Full text data of PEBP1
PEBP1
(PBP, PEBP)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Phosphatidylethanolamine-binding protein 1; PEBP-1 (HCNPpp; Neuropolypeptide h3; Prostatic-binding protein; Raf kinase inhibitor protein; RKIP; Hippocampal cholinergic neurostimulating peptide; HCNP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Phosphatidylethanolamine-binding protein 1; PEBP-1 (HCNPpp; Neuropolypeptide h3; Prostatic-binding protein; Raf kinase inhibitor protein; RKIP; Hippocampal cholinergic neurostimulating peptide; HCNP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00219446
IPI00219446 Phosphatidylethanolamine-binding protein Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00219446 Phosphatidylethanolamine-binding protein Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P30086
ID PEBP1_HUMAN Reviewed; 187 AA.
AC P30086; B2R4S1;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Phosphatidylethanolamine-binding protein 1;
DE Short=PEBP-1;
DE AltName: Full=HCNPpp;
DE AltName: Full=Neuropolypeptide h3;
DE AltName: Full=Prostatic-binding protein;
DE AltName: Full=Raf kinase inhibitor protein;
DE Short=RKIP;
DE Contains:
DE RecName: Full=Hippocampal cholinergic neurostimulating peptide;
DE Short=HCNP;
GN Name=PEBP1; Synonyms=PBP, PEBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8144042; DOI=10.1016/0378-1119(94)90562-2;
RA Hori N., Keon-Sang C., Murakawa K., Matoba R., Fukushima A., Okubo K.,
RA Matsubara K.;
RT "A human cDNA sequence homologue of bovine phosphatidylethanolamine-
RT binding protein.";
RL Gene 140:293-294(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=7637590; DOI=10.1016/0169-328X(95)00029-R;
RA Tohdoh N., Tojo S., Agui H., Ojika K.;
RT "Sequence homology of rat and human HCNP precursor proteins, bovine
RT phosphatidylethanolamine-binding protein and rat 23-kDa protein
RT associated with the opioid-binding protein.";
RL Brain Res. Mol. Brain Res. 30:381-384(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Hall L.;
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Hypothalamus, and Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [8]
RP PROTEIN SEQUENCE OF 8-39; 48-77; 81-113; 120-141 AND 162-187, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-187.
RC TISSUE=Brain;
RX PubMed=7807553; DOI=10.1007/BF00160411;
RA Seddiqi N., Bollengier F., Alliel P.M., Perin J.-P., Bonnet F.,
RA Bucquoy S., Jolles P., Schoentgen F.;
RT "Amino acid sequence of the Homo sapiens brain 21-23-kDa protein
RT (neuropolypeptide h3), comparison with its counterparts from Rattus
RT norvegicus and Bos taurus species, and expression of its mRNA in
RT different tissues.";
RL J. Mol. Evol. 39:655-660(1994).
RN [10]
RP CHARACTERIZATION OF HCNP.
RX PubMed=10622376; DOI=10.1016/S0301-0082(99)00021-0;
RA Ojika K., Mitake S., Tohdoh N., Appel S.H., Otsuka Y., Katada E.,
RA Matsukawa N.;
RT "Hippocampal cholinergic neurostimulating peptides (HCNP).";
RL Prog. Neurobiol. 60:37-83(2000).
RN [11]
RP INTERACTION WITH RAF-1.
RX PubMed=10490027; DOI=10.1038/43686;
RA Yeung K., Seitz T., Li S., Janosch P., McFerran B., Kaiser C., Fee F.,
RA Katsanakis K.D., Rose D.W., Mischak H., Sedivy J.M., Kolch W.;
RT "Suppression of Raf-1 kinase activity and MAP kinase signalling by
RT RKIP.";
RL Nature 401:173-177(1999).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH RAF1.
RX PubMed=18294816; DOI=10.1016/j.cellsig.2008.01.012;
RA Rath O., Park S., Tang H.H., Banfield M.J., Brady R.L., Lee Y.C.,
RA Dignam J.D., Sedivy J.M., Kolch W., Yeung K.C.;
RT "The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to
RT the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated
RT activated phosphorylation of MEK.";
RL Cell. Signal. 20:935-941(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42 AND SER-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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.,
RA Buerckstuemmer T., 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 [18]
RP INTERACTION WITH ALOX15.
RX PubMed=21831839; DOI=10.1073/pnas.1018075108;
RA Zhao J., O'Donnell V.B., Balzar S., St Croix C.M., Trudeau J.B.,
RA Wenzel S.E.;
RT "15-Lipoxygenase 1 interacts with phosphatidylethanolamine-binding
RT protein to regulate MAPK signaling in human airway epithelial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:14246-14251(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
RX PubMed=9782050; DOI=10.1016/S0969-2126(98)00125-7;
RA Banfield M.J., Barker J.J., Perry A.C., Brady R.L.;
RT "Function from structure? The crystal structure of human
RT phosphatidylethanolamine-binding protein suggests a role in membrane
RT signal transduction.";
RL Structure 6:1245-1254(1998).
CC -!- FUNCTION: Binds ATP, opioids and phosphatidylethanolamine. Has
CC lower affinity for phosphatidylinositol and phosphatidylcholine.
CC Serine protease inhibitor which inhibits thrombin, neuropsin and
CC chymotrypsin but not trypsin, tissue type plasminogen activator
CC and elastase (By similarity). Inhibits the kinase activity of RAF1
CC by inhibiting its activation and by dissociating the RAF1/MEK
CC complex and acting as a competitive inhibitor of MEK
CC phosphorylation.
CC -!- FUNCTION: HCNP may be involved in the function of the presynaptic
CC cholinergic neurons of the central nervous system. HCNP increases
CC the production of choline acetyltransferase but not
CC acetylcholinesterase. Seems to be mediated by a specific receptor
CC (By similarity).
CC -!- SUBUNIT: Has a tendency to form dimers by disulfide cross-linking
CC (By similarity). Interacts with RAF1 and this interaction is
CC enhanced if RAF1 is phosphorylated on residues 'Ser-338', 'Ser-
CC 339', 'Tyr-340' and 'Tyr-341'. Interacts with ALOX15; in response
CC to IL13/interleukin-13, prevents the interaction of PEBP1 with
CC RAF1 to activate the ERK signaling cascade.
CC -!- INTERACTION:
CC P04049:RAF1; NbExp=7; IntAct=EBI-716384, EBI-365996;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- SIMILARITY: Belongs to the phosphatidylethanolamine-binding
CC protein family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PEBP1ID44021ch12q24.html";
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DR EMBL; D16111; BAA03684.1; -; mRNA.
DR EMBL; X75252; CAA53031.1; -; mRNA.
DR EMBL; X85033; CAA59404.1; -; mRNA.
DR EMBL; AK311927; BAG34868.1; -; mRNA.
DR EMBL; CH471054; EAW98122.1; -; Genomic_DNA.
DR EMBL; BC008714; AAH08714.1; -; mRNA.
DR EMBL; BC017396; AAH17396.1; -; mRNA.
DR EMBL; BC031102; AAH31102.1; -; mRNA.
DR EMBL; S76773; AAD14234.1; -; mRNA.
DR PIR; I53745; I53745.
DR RefSeq; NP_002558.1; NM_002567.2.
DR UniGene; Hs.433863; -.
DR PDB; 1BD9; X-ray; 2.05 A; A/B=1-187.
DR PDB; 1BEH; X-ray; 1.75 A; A/B=1-187.
DR PDB; 2L7W; NMR; -; A=1-187.
DR PDB; 2QYQ; X-ray; 1.95 A; A=1-187.
DR PDBsum; 1BD9; -.
DR PDBsum; 1BEH; -.
DR PDBsum; 2L7W; -.
DR PDBsum; 2QYQ; -.
DR ProteinModelPortal; P30086; -.
DR SMR; P30086; 3-186.
DR DIP; DIP-44269N; -.
DR IntAct; P30086; 8.
DR MINT; MINT-5002544; -.
DR STRING; 9606.ENSP00000261313; -.
DR MEROPS; I51.002; -.
DR PhosphoSite; P30086; -.
DR DMDM; 1352726; -.
DR DOSAC-COBS-2DPAGE; P30086; -.
DR OGP; P30086; -.
DR REPRODUCTION-2DPAGE; IPI00219446; -.
DR REPRODUCTION-2DPAGE; P30086; -.
DR SWISS-2DPAGE; P30086; -.
DR UCD-2DPAGE; P30086; -.
DR PaxDb; P30086; -.
DR PeptideAtlas; P30086; -.
DR PRIDE; P30086; -.
DR Ensembl; ENST00000261313; ENSP00000261313; ENSG00000089220.
DR GeneID; 5037; -.
DR KEGG; hsa:5037; -.
DR UCSC; uc001twu.1; human.
DR CTD; 5037; -.
DR GeneCards; GC12P118573; -.
DR HGNC; HGNC:8630; PEBP1.
DR HPA; CAB009906; -.
DR HPA; CAB013493; -.
DR HPA; HPA008819; -.
DR MIM; 604591; gene.
DR neXtProt; NX_P30086; -.
DR PharmGKB; PA32968; -.
DR eggNOG; COG1881; -.
DR HOGENOM; HOG000237655; -.
DR HOVERGEN; HBG008165; -.
DR InParanoid; P30086; -.
DR OMA; NDVSSGC; -.
DR OrthoDB; EOG7P02K3; -.
DR PhylomeDB; P30086; -.
DR SignaLink; P30086; -.
DR ChiTaRS; PEBP1; human.
DR EvolutionaryTrace; P30086; -.
DR GeneWiki; Phosphatidylethanolamine_binding_protein_1; -.
DR GenomeRNAi; 5037; -.
DR NextBio; 19408; -.
DR PRO; PR:P30086; -.
DR ArrayExpress; P30086; -.
DR Bgee; P30086; -.
DR CleanEx; HS_PEBP1; -.
DR Genevestigator; P30086; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; TAS:ProtInc.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR Gene3D; 3.90.280.10; -; 1.
DR InterPro; IPR001858; Phosphotidylethanolamine-bd_CS.
DR InterPro; IPR008914; PtdEtn-bd_prot_PEBP.
DR Pfam; PF01161; PBP; 1.
DR SUPFAM; SSF49777; SSF49777; 1.
DR PROSITE; PS01220; PBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Lipid-binding;
KW Nucleotide-binding; Phosphoprotein; Protease inhibitor;
KW Reference proteome; Serine protease inhibitor.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 187 Phosphatidylethanolamine-binding protein
FT 1.
FT /FTId=PRO_0000023271.
FT PEPTIDE 2 12 Hippocampal cholinergic neurostimulating
FT peptide.
FT /FTId=PRO_0000023272.
FT REGION 93 134 Interaction with RAF1.
FT MOD_RES 42 42 Phosphothreonine.
FT MOD_RES 52 52 Phosphoserine.
FT VARIANT 9 9 S -> N.
FT /FTId=VAR_006048.
FT CONFLICT 8 8 W -> K (in Ref. 2).
FT HELIX 5 7
FT TURN 8 12
FT HELIX 14 16
FT STRAND 22 24
FT STRAND 26 28
FT STRAND 32 34
FT TURN 43 46
FT STRAND 51 54
FT STRAND 62 71
FT STRAND 76 78
FT STRAND 84 93
FT HELIX 97 99
FT STRAND 100 104
FT STRAND 118 129
FT STRAND 140 142
FT TURN 144 146
FT HELIX 151 157
FT STRAND 164 171
FT HELIX 177 183
FT TURN 184 186
SQ SEQUENCE 187 AA; 21057 MW; F1E9F17E2CD11C36 CRC64;
MPVDLSKWSG PLSLQEVDEQ PQHPLHVTYA GAAVDELGKV LTPTQVKNRP TSISWDGLDS
GKLYTLVLTD PDAPSRKDPK YREWHHFLVV NMKGNDISSG TVLSDYVGSG PPKGTGLHRY
VWLVYEQDRP LKCDEPILSN RSGDHRGKFK VASFRKKYEL RAPVAGTCYQ AEWDDYVPKL
YEQLSGK
//
ID PEBP1_HUMAN Reviewed; 187 AA.
AC P30086; B2R4S1;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Phosphatidylethanolamine-binding protein 1;
DE Short=PEBP-1;
DE AltName: Full=HCNPpp;
DE AltName: Full=Neuropolypeptide h3;
DE AltName: Full=Prostatic-binding protein;
DE AltName: Full=Raf kinase inhibitor protein;
DE Short=RKIP;
DE Contains:
DE RecName: Full=Hippocampal cholinergic neurostimulating peptide;
DE Short=HCNP;
GN Name=PEBP1; Synonyms=PBP, PEBP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8144042; DOI=10.1016/0378-1119(94)90562-2;
RA Hori N., Keon-Sang C., Murakawa K., Matoba R., Fukushima A., Okubo K.,
RA Matsubara K.;
RT "A human cDNA sequence homologue of bovine phosphatidylethanolamine-
RT binding protein.";
RL Gene 140:293-294(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Placenta;
RX PubMed=7637590; DOI=10.1016/0169-328X(95)00029-R;
RA Tohdoh N., Tojo S., Agui H., Ojika K.;
RT "Sequence homology of rat and human HCNP precursor proteins, bovine
RT phosphatidylethanolamine-binding protein and rat 23-kDa protein
RT associated with the opioid-binding protein.";
RL Brain Res. Mol. Brain Res. 30:381-384(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Hall L.;
RL Submitted (FEB-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, Hypothalamus, and Lung;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-11.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [8]
RP PROTEIN SEQUENCE OF 8-39; 48-77; 81-113; 120-141 AND 162-187, AND MASS
RP SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 48-187.
RC TISSUE=Brain;
RX PubMed=7807553; DOI=10.1007/BF00160411;
RA Seddiqi N., Bollengier F., Alliel P.M., Perin J.-P., Bonnet F.,
RA Bucquoy S., Jolles P., Schoentgen F.;
RT "Amino acid sequence of the Homo sapiens brain 21-23-kDa protein
RT (neuropolypeptide h3), comparison with its counterparts from Rattus
RT norvegicus and Bos taurus species, and expression of its mRNA in
RT different tissues.";
RL J. Mol. Evol. 39:655-660(1994).
RN [10]
RP CHARACTERIZATION OF HCNP.
RX PubMed=10622376; DOI=10.1016/S0301-0082(99)00021-0;
RA Ojika K., Mitake S., Tohdoh N., Appel S.H., Otsuka Y., Katada E.,
RA Matsukawa N.;
RT "Hippocampal cholinergic neurostimulating peptides (HCNP).";
RL Prog. Neurobiol. 60:37-83(2000).
RN [11]
RP INTERACTION WITH RAF-1.
RX PubMed=10490027; DOI=10.1038/43686;
RA Yeung K., Seitz T., Li S., Janosch P., McFerran B., Kaiser C., Fee F.,
RA Katsanakis K.D., Rose D.W., Mischak H., Sedivy J.M., Kolch W.;
RT "Suppression of Raf-1 kinase activity and MAP kinase signalling by
RT RKIP.";
RL Nature 401:173-177(1999).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH RAF1.
RX PubMed=18294816; DOI=10.1016/j.cellsig.2008.01.012;
RA Rath O., Park S., Tang H.H., Banfield M.J., Brady R.L., Lee Y.C.,
RA Dignam J.D., Sedivy J.M., Kolch W., Yeung K.C.;
RT "The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to
RT the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated
RT activated phosphorylation of MEK.";
RL Cell. Signal. 20:935-941(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42 AND SER-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
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.,
RA Buerckstuemmer T., 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 [18]
RP INTERACTION WITH ALOX15.
RX PubMed=21831839; DOI=10.1073/pnas.1018075108;
RA Zhao J., O'Donnell V.B., Balzar S., St Croix C.M., Trudeau J.B.,
RA Wenzel S.E.;
RT "15-Lipoxygenase 1 interacts with phosphatidylethanolamine-binding
RT protein to regulate MAPK signaling in human airway epithelial cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:14246-14251(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
RX PubMed=9782050; DOI=10.1016/S0969-2126(98)00125-7;
RA Banfield M.J., Barker J.J., Perry A.C., Brady R.L.;
RT "Function from structure? The crystal structure of human
RT phosphatidylethanolamine-binding protein suggests a role in membrane
RT signal transduction.";
RL Structure 6:1245-1254(1998).
CC -!- FUNCTION: Binds ATP, opioids and phosphatidylethanolamine. Has
CC lower affinity for phosphatidylinositol and phosphatidylcholine.
CC Serine protease inhibitor which inhibits thrombin, neuropsin and
CC chymotrypsin but not trypsin, tissue type plasminogen activator
CC and elastase (By similarity). Inhibits the kinase activity of RAF1
CC by inhibiting its activation and by dissociating the RAF1/MEK
CC complex and acting as a competitive inhibitor of MEK
CC phosphorylation.
CC -!- FUNCTION: HCNP may be involved in the function of the presynaptic
CC cholinergic neurons of the central nervous system. HCNP increases
CC the production of choline acetyltransferase but not
CC acetylcholinesterase. Seems to be mediated by a specific receptor
CC (By similarity).
