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Q9NRY6 (PLS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phospholipid scramblase 3

Short name=PL scramblase 3
Alternative name(s):
Ca(2+)-dependent phospholipid scramblase 3
Gene names
Name:PLSCR3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length295 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Cofactor

Calcium By similarity.

Subunit structure

Interacts with PDCD6 in a calcium-dependent manner. Ref.7

Subcellular location

Mitochondrion membrane; Single-pass type II membrane protein Ref.6.

Tissue specificity

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.

Post-translational modification

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

Sequence similarities

Belongs to the phospholipid scramblase family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PDCD6O753409EBI-750734,EBI-352915

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 295295Phospholipid scramblase 3
PRO_0000100789

Regions

Topological domain1 – 265265Cytoplasmic By similarity
Transmembrane266 – 28217Helical; By similarity
Topological domain283 – 29513Extracellular By similarity
Motif7 – 159SH3-binding 1 Potential
Motif15 – 184WW-binding Potential
Motif21 – 277SH3-binding 2 Potential
Motif65 – 706SH3-binding 3 Potential
Compositional bias12 – 198Poly-Pro
Compositional bias158 – 1658Cys-rich

Amino acid modifications

Modified residue211Phosphothreonine; by PKC/PRKCD Ref.6
Lipidation2111S-palmitoyl cysteine Probable
Lipidation2141S-palmitoyl cysteine Probable
Lipidation2161S-palmitoyl cysteine Probable

Natural variations

Natural variant2931V → I. Ref.1 Ref.2 Ref.4 Ref.5
Corresponds to variant rs3744549 [ dbSNP | Ensembl ].
VAR_015568

Experimental info

Mutagenesis211T → A: Fails to enhance apoptosis mediated by PRKCD activators. Ref.6
Mutagenesis211T → D: Promotes apoptosis, more potent in lipid flippase activity. Ref.6
Mutagenesis491F → A: Reduces interaction with PDCD6. Abolishes interaction with PDCD6; when associated with A-52. Ref.7
Mutagenesis491F → W: No effect on the interaction with PDCD6. Ref.7
Mutagenesis491F → Y or L: Reduces interaction with PDCD6. Ref.7
Mutagenesis521F → A: Abolishes interaction with PDCD6; when associated with A-49. Ref.7
Sequence conflict1491V → L in AAH11735. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q9NRY6 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: B53AAA8166E6D99E

FASTA29531,648
        10         20         30         40         50         60 
MAGYLPPKGY APSPPPPYPV TPGYPEPALH PGPGQAPVPA QVPAPAPGFA LFPSPGPVAL 

        70         80         90        100        110        120 
GSAAPFLPLP GVPSGLEFLV QIDQILIHQK AERVETFLGW ETCNRYELRS GAGQPLGQAA 

       130        140        150        160        170        180 
EESNCCARLC CGARRPLRVR LADPGDREVL RLLRPLHCGC SCCPCGLQEM EVQAPPGTTI 

       190        200        210        220        230        240 
GHVLQTWHPF LPKFSIQDAD RQTVLRVVGP CWTCGCGTDT NFEVKTRDES RSVGRISKQW 

       250        260        270        280        290 
GGLVREALTD ADDFGLQFPL DLDVRVKAVL LGATFLIDYM FFEKRGGAGP SAVTS 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001188505.1. NM_001201576.1.
NP_065093.2. NM_020360.3.
UniGeneHs.534591.
Hs.736428.

3D structure databases

ProteinModelPortalQ9NRY6.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121341. 6 interactions.
IntActQ9NRY6. 11 interactions.
MINTMINT-1460986.
STRING9606.ENSP00000316021.

PTM databases

PhosphoSiteQ9NRY6.

Polymorphism databases

DMDM296452876.

Proteomic databases

PaxDbQ9NRY6.
PRIDEQ9NRY6.

Protocols and materials databases

DNASU57048.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID57048.
KEGGhsa:57048.
UCSCuc002ggm.2. human.

Organism-specific databases

CTD57048.
GeneCardsGC17M007294.
H-InvDBHIX0013495.
HIX0079952.
HGNCHGNC:16495. PLSCR3.
MIM607611. gene.
neXtProtNX_Q9NRY6.
PharmGKBPA33421.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG119855.
HOVERGENHBG019157.
InParanoidQ9NRY6.
OMAVTPGYPE.
OrthoDBEOG77T14X.
TreeFamTF314939.

Gene expression databases

ArrayExpressQ9NRY6.
BgeeQ9NRY6.
CleanExHS_PLSCR3.
GenevestigatorQ9NRY6.

Family and domain databases

InterProIPR005552. Scramblase.
[Graphical view]
PANTHERPTHR23248. PTHR23248. 1 hit.
PfamPF03803. Scramblase. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPLSCR3.
GenomeRNAi57048.
NextBio62812.
PROQ9NRY6.
SOURCESearch...

Entry information

Entry namePLS3_HUMAN
AccessionPrimary (citable) accession number: Q9NRY6
Secondary accession number(s): A8K252 expand/collapse secondary AC list , Q567U0, Q8NBW6, Q96F13
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: May 18, 2010
Last modified: March 19, 2014
This is version 115 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM