PLAP_HUMAN
ID PLAP_HUMAN Reviewed; 795 AA.
AC Q9Y263; Q53EU5; Q5VY33; Q9NUL8; Q9NVE9; Q9UF53; Q9Y5L1;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Phospholipase A-2-activating protein;
DE Short=PLA2P;
DE Short=PLAP;
GN Name=PLAA; Synonyms=PLAP;
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 [LARGE SCALE MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 3-795.
RX PubMed=10644453; DOI=10.1006/geno.1999.5999;
RA Beatty B., Qi S., Pienkowska M., Scherer S.W., Testa J.R., Cheng J.Q.,
RA Herbrick J.-A., Scheidl T., Zhang Z., Kola I., Seth A.;
RT "Chromosomal localization of phospholipase A2 activating protein, an ets2
RT target gene, to 9p21.";
RL Genomics 62:529-532(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 48-795.
RC TISSUE=Kidney;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 49-795.
RC TISSUE=Fetal brain;
RX PubMed=10571045; DOI=10.1016/s0378-1119(99)00354-6;
RA Ruiz A., Nadal M., Puig S., Estivill X.;
RT "Cloning of the human phospholipase A2 activating protein (hPLAP) gene on
RT the chromosome 9p21 melanoma deleted region.";
RL Gene 239:155-161(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 58-795.
RX PubMed=9931468; DOI=10.1016/s0167-4781(98)00249-8;
RA Chopra A.K., Ribardo D.A., Wood T.G., Prusak D.J., Xu X.-J., Peterson J.W.;
RT "Molecular characterization of cDNA for phospholipase A2-activating
RT protein.";
RL Biochim. Biophys. Acta 1444:125-130(1999).
RN [9]
RP FUNCTION, AND INDUCTION.
RX PubMed=18291623; DOI=10.1016/j.cellsig.2008.01.004;
RA Zhang F., Sha J., Wood T.G., Galindo C.L., Garner H.R., Burkart M.F.,
RA Suarez G., Sierra J.C., Agar S.L., Peterson J.W., Chopra A.K.;
RT "Alteration in the activation state of new inflammation-associated targets
RT by phospholipase A2-activating protein (PLAA).";
RL Cell. Signal. 20:844-861(2008).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-529, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-50, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [13]
RP FUNCTION, INTERACTION WITH UBXN6; VCP AND YOD1, AND SUBCELLULAR LOCATION.
RX PubMed=27753622; DOI=10.15252/embj.201695148;
RA Papadopoulos C., Kirchner P., Bug M., Grum D., Koerver L., Schulze N.,
RA Poehler R., Dressler A., Fengler S., Arhzaouy K., Lux V., Ehrmann M.,
RA Weihl C.C., Meyer H.;
RT "VCP/p97 cooperates with YOD1, UBXD1 and PLAA to drive clearance of
RT ruptured lysosomes by autophagy.";
RL EMBO J. 36:135-150(2017).
RN [14]
RP STRUCTURE BY NMR OF 386-465, AND INTERACTION WITH UBIQUITIN.
RX PubMed=19423704; DOI=10.1074/jbc.m109.009126;
RA Fu Q.-S., Zhou C.-J., Gao H.-C., Jiang Y.-J., Zhou Z.-R., Hong J.,
RA Yao W.-M., Song A.-X., Lin D.-H., Hu H.-Y.;
RT "Structural basis for ubiquitin recognition by a novel domain from human
RT phospholipase A2-activating protein.";
RL J. Biol. Chem. 284:19043-19052(2009).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 511-795 IN COMPLEX WITH VCP, AND
RP DOMAIN ARM REPEATS.
RX PubMed=19887378; DOI=10.1074/jbc.m109.044685;
RA Qiu L., Pashkova N., Walker J.R., Winistorfer S., Allali-Hassani A.,
RA Akutsu M., Piper R., Dhe-Paganon S.;
RT "Structure and function of the PLAA/Ufd3-p97/Cdc48 complex.";
RL J. Biol. Chem. 285:365-372(2010).
RN [16]
RP VARIANT NDMSBA VAL-23, CHARACTERIZATION OF VARIANT NDMSBA VAL-23, AND
RP INVOLVEMENT IN NDMSBA.
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 [17]
RP VARIANT NDMSBA PHE-752, CHARACTERIZATION OF VARIANT NDMSBA PHE-752,
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 (PubMed:27753622).
