O15162 (PLS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phospholipid scramblase 1
Short name=PL scramblase 1

Alternative name(s):
Ca(2+)-dependent phospholipid scramblase 1
Erythrocyte phospholipid scramblase
MmTRA1b

Gene names

Name:

PLSCR1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	318 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. Ref.7 Ref.12 May play a role in the antiviral response of interferon (IFN) by amplifying and enhancing the IFN response through increased expression of select subset of potent antiviral genes. May contribute to cytokine-regulated cell proliferation and differentiation. Ref.7 Ref.12
Cofactor	Calcium.
Subunit structure	Interacts with ABL.
Subcellular location	Membrane; Single-pass type II membrane protein.
Tissue specificity	Expressed in platelets, erythrocyte membranes, lymphocytes, spleen, thymus, prostate, testis, uterus, intestine, colon, heart, placenta, lung, liver, kidney and pancreas. Not detected in brain and skeletal muscle.
Induction	By phosphorylation by PKC. Induced by IFNB1/IFN-beta in response to a viral infection. Ref.12
Post-translational modification	Known to be palmitoylated at one, yet undefined, site. Ref.10
Sequence similarities	Belongs to the phospholipid scramblase family.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat SH3-binding Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	acute-phase response Inferred from sequence or structural similarity. Source: UniProtKB apoptotic process Inferred from direct assay Ref.8. Source: UniProtKB defense response to virus Inferred from mutant phenotype Ref.12. Source: UniProtKB negative regulation of viral genome replication Inferred from mutant phenotype Ref.12. Source: UniProtKB phosphatidylserine biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB phospholipid scrambling Inferred from direct assay Ref.8Ref.1. Source: UniProtKB platelet activation Non-traceable author statement Ref.1. Source: UniProtKB positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity Inferred from direct assay. Source: UniProtKB positive regulation of innate immune response Inferred from mutant phenotype Ref.12. Source: UniProtKB regulation of Fc receptor mediated stimulatory signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of mast cell activation Inferred from sequence or structural similarity. Source: UniProtKB response to interferon-beta Inferred from mutant phenotype Ref.12. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: UniProtKB cytosol Inferred from direct assay. Source: UniProtKB extracellular matrix Inferred from direct assay. Source: UniProtKB integral to plasma membrane Inferred from direct assay Ref.1. Source: UniProtKB membrane raft Inferred from direct assay. Source: UniProtKB nucleolus Inferred from direct assay. Source: UniProtKB
Molecular function	CD4 receptor binding Inferred from physical interaction. Source: UniProtKB RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay. Source: UniProtKB SH3 domain binding Inferred from direct assay Ref.9. Source: UniProtKB calcium ion binding Inferred from direct assay. Source: UniProtKB enzyme binding Inferred from physical interaction. Source: UniProtKB epidermal growth factor receptor binding Inferred from physical interaction. Source: UniProtKB phospholipid scramblase activity Inferred from direct assay Ref.8Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CPSF6	Q16630	2	EBI-740019,EBI-358410
NEU4	Q8WWR8	2	EBI-740019,EBI-746964
TFG	Q92734	2	EBI-740019,EBI-357061

