PLS2_HUMAN
ID PLS2_HUMAN Reviewed; 297 AA.
AC Q9NRY7; B4DXC3; J3KR76; Q0VAQ1; Q6NSW9; Q7Z4L7;
DT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 09-JUL-2014, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Phospholipid scramblase 2;
DE Short=PL scramblase 2;
DE AltName: Full=Ca(2+)-dependent phospholipid scramblase 2;
GN Name=PLSCR2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CALCIUM-BINDING, AND TISSUE
RP SPECIFICITY.
RX PubMed=10930526; DOI=10.1016/s0005-2736(00)00236-4;
RA Wiedmer T., Zhou Q., Kwoh D.Y., Sims P.J.;
RT "Identification of three new members of the phospholipid scramblase gene
RT family.";
RL Biochim. Biophys. Acta 1467:244-253(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION (ISOFORM 1), ABSENCE OF SCRAMBLASE ACTIVITY (ISOFORM 1),
RP CALCIUM-BINDING, AND SUBCELLULAR LOCATION (ISOFORM 1).
RX PubMed=24648509; DOI=10.1074/jbc.m113.522953;
RA Rayala S., Francis V.G., Sivagnanam U., Gummadi S.N.;
RT "N-terminal proline-rich domain is required for scrambling activity of
RT human phospholipid scramblases.";
RL J. Biol. Chem. 289:13206-13218(2014).
CC -!- FUNCTION: May mediate accelerated ATP-independent bidirectional
CC transbilayer migration of phospholipids upon binding calcium ions that
CC results in a loss of phospholipid asymmetry in the plasma membrane. May
CC play a central role in the initiation of fibrin clot formation, in the
CC activation of mast cells and in the recognition of apoptotic and
CC injured cells by the reticuloendothelial system.
CC -!- FUNCTION: Isoform 1 has no prospholipid scramblase activity, due to the
CC lack of a N-terminal proline-rich domain.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC Q9NRY7; P29972: AQP1; NbExp=3; IntAct=EBI-3937430, EBI-745213;
CC Q9NRY7; Q8WZ55: BSND; NbExp=3; IntAct=EBI-3937430, EBI-7996695;
CC Q9NRY7; O75208: COQ9; NbExp=3; IntAct=EBI-3937430, EBI-724524;
CC Q9NRY7; A6H8Z2: FAM221B; NbExp=3; IntAct=EBI-3937430, EBI-12006844;
CC Q9NRY7; Q9P2W3: GNG13; NbExp=3; IntAct=EBI-3937430, EBI-11427343;
CC Q9NRY7; P49639: HOXA1; NbExp=3; IntAct=EBI-3937430, EBI-740785;
CC Q9NRY7; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-3937430, EBI-11962058;
CC Q9NRY7; Q5TA76: LCE3A; NbExp=3; IntAct=EBI-3937430, EBI-9394625;
CC Q9NRY7; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-3937430, EBI-10245456;
CC Q9NRY7; Q5TCM9: LCE5A; NbExp=3; IntAct=EBI-3937430, EBI-11955689;
CC Q9NRY7; Q8N2G4-2: LYPD1; NbExp=3; IntAct=EBI-3937430, EBI-18973558;
CC Q9NRY7; P32242: OTX1; NbExp=3; IntAct=EBI-3937430, EBI-740446;
CC Q9NRY7; Q12837: POU4F2; NbExp=5; IntAct=EBI-3937430, EBI-17236143;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type II
CC membrane protein {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:24648509}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=2;
CC IsoId=Q9NRY7-2; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9NRY7-1; Sequence=VSP_055239;
CC Name=3;
CC IsoId=Q9NRY7-3; Sequence=VSP_055240;
CC -!- TISSUE SPECIFICITY: Expression of isoform 1 seems restricted to testis.
CC {ECO:0000269|PubMed:10930526}.
CC -!- DOMAIN: The N-terminal proline-rich domain (PRD) is required for
CC phospholipid scramblase activity. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the phospholipid scramblase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH55415.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Scramblase entry;
CC URL="https://en.wikipedia.org/wiki/Scramblase";
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DR EMBL; AF159441; AAF91082.1; -; mRNA.
DR EMBL; AK301909; BAG63335.1; -; mRNA.
DR EMBL; AC069528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC055415; AAH55415.1; ALT_INIT; mRNA.
DR EMBL; BC069785; AAH69785.2; -; mRNA.
DR EMBL; BC120969; AAI20970.1; -; mRNA.
DR EMBL; BC141969; AAI41970.1; -; mRNA.
DR CCDS; CCDS3134.1; -. [Q9NRY7-1]
DR CCDS; CCDS56284.1; -. [Q9NRY7-2]
DR CCDS; CCDS75029.1; -. [Q9NRY7-3]
DR RefSeq; NP_001186907.1; NM_001199978.1. [Q9NRY7-2]
DR RefSeq; NP_001186908.1; NM_001199979.1. [Q9NRY7-3]
DR RefSeq; NP_065092.1; NM_020359.2. [Q9NRY7-1]
DR RefSeq; XP_016862394.1; XM_017006905.1.
DR RefSeq; XP_016862395.1; XM_017006906.1.
DR RefSeq; XP_016862396.1; XM_017006907.1.
DR RefSeq; XP_016862397.1; XM_017006908.1.
DR RefSeq; XP_016862398.1; XM_017006909.1.
