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PLSCR3 phospholipid scramblase 3 [ Homo sapiens (human) ]

Gene ID: 57048, updated on 11-Apr-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 several functions, including calcium-dependent protein binding activity; metal ion binding activity; and phospholipid scramblase activity. Involved in several processes, including cardiolipin biosynthetic process; regulation of apoptotic process; and regulation of release of cytochrome c from mitochondria. Located in cytosol; mitochondrion; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in spleen (RPKM 12.9), fat (RPKM 12.1) and 25 other tissues See more
Orthologs
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (7389727..7394525, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (7293769..7298567, complement)
105.20220307 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

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. 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
  2. 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
  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. 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
  5. Phospholipid scramblase 3 controls mitochondrial structure, function, and apoptotic response. Liu J, et al. Mol Cancer Res, 2003 Oct. PMID 14573790

See all (31) 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)

Genotypes

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 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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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_2023_10

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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