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    PLSCR3 phospholipid scramblase 3 [ Homo sapiens (human) ]

    Gene ID: 57048, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PLSCR3provided by HGNC
    Official Full Name
    phospholipid scramblase 3provided by HGNC
    Primary source
    HGNC:HGNC:16495
    See related
    Ensembl:ENSG00000187838 MIM:607611; AllianceGenome:HGNC:16495
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    Enables calcium-dependent protein binding activity; metal ion binding activity; and phospholipid scramblase activity. Involved in several processes, including apoptotic process; cardiolipin biosynthetic process; and regulation of release of cytochrome c from mitochondria. Located in cytosol; mitochondrion; and plasma membrane. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in spleen (RPKM 12.9), fat (RPKM 12.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PLSCR3 in Genome Data Viewer
    Location:
    17p13.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (7389727..7394525, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (7293769..7298567, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (7293046..7297844, complement)

    Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8113 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:7258016-7258542 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:7258543-7259069 Neighboring gene potassium channel tetramerization domain containing 11 Neighboring gene transmembrane protein 95 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:7269638-7269860 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:7283926-7284426 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8114 Neighboring gene tyrosine kinase non receptor 1 Neighboring gene TMEM256-PLSCR3 readthrough (NMD candidate) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8115 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11618 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8116 Neighboring gene transmembrane protein 256 Neighboring gene neuroligin 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7323127-7323646

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Bibliography

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    Related articles in PubMed

    1. Phospholipid scramblase 3 controls mitochondrial structure, function, and apoptotic response. Liu J, et al. Mol Cancer Res, 2003 Oct. PMID 14573790
    2. Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing HeLa cells. Van Q, et al. Biochem J, 2007 Jan 1. PMID 16939411, Free PMC Article
    3. Role of phospholipid scramblase 3 in the regulation of tumor necrosis factor-alpha-induced apoptosis. Liu J, et al. Biochemistry, 2008 Apr 15. PMID 18358005
    4. Heavy-Metals-Mediated Phospholipids Scrambling by Human Phospholipid Scramblase 3: A Probable Role in Mitochondrial Apoptosis. Palanirajan SK, et al. Chem Res Toxicol, 2020 Feb 17. PMID 31769662
    5. In vitro reconstitution and biochemical characterization of human phospholipid scramblase 3: phospholipid specificity and metal ion binding studies. Palanirajan SK, et al. Biol Chem, 2018 Mar 28. PMID 29337693

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The results revealed that Ca2+ and Mg2+ bind to Human phospholipid scramblase 3 (hPLSCR3) and trigger conformational changes mediated by aggregation.
      Title: In vitro reconstitution and biochemical characterization of human phospholipid scramblase 3: phospholipid specificity and metal ion binding studies.
    2. Secreted Scr3 was taken up by HeLa cells, suggesting that Scr3 functions as a cell-to-cell transferable modulator carried by exosomes in a paracrine manner.
      Title: ALG-2-interacting Tubby-like protein superfamily member PLSCR3 is secreted by an exosomal pathway and taken up by recipient cultured cells.
    3. Results show that binding affinities of the peptides are in the order hPLSCR1>hPLSCR3>hPLSCR2>hPLSCR4 for Ca2+ and in the order hPLSCR1>hPLSCR2>hPLSCR3>hPLSCR4 for Mg2+.
      Title: Calcium binding studies of peptides of human phospholipid scramblases 1 to 4 suggest that scramblases are new class of calcium binding proteins in the cell.
    4. TRAIL-induced activation of PKC-delta mediates regulation of the phospholipid scramblase3-induced changes in cardiolipin.
      Title: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced mitochondrial pathway to apoptosis and caspase activation is potentiated by phospholipid scramblase-3.
    5. Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants
      Title: Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants.
    6. These findings indicate that phosphorylation of PLS3 by PKC-delta induces PLS3 activation to facilitate mitochondrial targeting of tBid and apoptosis.
      Title: Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C-delta induces its activation and facilitates mitochondrial targeting of tBid.
    7. PLS3 is a downstream effector of PKC-delta in the mitochondria.
      Title: Phospholipid scramblase 3 is the mitochondrial target of protein kinase C delta-induced apoptosis.
    8. PLS3 as a critical regulator of mitochondrial structure and respiration, and CL transport in apoptosis.
      Title: Phospholipid scramblase 3 controls mitochondrial structure, function, and apoptotic response.
    9. This enzyme is a novel regulator of cardiolipin de novo biosynthesis and its resynthesis.
      Title: Phospholipid scramblase-3 regulates cardiolipin de novo biosynthesis and its resynthesis in growing HeLa cells.
    Submit: New GeneRIF Correction

