ID PEA15_MOUSE Reviewed; 130 AA.
AC Q62048; Q3U5N7;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 27-MAR-2024, entry version 174.
DE RecName: Full=Astrocytic phosphoprotein PEA-15;
DE AltName: Full=15 kDa phosphoprotein enriched in astrocytes;
GN Name=Pea15; Synonyms=Pea15a;
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 [GENOMIC DNA] (ISOFORM 1), AND PARTIAL PROTEIN
RP SEQUENCE.
RC STRAIN=SWR/J; TISSUE=Astrocyte;
RX PubMed=8662970; DOI=10.1074/jbc.271.25.14800;
RA Estelles A., Yokoyama M., Nothias F., Vincent J.-D., Glowinski J.,
RA Vernier P., Chneiweiss H.;
RT "The major astrocytic phosphoprotein PEA-15 is encoded by two mRNAs
RT conserved on their full length in mouse and human.";
RL J. Biol. Chem. 271:14800-14806(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11210189; DOI=10.1007/s003350010243;
RA Underhill D.A., Vogan K.J., Underhill T.M., Gros P.;
RT "Identification of a novel, alternatively spliced isoform and single
RT nucleotide polymorphisms in the murine Pea-15 gene.";
RL Mamm. Genome 12:172-174(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Cerebellum, and Thymus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Retina;
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 PROTEIN SEQUENCE OF 58-71, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [6]
RP FUNCTION, PHOSPHORYLATION AT SER-104 AND SER-116, AND MUTAGENESIS OF
RP SER-104 AND SER-116.
RX PubMed=10588860; DOI=10.1006/dbio.1999.9510;
RA Estelles A., Charlton C.A., Blau H.M.;
RT "The phosphoprotein protein PEA-15 inhibits Fas- but increases TNF-R1-
RT mediated caspase-8 activity and apoptosis.";
RL Dev. Biol. 216:16-28(1999).
RN [7]
RP INTERACTION WITH PLD1 AND PLD2, AND SUBCELLULAR LOCATION.
RX PubMed=10926929; DOI=10.1074/jbc.m003329200;
RA Zhang Y., Redina O., Altshuller Y.M., Yamazaki M., Ramos J., Chneiweiss H.,
RA Kanaho Y., Frohman M.A.;
RT "Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel
RT protein that interacts with them.";
RL J. Biol. Chem. 275:35224-35232(2000).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND SER-116, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-90 AND SER-116, AND
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).
CC -!- FUNCTION: Blocks Ras-mediated inhibition of integrin activation and
CC modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by
CC retaining it in the cytoplasm. Inhibits both TNFRSF6- and TNFRSF1A-
CC mediated CASP8 activity and apoptosis. Regulates glucose transport by
CC controlling both the content of SLC2A1 glucose transporters on the
CC plasma membrane and the insulin-dependent trafficking of SLC2A4 from
CC the cell interior to the surface (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:10588860}.
CC -!- SUBUNIT: Binds RPS6KA3, MAPK3 and MAPK1. Interacts with CASP8 and FADD
CC (By similarity). Transient interaction with PLD1 and PLD2.
CC {ECO:0000250, ECO:0000269|PubMed:10926929}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10926929}.
CC Note=Associated with microtubules.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q62048-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q62048-2; Sequence=VSP_007736, VSP_007737;
CC -!- TISSUE SPECIFICITY: Predominantly expressed in the brain. Low levels in
CC some peripheral organs.
CC -!- PTM: Phosphorylated by protein kinase C and calcium-calmodulin-
CC dependent protein kinase. These phosphorylation events are modulated by
CC neurotransmitters or hormones. {ECO:0000269|PubMed:10588860}.
CC -!- MISCELLANEOUS: Increases PLD1 and PLD2 levels, possibly by stabilizing
CC the protein.
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DR EMBL; X86694; CAA60387.1; -; Genomic_DNA.
DR EMBL; AK089070; BAC40734.1; -; mRNA.
DR EMBL; AK153141; BAE31752.1; -; mRNA.
DR EMBL; AK153493; BAE32041.1; -; mRNA.
DR EMBL; AK161635; BAE36504.1; -; mRNA.
DR EMBL; AK161977; BAE36662.1; -; mRNA.
DR EMBL; BC038282; AAH38282.1; -; mRNA.
DR CCDS; CCDS15510.1; -. [Q62048-1]
DR CCDS; CCDS87924.1; -. [Q62048-2]
DR PIR; S55385; S55385.
DR RefSeq; NP_001316798.1; NM_001329869.1. [Q62048-1]
DR RefSeq; NP_001316800.1; NM_001329871.1. [Q62048-2]
DR RefSeq; NP_035193.1; NM_011063.3. [Q62048-1]
DR RefSeq; XP_006496765.1; XM_006496702.1. [Q62048-1]
DR PDB; 2LS7; NMR; -; A=1-92.
DR PDBsum; 2LS7; -.
DR AlphaFoldDB; Q62048; -.
DR BMRB; Q62048; -.
DR SMR; Q62048; -.
DR BioGRID; 202103; 5.
DR DIP; DIP-60009N; -.
