PLAP_MOUSE
ID PLAP_MOUSE Reviewed; 794 AA.
AC P27612; A4QPD6; Q8C6C4;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Phospholipase A-2-activating protein;
DE Short=PLA2P;
DE Short=PLAP;
GN Name=Plaa; Synonyms=Plap;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 1-312, AND INDUCTION.
RX PubMed=2052621; DOI=10.1073/pnas.88.12.5418;
RA Clark M.A., Oezguer L.E., Conway T.M., Dispoto J., Crooke S.T.,
RA Bomalaski J.S.;
RT "Cloning of a phospholipase A2-activating protein.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:5418-5422(1991).
RN [6]
RP SEQUENCE REVISION.
RX PubMed=7665086; DOI=10.1016/0378-1119(95)00253-3;
RA Wang H., Lemasters J.J., Herman B.;
RT "Cloning of a rat cDNA encoding a protein with high homology to mouse
RT phospholipase A2-activating protein.";
RL Gene 161:237-241(1995).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-529, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-23.
RX PubMed=28413018; DOI=10.1016/j.ajhg.2017.03.008;
RA Hall E.A., Nahorski M.S., Murray L.M., Shaheen R., Perkins E.,
RA Dissanayake K.N., Kristaryanto Y., Jones R.A., Vogt J., Rivagorda M.,
RA Handley M.T., Mali G.R., Quidwai T., Soares D.C., Keighren M.A., McKie L.,
RA Mort R.L., Gammoh N., Garcia-Munoz A., Davey T., Vermeren M., Walsh D.,
RA Budd P., Aligianis I.A., Faqeih E., Quigley A.J., Jackson I.J., Kulathu Y.,
RA Jackson M., Ribchester R.R., von Kriegsheim A., Alkuraya F.S., Woods C.G.,
RA Maher E.R., Mill P.;
RT "PLAA mutations cause a lethal infantile epileptic encephalopathy by
RT disrupting ubiquitin-mediated endolysosomal degradation of synaptic
RT proteins.";
RL Am. J. Hum. Genet. 100:706-724(2017).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28007986; DOI=10.1093/brain/aww295;
RA Falik Zaccai T.C., Savitzki D., Zivony-Elboum Y., Vilboux T., Fitts E.C.,
RA Shoval Y., Kalfon L., Samra N., Keren Z., Gross B., Chasnyk N.,
RA Straussberg R., Mullikin J.C., Teer J.K., Geiger D., Kornitzer D.,
RA Bitterman-Deutsch O., Samson A.O., Wakamiya M., Peterson J.W.,
RA Kirtley M.L., Pinchuk I.V., Baze W.B., Gahl W.A., Kleta R., Anikster Y.,
RA Chopra A.K.;
RT "Phospholipase A2-activating protein is associated with a novel form of
RT leukoencephalopathy.";
RL Brain 140:370-386(2017).
CC -!- FUNCTION: Plays a role in protein ubiquitination, sorting and
CC degradation through its association with VCP (By similarity). Involved
CC in ubiquitin-mediated membrane proteins trafficking to late endosomes
CC in an ESCRT-dependent manner, and hence plays a role in synaptic
CC vesicle recycling (PubMed:28413018). May play a role in macroautophagy,
CC regulating for instance the clearance of damaged lysosomes (By
CC similarity). Plays a role in cerebellar Purkinje cell development
CC (PubMed:28413018). Positively regulates cytosolic and calcium-
CC independent phospholipase A2 activities in a tumor necrosis factor
CC alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner, and
CC hence prostaglandin E2 biosynthesis (PubMed:28007986).
CC {ECO:0000250|UniProtKB:Q9Y263, ECO:0000269|PubMed:28007986,
CC ECO:0000269|PubMed:28413018}.
CC -!- SUBUNIT: Interacts with ubiquitin. Interacts with UBXN6, VCP and YOD1;
CC may form a complex involved in macroautophagy.
CC {ECO:0000250|UniProtKB:Q9Y263}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28413018}. Cytoplasm
CC {ECO:0000269|PubMed:28413018}. Synapse {ECO:0000269|PubMed:28413018}.
CC Note=Recruited to damaged lysosomes decorated with K48-linked ubiquitin
CC chains. {ECO:0000250|UniProtKB:Q9Y263}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, with highest levels in
CC hippocampal neurons, cerebellar granular cell layer and Purkinje cells
CC (PubMed:28413018). {ECO:0000269|PubMed:28413018}.
