Full text data of PLCB3
PLCB3
[Confidence: low (only semi-automatic identification from reviews)]
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3; 3.1.4.11 (Phosphoinositide phospholipase C-beta-3; Phospholipase C-beta-3; PLC-beta-3)
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3; 3.1.4.11 (Phosphoinositide phospholipase C-beta-3; Phospholipase C-beta-3; PLC-beta-3)
UniProt
Q01970
ID PLCB3_HUMAN Reviewed; 1234 AA.
AC Q01970; A5PKZ6; G5E960; Q8N1A4;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3;
DE EC=3.1.4.11;
DE AltName: Full=Phosphoinositide phospholipase C-beta-3;
DE AltName: Full=Phospholipase C-beta-3;
DE Short=PLC-beta-3;
GN Name=PLCB3;
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 [GENOMIC DNA].
RX PubMed=7612006; DOI=10.1006/bbrc.1995.1955;
RA Mazuruk K., Schoen T.J., Chader G.J., Rodriguez I.R.;
RT "Structural organization and expression of the human
RT phosphatidylinositol-specific phospholipase C beta-3 gene.";
RL Biochem. Biophys. Res. Commun. 212:190-195(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7607669; DOI=10.1016/0888-7543(95)80164-H;
RA Lagercrantz J., Carson E., Phelan C., Grimmond S., Rosen A., Dare E.,
RA Nordenskjoeld M., Hayward N.K., Larsson C., Weber G.;
RT "Genomic organization and complete cDNA sequence of the human
RT phosphoinositide-specific phospholipase C beta 3 gene (PLCB3).";
RL Genomics 26:467-472(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 184-1234 (ISOFORM 1/2).
RX PubMed=1333955; DOI=10.1111/j.1432-1033.1992.tb17450.x;
RA Carozzi A.J., Kriz R.W., Webster C., Parker P.J.;
RT "Identification, purification and characterization of a novel
RT phosphatidylinositol-specific phospholipase C, a third member of the
RT beta subfamily.";
RL Eur. J. Biochem. 210:521-529(1992).
RN [7]
RP INTERACTION WITH LPAR2.
RX PubMed=15143197; DOI=10.1128/MCB.24.11.5069-5079.2004;
RA Oh Y.-S., Jo N.W., Choi J.W., Kim H.S., Seo S.-W., Kang K.-O.,
RA Hwang J.-I., Heo K., Kim S.-H., Kim Y.-H., Kim I.-H., Kim J.H.,
RA Banno Y., Ryu S.H., Suh P.-G.;
RT "NHERF2 specifically interacts with LPA2 receptor and defines the
RT specificity and efficiency of receptor-mediated phospholipase C-beta3
RT activation.";
RL Mol. Cell. Biol. 24:5069-5079(2004).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, 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 [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474; SER-537 AND
RP SER-1105, AND MASS 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).
CC -!- FUNCTION: The production of the second messenger molecules
CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is
CC mediated by activated phosphatidylinositol-specific phospholipase
CC C enzymes.
CC -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5-
CC bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate +
CC diacylglycerol.
CC -!- COFACTOR: Calcium.
CC -!- SUBUNIT: Interacts with SHANK2 (By similarity). Interacts with
CC LPAR2.
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q01970-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q01970-2; Sequence=VSP_046054;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SIMILARITY: Contains 1 PI-PLC X-box domain.
CC -!- SIMILARITY: Contains 1 PI-PLC Y-box domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32659.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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DR EMBL; U26425; AAA77683.1; -; Genomic_DNA.
DR EMBL; Z37544; CAA85776.1; -; Genomic_DNA.
DR EMBL; Z37545; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37546; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37547; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37548; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37549; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37550; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37551; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37552; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37553; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37554; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37555; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37556; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37557; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37558; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37559; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37560; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37561; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37562; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37564; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37565; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37566; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37567; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37568; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37569; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37570; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37571; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37572; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37573; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37574; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; AP001453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74230.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74231.1; -; Genomic_DNA.
DR EMBL; BC032659; AAH32659.1; ALT_INIT; mRNA.
