTDN DLLWLHTIFA VIYLFLTVGF MRHHTQSIKY KEENLVRRTL FITGLPRDAR
KETVESHFRD AYPTCEVVDV QLCYNVAKLI YLCKEKKKTE KSLTYYTNLQ VKTGQRTLIN
PKPCGQFCCC EVLGCEWEDA ISYYTRMKDR LLERITEEER HVQDQPLGMA FVTFQEKSMA
TYILKDFNAC KCQSLQCKGE PQPSSHSREL YTSKWTVTFA ADPEDICWKN LSIQGLRWWL
QWLGINFTLF LGLFFLTTPS IILSTMDKFN VTKPIHALNN PIISQFFPTL LLWSFSALLP
SIVYYSTLLE SHWTKSGENQ IMMTKVYIFL IFMVLILPSL GLTSLDFFFR WLFDKTSSEA
SIRLECVFLP DQGAFFVNYV IASAFIGNGM ELLRLPGLIL YTFRMIMAKT AADRRNVKQN
QAFQYEFGAM YAWMLCVFTV IVAYSITCPI IAPFGLIYIL LKHMVDRHNL YFVYLPAKLE
KGIHFAAVNQ ALAAPILCLF WLYFFSFLRL GMKAPATLFT FLVLLLTILV CLAHTCFGCF
KHLSPLNYKT EEPASDKGSE AEAHMPPPFT PYVPRILNGL ASERTALSPQ QQQQQTYGAI
HNISGTIPGQ CLAQSATGSV AAAPQEA