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Readthrough TMEM256-PLSCR3

    Readthrough gene: TMEM256-PLSCR3, Included gene: TMEM256

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SH3 domain binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables calcium ion binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables calcium ion binding NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables calcium-dependent protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables lead ion binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables magnesium ion binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables mercury ion binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables phospholipid scramblase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phospholipid scramblase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables phospholipid scramblase activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cardiolipin biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cholesterol homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in glucose homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in plasma membrane phospholipid scrambling IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in plasma membrane phospholipid scrambling NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of release of cytochrome c from mitochondria IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial inner membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in plasma membrane NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    phospholipid scramblase 3
    Names
    PL scramblase 3
    ca(2+)-dependent phospholipid scramblase 3

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001201576.2 → NP_001188505.1  phospholipid scramblase 3 isoform 1

      See identical proteins and their annotated locations for NP_001188505.1

      Status: VALIDATED

      Source sequence(s)
      AC113189
      Consensus CDS
      CCDS42253.1
      UniProtKB/Swiss-Prot
      A8K252, Q567U0, Q8NBW6, Q96F13, Q9NRY6
      UniProtKB/TrEMBL
      B2RBF8
      Related
      ENSP00000316021.11, ENST00000324822.15
      Conserved Domains (2) summary
      PRK05641
      Location:31 → 71
      PRK05641; putative acetyl-CoA carboxylase biotin carboxyl carrier protein subunit; Validated
      pfam03803
      Location:62 → 284
      Scramblase

    2. NM_001369407.1 → NP_001356336.1  phospholipid scramblase 3 isoform 1

      Status: VALIDATED

      Source sequence(s)
      AC113189
      Consensus CDS
      CCDS42253.1
      UniProtKB/Swiss-Prot
      A8K252, Q567U0, Q8NBW6, Q96F13, Q9NRY6
      UniProtKB/TrEMBL
      B2RBF8
      Related
      ENSP00000459019.1, ENST00000574401.5
      Conserved Domains (2) summary
      PRK05641
      Location:31 → 71
      PRK05641; putative acetyl-CoA carboxylase biotin carboxyl carrier protein subunit; Validated
      pfam03803
      Location:62 → 284
      Scramblase

    3. NM_001369420.1 → NP_001356349.1  phospholipid scramblase 3 isoform 2

      Status: VALIDATED

      Source sequence(s)
      AC113189
      Conserved Domains (1) summary
      cl02043
      Location:62 → 219
      LOR; LURP-one-related

    4. NM_001369421.1 → NP_001356350.1  phospholipid scramblase 3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC113189
      Conserved Domains (1) summary
      cl02043
      Location:1 → 115
      LOR; LURP-one-related

    5. NM_001369422.1 → NP_001356351.1  phospholipid scramblase 3 isoform 3

      Status: VALIDATED

      Source sequence(s)
      AC113189
      Conserved Domains (1) summary
      cl02043
      Location:1 → 115
      LOR; LURP-one-related

    6. NM_020360.4 → NP_065093.2  phospholipid scramblase 3 isoform 1

      See identical proteins and their annotated locations for NP_065093.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      BC011735, BC093026
      Consensus CDS
      CCDS42253.1
      UniProtKB/Swiss-Prot
      A8K252, Q567U0, Q8NBW6, Q96F13, Q9NRY6
      UniProtKB/TrEMBL
      B2RBF8
      Related
      ENSP00000483743.2, ENST00000619711.5
      Conserved Domains (2) summary
      PRK05641
      Location:31 → 71
      PRK05641; putative acetyl-CoA carboxylase biotin carboxyl carrier protein subunit; Validated
      pfam03803
      Location:62 → 284
      Scramblase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

      Range
      7389727..7394525 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_016107299.1 Reference GRCh38.p14 PATCHES

      Range
      10184..14982 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060941.1 Alternate T2T-CHM13v2.0

      Range
      7293769..7298567 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NRY6.2 GenPept UniProtKB/Swiss-Prot:Q9NRY6

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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