DR EMBL; BC142681; AAI42682.1; -; mRNA.
DR EMBL; Z16411; CAA78903.1; -; mRNA.
DR PIR; I38994; I38994.
DR PIR; S27002; S27002.
DR PIR; S52099; S52099.
DR RefSeq; NP_000923.1; NM_000932.2.
DR RefSeq; NP_001171812.1; NM_001184883.1.
DR RefSeq; XP_005274109.1; XM_005274052.1.
DR UniGene; Hs.523761; -.
DR PDB; 3OHM; X-ray; 2.70 A; B=10-886.
DR PDB; 4GNK; X-ray; 4.00 A; B/D=10-1234, E=934-1192.
DR PDBsum; 3OHM; -.
DR PDBsum; 4GNK; -.
DR ProteinModelPortal; Q01970; -.
DR SMR; Q01970; 10-505, 527-881, 934-1192.
DR DIP; DIP-41928N; -.
DR MINT; MINT-4999151; -.
DR STRING; 9606.ENSP00000279230; -.
DR BindingDB; Q01970; -.
DR PhosphoSite; Q01970; -.
DR DMDM; 1730573; -.
DR PaxDb; Q01970; -.
DR PRIDE; Q01970; -.
DR Ensembl; ENST00000279230; ENSP00000279230; ENSG00000149782.
DR Ensembl; ENST00000325234; ENSP00000324660; ENSG00000149782.
DR Ensembl; ENST00000540288; ENSP00000443631; ENSG00000149782.
DR GeneID; 5331; -.
DR KEGG; hsa:5331; -.
DR UCSC; uc009yph.2; human.
DR CTD; 5331; -.
DR GeneCards; GC11P064019; -.
DR HGNC; HGNC:9056; PLCB3.
DR HPA; CAB009257; -.
DR MIM; 600230; gene.
DR neXtProt; NX_Q01970; -.
DR PharmGKB; PA33386; -.
DR eggNOG; NOG149692; -.
DR HOGENOM; HOG000232046; -.
DR HOVERGEN; HBG053609; -.
DR InParanoid; Q01970; -.
DR KO; K05858; -.
DR OMA; KEMNERE; -.
DR OrthoDB; EOG7WDN1N; -.
DR PhylomeDB; Q01970; -.
DR BRENDA; 3.1.4.11; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_13685; Neuronal System.
DR GeneWiki; PLCB3; -.
DR GenomeRNAi; 5331; -.
DR NextBio; 20644; -.
DR PRO; PR:Q01970; -.
DR Bgee; Q01970; -.
DR CleanEx; HS_PLCB3; -.
DR Genevestigator; Q01970; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043234; C:protein complex; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IEA:UniProtKB-EC.
DR GO; GO:0004629; F:phospholipase C activity; TAS:ProtInc.
DR GO; GO:0004871; F:signal transducer activity; IEA:UniProtKB-KW.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IDA:MGI.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.20.20.190; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001192; PI-PLC_fam.
DR InterPro; IPR016280; PLC-beta.
DR InterPro; IPR028390; PLC-beta3.
DR InterPro; IPR014815; PLC-beta_C.
DR InterPro; IPR009535; PLC-beta_CS.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR InterPro; IPR015359; PLipase_C_EF-hand-like.
DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR PANTHER; PTHR10336; PTHR10336; 1.
DR PANTHER; PTHR10336:SF11; PTHR10336:SF11; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF06631; DUF1154; 1.
DR Pfam; PF09279; EF-hand_like; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR Pfam; PF08703; PLC-beta_C; 1.
DR PIRSF; PIRSF000956; PLC-beta; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR SMART; SM00239; C2; 1.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51695; SSF51695; 2.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Complete proteome;
KW Hydrolase; Lipid degradation; Lipid metabolism; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Transducer.
FT CHAIN 1 1234 1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase beta-3.
FT /FTId=PRO_0000088491.
FT DOMAIN 318 468 PI-PLC X-box.
FT DOMAIN 590 706 PI-PLC Y-box.
FT DOMAIN 713 810 C2.