CC Involved in ubiquitin-mediated membrane proteins trafficking to late
CC endosomes in an ESCRT-dependent manner, and hence plays a role in
CC synaptic vesicle recycling (By similarity). May play a role in
CC macroautophagy, regulating for instance the clearance of damaged
CC lysosomes (PubMed:27753622). Plays a role in cerebellar Purkinje cell
CC development (By similarity). Positively regulates cytosolic and
CC calcium-independent phospholipase A2 activities in a tumor necrosis
CC factor alpha (TNF-alpha)- or lipopolysaccharide (LPS)-dependent manner,
CC and hence prostaglandin E2 biosynthesis (PubMed:18291623,
CC PubMed:28007986). {ECO:0000250|UniProtKB:P27612,
CC ECO:0000269|PubMed:18291623, ECO:0000269|PubMed:27753622,
CC ECO:0000269|PubMed:28007986}.
CC -!- SUBUNIT: Interacts with ubiquitin (PubMed:19423704). Interacts with
CC UBXN6, VCP and YOD1; may form a complex involved in macroautophagy
CC (PubMed:27753622, PubMed:19887378). {ECO:0000269|PubMed:19423704,
CC ECO:0000269|PubMed:19887378, ECO:0000269|PubMed:27753622}.
CC -!- INTERACTION:
CC Q9Y263; Q96D03: DDIT4L; NbExp=3; IntAct=EBI-1994037, EBI-742054;
CC Q9Y263; V9HW80: HEL-S-70; NbExp=3; IntAct=EBI-1994037, EBI-10175326;
CC Q9Y263; O00629: KPNA4; NbExp=3; IntAct=EBI-1994037, EBI-396343;
CC Q9Y263; Q04323: UBXN1; NbExp=5; IntAct=EBI-1994037, EBI-1058647;
CC Q9Y263; Q04323-2: UBXN1; NbExp=3; IntAct=EBI-1994037, EBI-11530712;
CC Q9Y263; P55072: VCP; NbExp=3; IntAct=EBI-1994037, EBI-355164;
CC Q9Y263; Q76353; Xeno; NbExp=3; IntAct=EBI-1994037, EBI-6248077;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:28007986}. Cytoplasm
CC {ECO:0000269|PubMed:27753622, ECO:0000269|PubMed:28007986}. Synapse
CC {ECO:0000250|UniProtKB:P27612}. Note=Recruited to damaged lysosomes
CC decorated with K48-linked ubiquitin chains.
CC {ECO:0000269|PubMed:27753622}.
CC -!- INDUCTION: Up-regulated by tumor necrosis factor alpha (TNF-alpha) (at
CC protein level) (PubMed:18291623). {ECO:0000269|PubMed:18291623}.
CC -!- DOMAIN: The PUL domain is composed of 6 armadillo-like repeats and
CC mediates the interaction with VCP C-terminus.
CC {ECO:0000269|PubMed:19887378}.
CC -!- DOMAIN: The PFU domain mediates interaction with ubiquitin.
CC {ECO:0000269|PubMed:19887378}.
CC -!- DISEASE: Neurodevelopmental disorder with progressive microcephaly,
CC spasticity, and brain anomalies (NDMSBA) [MIM:617527]: An autosomal
CC recessive neurodevelopmental disorder characterized by progressive
CC microcephaly, spastic quadriparesis, global developmental delay,
CC profound intellectual disability and severely impaired or absent motor
CC function. More variable features include seizures and optic atrophy.
CC {ECO:0000269|PubMed:28007986, ECO:0000269|PubMed:28413018}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the WD repeat PLAP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD03030.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD42075.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD42075.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAA92105.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD97264.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAB42881.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK001642; BAA91803.1; -; mRNA.
DR EMBL; AK002143; BAA92105.1; ALT_SEQ; mRNA.
DR EMBL; AL133608; CAB63739.1; -; mRNA.
DR EMBL; AL356133; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC032551; AAH32551.1; -; mRNA.
DR EMBL; AF145020; AAD42075.1; ALT_SEQ; mRNA.
DR EMBL; AK223544; BAD97264.1; ALT_INIT; mRNA.
DR EMBL; AJ238243; CAB42881.1; ALT_INIT; mRNA.
DR EMBL; AF083395; AAD03030.1; ALT_INIT; mRNA.
DR CCDS; CCDS35000.1; -.
DR PIR; T43447; T43447.
DR RefSeq; NP_001026859.1; NM_001031689.2.
DR PDB; 2K89; NMR; -; A=386-465.
DR PDB; 2K8A; NMR; -; A=386-465.
DR PDB; 2K8B; NMR; -; B=386-465.
DR PDB; 2K8C; NMR; -; B=386-465.