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 318	318	Phospholipid scramblase 1		PRO_0000100784
Regions
	Topological domain	1 – 288	288	Cytoplasmic
	Transmembrane	289 – 305	17	Helical; Potential
	Topological domain	306 – 318	13	Extracellular
	Motif	18 – 26	9	SH3-binding 1 Potential
	Motif	22 – 25	4	WW-binding 1 Potential
	Motif	33 – 36	4	WW-binding 2 Potential
	Motif	42 – 50	9	SH3-binding 2 Potential
	Motif	84 – 92	9	SH3-binding 3 Potential
	Compositional bias	181 – 189	9	Cys-rich
Amino acid modifications
	Modified residue	69	1	Phosphotyrosine; by ABL Ref.9
	Modified residue	74	1	Phosphotyrosine; by ABL Ref.9
	Modified residue	161	1	Phosphothreonine; by PKC Ref.8
	Lipidation	234	1	S-palmitoyl cysteine Potential
	Lipidation	237	1	S-palmitoyl cysteine Potential
	Lipidation	239	1	S-palmitoyl cysteine Potential
	Lipidation	240	1	S-palmitoyl cysteine Potential
Natural variations
	Natural variant	262	1	H → Y. Corresponds to variant rs343320 [ dbSNP | Ensembl ].		VAR_034388
Experimental info
	Mutagenesis	69	1	Y → F: Decrease in phosphorylation.
	Mutagenesis	74	1	Y → F: Decrease in phosphorylation.
	Mutagenesis	161	1	T → A: No induction by PKC.
	Mutagenesis	273	1	D → A: Reduces the Ca(2+)-dependent phospholipid scrambling.
	Mutagenesis	275	1	D → A: Complete inactivation of the Ca(2+)-dependent phospholipid scrambling.
	Mutagenesis	277	1	F → A: Reduces the Ca(2+)-dependent phospholipid scrambling.
	Mutagenesis	279	1	I → A: Reduces the Ca(2+)-dependent phospholipid scrambling.
	Mutagenesis	281	1	F → A: Complete inactivation of the Ca(2+)-dependent phospholipid scrambling.
	Mutagenesis	284	1	D → A: Reduces the Ca(2+)-dependent phospholipid scrambling.

Sequences

	Sequence		Length	Mass (Da)
	O15162 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 9860744DEC40616E	FASTA	318	35,049
	10 20 30 40 50 60 MDKQNSQMNA SHPETNLPVG YPPQYPPTAF QGPPGYSGYP GPQVSYPPPP AGHSGPGPAG 70 80 90 100 110 120 FPVPNQPVYN QPVYNQPVGA AGVPWMPAPQ PPLNCPPGLE YLSQIDQILI HQQIELLEVL 130 140 150 160 170 180 TGFETNNKYE IKNSFGQRVY FAAEDTDCCT RNCCGPSRPF TLRIIDNMGQ EVITLERPLR 190 200 210 220 230 240 CSSCCCPCCL QEIEIQAPPG VPIGYVIQTW HPCLPKFTIQ NEKREDVLKI SGPCVVCSCC 250 260 270 280 290 300 GDVDFEIKSL DEQCVVGKIS KHWTGILREA FTDADNFGIQ FPLDLDVKMK AVMIGACFLI 310 DFMFFESTGS QEQKSGVW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human plasma membrane phospholipid scramblase. A protein mediating transbilayer movement of plasma membrane phospholipids." Zhou Q., Zhao J., Stout J.G., Luhm R.A., Wiedmer T., Sims P.J. J. Biol. Chem. 272:18240-18244(1997) [PubMed: 9218461] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 87-118. Tissue: Erythrocyte.
[2]	"Identity of human normal counterpart (MmTRA1b) of mouse leukemogenesis-associated gene (MmTRA1a) product as plasma membrane phospholipid scramblase and chromosome mapping of the human MmTRA1b/phospholipid scramblase gene." Kasukabe T., Kobayashi H., Kaneko Y., Okabe-Kado J., Honma Y. Biochem. Biophys. Res. Commun. 249:449-455(1998) [PubMed: 9712717] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Monocytic leukemia.
[3]	"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: 10930526] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[5]	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].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Uterus.
[7]	"Isolation of an erythrocyte membrane protein that mediates Ca2+-dependent transbilayer movement of phospholipid." Basse F., Stout J.G., Sims P.J., Wiedmer T. J. Biol. Chem. 271:17205-17210(1996) [PubMed: 8663431] [Abstract] Cited for: CHARACTERIZATION, FUNCTION. Tissue: Erythrocyte.
[8]	"Regulation of phospholipid scramblase activity during apoptosis and cell activation by protein kinase Cdelta." Frasch S.C., Henson P.M., Kailey J.M., Richter D.A., Janes M.S., Fadok V.A., Bratton D.L. J. Biol. Chem. 275:23065-23073(2000) [PubMed: 10770950] [Abstract] Cited for: PHOSPHORYLATION AT THR-161, MUTAGENESIS.
[9]	"c-Abl tyrosine kinase binds and phosphorylates phospholipid scramblase 1." Sun J., Zhao J., Schwartz M.A., Wang J.Y., Wiedmer T., Sims P.J. J. Biol. Chem. 276:28984-28990(2001) [PubMed: 11390389] [Abstract] Cited for: PHOSPHORYLATION AT TYR-69 AND TYR-74, MUTAGENESIS.
[10]	"Palmitoylation of phospholipid scramblase is required for normal function in promoting Ca2+-activated transbilayer movement of membrane phospholipids." Zhao J., Zhou Q., Wiedmer T., Sims P.J. Biochemistry 37:6361-6366(1998) [PubMed: 9572851] [Abstract] Cited for: PALMITOYLATION.
[11]	"Identity of a conserved motif in phospholipid scramblase that is required for Ca2+-accelerated transbilayer movement of membrane phospholipids." Zhou Q., Sims P.J., Wiedmer T. Biochemistry 37:2356-2360(1998) [PubMed: 9485382] [Abstract] Cited for: MUTAGENESIS.
[12]	"Phospholipid scramblase 1 potentiates the antiviral activity of interferon." Dong B., Zhou Q., Zhao J., Zhou A., Harty R.N., Bose S., Banerjee A., Slee R., Guenther J., Williams B.R.G., Wiedmer T., Sims P.J., Silverman R.H. J. Virol. 78:8983-8993(2004) [PubMed: 15308695] [Abstract] Cited for: FUNCTION, INDUCTION.
+	Additional computationally mapped references.

