PEA15_CRIGR
ID PEA15_CRIGR Reviewed; 130 AA.
AC Q9Z297;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 25-MAY-2022, entry version 109.
DE RecName: Full=Astrocytic phosphoprotein PEA-15;
DE AltName: Full=15 kDa phosphoprotein enriched in astrocytes;
GN Name=PEA15;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF ASP-74.
RC TISSUE=Ovary;
RX PubMed=9852038; DOI=10.1074/jbc.273.51.33897;
RA Ramos J.W., Kojima T.K., Hughes P.E., Fenczik C.A., Ginsberg M.H.;
RT "The death effector domain of PEA-15 is involved in its regulation of
RT integrin activation.";
RL J. Biol. Chem. 273:33897-33900(1998).
RN [2]
RP FUNCTION.
RX PubMed=10982386; DOI=10.1091/mbc.11.9.2863;
RA Ramos J.W., Hughes P.E., Renshaw M.W., Schwartz M.A., Formstecher E.,
RA Chneiweiss H., Ginsberg M.H.;
RT "Death effector domain protein PEA-15 potentiates Ras activation of
RT extracellular signal receptor-activated kinase by an adhesion-independent
RT mechanism.";
RL Mol. Biol. Cell 11:2863-2872(2000).
RN [3]
RP INTERACTION WITH RPS6KA3.
RX PubMed=12796492; DOI=10.1074/jbc.m303988200;
RA Vaidyanathan H., Ramos J.W.;
RT "RSK2 activity is regulated by its interaction with PEA-15.";
RL J. Biol. Chem. 278:32367-32372(2003).
RN [4]
RP FUNCTION, AND INTERACTION WITH MAPK1 AND MAPK3.
RX PubMed=14506247; DOI=10.1074/jbc.m309322200;
RA Chou F.-L., Hill J.M., Hsieh J.-C., Pouyssegur J., Brunet A., Glading A.,
RA Ueberall F., Ramos J.W., Werner M.H., Ginsberg M.H.;
RT "PEA-15 binding to ERK1/2 MAPKs is required for its modulation of integrin
RT activation.";
RL J. Biol. Chem. 278:52587-52597(2003).
RN [5]
RP STRUCTURE BY NMR, INTERACTION WITH MAPK1, AND MUTAGENESIS OF ASN-14;
RP THR-16; GLU-18; ARG-71; ASP-74; ILE-121; LYS-122; LEU-123; LYS-128 AND
RP LYS-129.
RX PubMed=12456656; DOI=10.1093/emboj/cdf641;
RA Hill J.M., Vaidyanathan H., Ramos J.W., Ginsberg M.H., Werner M.H.;
RT "Recognition of ERK MAP kinase by PEA-15 reveals a common docking site
RT within the death domain and death effector domain.";
RL EMBO J. 21:6494-6504(2002).
CC -!- FUNCTION: Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity
CC and apoptosis. Regulates glucose transport by controlling both the
CC content of SLC2A1 glucose transporters on the plasma membrane and the
CC insulin-dependent trafficking of SLC2A4 from the cell interior to the
CC surface (By similarity). Blocks Ras-mediated inhibition of integrin
CC activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3
CC activities by retaining it in the cytoplasm. {ECO:0000250,
CC ECO:0000269|PubMed:10982386, ECO:0000269|PubMed:14506247,
CC ECO:0000269|PubMed:9852038}.
CC -!- SUBUNIT: Interacts with CASP8 and FADD. Transient interaction with PLD1
CC and PLD2 (By similarity). Binds RPS6KA3, MAPK1 and MAPK3. {ECO:0000250,
CC ECO:0000269|PubMed:12456656, ECO:0000269|PubMed:12796492,
CC ECO:0000269|PubMed:14506247}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Note=Associated with microtubules.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by protein kinase C and calcium-calmodulin-
CC dependent protein kinase. These phosphorylation events are modulated by
CC neurotransmitters or hormones (By similarity). {ECO:0000250}.