FT REGION 1231 1234 Interaction with SHANK2 (By similarity).
FT ACT_SITE 332 332 By similarity.
FT ACT_SITE 379 379 By similarity.
FT MOD_RES 474 474 Phosphoserine.
FT MOD_RES 537 537 Phosphoserine.
FT MOD_RES 1105 1105 Phosphoserine.
FT VAR_SEQ 33 99 Missing (in isoform 2).
FT /FTId=VSP_046054.
FT VARIANT 483 483 R -> H (in dbSNP:rs12146487).
FT /FTId=VAR_029229.
FT CONFLICT 845 845 S -> L (in Ref. 6; CAA78903).
FT CONFLICT 881 881 G -> E (in Ref. 2; CAA85776).
FT CONFLICT 1089 1119 REKKELQKILDRKRHNSISEAKMRDKHKKEA -> SWPSWP
FT RSVRSSGRGSPRRSAGACWARCRRG (in Ref. 2;
FT CAA85776).
FT HELIX 20 24
FT STRAND 26 31
FT STRAND 40 45
FT STRAND 51 55
FT HELIX 57 59
FT STRAND 61 65
FT HELIX 66 68
FT STRAND 69 74
FT TURN 75 77
FT HELIX 84 88
FT STRAND 103 108
FT HELIX 112 114
FT STRAND 116 126
FT HELIX 127 140
FT HELIX 142 145
FT HELIX 149 162
FT HELIX 172 177
FT HELIX 180 182
FT HELIX 183 191
FT TURN 192 194
FT HELIX 205 207
FT HELIX 210 220
FT HELIX 224 232
FT HELIX 243 253
FT TURN 261 263
FT HELIX 269 279
FT HELIX 283 287
FT HELIX 293 300
FT HELIX 310 313
FT HELIX 323 325
FT STRAND 326 328
FT STRAND 331 333
FT STRAND 336 338
FT STRAND 340 343
FT HELIX 348 355
FT STRAND 360 366
FT STRAND 370 372
FT STRAND 382 384
FT HELIX 389 399
FT STRAND 408 415
FT HELIX 421 433
FT HELIX 434 436
FT STRAND 447 450
FT TURN 456 461
FT STRAND 463 466
FT HELIX 578 580
FT HELIX 588 591
FT HELIX 605 611
FT STRAND 616 621
FT HELIX 622 631
FT HELIX 633 642
FT STRAND 645 648
FT HELIX 662 665
FT TURN 666 668
FT STRAND 670 672
FT HELIX 681 690
FT HELIX 693 695
FT STRAND 697 700
FT HELIX 703 705
FT STRAND 726 737
FT STRAND 745 754
FT TURN 755 757
FT STRAND 771 773
FT STRAND 781 787
FT HELIX 789 791
FT STRAND 793 800
FT TURN 801 803
FT STRAND 804 812
FT TURN 813 815
FT STRAND 819 826
FT STRAND 832 846
FT HELIX 850 852
FT HELIX 853 860
FT HELIX 862 875
FT HELIX 877 880
SQ SEQUENCE 1234 AA; 138799 MW; C5106EFBA8037788 CRC64;
MAGAQPGVHA LQLEPPTVVE TLRRGSKFIK WDEETSSRNL VTLRVDPNGF FLYWTGPNME
VDTLDISSIR DTRTGRYARL PKDPKIREVL GFGGPDARLE EKLMTVVSGP DPVNTVFLNF
MAVQDDTAKV WSEELFKLAM NILAQNASRN TFLRKAYTKL KLQVNQDGRI PVKNILKMFS
ADKKRVETAL ESCGLKFNRS ESIRPDEFSL EIFERFLNKL CLRPDIDKIL LEIGAKGKPY
LTLEQLMDFI NQKQRDPRLN EVLYPPLRPS QARLLIEKYE PNQQFLERDQ MSMEGFSRYL
GGEENGILPL EALDLSTDMT QPLSAYFINS SHNTYLTAGQ LAGTSSVEMY RQALLWGCRC
VELDVWKGRP PEEEPFITHG FTMTTEVPLR DVLEAIAETA FKTSPYPVIL SFENHVDSAK