CC -!- SUBUNIT: Has a tendency to form dimers by disulfide cross-linking
CC (By similarity). Interacts with RAF1 and this interaction is
CC enhanced if RAF1 is phosphorylated on residues 'Ser-338', 'Ser-
CC 339', 'Tyr-340' and 'Tyr-341'. Interacts with ALOX15; in response
CC to IL13/interleukin-13, prevents the interaction of PEBP1 with
CC RAF1 to activate the ERK signaling cascade.
CC -!- INTERACTION:
CC P04049:RAF1; NbExp=7; IntAct=EBI-716384, EBI-365996;
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity).
CC -!- SIMILARITY: Belongs to the phosphatidylethanolamine-binding
CC protein family.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PEBP1ID44021ch12q24.html";
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DR EMBL; D16111; BAA03684.1; -; mRNA.
DR EMBL; X75252; CAA53031.1; -; mRNA.
DR EMBL; X85033; CAA59404.1; -; mRNA.
DR EMBL; AK311927; BAG34868.1; -; mRNA.
DR EMBL; CH471054; EAW98122.1; -; Genomic_DNA.
DR EMBL; BC008714; AAH08714.1; -; mRNA.
DR EMBL; BC017396; AAH17396.1; -; mRNA.
DR EMBL; BC031102; AAH31102.1; -; mRNA.
DR EMBL; S76773; AAD14234.1; -; mRNA.
DR PIR; I53745; I53745.
DR RefSeq; NP_002558.1; NM_002567.2.
DR UniGene; Hs.433863; -.
DR PDB; 1BD9; X-ray; 2.05 A; A/B=1-187.
DR PDB; 1BEH; X-ray; 1.75 A; A/B=1-187.
DR PDB; 2L7W; NMR; -; A=1-187.
DR PDB; 2QYQ; X-ray; 1.95 A; A=1-187.
DR PDBsum; 1BD9; -.
DR PDBsum; 1BEH; -.
DR PDBsum; 2L7W; -.
DR PDBsum; 2QYQ; -.
DR ProteinModelPortal; P30086; -.
DR SMR; P30086; 3-186.
DR DIP; DIP-44269N; -.
DR IntAct; P30086; 8.
DR MINT; MINT-5002544; -.
DR STRING; 9606.ENSP00000261313; -.
DR MEROPS; I51.002; -.
DR PhosphoSite; P30086; -.
DR DMDM; 1352726; -.
DR DOSAC-COBS-2DPAGE; P30086; -.
DR OGP; P30086; -.
DR REPRODUCTION-2DPAGE; IPI00219446; -.
DR REPRODUCTION-2DPAGE; P30086; -.
DR SWISS-2DPAGE; P30086; -.
DR UCD-2DPAGE; P30086; -.
DR PaxDb; P30086; -.
DR PeptideAtlas; P30086; -.
DR PRIDE; P30086; -.
DR Ensembl; ENST00000261313; ENSP00000261313; ENSG00000089220.
DR GeneID; 5037; -.
DR KEGG; hsa:5037; -.
DR UCSC; uc001twu.1; human.
DR CTD; 5037; -.
DR GeneCards; GC12P118573; -.
DR HGNC; HGNC:8630; PEBP1.
DR HPA; CAB009906; -.
DR HPA; CAB013493; -.
DR HPA; HPA008819; -.
DR MIM; 604591; gene.
DR neXtProt; NX_P30086; -.
DR PharmGKB; PA32968; -.
DR eggNOG; COG1881; -.
DR HOGENOM; HOG000237655; -.
DR HOVERGEN; HBG008165; -.
DR InParanoid; P30086; -.
DR OMA; NDVSSGC; -.
DR OrthoDB; EOG7P02K3; -.
DR PhylomeDB; P30086; -.
DR SignaLink; P30086; -.
DR ChiTaRS; PEBP1; human.
DR EvolutionaryTrace; P30086; -.
DR GeneWiki; Phosphatidylethanolamine_binding_protein_1; -.
DR GenomeRNAi; 5037; -.
DR NextBio; 19408; -.
DR PRO; PR:P30086; -.
DR ArrayExpress; P30086; -.
DR Bgee; P30086; -.
DR CleanEx; HS_PEBP1; -.
DR Genevestigator; P30086; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; TAS:ProtInc.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR Gene3D; 3.90.280.10; -; 1.
DR InterPro; IPR001858; Phosphotidylethanolamine-bd_CS.
DR InterPro; IPR008914; PtdEtn-bd_prot_PEBP.
DR Pfam; PF01161; PBP; 1.
DR SUPFAM; SSF49777; SSF49777; 1.
DR PROSITE; PS01220; PBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Disulfide bond; Lipid-binding;
KW Nucleotide-binding; Phosphoprotein; Protease inhibitor;
KW Reference proteome; Serine protease inhibitor.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 187 Phosphatidylethanolamine-binding protein
FT 1.
FT /FTId=PRO_0000023271.
FT PEPTIDE 2 12 Hippocampal cholinergic neurostimulating
FT peptide.
FT /FTId=PRO_0000023272.
FT REGION 93 134 Interaction with RAF1.
FT MOD_RES 42 42 Phosphothreonine.
FT MOD_RES 52 52 Phosphoserine.
FT VARIANT 9 9 S -> N.
FT /FTId=VAR_006048.
FT CONFLICT 8 8 W -> K (in Ref. 2).