DR PDB; 3EBB; X-ray; 1.90 A; A/B/C/D=511-795.
DR PDBsum; 2K89; -.
DR PDBsum; 2K8A; -.
DR PDBsum; 2K8B; -.
DR PDBsum; 2K8C; -.
DR PDBsum; 3EBB; -.
DR AlphaFoldDB; Q9Y263; -.
DR BMRB; Q9Y263; -.
DR SMR; Q9Y263; -.
DR BioGRID; 114774; 76.
DR IntAct; Q9Y263; 29.
DR MINT; Q9Y263; -.
DR STRING; 9606.ENSP00000380460; -.
DR BindingDB; Q9Y263; -.
DR ChEMBL; CHEMBL6114; -.
DR GlyGen; Q9Y263; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y263; -.
DR MetOSite; Q9Y263; -.
DR PhosphoSitePlus; Q9Y263; -.
DR BioMuta; PLAA; -.
DR DMDM; 108935868; -.
DR EPD; Q9Y263; -.
DR jPOST; Q9Y263; -.
DR MassIVE; Q9Y263; -.
DR MaxQB; Q9Y263; -.
DR PaxDb; Q9Y263; -.
DR PeptideAtlas; Q9Y263; -.
DR PRIDE; Q9Y263; -.
DR ProteomicsDB; 85667; -.
DR Antibodypedia; 3560; 428 antibodies from 29 providers.
DR DNASU; 9373; -.
DR Ensembl; ENST00000397292.8; ENSP00000380460.3; ENSG00000137055.15.
DR GeneID; 9373; -.
DR KEGG; hsa:9373; -.
DR MANE-Select; ENST00000397292.8; ENSP00000380460.3; NM_001031689.3; NP_001026859.1.
DR UCSC; uc003zqd.4; human.
DR CTD; 9373; -.
DR DisGeNET; 9373; -.
DR GeneCards; PLAA; -.
DR HGNC; HGNC:9043; PLAA.
DR HPA; ENSG00000137055; Low tissue specificity.
DR MalaCards; PLAA; -.
DR MIM; 603873; gene.
DR MIM; 617527; phenotype.
DR neXtProt; NX_Q9Y263; -.
DR OpenTargets; ENSG00000137055; -.
DR Orphanet; 521426; PLAA-associated neurodevelopmental disorder.
DR PharmGKB; PA33370; -.
DR VEuPathDB; HostDB:ENSG00000137055; -.
DR eggNOG; KOG0301; Eukaryota.
DR GeneTree; ENSGT00550000074944; -.
DR HOGENOM; CLU_011791_2_0_1; -.
DR InParanoid; Q9Y263; -.
DR OMA; HNVCALD; -.
DR OrthoDB; 1274776at2759; -.
DR PhylomeDB; Q9Y263; -.
DR TreeFam; TF105944; -.
DR PathwayCommons; Q9Y263; -.
DR SignaLink; Q9Y263; -.
DR BioGRID-ORCS; 9373; 21 hits in 1075 CRISPR screens.
DR ChiTaRS; PLAA; human.
DR EvolutionaryTrace; Q9Y263; -.
DR GeneWiki; PLAA_(gene); -.
DR GenomeRNAi; 9373; -.
DR Pharos; Q9Y263; Tchem.
DR PRO; PR:Q9Y263; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9Y263; protein.
DR Bgee; ENSG00000137055; Expressed in gastrocnemius and 183 other tissues.
DR ExpressionAtlas; Q9Y263; baseline and differential.
DR Genevisible; Q9Y263; HS.
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; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0016005; F:phospholipase A2 activator activity; TAS:ProtInc.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0016236; P:macroautophagy; IMP:UniProtKB.
DR GO; GO:1900045; P:negative regulation of protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; TAS:ProtInc.
DR GO; GO:1903861; P:positive regulation of dendrite extension; ISS:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0032430; P:positive regulation of phospholipase A2 activity; IMP:UniProtKB.
DR GO; GO:1903423; P:positive regulation of synaptic vesicle recycling; ISS:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISS:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; ISS:UniProtKB.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.10.20.870; -; 1.
DR IDEAL; IID00228; -.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
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; SSF48371; SSF48371; 1.
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 3D-structure; Acetylation; Cytoplasm; Developmental protein;
KW Disease variant; Intellectual disability; Neurogenesis; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Synapse; WD repeat.
