Q9NRY6 (PLS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phospholipid scramblase 3
Short name=PL scramblase 3

Alternative name(s):
Ca(2+)-dependent phospholipid scramblase 3

Gene names

Name:

PLSCR3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	295 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Repeat SH3-binding Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara cholesterol homeostasis Inferred from electronic annotation. Source: Compara glucose homeostasis Inferred from electronic annotation. Source: Compara phospholipid scrambling Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay PubMed 19333378. Source: UniProtKB
Molecular_function	calcium ion binding Non-traceable author statement Ref.1. Source: UniProtKB phospholipid scramblase activity Non-traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PDCD6	O75340	9	EBI-750734,EBI-352915

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 295	295	Phospholipid scramblase 3		PRO_0000100789
Regions
	Topological domain	1 – 265	265	Cytoplasmic By similarity
	Transmembrane	266 – 282	17	Helical; By similarity
	Topological domain	283 – 295	13	Extracellular By similarity
	Motif	7 – 15	9	SH3-binding 1 Potential
	Motif	15 – 18	4	WW-binding Potential
	Motif	21 – 27	7	SH3-binding 2 Potential
	Motif	65 – 70	6	SH3-binding 3 Potential
	Compositional bias	12 – 19	8	Poly-Pro
	Compositional bias	158 – 165	8	Cys-rich
Amino acid modifications
	Modified residue	21	1	Phosphothreonine; by PKC/PRKCD Ref.6
	Lipidation	211	1	S-palmitoyl cysteine Probable
	Lipidation	214	1	S-palmitoyl cysteine Probable
	Lipidation	216	1	S-palmitoyl cysteine Probable
Natural variations
	Natural variant	293	1	V → I. Ref.1 Ref.2 Ref.4 Ref.5 Corresponds to variant rs3744549 [ dbSNP | Ensembl ].		VAR_015568
Experimental info
	Mutagenesis	21	1	T → A: Fails to enhance apoptosis mediated by PRKCD activators. Ref.6
	Mutagenesis	21	1	T → D: Promotes apoptosis, more potent in lipid flippase activity. Ref.6
	Mutagenesis	49	1	F → A: Reduces interaction with PDCD6. Abolishes interaction with PDCD6; when associated with A-52. Ref.7
	Mutagenesis	49	1	F → W: No effect on the interaction with PDCD6. Ref.7
	Mutagenesis	49	1	F → Y or L: Reduces interaction with PDCD6. Ref.7
	Mutagenesis	52	1	F → A: Abolishes interaction with PDCD6; when associated with A-49. Ref.7
	Sequence conflict	149	1	V → L in AAH11735. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9NRY6 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: B53AAA8166E6D99E	FASTA	295	31,648
	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

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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.
[8]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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.
IPI	IPI00216127.
RefSeq	NP_001188505.1. NM_001201576.1. NP_065093.2. NM_020360.3.
UniGene	Hs.534591.
3D structure databases
ProteinModelPortal	Q9NRY6.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NRY6. 11 interactions.
MINT	MINT-1460986.
STRING	9606.ENSP00000316021.
PTM databases
PhosphoSite	Q9NRY6.
Polymorphism databases
DMDM	296452876.
Proteomic databases
PaxDb	Q9NRY6.
PRIDE	Q9NRY6.
Protocols and materials databases
DNASU	57048.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324822; ENSP00000316021; ENSG00000187838. ENST00000535512; ENSP00000438547; ENSG00000187838. ENST00000574401; ENSP00000459019; ENSG00000187838. ENST00000576201; ENSP00000459419; ENSG00000187838.
GeneID	57048.
KEGG	hsa:57048.
UCSC	uc002ggm.2. human.
Organism-specific databases
CTD	57048.
GeneCards	GC17M007294.
H-InvDB	HIX0013495. HIX0079952.
HGNC	HGNC:16495. PLSCR3.
MIM	607611. gene.
neXtProt	NX_Q9NRY6.
PharmGKB	PA33421.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG119855.
HOVERGEN	HBG019157.
InParanoid	Q9NRY6.
OMA	HQKAERV.
OrthoDB	EOG45MN60.
Gene expression databases
ArrayExpress	Q9NRY6.
Bgee	Q9NRY6.
CleanEx	HS_PLSCR3.
Genevestigator	Q9NRY6.
GermOnline	ENSG00000187838. Homo sapiens.
Family and domain databases
InterPro	IPR005552. Scramblase. [Graphical view]
PANTHER	PTHR23248. PTHR23248. 1 hit.
Pfam	PF03803. Scramblase. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	57048.
NextBio	62812.
SOURCE	Search...

Entry information

Entry name

PLS3_HUMAN

Accession

Primary (citable) accession number: Q9NRY6
Secondary accession number(s): A8K252 , Q567U0, Q8NBW6, Q96F13

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 108 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.