CC -!- DEVELOPMENTAL STAGE: At stage 11.5 dpc ubiquitously expressed
CC (PubMed:28413018). {ECO:0000269|PubMed:28413018}.
CC -!- INDUCTION: In smooth muscle and endothelial cells by leukotriene D4, by
CC tumor necrosis factor in endothelial cells and by uric acid crystals in
CC macrophages. {ECO:0000269|PubMed:2052621}.
CC -!- DOMAIN: The PUL domain is composed of 6 armadillo-like repeats and
CC mediates the interaction with VCP C-terminus.
CC {ECO:0000250|UniProtKB:Q9Y263}.
CC -!- DOMAIN: The PFU domain mediates interaction with ubiquitin.
CC {ECO:0000250|UniProtKB:Q9Y263}.
CC -!- DISRUPTION PHENOTYPE: Mice die perinatally and exhibit spleen, lung and
CC brain developmental anomalies (PubMed:28413018, PubMed:28007986).
CC Display less matured and differentiated embryonic cortical neurons
CC (PubMed:28007986). Display reduced ubiquitin-dependent membrane protein
CC trafficking from early to late endosomes (PubMed:28413018). Show
CC reduced prostaglandin E2 biosynthesis in embryonic brain, lung and
CC heart, but not in liver at 18 dpc (PubMed:28007986).
CC {ECO:0000269|PubMed:28007986, ECO:0000269|PubMed:28413018}.
CC -!- SIMILARITY: Belongs to the WD repeat PLAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA39943.1; Type=Miscellaneous discrepancy; Note=Several frameshifts and contaminating sequence.; Evidence={ECO:0000305};
CC Sequence=Ref.3; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK075934; BAC36064.1; -; mRNA.
DR EMBL; AL732597; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466527; EDL30936.1; -; Genomic_DNA.
DR EMBL; BC139355; AAI39356.1; -; mRNA.
DR EMBL; BC139356; AAI39357.1; -; mRNA.
DR EMBL; BC139773; AAI39774.1; -; mRNA.
DR EMBL; M57958; AAA39943.1; ALT_SEQ; mRNA.
DR CCDS; CCDS18359.1; -.
DR PIR; A40963; A40963.
DR RefSeq; NP_766283.2; NM_172695.2.
DR AlphaFoldDB; P27612; -.
DR SMR; P27612; -.
DR BioGRID; 202224; 24.
DR IntAct; P27612; 1.
DR MINT; P27612; -.
DR STRING; 10090.ENSMUSP00000102724; -.
DR iPTMnet; P27612; -.
DR PhosphoSitePlus; P27612; -.
DR EPD; P27612; -.
DR MaxQB; P27612; -.
DR PaxDb; P27612; -.
DR PeptideAtlas; P27612; -.
DR PRIDE; P27612; -.
DR ProteomicsDB; 289520; -.
DR Antibodypedia; 3560; 428 antibodies from 29 providers.
DR DNASU; 18786; -.
DR Ensembl; ENSMUST00000107107; ENSMUSP00000102724; ENSMUSG00000028577.
DR GeneID; 18786; -.
DR KEGG; mmu:18786; -.
DR UCSC; uc008tsd.1; mouse.
DR CTD; 9373; -.
DR MGI; MGI:104810; Plaa.
DR VEuPathDB; HostDB:ENSMUSG00000028577; -.
DR eggNOG; KOG0301; Eukaryota.
DR GeneTree; ENSGT00550000074944; -.
DR HOGENOM; CLU_011791_2_0_1; -.
DR InParanoid; P27612; -.
DR OMA; HNVCALD; -.
DR OrthoDB; 1274776at2759; -.
DR PhylomeDB; P27612; -.
DR TreeFam; TF105944; -.
DR BioGRID-ORCS; 18786; 9 hits in 77 CRISPR screens.
DR ChiTaRS; Plaa; mouse.
DR PRO; PR:P27612; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P27612; protein.
DR Bgee; ENSMUSG00000028577; Expressed in embryonic post-anal tail and 256 other tissues.
DR ExpressionAtlas; P27612; baseline and differential.
DR Genevisible; P27612; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0016005; F:phospholipase A2 activator activity; IDA:MGI.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IDA:MGI.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:1900045; P:negative regulation of protein K63-linked ubiquitination; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:1903861; P:positive regulation of dendrite extension; IMP:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0032430; P:positive regulation of phospholipase A2 activity; ISS:UniProtKB.
DR GO; GO:1903423; P:positive regulation of synaptic vesicle recycling; IMP:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0010992; P:ubiquitin recycling; IBA:GO_Central.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.10.20.870; -; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR015155; PFU.