FT CHAIN 1..795
FT /note="Phospholipase A-2-activating protein"
FT /id="PRO_0000051130"
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..794
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..669
FT /note="ARM 3"
FT REPEAT 670..715
FT /note="ARM 4"
FT REPEAT 716..755
FT /note="ARM 5"
FT REPEAT 756..795
FT /note="ARM 6"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 529
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 23
FT /note="G -> V (in NDMSBA; dbSNP:rs747956857)"
FT /evidence="ECO:0000269|PubMed:28413018"
FT /id="VAR_079276"
FT VARIANT 752
FT /note="L -> F (in NDMSBA; no effect on protein stability;
FT no effect on subcellular localization; decreased function
FT in positive regulation of cytosolic phospholipase A2
FT activity; in patient cells homozygous for the mutation;
FT dbSNP:rs1114167457)"
FT /evidence="ECO:0000269|PubMed:28007986"
FT /id="VAR_079277"
FT CONFLICT 14
FT /note="L -> F (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 57
FT /note="E -> D (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="A -> F (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="F -> L (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="D -> G (in Ref. 1; BAA91803)"
FT /evidence="ECO:0000305"
FT CONFLICT 363
FT /note="E -> K (in Ref. 6; BAD97264)"
FT /evidence="ECO:0000305"
FT CONFLICT 422
FT /note="T -> A (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="N -> S (in Ref. 1; BAA92105)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="M -> L (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="V -> L (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT CONFLICT 746
FT /note="L -> P (in Ref. 5; AAD42075)"
FT /evidence="ECO:0000305"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:2K89"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:2K89"
FT STRAND 399..407
FT /evidence="ECO:0007829|PDB:2K89"
FT STRAND 410..412
FT /evidence="ECO:0007829|PDB:2K89"
FT STRAND 416..420
FT /evidence="ECO:0007829|PDB:2K89"
FT HELIX 426..437
FT /evidence="ECO:0007829|PDB:2K89"
FT HELIX 443..455
FT /evidence="ECO:0007829|PDB:2K89"
FT TURN 457..460
FT /evidence="ECO:0007829|PDB:2K89"
FT HELIX 548..559
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 564..566
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 571..584
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 593..603
FT /evidence="ECO:0007829|PDB:3EBB"
FT TURN 607..609
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 611..620
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 624..631
FT /evidence="ECO:0007829|PDB:3EBB"
FT TURN 633..635
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 636..645
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 653..665
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 666..668
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 670..678
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 680..688
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 689..691
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 696..715
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 719..733
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 739..753
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 757..765
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 768..771
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 772..777
FT /evidence="ECO:0007829|PDB:3EBB"
FT HELIX 782..792
FT /evidence="ECO:0007829|PDB:3EBB"
SQ SEQUENCE 795 AA; 87157 MW; D6E7330AC9891637 CRC64;
MTSGATRYRL SCSLRGHELD VRGLVCCAYP PGAFVSVSRD RTTRLWAPDS PNRSFTEMHC
MSGHSNFVSC VCIIPSSDIY PHGLIATGGN DHNICIFSLD SPMPLYILKG HKNTVCSLSS
GKFGTLLSGS WDTTAKVWLN DKCMMTLQGH TAAVWAVKIL PEQGLMLTGS ADKTVKLWKA
GRCERTFSGH EDCVRGLAIL SETEFLSCAN DASIRRWQIT GECLEVYYGH TNYIYSISVF
PNCRDFVTTA EDRSLRIWKH GECAQTIRLP AQSIWCCCVL DNGDIVVGAS DGIIRVFTES
EDRTASAEEI KAFEKELSHA TIDSKTGDLG DINAEQLPGR EHLNEPGTRE GQTRLIRDGE
KVEAYQWSVS EGRWIKIGDV VGSSGANQQT SGKVLYEGKE FDYVFSIDVN EGGPSYKLPY
NTSDDPWLTA YNFLQKNDLN PMFLDQVAKF IIDNTKGQML GLGNPSFSDP FTGGGRYVPG
SSGSSNTLPT ADPFTGAGRY VPGSASMGTT MAGVDPFTGN SAYRSAASKT MNIYFPKKEA
VTFDQANPTQ ILGKLKELNG TAPEEKKLTE DDLILLEKIL SLICNSSSEK PTVQQLQILW
KAINCPEDIV FPALDILRLS IKHPSVNENF CNEKEGAQFS SHLINLLNPK GKPANQLLAL
RTFCNCFVGQ AGQKLMMSQR ESLMSHAIEL KSGSNKNIHI ALATLALNYS VCFHKDHNIE
GKAQCLSLIS TILEVVQDLE ATFRLLVALG TLISDDSNAV QLAKSLGVDS QIKKYSSVSE
PAKVSECCRF ILNLL
