UniProtKB - Q9NRY6 (PLS3_HUMAN)
Protein
Phospholipid scramblase 3
Gene
PLSCR3
Organism
Homo sapiens (Human)
Status
Functioni
Catalyzes calcium-induced ATP-independent rapid bidirectional and non-specific movement of the phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer membrane of the mitochondria (PubMed:14573790, PubMed:17226776, PubMed:18358005, PubMed:29337693, PubMed:31769662). Plays an important role in mitochondrial respiratory function, morphology, and apoptotic response (PubMed:14573790, PubMed:17226776, PubMed:18358005, PubMed:12649167). Mediates the translocation of cardiolipin from the mitochondrial inner membrane to outer membrane enhancing t-Bid induced cytochrome c release and apoptosis (PubMed:14573790, PubMed:17226776, PubMed:18358005). Enhances TNFSF10-induced apoptosis by regulating the distribution of cardiolipin in the mitochondrial membrane resulting in increased release of apoptogenic factors and consequent amplification of the activity of caspases (PubMed:18491232). Regulates cardiolipin de novo biosynthesis and its resynthesis (PubMed:16939411).8 Publications
Catalytic activityi
- This reaction proceeds in the forward1 Publication direction.
- a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(in) = a 1,2-diacyl-sn-glycero-3-phosphoethanolamine(out)2 Publications
- a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out)1 PublicationThis reaction proceeds in the forward1 Publication direction.
- a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out)1 PublicationThis reaction proceeds in the forward1 Publication direction.
- 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(in) = 1,2-diacyl-sn-glycero-3-phospho-(1'-sn-glycerol)(out)1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
Activity regulationi
Activated by Pb2+ and Hg2+ ions.1 Publication
GO - Molecular functioni
- calcium-dependent protein binding Source: UniProtKB
- calcium ion binding Source: UniProtKB
- lead ion binding Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- mercury ion binding Source: UniProtKB
- phospholipid scramblase activity Source: UniProtKB
- protein self-association Source: UniProtKB
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- apoptotic process Source: UniProtKB
- cardiolipin biosynthetic process Source: UniProtKB
- cellular response to lipopolysaccharide Source: Ensembl
- cholesterol homeostasis Source: Ensembl
- glucose homeostasis Source: Ensembl
- plasma membrane phospholipid scrambling Source: GO_Central
- regulation of apoptotic process Source: UniProtKB
- regulation of release of cytochrome c from mitochondria Source: UniProtKB
Keywordsi
Biological process | Apoptosis |
Ligand | Calcium |
Enzyme and pathway databases
BRENDAi | 3.6.99.B1, 2681 |
PathwayCommonsi | Q9NRY6 |
SIGNORi | Q9NRY6 |
Protein family/group databases
TCDBi | 9.A.36.1.6, the ca(2+)-dependent phospholipid scramblase (scramblase) family |
Chemistry databases
SwissLipidsi | SLP:000001107 |
Names & Taxonomyi
Protein namesi | Recommended name: Phospholipid scramblase 3Short name: PL scramblase 3 Alternative name(s): Ca(2+)-dependent phospholipid scramblase 3 |
Gene namesi | Name:PLSCR3 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:16495, PLSCR3 |
MIMi | 607611, gene |
neXtProti | NX_Q9NRY6 |
VEuPathDBi | HostDB:ENSG00000187838.16 |
Subcellular locationi
Mitochondrion
- Mitochondrion membrane 3 Publications; Single-pass type II membrane protein By similarity
- Mitochondrion inner membrane By similarity; Single-pass type II membrane protein By similarity
Nucleus
- Nucleus By similarity
Note: Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus.By similarity
Cytosol
- cytosol Source: UniProtKB
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 265 | Mitochondrial intermembraneBy similarityAdd BLAST | 265 | |
Transmembranei | 266 – 282 | HelicalSequence analysisAdd BLAST | 17 |
Keywords - Cellular componenti
Membrane, Mitochondrion, Mitochondrion inner membrane, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 21 | T → A: Fails to enhance apoptosis mediated by PRKCD activators. 1 Publication | 1 | |
Mutagenesisi | 21 | T → D: Promotes apoptosis, more potent in lipid flippase activity. 1 Publication | 1 | |
Mutagenesisi | 49 | F → A: Reduces interaction with PDCD6. Abolishes interaction with PDCD6; when associated with A-52. 1 Publication | 1 | |