QQAKMAEYCR SIFGDALLIE PLDKYPLAPG VPLPSPQDLM GRILVKNKKR HRPSAGGPDS
AGRKRPLEQS NSALSESSAA TEPSSPQLGS PSSDSCPGLS NGEEVGLEKP SLEPQKSLGD
EGLNRGPYVL GPADREDEEE DEEEEEQTDP KKPTTDEGTA SSEVNATEEM STLVNYIEPV
KFKSFEAARK RNKCFEMSSF VETKAMEQLT KSPMEFVEYN KQQLSRIYPK GTRVDSSNYM
PQLFWNVGCQ LVALNFQTLD VAMQLNAGVF EYNGRSGYLL KPEFMRRPDK SFDPFTEVIV
DGIVANALRV KVISGQFLSD RKVGIYVEVD MFGLPVDTRR KYRTRTSQGN SFNPVWDEEP
FDFPKVVLPT LASLRIAAFE EGGKFVGHRI LPVSAIRSGY HYVCLRNEAN QPLCLPALLI
YTEASDYIPD DHQDYAEALI NPIKHVSLMD QRARQLAALI GESEAQAGQE TCQDTQSQQL
GSQPSSNPTP SPLDASPRRP PGPTTSPAST SLSSPGQRDD LIASILSEVA PTPLDELRGH
KALVKLRSRQ ERDLRELRKK HQRKAVTLTR RLLDGLAQAQ AEGRCRLRPG ALGGAADVED
TKEGEDEAKR YQEFQNRQVQ SLLELREAQV DAEAQRRLEH LRQALQRLRE VVLDANTTQF
KRLKEMNERE KKELQKILDR KRHNSISEAK MRDKHKKEAE LTEINRRHIT ESVNSIRRLE
EAQKQRHDRL VAGQQQVLQQ LAEEEPKLLA QLAQECQEQR ARLPQEIRRS LLGEMPEGLG
DGPLVACASN GHAPGSSGHL SGADSESQEE NTQL
//
ID PLCB3_HUMAN Reviewed; 1234 AA.
AC Q01970; A5PKZ6; G5E960; Q8N1A4;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 138.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3;
DE EC=3.1.4.11;
DE AltName: Full=Phosphoinositide phospholipase C-beta-3;
DE AltName: Full=Phospholipase C-beta-3;
DE Short=PLC-beta-3;
GN Name=PLCB3;
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 [GENOMIC DNA].
RX PubMed=7612006; DOI=10.1006/bbrc.1995.1955;
RA Mazuruk K., Schoen T.J., Chader G.J., Rodriguez I.R.;
RT "Structural organization and expression of the human
RT phosphatidylinositol-specific phospholipase C beta-3 gene.";
RL Biochem. Biophys. Res. Commun. 212:190-195(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=7607669; DOI=10.1016/0888-7543(95)80164-H;
RA Lagercrantz J., Carson E., Phelan C., Grimmond S., Rosen A., Dare E.,
RA Nordenskjoeld M., Hayward N.K., Larsson C., Weber G.;
RT "Genomic organization and complete cDNA sequence of the human
RT phosphoinositide-specific phospholipase C beta 3 gene (PLCB3).";
RL Genomics 26:467-472(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F.,
RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 184-1234 (ISOFORM 1/2).
RX PubMed=1333955; DOI=10.1111/j.1432-1033.1992.tb17450.x;
RA Carozzi A.J., Kriz R.W., Webster C., Parker P.J.;
RT "Identification, purification and characterization of a novel
RT phosphatidylinositol-specific phospholipase C, a third member of the
RT beta subfamily.";
RL Eur. J. Biochem. 210:521-529(1992).
RN [7]
RP INTERACTION WITH LPAR2.