FT HELIX 5 7
FT TURN 8 12
FT HELIX 14 16
FT STRAND 22 24
FT STRAND 26 28
FT STRAND 32 34
FT TURN 43 46
FT STRAND 51 54
FT STRAND 62 71
FT STRAND 76 78
FT STRAND 84 93
FT HELIX 97 99
FT STRAND 100 104
FT STRAND 118 129
FT STRAND 140 142
FT TURN 144 146
FT HELIX 151 157
FT STRAND 164 171
FT HELIX 177 183
FT TURN 184 186
SQ SEQUENCE 187 AA; 21057 MW; F1E9F17E2CD11C36 CRC64;
MPVDLSKWSG PLSLQEVDEQ PQHPLHVTYA GAAVDELGKV LTPTQVKNRP TSISWDGLDS
GKLYTLVLTD PDAPSRKDPK YREWHHFLVV NMKGNDISSG TVLSDYVGSG PPKGTGLHRY
VWLVYEQDRP LKCDEPILSN RSGDHRGKFK VASFRKKYEL RAPVAGTCYQ AEWDDYVPKL
YEQLSGK
//
MIM
604591
*RECORD*
*FIELD* NO
604591
*FIELD* TI
*604591 PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN 1; PEBP1
;;PBP;;
RAF KINASE INHIBITOR PROTEIN; RKIP;;
read moreHIPPOCAMPAL CHOLINERGIC NEUROSTIMULATING PEPTIDE PRECURSOR PROTEIN;;
HCNP PRECURSOR PROTEIN
*FIELD* TX
CLONING
Yeung et al. (1999) used a yeast 2-hybrid screen to identify RAF1
(164760)-interacting proteins. They identified a protein, designated
RKIP (RAF kinase inhibitor protein), that inhibits the phosphorylation
and activation of MEK (176872) by RAF1. MEK is a kinase that activates
the extracellular signal-regulated kinases (ERKs; see 176872). This
kinase cascade controls the proliferation and differentiation of
different cell types. RKIP is identical to the
phosphatidylethanolamine-binding protein (PBP) with a relative molecular
mass of 23 kD.
Seddiqi et al. (1994) determined that the human RKIP cDNA encodes a
protein of 186 amino acids, the sequence of which is 95% identical to
the bovine 21- to 23-kD protein. The rat protein shows 85.5% identity
with the human protein. Schoentgen and Jolles (1995) demonstrated that
the bovine protein was highly expressed in the brain and associated with
cytosolic proteins and small GTP-binding proteins. Multiple tissue
Northern blots revealed the presence of a single mRNA in the different
tissues of each species; a single band of 1.8 kb was identified in
human, 1.45 kb in mouse, and 1.2 kb in rat tissues. The mRNA is
particularly highly expressed in rat and mouse testis, where the level
was 30 times higher than that in the brain. The mRNA was not observed in
human testis by Northern blot analysis, and was detected only by PCR.
Tohdoh et al. (1995) cloned phosphatidylethanolamine-binding protein,
which they called the hippocampal cholinergic neurostimulating peptide,
or HCNP, precursor protein. Hori et al. (1994) sequenced about 1,000
3-prime-directed cDNA clones from the human HepG2 cell line and found
that 1 of the cDNAs encoded the human homolog of bovine PBP. They found
that the cDNA consists of 1,434 nucleotides with a 91-nucleotide 5-prime
noncoding sequence followed by a 187-amino acid coding region and a
779-nucleotide 3-prime noncoding sequence. Moore et al. (1996) cloned
the brain phosphatidylethanolamine-binding protein and found it to be
identical in sequence to the protein cloned by Hori et al. (1994). Moore
et al. (1996) used polyclonal antibodies in immunohistochemical studies
in brain tissue and found that PBP is expressed strongly in the cell
bodies of oligodendrocytes but only weakly elsewhere. Schwann cells and
spinal nerve roots showed intense cytoplasmic PBP immunoreactivity.
GENE FUNCTION
Yeung et al. (1999) demonstrated that, in vitro, RKIP binds to RAF1,
MEK, and ERK, but not to RAS (190020). RKIP coimmunoprecipitates with
RAF1 and MEK from cell lysates and colocalizes with RAF1 when examined
by confocal microscopy. RKIP is not a substrate for RAF1 or MEK but
competitively disrupts the interaction between these kinases. RKIP
overexpression interferes with the activation of MEK and ERK, induction
of AP1 (165160)-dependent reporter genes, and transformation elicited by
an oncogenically activated RAF1 kinase. Downregulation of endogenous
RKIP by expression of antisense RNA or antibody microinjection induces
the activation of MEK-, ERK-, and AP1-dependent transcription. Yeung et
al. (1999) concluded that RKIP represents a class of protein kinase
inhibitor protein that regulates the activity of the Raf/MEK/ERK module.
Hengst et al. (2001) determined that the residual thrombin (176930)
inhibitory activity in the brains of nexin (PI7; 177010)-null mice was
due to Pbp. By coimmunoprecipitation and mobility shift assays, they
demonstrated direct binding between recombinant human thrombin and Pbp
in mouse brain lysates. By in vitro assay of PBP against several serine
proteases, they determined that PBP is a competitive inhibitor of
thrombin and chymotrypsin (see CTRB1, 118890) but not of trypsin, tissue
plasminogen activator, or pancreatic elastase. Hengst et al. (2001) also
detected Pbp immunostaining on the extracellular surface of transfected
cells as well as in the conditioned medium.
Lorenz et al. (2003) demonstrated that RKIP is a physiologic inhibitor
of GRK2 (109635). After stimulation of G protein-coupled receptors, RKIP
dissociates from its known target, RAF1, to associate with GRK2 and
block its activity. This switch is triggered by a protein kinase C (PKC;
see 176960)-dependent phosphorylation of RKIP on serine-153. Lorenz et
al. (2003) concluded that their data delineate a new principle in signal
transduction: by activating PKC, the incoming receptor signal is
enhanced both by removing an inhibitor from RAF1 and by blocking
receptor internalization. A physiologic role for this mechanism is shown
in cardiomyocytes in which the downregulation of RKIP restrains
beta-adrenergic signaling and contractile activity.
