CRLS1_HUMAN
ID CRLS1_HUMAN Reviewed; 301 AA.
AC Q9UJA2; D3DW09; E9PAT4; Q27RP0; Q69YQ5;
DT 03-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Cardiolipin synthase (CMP-forming);
DE Short=CLS;
DE EC=2.7.8.41 {ECO:0000269|PubMed:16678169};
DE AltName: Full=Protein GCD10 homolog;
GN Name=CRLS1; Synonyms=C20orf155, CLS1;
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 [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, AND PH DEPENDENCE.
RX PubMed=16678169; DOI=10.1016/j.febslet.2006.04.054;
RA Houtkooper R.H., Akbari H., van Lenthe H., Kulik W., Wanders R.J.A.,
RA Frentzen M., Vaz F.M.;
RT "Identification and characterization of human cardiolipin synthase.";
RL FEBS Lett. 580:3059-3064(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver cancer;
RA Cheng Z., Gao G., Peng Y., Ren S., Chen Z., Han Z.;
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-301 (ISOFORM 1).
RC TISSUE=Melanoma;
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 [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16547353; DOI=10.1194/jlr.c600004-jlr200;
RA Lu B., Xu F.Y., Jiang Y.J., Choy P.C., Hatch G.M., Grunfeld C.,
RA Feingold K.R.;
RT "Cloning and characterization of a cDNA encoding human cardiolipin synthase
RT (hCLS1).";
RL J. Lipid Res. 47:1140-1145(2006).
CC -!- FUNCTION: Catalyzes the synthesis of cardiolipin (CL)
CC (diphosphatidylglycerol) by specifically transferring a phosphatidyl
CC group from CDP-diacylglycerol to phosphatidylglycerol (PG). CL is a key
CC phospholipid in mitochondrial membranes and plays important roles in
CC maintaining the functional integrity and dynamics of mitochondria under
CC both optimal and stress conditions. {ECO:0000269|PubMed:16547353,
CC ECO:0000269|PubMed:16678169}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol) + a CDP-1,2-
CC diacyl-sn-glycerol = a cardiolipin + CMP + H(+);
CC Xref=Rhea:RHEA:32931, ChEBI:CHEBI:15378, ChEBI:CHEBI:58332,
CC ChEBI:CHEBI:60377, ChEBI:CHEBI:62237, ChEBI:CHEBI:64716; EC=2.7.8.41;
CC Evidence={ECO:0000269|PubMed:16678169};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000269|PubMed:16678169};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.2. {ECO:0000269|PubMed:16678169};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:16547353}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16547353}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UJA2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UJA2-2; Sequence=VSP_041398, VSP_041399;
CC -!- TISSUE SPECIFICITY: Highly expressed in tissues such as heart, skeletal
CC muscle and liver. {ECO:0000269|PubMed:16547353}.
CC -!- SIMILARITY: Belongs to the CDP-alcohol phosphatidyltransferase class-I
CC family. {ECO:0000305}.
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DR EMBL; DQ386730; ABD46888.1; -; mRNA.
DR EMBL; AF241784; AAG44472.1; -; mRNA.
DR EMBL; AL035461; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10401.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10402.1; -; Genomic_DNA.
DR EMBL; AL832419; CAH10649.1; -; mRNA.
DR CCDS; CCDS13096.1; -. [Q9UJA2-1]
DR CCDS; CCDS46578.1; -. [Q9UJA2-2]
DR RefSeq; NP_001120930.1; NM_001127458.1. [Q9UJA2-2]
DR RefSeq; NP_001310490.1; NM_001323561.1.
DR RefSeq; NP_001310491.1; NM_001323562.1.
DR RefSeq; NP_001310492.1; NM_001323563.1.
DR RefSeq; NP_001310493.1; NM_001323564.1.
DR RefSeq; NP_061968.1; NM_019095.5. [Q9UJA2-1]
DR AlphaFoldDB; Q9UJA2; -.
DR SMR; Q9UJA2; -.
DR BioGRID; 120096; 4.
DR IntAct; Q9UJA2; 1.
DR MINT; Q9UJA2; -.
DR STRING; 9606.ENSP00000368140; -.
DR SwissLipids; SLP:000000125; -.
DR iPTMnet; Q9UJA2; -.
DR PhosphoSitePlus; Q9UJA2; -.
DR BioMuta; CRLS1; -.
DR DMDM; 37537857; -.
DR EPD; Q9UJA2; -.
DR jPOST; Q9UJA2; -.
DR MassIVE; Q9UJA2; -.
DR MaxQB; Q9UJA2; -.
DR PaxDb; Q9UJA2; -.
DR PeptideAtlas; Q9UJA2; -.
DR PRIDE; Q9UJA2; -.
DR ProteomicsDB; 84608; -. [Q9UJA2-1]
DR ProteomicsDB; 84609; -. [Q9UJA2-2]
DR Antibodypedia; 23985; 143 antibodies from 27 providers.