Mutagenesisi | 49 | F → W: No effect on the interaction with PDCD6. 1 Publication | 1 | |
Mutagenesisi | 49 | F → Y or L: Reduces interaction with PDCD6. 1 Publication | 1 | |
Mutagenesisi | 52 | F → A: Abolishes interaction with PDCD6; when associated with A-49. 1 Publication | 1 | |
Mutagenesisi | 258 | F → V: Reduced phospholipid scramblase activity. Reduced calcium and magnesium-binding. Diminished apoptotic responsiveness. Defective mitochondrial structure and oxidative function. Reduced binding affinity for Pb(2+) and Hg(2+) ions. Increased cardiolipin biosynthesis from glycerol and decreased cardiolipin resynthesis from linoleic acid. 7 Publications | 1 |
Organism-specific databases
DisGeNETi | 57048 |
OpenTargetsi | ENSG00000187838 |
PharmGKBi | PA33421 |
Miscellaneous databases
Pharosi | Q9NRY6, Tbio |
Genetic variation databases
BioMutai | PLSCR3 |
DMDMi | 296452876 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000100789 | 1 – 295 | Phospholipid scramblase 3Add BLAST | 295 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 21 | Phosphothreonine; by PKC/PRKCD1 Publication | 1 | |
Lipidationi | 158 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 160 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 162 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 163 | S-palmitoyl cysteineBy similarity | 1 | |
Lipidationi | 165 | S-palmitoyl cysteineBy similarity | 1 |
Post-translational modificationi
Phosphorylation at Thr-21 by PKC/PRKCD upon apoptotic stimuli enhances phospholipid scramblase activity.1 Publication1 Publication
Palmitoylation regulates its localization to the cell membrane or the nucleus; trafficking to the cell membrane is dependent upon palmitoylation whereas in the absence of palmitoylation, localizes to the nucleus.By similarity
Keywords - PTMi
Lipoprotein, Palmitate, PhosphoproteinProteomic databases
EPDi | Q9NRY6 |
jPOSTi | Q9NRY6 |
MassIVEi | Q9NRY6 |
MaxQBi | Q9NRY6 |
PaxDbi | Q9NRY6 |
PeptideAtlasi | Q9NRY6 |
PRIDEi | Q9NRY6 |
ProteomicsDBi | 82444 |
PTM databases
iPTMneti | Q9NRY6 |
PhosphoSitePlusi | Q9NRY6 |
SwissPalmi | Q9NRY6 |
Expressioni
Tissue specificityi
Expressed in heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, uterus, small intestine and peripheral blood lymphocytes. Not detected in testis, brain and liver.
Gene expression databases
Bgeei | ENSG00000187838, Expressed in granulocyte and 116 other tissues |
ExpressionAtlasi | Q9NRY6, baseline and differential |
Genevisiblei | Q9NRY6, HS |
Organism-specific databases
HPAi | ENSG00000187838, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ9NRY6
GO - Molecular functioni
- calcium-dependent protein binding Source: UniProtKB
- protein self-association Source: UniProtKB
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGRIDi | 121341, 43 interactors |
IntActi | Q9NRY6, 43 interactors |
STRINGi | 9606.ENSP00000438547 |
Miscellaneous databases
RNActi | Q9NRY6, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 57 | Proline-rich domain (PRD)By similarityAdd BLAST | 57 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 7 – 15 | SH3-binding 1Sequence analysis | 9 | |
Motifi | 15 – 18 | PPxY motifSequence analysis | 4 | |
Motifi | 21 – 27 | SH3-binding 2Sequence analysis | 7 | |
Motifi | 65 – 70 | SH3-binding 3Sequence analysis | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 12 – 19 | Poly-Pro | 8 | |
Compositional biasi | 158 – 165 | Cys-rich | 8 |
Domaini
The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity.By similarity
Sequence similaritiesi
Belongs to the phospholipid scramblase family.Curated
Keywords - Domaini
Repeat, SH3-binding, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0621, Eukaryota |
GeneTreei | ENSGT00940000161755 |
HOGENOMi | CLU_053024_1_0_1 |
InParanoidi | Q9NRY6 |
OMAi | ESGCCER |
OrthoDBi | 1015148at2759 |
PhylomeDBi | Q9NRY6 |
TreeFami | TF314939 |
Family and domain databases
InterProi | View protein in InterPro IPR005552, Scramblase |
PANTHERi | PTHR23248, PTHR23248, 1 hit |
Pfami | View protein in Pfam PF03803, Scramblase, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 6 potential isoforms that are computationally mapped.Show allAlign All
Q9NRY6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MAGYLPPKGY APSPPPPYPV TPGYPEPALH PGPGQAPVPA QVPAPAPGFA
60 70 80 90 100
LFPSPGPVAL GSAAPFLPLP GVPSGLEFLV QIDQILIHQK AERVETFLGW
110 120 130 140 150