DR InterPro; IPR038122; PFU_sf.
DR InterPro; IPR013535; PUL_dom.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF09070; PFU; 1.
DR Pfam; PF08324; PUL; 1.
DR Pfam; PF00400; WD40; 6.
DR SMART; SM00320; WD40; 7.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS51394; PFU; 1.
DR PROSITE; PS51396; PUL; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 3.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Developmental protein; Neurogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; WD repeat.
FT CHAIN 1..794
FT /note="Phospholipase A-2-activating protein"
FT /id="PRO_0000051131"
FT REPEAT 17..56
FT /note="WD 1"
FT REPEAT 63..107
FT /note="WD 2"
FT REPEAT 110..148
FT /note="WD 3"
FT REPEAT 149..188
FT /note="WD 4"
FT REPEAT 190..227
FT /note="WD 5"
FT REPEAT 229..268
FT /note="WD 6"
FT REPEAT 270..307
FT /note="WD 7"
FT DOMAIN 366..465
FT /note="PFU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00727"
FT DOMAIN 533..793
FT /note="PUL"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00729"
FT REPEAT 546..588
FT /note="ARM 1"
FT REPEAT 589..620
FT /note="ARM 2"
FT REPEAT 621..668
FT /note="ARM 3"
FT REPEAT 669..714
FT /note="ARM 4"
FT REPEAT 715..754
FT /note="ARM 5"
FT REPEAT 755..794
FT /note="ARM 6"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y263"
FT MOD_RES 529
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MUTAGEN 23
FT /note="G->V: Loss of protein abundance. Increased abundance
FT of ubiquitinated synaptic proteins. Decreased ubiquitin-
FT mediated trafficking of membrane proteins through the
FT endolysosomal pathway. Decreased synaptic vesicle
FT recycling. Decreased cerebellar Purkinje cell migration and
FT dendrite extension."
FT /evidence="ECO:0000269|PubMed:28413018"
FT CONFLICT 60
FT /note="C -> Y (in Ref. 2; AAA39943)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="C -> Y (in Ref. 2; AAA39943)"
FT /evidence="ECO:0000305"
FT CONFLICT 300..301
FT /note="SE -> AD (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="S -> T (in Ref. 1; BAC36064)"
FT /evidence="ECO:0000305"
FT CONFLICT 546
FT /note="A -> T (in Ref. 6)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="A -> R (in Ref. 6)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 794 AA; 87221 MW; 7D8B1D55B07563CC CRC64;
MASGASRYRL SCSLPGHELD VRGLVCCLYP PGAFVSVSRD RTTRLWAPDS PNRGFTEMHC
MSGHSNFVSC VCIIPSSDIY PHGLIATGGN DHNICIFSLD SPMPLYILKG HKDTVCSLSS
GKFGTLLSGS WDTTAKVWLN DKCMMTLQGH TAAVWAVKIL PEQGLMLTGS ADKTIKLWKA
GRCERTFLGH EDCVRGLAIL SETEFLSCAN DASIRRWQIT GECLEVYFGH TNYIYSISVF
PNSKDFVTTA EDRSLRIWKH GECAQTIRLP AQSIWCCCVL ENGDIVVGAS DGIIRVFTES
EERTASAEEI KAFERELSQA TIDSKTGDLG DINAEQLPGR EHLSEPGTRE GQTRLIRDGE
RVEAYQWSVS DGRWIKIGDV VGSSGANQQT SGKVLYEGKE FDYVFSIDVN EGGPSYKLPY
NVSDDPWLVA YNFLQKNDLN PMFLDQVAKF IIDNTKGQTL GLGNTSFSDP FTGGGRYVPG
TSGPSNTVQT ADPFTGAGRY MPGSAGMDTT MTGVDPFTGN SAYRSAASKT VNIYFPKKEA
LTFDQANPTQ ILGKLKELNG TAPEEKKLTE DDLVLLEKIL SLICNNSSEK PTAQQLQILW
KAINWPEDIV FPALDILRLS IKHPNVNENF CNEKGDQFSS HLINLLNPKG KPANQLLALR
TFCNCFVSQA GQKLMMSQRE SLMSHAIELK SGSNKNIHIA LATLTLNYSV CFHKDHNIEG
KAQCLSVIST ILEVVQDLEA TFRLLVALGT LISDDSNAIQ LAKSLGVDSQ IKKYVSVSEP
AKVSECCRLV LHLL