DR RefSeq; XP_016862399.1; XM_017006910.1. [Q9NRY7-1]
DR RefSeq; XP_016862400.1; XM_017006911.1. [Q9NRY7-1]
DR RefSeq; XP_016862403.1; XM_017006914.1.
DR RefSeq; XP_016862404.1; XM_017006915.1.
DR AlphaFoldDB; Q9NRY7; -.
DR BioGRID; 121340; 14.
DR IntAct; Q9NRY7; 14.
DR STRING; 9606.ENSP00000420132; -.
DR TCDB; 9.A.36.1.5; the ca(2+)-dependent phospholipid scramblase (scramblase) family.
DR iPTMnet; Q9NRY7; -.
DR PhosphoSitePlus; Q9NRY7; -.
DR BioMuta; PLSCR2; -.
DR MassIVE; Q9NRY7; -.
DR PaxDb; Q9NRY7; -.
DR PeptideAtlas; Q9NRY7; -.
DR PRIDE; Q9NRY7; -.
DR ProteomicsDB; 82445; -. [Q9NRY7-2]
DR Antibodypedia; 52901; 32 antibodies from 14 providers.
DR DNASU; 57047; -.
DR Ensembl; ENST00000336685.6; ENSP00000338707.2; ENSG00000163746.12. [Q9NRY7-1]
DR Ensembl; ENST00000497985.5; ENSP00000420132.1; ENSG00000163746.12. [Q9NRY7-2]
DR Ensembl; ENST00000610787.5; ENSP00000478044.1; ENSG00000163746.12. [Q9NRY7-1]
DR Ensembl; ENST00000613069.4; ENSP00000478902.1; ENSG00000163746.12. [Q9NRY7-3]
DR GeneID; 57047; -.
DR KEGG; hsa:57047; -.
DR UCSC; uc003evv.3; human. [Q9NRY7-2]
DR CTD; 57047; -.
DR DisGeNET; 57047; -.
DR GeneCards; PLSCR2; -.
DR HGNC; HGNC:16494; PLSCR2.
DR HPA; ENSG00000163746; Tissue enriched (testis).
DR MIM; 607610; gene.
DR neXtProt; NX_Q9NRY7; -.
DR OpenTargets; ENSG00000163746; -.
DR PharmGKB; PA33420; -.
DR VEuPathDB; HostDB:ENSG00000163746; -.
DR eggNOG; KOG0621; Eukaryota.
DR GeneTree; ENSGT00940000164933; -.
DR HOGENOM; CLU_053024_2_2_1; -.
DR InParanoid; Q9NRY7; -.
DR OMA; WHPLSPK; -.
DR OrthoDB; 1015148at2759; -.
DR PhylomeDB; Q9NRY7; -.
DR TreeFam; TF314939; -.
DR BRENDA; 7.6.2.1; 2681.
DR PathwayCommons; Q9NRY7; -.
DR SignaLink; Q9NRY7; -.
DR BioGRID-ORCS; 57047; 12 hits in 1061 CRISPR screens.
DR ChiTaRS; PLSCR2; human.
DR GeneWiki; PLSCR2; -.
DR GenomeRNAi; 57047; -.
DR Pharos; Q9NRY7; Tdark.
DR PRO; PR:Q9NRY7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NRY7; protein.
DR Bgee; ENSG00000163746; Expressed in sperm and 107 other tissues.
DR ExpressionAtlas; Q9NRY7; baseline and differential.
DR Genevisible; Q9NRY7; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; NAS:UniProtKB.
DR GO; GO:0017128; F:phospholipid scramblase activity; IBA:GO_Central.
DR GO; GO:0017121; P:plasma membrane phospholipid scrambling; IBA:GO_Central.
DR InterPro; IPR005552; Scramblase.
DR PANTHER; PTHR23248; PTHR23248; 1.
DR Pfam; PF03803; Scramblase; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Lipoprotein; Membrane; Metal-binding;
KW Nucleus; Palmitate; Phosphoprotein; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..297
FT /note="Phospholipid scramblase 2"
FT /id="PRO_0000100787"
FT TOPO_DOM 1..276
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 277..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 294..297
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT REGION 1..72
FT /note="Proline-rich domain (PRD)"
FT /evidence="ECO:0000250"
FT MOD_RES 149
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250"
FT LIPID 172
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 173
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 174
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 176
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT LIPID 177
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O15162"
FT VAR_SEQ 1..73
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10930526,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_055239"
FT VAR_SEQ 1..14
FT /note="MRSWNSLFCLNSSR -> MKPFQIHLPG (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_055240"
FT CONFLICT 272..274
FT /note="DLD -> NLN (in Ref. 2; BAG63335)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 297 AA; 33504 MW; 58F50C24AB438729 CRC64;
MRSWNSLFCL NSSRPPGHIV YPKHQAGHTG KQADHLGSQA FYPGRQHDYL VPPAGTAGIP
VQNQPGRPEG VPWMPAPPPP LNCPPGLEYL SQIDMILIHQ QIELLEVLFS FESSNMYEIK
NSFGQRIYFA AEDTNFCIRN CCGRSRPFTL RITDNVGREV ITLERPLRCN CCCCPCCLQE
IEIQAPPGVP VGYVTQTWHP CLTKFTIKNQ KREDVLKISG PCIVCSCIAG VDFEITSLDE
QIVVGRISKH WSGFLREAFT DADNFGIQFP RDLDVKMKAV MIGACFLIDY MFFERTR