Chatterjee et al. (2004) found that RKIP expression was rapidly
upregulated during induction of chemotherapy-triggered apoptosis in
human prostate and breast cancer cell lines, and maximal RKIP expression
correlated perfectly with the onset of apoptosis. However, in cells
resistant to DNA-damaging agents, treatment with drugs did not
upregulate RKIP expression. Ectopic expression of RKIP sensitized
resistant cells to undergo apoptosis, and downregulation of RKIP with an
RKIP antisense and small interfering RNA conferred resistance to
anticancer drug-induced apoptosis. RKIP induced apoptosis by both
antagonizing RAF and NF-kappa-B (see 164011) signaling.
Trakul et al. (2005) found that Rkip inhibited activation of Raf1 in
cultured embryonic rat hippocampal cells by blocking phosphorylation of
the Raf1 kinase domain by p21-activated kinase (see 602590) and Src
family kinases (see 190090). Rkip depletion increased the amplitude and
the sensitivity of Mapk and DNA synthesis to EGF (131530) stimulation.
Eves et al. (2006) found that RKIP associated with centrosomes and
kinetochores and regulated the spindle checkpoint in mammalian cells,
including human cell lines. RKIP depletion decreased the mitotic index,
the number of metaphase cells, traversal times from nuclear envelope
breakdown to anaphase, and an override of mitotic checkpoints induced by
spindle poisons. RAF1 depletion or MEK inhibition reversed the reduction
in the mitotic index, whereas hyperactivation of RAF mimicked the
RKIP-depletion phenotype. RKIP depletion or RAF hyperactivation reduced
kinetochore localization and kinase activity of Aurora B (604970), a
regulator of the spindle checkpoint. Eves et al. (2006) concluded that
RKIP regulates Aurora kinase B and the spindle checkpoint via the
RAF1/MEK/ERK cascade and that small changes in the MAPK pathway can
profoundly impact the fidelity of the cell cycle.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PBP
gene to chromosome 12 (TMAP RH26435).
*FIELD* RF
1. Chatterjee, D.; Bai, Y.; Wang, Z.; Beach, S.; Mott, S.; Roy, R.;
Braastad, C.; Sun, Y.; Mukhopadhyay, A.; Aggarwal, B. B.; Darnowski,
J.; Pantazis, P.; Wyche, J.; Fu, Z.; Kitagwa, Y.; Keller, E. T.; Sedivy,
J. M.; Yeung, K. C.: RKIP sensitizes prostate and breast cancer cells
to drug-induced apoptosis. J. Biol. Chem. 279: 17515-17523, 2004.
2. Eves, E. M.; Shapiro, P.; Naik, K.; Klein, U. R.; Trakul, N.; Rosner,
M. R.: Raf kinase inhibitory protein regulates Aurora B kinase and
the spindle checkpoint. Molec. Cell 23: 561-574, 2006.
3. Hengst, U.; Albrecht, H.; Hess, D.; Monard, D.: The phosphatidylethanolamine-binding
protein is the prototype of a novel family of serine protease inhibitors. J.
Biol. Chem. 276: 535-540, 2001.
4. Hori, N.; Chae, K.; Murakawa, K.; Matoba, R.; Fukushima, A.; Okubo,
K.; Matsubara, K.: A human cDNA sequence homologue of bovine phosphatidylethanolamine-binding
protein. Gene 140: 293-294, 1994.
5. Lorenz, K.; Lohse, M. J.; Quitterer, U.: Protein kinase C switches
the Raf kinase inhibitor from Raf-1 to GRK-2. Nature 426: 574-579,
2003.
6. Moore, C.; Perry, A. C. F.; Love, S.; Hall, L.: Sequence analysis
and immunolocalisation of phosphatidylethanolamine binding protein
(PBP) in human brain tissue. Molec. Brain Res. 37: 74-78, 1996.
7. Schoentgen, F.; Jolles, P.: From structure to function: possible
biological roles of a new widespread protein family binding hydrophobic
ligands and displaying a nucleotide binding site. FEBS Lett. 369:
22-26, 1995.
8. Seddiqi, N.; Bollengier, F.; Alliel, P. M.; Perin, J.-P.; Bonnet,
F.; Bucquoy, S.; Jolles, P.; Schoentgen, F.: Amino acid sequence
of the Homo sapiens brain 21-23-kDa protein (neuropolypeptide h3),
comparison with its counterparts from Rattus norvegicus and Bos taurus
species, and expression of its mRNA in different tissues. J. Molec.
Evol. 39: 655-660, 1994.
9. Tohdoh, N.; Tojo, S.; Agui, H.; Ojika, K.: Sequence homology of
rat and human HCNP precursor proteins, bovine phosphatidylethanolamine-binding
protein and rat 23-kDa protein associated with the opioid-binding
protein. Molec. Brain Res. 30: 381-384, 1995.
10. Trakul, N.; Menard, R. E.; Schade, G. R.; Qian, Z.; Rosner, M.
R.: Raf kinase inhibitory protein regulates Raf-1 but not B-Raf kinase
activation. J. Biol. Chem. 280: 24931-24940, 2005.
