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Protein

Phospholipid scramblase 2

Gene

PLSCR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.
Isoform 1 has no prospholipid scramblase activity, due to the lack of a N-terminal proline-rich domain.

Cofactori

Ca2+By similarity

GO - Molecular functioni

  1. calcium ion binding Source: UniProtKB
  2. phospholipid scramblase activity Source: UniProtKB

GO - Biological processi

  1. phospholipid scrambling Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Phospholipid scramblase 2
Short name:
PL scramblase 2
Alternative name(s):
Ca(2+)-dependent phospholipid scramblase 2
Gene namesi
Name:PLSCR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:16494. PLSCR2.

Subcellular locationi

Membrane By similarity; Single-pass type II membrane protein By similarity
Isoform 1 : Nucleus 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 276276CytoplasmicBy similarityAdd
BLAST
Transmembranei277 – 29317HelicalSequence AnalysisAdd
BLAST
Topological domaini294 – 2974ExtracellularBy similarity

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA33420.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 297297Phospholipid scramblase 2PRO_0000100787Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei149 – 1491Phosphothreonine; by PKCBy similarity
Lipidationi222 – 2221S-palmitoyl cysteineCurated
Lipidationi225 – 2251S-palmitoyl cysteineCurated
Lipidationi227 – 2271S-palmitoyl cysteineCurated

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiQ9NRY7.
PRIDEiQ9NRY7.

Expressioni

Tissue specificityi

Expression of isoform 1 seems restricted to testis.1 Publication

Gene expression databases

BgeeiQ9NRY7.
CleanExiHS_PLSCR2.
ExpressionAtlasiQ9NRY7. baseline.
GenevestigatoriQ9NRY7.

Organism-specific databases

HPAiHPA051352.

Interactioni

Protein-protein interaction databases

BioGridi121340. 1 interaction.
IntActiQ9NRY7. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ9NRY7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7272Proline-rich domain (PRD)By similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi75 – 806Poly-Pro
Compositional biasi169 – 1779Cys-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

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG119855.
GeneTreeiENSGT00390000002884.
HOGENOMiHOG000237356.
HOVERGENiHBG019157.
InParanoidiQ9NRY7.
OMAiPLRCNCC.
TreeFamiTF314939.

Family and domain databases

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

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 2 (identifier: Q9NRY7-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRSWNSLFCL NSSRPPGHIV YPKHQAGHTG KQADHLGSQA FYPGRQHDYL
60 70 80 90 100
VPPAGTAGIP VQNQPGRPEG VPWMPAPPPP LNCPPGLEYL SQIDMILIHQ
110 120 130 140 150
QIELLEVLFS FESSNMYEIK NSFGQRIYFA AEDTNFCIRN CCGRSRPFTL
160 170 180 190 200
RITDNVGREV ITLERPLRCN CCCCPCCLQE IEIQAPPGVP VGYVTQTWHP
210 220 230 240 250
CLTKFTIKNQ KREDVLKISG PCIVCSCIAG VDFEITSLDE QIVVGRISKH
260 270 280 290
WSGFLREAFT DADNFGIQFP RDLDVKMKAV MIGACFLIDY MFFERTR

Note: No experimental confirmation available.

Length:297
Mass (Da):33,504
Last modified:July 9, 2014 - v2
Checksum:i58F50C24AB438729
GO
Isoform 1 (identifier: Q9NRY7-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: Missing.

Show »
Length:224
Mass (Da):25,523
Checksum:iFD218C63C59D239A
GO
Isoform 3 (identifier: Q9NRY7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-14: MRSWNSLFCLNSSR → MKPFQIHLPG

Note: No experimental confirmation available.

Show »
Length:293
Mass (Da):32,970
Checksum:iD4FFE4925247787F
GO

Sequence cautioni

The sequence AAH55415.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti272 – 2743DLD → NLN in BAG63335 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 7373Missing in isoform 1. 2 PublicationsVSP_055239Add
BLAST
Alternative sequencei1 – 1414MRSWN…LNSSR → MKPFQIHLPG in isoform 3. 1 PublicationVSP_055240Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF159441 mRNA. Translation: AAF91082.1.
AK301909 mRNA. Translation: BAG63335.1.
AC069528 Genomic DNA. No translation available.
BC055415 mRNA. Translation: AAH55415.1. Different initiation.
BC069785 mRNA. Translation: AAH69785.2.
BC120969 mRNA. Translation: AAI20970.1.
BC141969 mRNA. Translation: AAI41970.1.
CCDSiCCDS3134.1. [Q9NRY7-1]
CCDS56284.1. [Q9NRY7-2]
CCDS75029.1. [Q9NRY7-3]
RefSeqiNP_001186907.1. NM_001199978.1. [Q9NRY7-2]
NP_001186908.1. NM_001199979.1. [Q9NRY7-3]
NP_065092.1. NM_020359.2. [Q9NRY7-1]
UniGeneiHs.744414.

