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Q9NRY6

- PLS3_HUMAN

UniProt

Q9NRY6 - PLS3_HUMAN

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Protein

Phospholipid scramblase 3

Gene

PLSCR3

Organism
Homo sapiens (Human)
Status
Reviewed - 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

Calcium.By similarity

GO - Molecular functioni

  1. calcium-dependent protein binding Source: UniProtKB
  2. calcium ion binding Source: UniProtKB
  3. phospholipid scramblase activity Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB-KW
  2. cellular response to lipopolysaccharide Source: Ensembl
  3. cholesterol homeostasis Source: Ensembl
  4. glucose homeostasis Source: Ensembl
  5. phospholipid scrambling Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

Calcium

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
ProteomesiUP000005640: Chromosome 17

Organism-specific databases

HGNCiHGNC:16495. PLSCR3.

Subcellular locationi

Mitochondrion membrane 1 Publication; Single-pass type II membrane protein 1 Publication

GO - Cellular componenti

  1. integral component of membrane Source: UniProtKB-KW
  2. mitochondrion Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi21 – 211T → A: Fails to enhance apoptosis mediated by PRKCD activators. 1 Publication
Mutagenesisi21 – 211T → D: Promotes apoptosis, more potent in lipid flippase activity. 1 Publication
Mutagenesisi49 – 491F → A: Reduces interaction with PDCD6. Abolishes interaction with PDCD6; when associated with A-52. 1 Publication
Mutagenesisi49 – 491F → W: No effect on the interaction with PDCD6. 1 Publication
Mutagenesisi49 – 491F → Y or L: Reduces interaction with PDCD6. 1 Publication
Mutagenesisi52 – 521F → A: Abolishes interaction with PDCD6; when associated with A-49. 1 Publication

Organism-specific databases

PharmGKBiPA33421.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 295295Phospholipid scramblase 3PRO_0000100789Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei21 – 211Phosphothreonine; by PKC/PRKCD1 Publication
Lipidationi211 – 2111S-palmitoyl cysteineCurated
Lipidationi214 – 2141S-palmitoyl cysteineCurated
Lipidationi216 – 2161S-palmitoyl cysteineCurated

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

MaxQBiQ9NRY6.
PaxDbiQ9NRY6.
PRIDEiQ9NRY6.

PTM databases

PhosphoSiteiQ9NRY6.

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

BgeeiQ9NRY6.
CleanExiHS_PLSCR3.
ExpressionAtlasiQ9NRY6. baseline.
GenevestigatoriQ9NRY6.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
PDCD6O753409EBI-750734,EBI-352915

Protein-protein interaction databases

BioGridi121341. 6 interactions.
IntActiQ9NRY6. 12 interactions.
MINTiMINT-1460986.
STRINGi9606.ENSP00000316021.

Structurei

3D structure databases

ProteinModelPortaliQ9NRY6.
ModBaseiSearch...
MobiDBiSearch...

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 265265CytoplasmicBy similarityAdd
BLAST
Topological domaini283 – 29513ExtracellularBy similarityAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei266 – 28217HelicalBy similarityAdd
BLAST

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 5757Proline-rich domain (PRD)By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi7 – 159SH3-binding 1Sequence Analysis
Motifi15 – 184WW-bindingSequence Analysis
Motifi21 – 277SH3-binding 2Sequence Analysis
Motifi65 – 706SH3-binding 3Sequence Analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi12 – 198Poly-Pro
Compositional biasi158 – 1658Cys-rich

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

eggNOGiNOG119855.
GeneTreeiENSGT00390000002884.
HOVERGENiHBG019157.
InParanoidiQ9NRY6.
OMAiVTPGYPE.
OrthoDBiEOG77T14X.
PhylomeDBiQ9NRY6.
TreeFamiTF314939.

Family and domain databases

InterProiIPR005552. Scramblase.
[Graphical view]
PANTHERiPTHR23248. PTHR23248. 1 hit.
PfamiPF03803. Scramblase. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti149 – 1491V → L in AAH11735. (PubMed:15489334)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti293 – 2931V → I.4 Publications
Corresponds to variant rs3744549 [ dbSNP | Ensembl ].
VAR_015568

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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

GeneIDi57048.
KEGGihsa:57048.
UCSCiuc002ggm.2. human.

Polymorphism databases

DMDMi296452876.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.534591.
Hs.736428.

3D structure databases

ProteinModelPortali Q9NRY6.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121341. 6 interactions.
IntActi Q9NRY6. 12 interactions.
MINTi MINT-1460986.
STRINGi 9606.ENSP00000316021.

PTM databases

PhosphoSitei Q9NRY6.

Polymorphism databases

DMDMi 296452876.

Proteomic databases

MaxQBi Q9NRY6.
PaxDbi Q9NRY6.
PRIDEi Q9NRY6.

Protocols and materials databases

DNASUi 57048.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 57048.
KEGGi hsa:57048.
UCSCi uc002ggm.2. human.

Organism-specific databases

CTDi 57048.
GeneCardsi GC17M007294.
GC17M007296.
H-InvDB HIX0013495.
HIX0079952.
HGNCi HGNC:16495. PLSCR3.
MIMi 607611. gene.
neXtProti NX_Q9NRY6.
PharmGKBi PA33421.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG119855.
GeneTreei ENSGT00390000002884.
HOVERGENi HBG019157.
InParanoidi Q9NRY6.
OMAi VTPGYPE.
OrthoDBi EOG77T14X.
PhylomeDBi Q9NRY6.
TreeFami TF314939.

Miscellaneous databases

GeneWikii PLSCR3.
GenomeRNAii 57048.
NextBioi 62812.
PROi Q9NRY6.
SOURCEi Search...

Gene expression databases

Bgeei Q9NRY6.
CleanExi HS_PLSCR3.
ExpressionAtlasi Q9NRY6. baseline.
Genevestigatori Q9NRY6.

Family and domain databases

InterProi IPR005552. Scramblase.
[Graphical view ]
PANTHERi PTHR23248. PTHR23248. 1 hit.
Pfami PF03803. Scramblase. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of three new members of the phospholipid scramblase gene family."
    Wiedmer T., Zhou Q., Kwoh D.Y., Sims P.J.
    Biochim. Biophys. Acta 1467:244-253(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-293.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-293.
    Tissue: Placenta and Thalamus.
  3. "DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
    Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L.
    , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
    Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ILE-293.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-293.
    Tissue: B-cell and Placenta.
  6. "Phosphorylation of mitochondrial phospholipid scramblase 3 by protein kinase C-delta induces its activation and facilitates mitochondrial targeting of tBid."
    He Y., Liu J., Grossman D., Durrant D., Sweatman T., Lothstein L., Epand R.F., Epand R.M., Lee R.M.
    J. Cell. Biochem. 101:1210-1221(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION AT THR-21, MUTAGENESIS OF THR-21, SUBCELLULAR LOCATION.
  7. "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."
    Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T., Maki M.
    J. Biol. Chem. 283:9623-9632(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PDCD6, MUTAGENESIS OF PHE-49 AND PHE-52.

Entry informationi

Entry nameiPLS3_HUMAN
AccessioniPrimary (citable) accession number: Q9NRY6
Secondary accession number(s): A8K252
, Q567U0, Q8NBW6, Q96F13
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 18, 2010
Last modified: October 29, 2014
This is version 121 of the entry and version 2 of the sequence. [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

External Data

Dasty 3