11. Yeung, K.; Seitz, T.; Li, S.; Janosch, P.; McFerran, B.; Kaiser,
C.; Fee, F.; Katsanakis, K. D.; Rose, D. W.; Mischak, H.; Sedivy,
J. M.; Kolch, W.: Suppression of Raf-1 kinase activity and MAP kinase
signalling by RKIP. Nature 401: 173-177, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 10/18/2006
Ada Hamosh - updated: 12/30/2003
Patricia A. Hartz - updated: 7/9/2002
Ada Hamosh - updated: 2/24/2000
*FIELD* CD
Ada Hamosh: 2/22/2000
*FIELD* ED
mgross: 08/14/2008
carol: 10/31/2006
terry: 10/18/2006
alopez: 12/31/2003
terry: 12/30/2003
carol: 7/9/2002
terry: 10/4/2000
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alopez: 3/2/2000
terry: 2/24/2000
alopez: 2/23/2000
alopez: 2/22/2000
*RECORD*
*FIELD* NO
604591
*FIELD* TI
*604591 PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN 1; PEBP1
;;PBP;;
RAF KINASE INHIBITOR PROTEIN; RKIP;;
read moreHIPPOCAMPAL CHOLINERGIC NEUROSTIMULATING PEPTIDE PRECURSOR PROTEIN;;
HCNP PRECURSOR PROTEIN
*FIELD* TX
CLONING
Yeung et al. (1999) used a yeast 2-hybrid screen to identify RAF1
(164760)-interacting proteins. They identified a protein, designated
RKIP (RAF kinase inhibitor protein), that inhibits the phosphorylation
and activation of MEK (176872) by RAF1. MEK is a kinase that activates
the extracellular signal-regulated kinases (ERKs; see 176872). This
kinase cascade controls the proliferation and differentiation of
different cell types. RKIP is identical to the
phosphatidylethanolamine-binding protein (PBP) with a relative molecular
mass of 23 kD.
Seddiqi et al. (1994) determined that the human RKIP cDNA encodes a
protein of 186 amino acids, the sequence of which is 95% identical to
the bovine 21- to 23-kD protein. The rat protein shows 85.5% identity
with the human protein. Schoentgen and Jolles (1995) demonstrated that
the bovine protein was highly expressed in the brain and associated with
cytosolic proteins and small GTP-binding proteins. Multiple tissue
Northern blots revealed the presence of a single mRNA in the different
tissues of each species; a single band of 1.8 kb was identified in
human, 1.45 kb in mouse, and 1.2 kb in rat tissues. The mRNA is
particularly highly expressed in rat and mouse testis, where the level
was 30 times higher than that in the brain. The mRNA was not observed in
human testis by Northern blot analysis, and was detected only by PCR.
Tohdoh et al. (1995) cloned phosphatidylethanolamine-binding protein,
which they called the hippocampal cholinergic neurostimulating peptide,
or HCNP, precursor protein. Hori et al. (1994) sequenced about 1,000
3-prime-directed cDNA clones from the human HepG2 cell line and found
that 1 of the cDNAs encoded the human homolog of bovine PBP. They found
that the cDNA consists of 1,434 nucleotides with a 91-nucleotide 5-prime
noncoding sequence followed by a 187-amino acid coding region and a
779-nucleotide 3-prime noncoding sequence. Moore et al. (1996) cloned
the brain phosphatidylethanolamine-binding protein and found it to be
identical in sequence to the protein cloned by Hori et al. (1994). Moore
et al. (1996) used polyclonal antibodies in immunohistochemical studies
in brain tissue and found that PBP is expressed strongly in the cell
bodies of oligodendrocytes but only weakly elsewhere. Schwann cells and
spinal nerve roots showed intense cytoplasmic PBP immunoreactivity.
GENE FUNCTION
Yeung et al. (1999) demonstrated that, in vitro, RKIP binds to RAF1,
MEK, and ERK, but not to RAS (190020). RKIP coimmunoprecipitates with
RAF1 and MEK from cell lysates and colocalizes with RAF1 when examined
by confocal microscopy. RKIP is not a substrate for RAF1 or MEK but
competitively disrupts the interaction between these kinases. RKIP
overexpression interferes with the activation of MEK and ERK, induction
of AP1 (165160)-dependent reporter genes, and transformation elicited by
an oncogenically activated RAF1 kinase. Downregulation of endogenous
RKIP by expression of antisense RNA or antibody microinjection induces
the activation of MEK-, ERK-, and AP1-dependent transcription. Yeung et
al. (1999) concluded that RKIP represents a class of protein kinase
inhibitor protein that regulates the activity of the Raf/MEK/ERK module.
Hengst et al. (2001) determined that the residual thrombin (176930)
inhibitory activity in the brains of nexin (PI7; 177010)-null mice was
due to Pbp. By coimmunoprecipitation and mobility shift assays, they
demonstrated direct binding between recombinant human thrombin and Pbp
in mouse brain lysates. By in vitro assay of PBP against several serine
proteases, they determined that PBP is a competitive inhibitor of
thrombin and chymotrypsin (see CTRB1, 118890) but not of trypsin, tissue
plasminogen activator, or pancreatic elastase. Hengst et al. (2001) also
detected Pbp immunostaining on the extracellular surface of transfected
cells as well as in the conditioned medium.
Lorenz et al. (2003) demonstrated that RKIP is a physiologic inhibitor
of GRK2 (109635). After stimulation of G protein-coupled receptors, RKIP
dissociates from its known target, RAF1, to associate with GRK2 and
block its activity. This switch is triggered by a protein kinase C (PKC;
see 176960)-dependent phosphorylation of RKIP on serine-153. Lorenz et
al. (2003) concluded that their data delineate a new principle in signal
transduction: by activating PKC, the incoming receptor signal is
enhanced both by removing an inhibitor from RAF1 and by blocking
receptor internalization. A physiologic role for this mechanism is shown
in cardiomyocytes in which the downregulation of RKIP restrains
beta-adrenergic signaling and contractile activity.
Chatterjee et al. (2004) found that RKIP expression was rapidly
upregulated during induction of chemotherapy-triggered apoptosis in
human prostate and breast cancer cell lines, and maximal RKIP expression
correlated perfectly with the onset of apoptosis. However, in cells
resistant to DNA-damaging agents, treatment with drugs did not
upregulate RKIP expression. Ectopic expression of RKIP sensitized
resistant cells to undergo apoptosis, and downregulation of RKIP with an
RKIP antisense and small interfering RNA conferred resistance to
anticancer drug-induced apoptosis. RKIP induced apoptosis by both
antagonizing RAF and NF-kappa-B (see 164011) signaling.