Genome annotation databases

EnsembliENST00000336685; ENSP00000338707; ENSG00000163746. [Q9NRY7-1]
ENST00000497985; ENSP00000420132; ENSG00000163746. [Q9NRY7-2]
ENST00000610787; ENSP00000478044; ENSG00000163746. [Q9NRY7-1]
ENST00000613069; ENSP00000478902; ENSG00000163746. [Q9NRY7-3]
GeneIDi57047.
KEGGihsa:57047.
UCSCiuc003evv.2. human. [Q9NRY7-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Wikipedia

Scramblase entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF159441 mRNA. Translation: AAF91082.1.
AK301909 mRNA. Translation: BAG63335.1.
AC069528 Genomic DNA. No translation available.
BC055415 mRNA. Translation: AAH55415.1. Different initiation.
BC069785 mRNA. Translation: AAH69785.2.
BC120969 mRNA. Translation: AAI20970.1.
BC141969 mRNA. Translation: AAI41970.1.
CCDSiCCDS3134.1. [Q9NRY7-1]
CCDS56284.1. [Q9NRY7-2]
CCDS75029.1. [Q9NRY7-3]
RefSeqiNP_001186907.1. NM_001199978.1. [Q9NRY7-2]
NP_001186908.1. NM_001199979.1. [Q9NRY7-3]
NP_065092.1. NM_020359.2. [Q9NRY7-1]
UniGeneiHs.744414.

3D structure databases

ProteinModelPortaliQ9NRY7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121340. 1 interaction.
IntActiQ9NRY7. 1 interaction.

Proteomic databases

PaxDbiQ9NRY7.
PRIDEiQ9NRY7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000336685; ENSP00000338707; ENSG00000163746. [Q9NRY7-1]
ENST00000497985; ENSP00000420132; ENSG00000163746. [Q9NRY7-2]
ENST00000610787; ENSP00000478044; ENSG00000163746. [Q9NRY7-1]
ENST00000613069; ENSP00000478902; ENSG00000163746. [Q9NRY7-3]
GeneIDi57047.
KEGGihsa:57047.
UCSCiuc003evv.2. human. [Q9NRY7-2]

Organism-specific databases

CTDi57047.
GeneCardsiGC03M146110.
H-InvDBHIX0200552.
HGNCiHGNC:16494. PLSCR2.
HPAiHPA051352.
MIMi607610. gene.
neXtProtiNX_Q9NRY7.
PharmGKBiPA33420.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG119855.
GeneTreeiENSGT00390000002884.
HOGENOMiHOG000237356.
HOVERGENiHBG019157.
InParanoidiQ9NRY7.
OMAiPLRCNCC.
TreeFamiTF314939.

Miscellaneous databases

GeneWikiiPLSCR2.
GenomeRNAii57047.
NextBioi35535500.
PROiQ9NRY7.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NRY7.
CleanExiHS_PLSCR2.
ExpressionAtlasiQ9NRY7. baseline.
GenevestigatoriQ9NRY7.

Family and domain databases

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

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] (ISOFORM 1), CALCIUM-BINDING, TISSUE SPECIFICITY.
  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] (ISOFORM 2).
    Tissue: Testis.
  3. "The DNA sequence, annotation and analysis of human chromosome 3."
    Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
    , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
    Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORMS 1 AND 3).
    Tissue: Testis.
  5. "N-terminal proline-rich domain is required for scrambling activity of human phospholipid scramblases."
    Rayala S., Francis V.G., Sivagnanam U., Gummadi S.N.
    J. Biol. Chem. 289:13206-13218(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION (ISOFORM 1), ABSENCE OF SCRAMBLASE ACTIVITY (ISOFORM 1), CALCIUM-BINDING, SUBCELLULAR LOCATION (ISOFORM 1).

Entry informationi

Entry nameiPLS2_HUMAN
AccessioniPrimary (citable) accession number: Q9NRY7
Secondary accession number(s): B4DXC3
, J3KR76, Q0VAQ1, Q6NSW9, Q7Z4L7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2001
Last sequence update: July 9, 2014
Last modified: January 7, 2015
This is version 114 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 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.