Web resources

Wikipedia

Scramblase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF098642 mRNA. Translation: AAC99413.1.
AB006746 mRNA. Translation: BAA32568.1.
AF224492 Genomic DNA. Translation: AAF80593.1.
AK313377 mRNA. Translation: BAG36175.1.
CH471052 Genomic DNA. Translation: EAW78926.1.
BC021100 mRNA. Translation: AAH21100.1.
BC032718 mRNA. Translation: AAH32718.1.

IPI

IPI00005181.

PIR

JE0284.

RefSeq

NP_066928.1. NM_021105.2.

UniGene

Hs.130759.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y2A	X-ray	2.20	P	257-266	[»]

ProteinModelPortal

O15162.

ModBase

Search...

Protein-protein interaction databases

IntAct

O15162. 100 interactions.

MINT

MINT-201602.

STRING

O15162.

Protein family/group databases

TCDB

9.A.36.1.1. Ca2+-dependent phospholipid scramblase family.

PTM databases

PhosphoSite

O15162.

Proteomic databases

PRIDE

O15162.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000342435; ENSP00000345494; ENSG00000188313.

GeneID

5359.

KEGG

hsa:5359.

UCSC

uc003evx.2. human.

Organism-specific databases

CTD

5359.

GeneCards

GC03M146232.

H-InvDB

HIX0003753.

HGNC

HGNC:9092. PLSCR1.

MIM

604170. gene.

neXtProt

NX_O15162.

PharmGKB

PA33419.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG15180.

GeneTree

ENSGT00390000002884.

HOGENOM

HBG452824.

HOVERGEN

HBG019157.

InParanoid

O15162.

OMA

TIQNERR.

OrthoDB

EOG45MN60.

PhylomeDB

O15162.

Gene expression databases

ArrayExpress

O15162.

Bgee

O15162.

CleanEx

HS_PLSCR1.

Genevestigator

O15162.

GermOnline

ENSG00000188313. Homo sapiens.

Family and domain databases

InterPro

IPR005552. Scramblase.
[Graphical view]

PANTHER

PTHR23248. Scramblase. 1 hit.

Pfam

PF03803. Scramblase. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

20774.

SOURCE

Search...

Entry information

Entry name

PLS1_HUMAN

Accession

Primary (citable) accession number: O15162
Secondary accession number(s): B2R8H8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	January 1, 1998
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 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.