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Protein

Phospholipid scramblase 3

Gene

PLSCR3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system. Seems to play a role in apoptosis, through translocation of cardiolipin from the inner to the outer mitochondrial membrane which promotes BID recruitment and enhances tBid-induced mitochondrial damages.1 Publication

Cofactori

Ca2+By similarity

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • phospholipid scramblase activity Source: GO_Central
  • SH3 domain binding Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Biological processApoptosis
LigandCalcium

Enzyme and pathway databases

BRENDAi3.6.99.B1. 2681.
SIGNORiQ9NRY6.

Chemistry databases

SwissLipidsiSLP:000001107.

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid scramblase 3
Short name:
PL scramblase 3
Alternative name(s):
Ca(2+)-dependent phospholipid scramblase 3
Gene namesi
Name:PLSCR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:16495. PLSCR3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 265CytoplasmicBy similarityAdd BLAST265
Transmembranei266 – 282HelicalBy similarityAdd BLAST17
Topological domaini283 – 295ExtracellularBy similarityAdd BLAST13

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • mitochondrial membrane Source: UniProtKB-SubCell
  • mitochondrion Source: HPA
  • plasma membrane Source: UniProtKB

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi21T → A: Fails to enhance apoptosis mediated by PRKCD activators. 1 Publication1
Mutagenesisi21T → D: Promotes apoptosis, more potent in lipid flippase activity. 1 Publication1
Mutagenesisi49F → A: Reduces interaction with PDCD6. Abolishes interaction with PDCD6; when associated with A-52. 1 Publication1
Mutagenesisi49F → W: No effect on the interaction with PDCD6. 1 Publication1
Mutagenesisi49F → Y or L: Reduces interaction with PDCD6. 1 Publication1
Mutagenesisi52F → A: Abolishes interaction with PDCD6; when associated with A-49. 1 Publication1

Organism-specific databases

DisGeNETi57048.
OpenTargetsiENSG00000187838.
PharmGKBiPA33421.

Polymorphism and mutation databases

BioMutaiPLSCR3.
DMDMi296452876.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001007891 – 295Phospholipid scramblase 3Add BLAST295

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21Phosphothreonine; by PKC/PRKCD1 Publication1
Lipidationi211S-palmitoyl cysteineCurated1
Lipidationi214S-palmitoyl cysteineCurated1
Lipidationi216S-palmitoyl cysteineCurated1

Post-translational modificationi

Phosphorylation at Thr-21 by PKC/PRKCD upon apoptotic stimuli enhances flip-flop activity.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

EPDiQ9NRY6.
MaxQBiQ9NRY6.
PaxDbiQ9NRY6.
PeptideAtlasiQ9NRY6.
PRIDEiQ9NRY6.

PTM databases

iPTMnetiQ9NRY6.
PhosphoSitePlusiQ9NRY6.
SwissPalmiQ9NRY6.

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

BgeeiENSG00000187838.
CleanExiHS_PLSCR3.
ExpressionAtlasiQ9NRY6. baseline and differential.
GenevisibleiQ9NRY6. HS.

Organism-specific databases

HPAiHPA048387.
HPA068609.

Interactioni

Subunit structurei

Interacts with PDCD6 in a calcium-dependent manner.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

BioGridi121341. 8 interactors.
IntActiQ9NRY6. 44 interactors.
MINTiMINT-1460986.
STRINGi9606.ENSP00000316021.

Structurei

3D structure databases

ProteinModelPortaliQ9NRY6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 57Proline-rich domain (PRD)By similarityAdd BLAST57

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi7 – 15SH3-binding 1Sequence analysis9
Motifi15 – 18WW-bindingSequence analysis4
Motifi21 – 27SH3-binding 2Sequence analysis7
Motifi65 – 70SH3-binding 3Sequence analysis6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi12 – 19Poly-Pro8
Compositional biasi158 – 165Cys-rich8

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 helix

Phylogenomic databases

eggNOGiKOG0621. Eukaryota.
ENOG410XSYS. LUCA.
GeneTreeiENSGT00390000002884.
HOVERGENiHBG019157.
InParanoidiQ9NRY6.
OMAiESGCCER.
OrthoDBiEOG091G0CUL.
PhylomeDBiQ9NRY6.
TreeFamiTF314939.

Family and domain databases

InterProiView protein in InterPro
IPR005552. Scramblase.
PANTHERiPTHR23248. PTHR23248. 1 hit.
PfamiView protein in Pfam
PF03803. Scramblase. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9NRY6-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:295
Mass (Da):31,648
Last modified:May 18, 2010 - v2
Checksum:iB53AAA8166E6D99E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti149V → L in AAH11735 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_015568293V → 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.
CCDSiCCDS42253.1.
RefSeqiNP_001188505.1. NM_001201576.1.
NP_065093.2. NM_020360.3.
UniGeneiHs.534591.
Hs.736428.

Genome annotation databases

EnsembliENST00000324822; ENSP00000316021; ENSG00000187838.
ENST00000535512; ENSP00000438547; ENSG00000187838.
ENST00000574401; ENSP00000459019; ENSG00000187838.
ENST00000576201; ENSP00000459419; ENSG00000187838.
ENST00000639780; ENSP00000492083; ENSG00000284009.
ENST00000640053; ENSP00000491350; ENSG00000284009.
ENST00000640375; ENSP00000491393; ENSG00000284009.
ENST00000640848; ENSP00000492348; ENSG00000284009.
GeneIDi57048.
KEGGihsa:57048.
UCSCiuc002ggm.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiPLS3_HUMAN
AccessioniPrimary (citable) accession number: Q9NRY6
Secondary accession number(s): A8K252
, Q567U0, Q8NBW6, Q96F13
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 18, 2010
Last modified: July 5, 2017
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families