DR IntAct; Q62048; 1.
DR STRING; 10090.ENSMUSP00000013842; -.
DR iPTMnet; Q62048; -.
DR PhosphoSitePlus; Q62048; -.
DR EPD; Q62048; -.
DR jPOST; Q62048; -.
DR MaxQB; Q62048; -.
DR PaxDb; 10090-ENSMUSP00000013842; -.
DR PeptideAtlas; Q62048; -.
DR ProteomicsDB; 301785; -. [Q62048-1]
DR ProteomicsDB; 301786; -. [Q62048-2]
DR Pumba; Q62048; -.
DR Antibodypedia; 20486; 576 antibodies from 35 providers.
DR DNASU; 18611; -.
DR Ensembl; ENSMUST00000013842.12; ENSMUSP00000013842.6; ENSMUSG00000013698.13. [Q62048-1]
DR Ensembl; ENSMUST00000111247.8; ENSMUSP00000106878.2; ENSMUSG00000013698.13. [Q62048-2]
DR GeneID; 18611; -.
DR KEGG; mmu:18611; -.
DR UCSC; uc007dpy.1; mouse. [Q62048-1]
DR AGR; MGI:104799; -.
DR CTD; 18611; -.
DR MGI; MGI:104799; Pea15a.
DR VEuPathDB; HostDB:ENSMUSG00000013698; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00390000000230; -.
DR HOGENOM; CLU_159419_0_0_1; -.
DR InParanoid; Q62048; -.
DR OMA; IACSRDW; -.
DR OrthoDB; 5384276at2759; -.
DR PhylomeDB; Q62048; -.
DR TreeFam; TF332405; -.
DR Reactome; R-MMU-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 18611; 4 hits in 79 CRISPR screens.
DR ChiTaRS; Pea15a; mouse.
DR PRO; PR:Q62048; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q62048; Protein.
DR Bgee; ENSMUSG00000013698; Expressed in embryonic brain and 266 other cell types or tissues.
DR ExpressionAtlas; Q62048; baseline and differential.
DR Genevisible; Q62048; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005875; C:microtubule associated complex; NAS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005080; F:protein kinase C binding; TAS:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:MGI.
DR GO; GO:0000165; P:MAPK cascade; IEA:InterPro.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:MGI.
DR GO; GO:0046325; P:negative regulation of glucose import; ISS:UniProtKB.
DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:MGI.
DR CDD; cd08338; DED_PEA15; 1.
DR Gene3D; 1.10.533.10; Death Domain, Fas; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR029546; PEA15_DED.
DR PANTHER; PTHR48169:SF1; ASTROCYTIC PHOSPHOPROTEIN PEA-15; 1.
DR PANTHER; PTHR48169; DED DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF01335; DED; 1.
DR SMART; SM00031; DED; 1.
DR SUPFAM; SSF47986; DEATH domain; 1.
DR PROSITE; PS50168; DED; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cytoplasm;
KW Direct protein sequencing; Phosphoprotein; Reference proteome;
KW Sugar transport; Transport.
FT CHAIN 1..130
FT /note="Astrocytic phosphoprotein PEA-15"
FT /id="PRO_0000191283"
FT DOMAIN 3..81
FT /note="DED"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00065"
FT REGION 98..107
FT /note="Microtubule-binding"
FT /evidence="ECO:0000255"
FT REGION 122..129
FT /note="Microtubule-binding"
FT /evidence="ECO:0000255"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15121"
FT MOD_RES 90
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 104
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:10588860,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 116
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:10588860,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT VAR_SEQ 36..57
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11210189"
FT /id="VSP_007736"
FT VAR_SEQ 58
FT /note="D -> N (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11210189"
FT /id="VSP_007737"
FT MUTAGEN 104
FT /note="S->A: Abolishes inhibitory effect on FAS-mediated
FT apoptosis. Does not change effect on TNFRSF1A-mediated
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:10588860"
FT MUTAGEN 116
FT /note="S->A: Abolishes inhibitory effect on FAS-mediated
FT apoptosis. Does not change effect on TNFRSF1A-mediated
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:10588860"
FT HELIX 2..14
FT /evidence="ECO:0007829|PDB:2LS7"
FT HELIX 17..26
FT /evidence="ECO:0007829|PDB:2LS7"
FT TURN 27..30
FT /evidence="ECO:0007829|PDB:2LS7"
FT HELIX 33..37
FT /evidence="ECO:0007829|PDB:2LS7"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:2LS7"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:2LS7"
FT HELIX 61..69
FT /evidence="ECO:0007829|PDB:2LS7"
FT HELIX 73..89
FT /evidence="ECO:0007829|PDB:2LS7"
SQ SEQUENCE 130 AA; 15054 MW; 780F93A40B2834A8 CRC64;
MAEYGTLLQD LTNNITLEDL EQLKSACKED IPSEKSEEIT TGSAWFSFLE SHNKLDKDNL
SYIEHIFEIS RRPDLLTMVV DYRTRVLKIS EEEELDTKLT RIPSAKKYKD IIRQPSEEEI
IKLAPPPKKA
//