ETCNRYELRS GAGQPLGQAA EESNCCARLC CGARRPLRVR LADPGDREVL
160 170 180 190 200
RLLRPLHCGC SCCPCGLQEM EVQAPPGTTI GHVLQTWHPF LPKFSIQDAD
210 220 230 240 250
RQTVLRVVGP CWTCGCGTDT NFEVKTRDES RSVGRISKQW GGLVREALTD
260 270 280 290
ADDFGLQFPL DLDVRVKAVL LGATFLIDYM FFEKRGGAGP SAVTS
Computationally mapped potential isoform sequencesi
There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketI3L3X5 | I3L3X5_HUMAN | Phospholipid scramblase | PLSCR3 | 271 | Annotation score: | ||
I3L161 | I3L161_HUMAN | Phospholipid scramblase | PLSCR3 | 170 | Annotation score: | ||
I3NI29 | I3NI29_HUMAN | Phospholipid scramblase | PLSCR3 | 171 | Annotation score: | ||
I3L4F5 | I3L4F5_HUMAN | Phospholipid scramblase | PLSCR3 | 35 | Annotation score: | ||
I3L1P6 | I3L1P6_HUMAN | Phospholipid scramblase 3 | PLSCR3 | 118 | Annotation score: | ||
I3L1V1 | I3L1V1_HUMAN | Phospholipid scramblase 3 | PLSCR3 | 148 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 149 | V → L in AAH11735 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_015568 | 293 | V → I4 PublicationsCorresponds to variant dbSNP:rs3744549Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF159442 mRNA Translation: AAF91083.1 AK075188 mRNA Translation: BAC11458.1 AK290117 mRNA Translation: BAF82806.1 CH471108 Genomic DNA Translation: EAW90200.1 AC113189 Genomic DNA No translation available. BC011735 mRNA Translation: AAH11735.1 BC093026 mRNA Translation: AAH93026.1 |
CCDSi | CCDS42253.1 |
RefSeqi | NP_001188505.1, NM_001201576.1 NP_065093.2, NM_020360.3 |
Genome annotation databases
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF159442 mRNA Translation: AAF91083.1 AK075188 mRNA Translation: BAC11458.1 AK290117 mRNA Translation: BAF82806.1 CH471108 Genomic DNA Translation: EAW90200.1 AC113189 Genomic DNA No translation available. BC011735 mRNA Translation: AAH11735.1 BC093026 mRNA Translation: AAH93026.1 |
CCDSi | CCDS42253.1 |
RefSeqi | NP_001188505.1, NM_001201576.1 NP_065093.2, NM_020360.3 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 121341, 43 interactors |
IntActi | Q9NRY6, 43 interactors |
STRINGi | 9606.ENSP00000438547 |
Chemistry databases
SwissLipidsi | SLP:000001107 |
Protein family/group databases
TCDBi | 9.A.36.1.6, the ca(2+)-dependent phospholipid scramblase (scramblase) family |
PTM databases
iPTMneti | Q9NRY6 |
PhosphoSitePlusi | Q9NRY6 |
SwissPalmi | Q9NRY6 |
Genetic variation databases
BioMutai | PLSCR3 |
DMDMi | 296452876 |
Proteomic databases
EPDi | Q9NRY6 |
jPOSTi | Q9NRY6 |
MassIVEi | Q9NRY6 |
MaxQBi | Q9NRY6 |
PaxDbi | Q9NRY6 |
PeptideAtlasi | Q9NRY6 |
PRIDEi | Q9NRY6 |
ProteomicsDBi | 82444 |
Protocols and materials databases
Antibodypediai | 24083, 161 antibodies |
DNASUi | 57048 |
Genome annotation databases
Organism-specific databases
CTDi | 57048 |
DisGeNETi | 57048 |
GeneCardsi | PLSCR3 |
HGNCi | HGNC:16495, PLSCR3 |
HPAi | ENSG00000187838, Low tissue specificity |
MIMi | 607611, gene |
neXtProti | NX_Q9NRY6 |
OpenTargetsi | ENSG00000187838 |
PharmGKBi | PA33421 |
VEuPathDBi | HostDB:ENSG00000187838.16 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0621, Eukaryota |
GeneTreei | ENSGT00940000161755 |
HOGENOMi | CLU_053024_1_0_1 |
InParanoidi | Q9NRY6 |
OMAi | ESGCCER |
OrthoDBi | 1015148at2759 |
PhylomeDBi | Q9NRY6 |
TreeFami | TF314939 |
Enzyme and pathway databases
BRENDAi | 3.6.99.B1, 2681 |
PathwayCommonsi | Q9NRY6 |
SIGNORi | Q9NRY6 |
Miscellaneous databases
BioGRID-ORCSi | 57048, 8 hits in 916 CRISPR screens |
GeneWikii | PLSCR3 |
GenomeRNAii | 57048 |
Pharosi | Q9NRY6, Tbio |
PROi | PR:Q9NRY6 |
RNActi | Q9NRY6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000187838, Expressed in granulocyte and 116 other tissues |
ExpressionAtlasi | Q9NRY6, baseline and differential |
Genevisiblei | Q9NRY6, HS |
Family and domain databases
InterProi | View protein in InterPro IPR005552, Scramblase |
PANTHERi | PTHR23248, PTHR23248, 1 hit |
Pfami | View protein in Pfam PF03803, Scramblase, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PLS3_HUMAN | |
Accessioni | Q9NRY6Primary (citable) accession number: Q9NRY6 Secondary accession number(s): A8K252 Q96F13 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2001 |
Last sequence update: | May 18, 2010 | |
Last modified: | April 7, 2021 | |
This is version 177 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 17
Human chromosome 17: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families