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DR EMBL; AF080001; AAC97496.1; -; mRNA.
DR RefSeq; NP_001231780.1; NM_001244851.1.
DR PDB; 1N3K; NMR; -; A=1-130.
DR PDB; 4IZ7; X-ray; 1.80 A; B=1-96.
DR PDBsum; 1N3K; -.
DR PDBsum; 4IZ7; -.
DR AlphaFoldDB; Q9Z297; -.
DR BMRB; Q9Z297; -.
DR SMR; Q9Z297; -.
DR STRING; 10029.NP_001231780.1; -.
DR iPTMnet; Q9Z297; -.
DR Ensembl; ENSCGRT00001032217; ENSCGRP00001027969; ENSCGRG00001024826.
DR GeneID; 100736554; -.
DR KEGG; cge:100736554; -.
DR CTD; 8682; -.
DR eggNOG; KOG3573; Eukaryota.
DR GeneTree; ENSGT00390000000230; -.
DR OMA; VEYRTTV; -.
DR OrthoDB; 1425994at2759; -.
DR EvolutionaryTrace; Q9Z297; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
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; IEA:Ensembl.
DR GO; GO:0046325; P:negative regulation of glucose import; IEA:Ensembl.
DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR CDD; cd08338; DED_PEA15; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR001875; DED_dom.
DR InterPro; IPR029546; PEA15_DED.
DR Pfam; PF01335; DED; 1.
DR SMART; SM00031; DED; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR PROSITE; PS50168; DED; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; Cytoplasm; Phosphoprotein; Sugar transport;
KW Transport.
FT CHAIN 1..130
FT /note="Astrocytic phosphoprotein PEA-15"
FT /id="PRO_0000191281"
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:0000250|UniProtKB:Q62048"
FT MOD_RES 104
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q62048"
FT MOD_RES 116
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q62048"
FT MUTAGEN 14
FT /note="N->R: Reduces MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 16
FT /note="T->R: Reduces MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 18
FT /note="E->R: Slightly reduces MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 71
FT /note="R->A: Reduces MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 74
FT /note="D->A: Abolishes MAPK1 binding and the blocking of
FT Ras-mediated inhibition of integrin activation."
FT /evidence="ECO:0000269|PubMed:12456656,
FT ECO:0000269|PubMed:9852038"
FT MUTAGEN 121
FT /note="I->A,R: Abolishes MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 122
FT /note="K->E: Reduces MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 123
FT /note="L->A,R: Abolishes MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 128
FT /note="K->A,E: Abolishes MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT MUTAGEN 129
FT /note="K->A,R: Abolishes MAPK1 binding."
FT /evidence="ECO:0000269|PubMed:12456656"
FT HELIX 1..13
FT /evidence="ECO:0007829|PDB:4IZ7"
FT HELIX 17..27
FT /evidence="ECO:0007829|PDB:4IZ7"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:4IZ7"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:4IZ7"
FT HELIX 42..51
FT /evidence="ECO:0007829|PDB:4IZ7"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:1N3K"
FT HELIX 61..69
FT /evidence="ECO:0007829|PDB:4IZ7"
FT HELIX 73..85
FT /evidence="ECO:0007829|PDB:4IZ7"
FT TURN 86..88
FT /evidence="ECO:0007829|PDB:4IZ7"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:1N3K"
FT TURN 103..105
FT /evidence="ECO:0007829|PDB:1N3K"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:1N3K"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:1N3K"
SQ SEQUENCE 130 AA; 15040 MW; 8D0F93A40B299FB2 CRC64;
MAEYGTLLQD LTNNITLEDL EQLKSACKED IPSEKSEEIT TGSAWFSFLE SHNKLDKDNL
SYIEHIFEIS RRPDLLTMVV DYRTRVLKIS EEDELDTKLT RIPSAKKYKD IIRQPSEEEI
IKLAPPPKKA