Trakul et al. (2005) found that Rkip inhibited activation of Raf1 in
cultured embryonic rat hippocampal cells by blocking phosphorylation of
the Raf1 kinase domain by p21-activated kinase (see 602590) and Src
family kinases (see 190090). Rkip depletion increased the amplitude and
the sensitivity of Mapk and DNA synthesis to EGF (131530) stimulation.
Eves et al. (2006) found that RKIP associated with centrosomes and
kinetochores and regulated the spindle checkpoint in mammalian cells,
including human cell lines. RKIP depletion decreased the mitotic index,
the number of metaphase cells, traversal times from nuclear envelope
breakdown to anaphase, and an override of mitotic checkpoints induced by
spindle poisons. RAF1 depletion or MEK inhibition reversed the reduction
in the mitotic index, whereas hyperactivation of RAF mimicked the
RKIP-depletion phenotype. RKIP depletion or RAF hyperactivation reduced
kinetochore localization and kinase activity of Aurora B (604970), a
regulator of the spindle checkpoint. Eves et al. (2006) concluded that
RKIP regulates Aurora kinase B and the spindle checkpoint via the
RAF1/MEK/ERK cascade and that small changes in the MAPK pathway can
profoundly impact the fidelity of the cell cycle.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PBP
gene to chromosome 12 (TMAP RH26435).
*FIELD* RF
1. Chatterjee, D.; Bai, Y.; Wang, Z.; Beach, S.; Mott, S.; Roy, R.;
Braastad, C.; Sun, Y.; Mukhopadhyay, A.; Aggarwal, B. B.; Darnowski,
J.; Pantazis, P.; Wyche, J.; Fu, Z.; Kitagwa, Y.; Keller, E. T.; Sedivy,
J. M.; Yeung, K. C.: RKIP sensitizes prostate and breast cancer cells
to drug-induced apoptosis. J. Biol. Chem. 279: 17515-17523, 2004.
2. Eves, E. M.; Shapiro, P.; Naik, K.; Klein, U. R.; Trakul, N.; Rosner,
M. R.: Raf kinase inhibitory protein regulates Aurora B kinase and
the spindle checkpoint. Molec. Cell 23: 561-574, 2006.
3. Hengst, U.; Albrecht, H.; Hess, D.; Monard, D.: The phosphatidylethanolamine-binding
protein is the prototype of a novel family of serine protease inhibitors. J.
Biol. Chem. 276: 535-540, 2001.
4. Hori, N.; Chae, K.; Murakawa, K.; Matoba, R.; Fukushima, A.; Okubo,
K.; Matsubara, K.: A human cDNA sequence homologue of bovine phosphatidylethanolamine-binding
protein. Gene 140: 293-294, 1994.
5. Lorenz, K.; Lohse, M. J.; Quitterer, U.: Protein kinase C switches
the Raf kinase inhibitor from Raf-1 to GRK-2. Nature 426: 574-579,
2003.
6. Moore, C.; Perry, A. C. F.; Love, S.; Hall, L.: Sequence analysis
and immunolocalisation of phosphatidylethanolamine binding protein
(PBP) in human brain tissue. Molec. Brain Res. 37: 74-78, 1996.
7. Schoentgen, F.; Jolles, P.: From structure to function: possible
biological roles of a new widespread protein family binding hydrophobic
ligands and displaying a nucleotide binding site. FEBS Lett. 369:
22-26, 1995.
8. Seddiqi, N.; Bollengier, F.; Alliel, P. M.; Perin, J.-P.; Bonnet,
F.; Bucquoy, S.; Jolles, P.; Schoentgen, F.: Amino acid sequence
of the Homo sapiens brain 21-23-kDa protein (neuropolypeptide h3),
comparison with its counterparts from Rattus norvegicus and Bos taurus
species, and expression of its mRNA in different tissues. J. Molec.
Evol. 39: 655-660, 1994.
9. Tohdoh, N.; Tojo, S.; Agui, H.; Ojika, K.: Sequence homology of
rat and human HCNP precursor proteins, bovine phosphatidylethanolamine-binding
protein and rat 23-kDa protein associated with the opioid-binding
protein. Molec. Brain Res. 30: 381-384, 1995.
10. Trakul, N.; Menard, R. E.; Schade, G. R.; Qian, Z.; Rosner, M.
R.: Raf kinase inhibitory protein regulates Raf-1 but not B-Raf kinase
activation. J. Biol. Chem. 280: 24931-24940, 2005.
11. Yeung, K.; Seitz, T.; Li, S.; Janosch, P.; McFerran, B.; Kaiser,
C.; Fee, F.; Katsanakis, K. D.; Rose, D. W.; Mischak, H.; Sedivy,
J. M.; Kolch, W.: Suppression of Raf-1 kinase activity and MAP kinase
signalling by RKIP. Nature 401: 173-177, 1999.
*FIELD* CN
Patricia A. Hartz - updated: 10/18/2006
Ada Hamosh - updated: 12/30/2003
Patricia A. Hartz - updated: 7/9/2002
Ada Hamosh - updated: 2/24/2000
*FIELD* CD
Ada Hamosh: 2/22/2000
*FIELD* ED
mgross: 08/14/2008
carol: 10/31/2006
terry: 10/18/2006
alopez: 12/31/2003
terry: 12/30/2003
carol: 7/9/2002
terry: 10/4/2000
alopez: 3/3/2000
alopez: 3/2/2000
terry: 2/24/2000
alopez: 2/23/2000
alopez: 2/22/2000