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Q9NRY6

- PLS3_HUMAN

UniProt

Q9NRY6 - PLS3_HUMAN

Protein

Phospholipid scramblase 3

Gene

PLSCR3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    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
    4. protein binding Source: IntAct

    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

    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. mitochondrial membrane Source: UniProtKB-SubCell
    3. plasma membrane Source: UniProtKB

    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.
    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. 11 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.
    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

    MAGYLPPKGY APSPPPPYPV TPGYPEPALH PGPGQAPVPA QVPAPAPGFA    50
    LFPSPGPVAL GSAAPFLPLP GVPSGLEFLV QIDQILIHQK AERVETFLGW 100
    ETCNRYELRS GAGQPLGQAA EESNCCARLC CGARRPLRVR LADPGDREVL 150
    RLLRPLHCGC SCCPCGLQEM EVQAPPGTTI GHVLQTWHPF LPKFSIQDAD 200
    RQTVLRVVGP CWTCGCGTDT NFEVKTRDES RSVGRISKQW GGLVREALTD 250
    ADDFGLQFPL DLDVRVKAVL LGATFLIDYM FFEKRGGAGP SAVTS 295
    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. 11 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.
    H-InvDB HIX0013495.
    HIX0079952.
    HGNCi HGNC:16495. PLSCR3.
    MIMi 607611. gene.
    neXtProti NX_Q9NRY6.
    PharmGKBi PA33421.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG119855.
    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.
    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

    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 1, 2014
    This is version 120 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