DR DNASU; 54675; -.
DR Ensembl; ENST00000378863.9; ENSP00000368140.4; ENSG00000088766.12. [Q9UJA2-1]
DR Ensembl; ENST00000378868.4; ENSP00000368145.3; ENSG00000088766.12. [Q9UJA2-2]
DR GeneID; 54675; -.
DR KEGG; hsa:54675; -.
DR MANE-Select; ENST00000378863.9; ENSP00000368140.4; NM_019095.6; NP_061968.1.
DR UCSC; uc002wmn.5; human. [Q9UJA2-1]
DR CTD; 54675; -.
DR DisGeNET; 54675; -.
DR GeneCards; CRLS1; -.
DR HGNC; HGNC:16148; CRLS1.
DR HPA; ENSG00000088766; Tissue enhanced (liver).
DR MIM; 608188; gene.
DR neXtProt; NX_Q9UJA2; -.
DR OpenTargets; ENSG00000088766; -.
DR PharmGKB; PA25697; -.
DR VEuPathDB; HostDB:ENSG00000088766; -.
DR eggNOG; KOG1617; Eukaryota.
DR GeneTree; ENSGT00390000001607; -.
DR HOGENOM; CLU_051314_0_1_1; -.
DR InParanoid; Q9UJA2; -.
DR OMA; KRFNMAS; -.
DR OrthoDB; 1169813at2759; -.
DR PhylomeDB; Q9UJA2; -.
DR TreeFam; TF314169; -.
DR BRENDA; 2.7.8.41; 2681.
DR PathwayCommons; Q9UJA2; -.
DR Reactome; R-HSA-1482925; Acyl chain remodelling of PG.
DR Reactome; R-HSA-1483076; Synthesis of CL.
DR SignaLink; Q9UJA2; -.
DR SIGNOR; Q9UJA2; -.
DR BioGRID-ORCS; 54675; 464 hits in 1084 CRISPR screens.
DR ChiTaRS; CRLS1; human.
DR GenomeRNAi; 54675; -.
DR Pharos; Q9UJA2; Tbio.
DR PRO; PR:Q9UJA2; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9UJA2; protein.
DR Bgee; ENSG00000088766; Expressed in right lobe of liver and 96 other tissues.
DR ExpressionAtlas; Q9UJA2; baseline and differential.
DR Genevisible; Q9UJA2; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0003841; F:1-acylglycerol-3-phosphate O-acyltransferase activity; TAS:Reactome.
DR GO; GO:0047144; F:2-acylglycerol-3-phosphate O-acyltransferase activity; TAS:Reactome.
DR GO; GO:0008808; F:cardiolipin synthase activity; IBA:GO_Central.
DR GO; GO:0043337; F:CDP-diacylglycerol-phosphatidylglycerol phosphatidyltransferase activity; TAS:Reactome.
DR GO; GO:0032049; P:cardiolipin biosynthetic process; IBA:GO_Central.
DR GO; GO:0046474; P:glycerophospholipid biosynthetic process; IBA:GO_Central.
DR GO; GO:0036148; P:phosphatidylglycerol acyl-chain remodeling; TAS:Reactome.
DR GO; GO:1905711; P:response to phosphatidylethanolamine; IEA:Ensembl.
DR GO; GO:0097068; P:response to thyroxine; IEA:Ensembl.
DR Gene3D; 1.20.120.1760; -; 1.
DR InterPro; IPR000462; CDP-OH_P_trans.
DR InterPro; IPR043130; CDP-OH_PTrfase_TM_dom.
DR Pfam; PF01066; CDP-OH_P_transf; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Lipid biosynthesis; Lipid metabolism; Membrane;
KW Mitochondrion; Mitochondrion inner membrane; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..301
FT /note="Cardiolipin synthase (CMP-forming)"
FT /id="PRO_0000056816"
FT TRANSMEM 109..129
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 133..153
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..292
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 70..93
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..99
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041398"
FT VAR_SEQ 100..102
FT /note="PSL -> MPQ (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_041399"
SQ SEQUENCE 301 AA; 32593 MW; 15CD406D29D3C405 CRC64;
MLALRVARGS WGALRGAAWA PGTRPSKRRA CWALLPPVPC CLGCLAERWR LRPAALGLRL
PGIGQRNHCS GAGKAAPRPA AGAGAAAEAP GGQWGPASTP SLYENPWTIP NMLSMTRIGL
APVLGYLIIE EDFNIALGVF ALAGLTDLLD GFIARNWANQ RSALGSALDP LADKILISIL
YVSLTYADLI PVPLTYMIIS RDVMLIAAVF YVRYRTLPTP RTLAKYFNPC YATARLKPTF
ISKVNTAVQL ILVAASLAAP VFNYADSIYL QILWCFTAFT TAASAYSYYH YGRKTVQVIK
D