RX PubMed=15143197; DOI=10.1128/MCB.24.11.5069-5079.2004;
RA Oh Y.-S., Jo N.W., Choi J.W., Kim H.S., Seo S.-W., Kang K.-O.,
RA Hwang J.-I., Heo K., Kim S.-H., Kim Y.-H., Kim I.-H., Kim J.H.,
RA Banno Y., Ryu S.H., Suh P.-G.;
RT "NHERF2 specifically interacts with LPA2 receptor and defines the
RT specificity and efficiency of receptor-mediated phospholipase C-beta3
RT activation.";
RL Mol. Cell. Biol. 24:5069-5079(2004).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-537, 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 [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474; SER-537 AND
RP SER-1105, AND MASS 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).
CC -!- FUNCTION: The production of the second messenger molecules
CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is
CC mediated by activated phosphatidylinositol-specific phospholipase
CC C enzymes.
CC -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5-
CC bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate +
CC diacylglycerol.
CC -!- COFACTOR: Calcium.
CC -!- SUBUNIT: Interacts with SHANK2 (By similarity). Interacts with
CC LPAR2.
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q01970-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q01970-2; Sequence=VSP_046054;
CC Note=No experimental confirmation available;
CC -!- SIMILARITY: Contains 1 C2 domain.
CC -!- SIMILARITY: Contains 1 PI-PLC X-box domain.
CC -!- SIMILARITY: Contains 1 PI-PLC Y-box domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH32659.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; U26425; AAA77683.1; -; Genomic_DNA.
DR EMBL; Z37544; CAA85776.1; -; Genomic_DNA.
DR EMBL; Z37545; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37546; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37547; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37548; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37549; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37550; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37551; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37552; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37553; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37554; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37555; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37556; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37557; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37558; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37559; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37560; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37561; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37562; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37564; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37565; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37566; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37567; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37568; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37569; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37570; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37571; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37572; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37573; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; Z37574; CAA85776.1; JOINED; Genomic_DNA.
DR EMBL; AP001453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW74230.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW74231.1; -; Genomic_DNA.
DR EMBL; BC032659; AAH32659.1; ALT_INIT; mRNA.
DR EMBL; BC142681; AAI42682.1; -; mRNA.
DR EMBL; Z16411; CAA78903.1; -; mRNA.
DR PIR; I38994; I38994.
DR PIR; S27002; S27002.
DR PIR; S52099; S52099.
DR RefSeq; NP_000923.1; NM_000932.2.
DR RefSeq; NP_001171812.1; NM_001184883.1.
DR RefSeq; XP_005274109.1; XM_005274052.1.
DR UniGene; Hs.523761; -.
DR PDB; 3OHM; X-ray; 2.70 A; B=10-886.
DR PDB; 4GNK; X-ray; 4.00 A; B/D=10-1234, E=934-1192.
DR PDBsum; 3OHM; -.
DR PDBsum; 4GNK; -.
DR ProteinModelPortal; Q01970; -.
DR SMR; Q01970; 10-505, 527-881, 934-1192.
DR DIP; DIP-41928N; -.
DR MINT; MINT-4999151; -.
DR STRING; 9606.ENSP00000279230; -.
DR BindingDB; Q01970; -.
DR PhosphoSite; Q01970; -.
DR DMDM; 1730573; -.
DR PaxDb; Q01970; -.
DR PRIDE; Q01970; -.
DR Ensembl; ENST00000279230; ENSP00000279230; ENSG00000149782.
DR Ensembl; ENST00000325234; ENSP00000324660; ENSG00000149782.
DR Ensembl; ENST00000540288; ENSP00000443631; ENSG00000149782.
DR GeneID; 5331; -.
DR KEGG; hsa:5331; -.
DR UCSC; uc009yph.2; human.
DR CTD; 5331; -.
DR GeneCards; GC11P064019; -.
DR HGNC; HGNC:9056; PLCB3.
DR HPA; CAB009257; -.
DR MIM; 600230; gene.
DR neXtProt; NX_Q01970; -.
DR PharmGKB; PA33386; -.
DR eggNOG; NOG149692; -.
DR HOGENOM; HOG000232046; -.
DR HOVERGEN; HBG053609; -.
DR InParanoid; Q01970; -.
DR KO; K05858; -.
DR OMA; KEMNERE; -.
DR OrthoDB; EOG7WDN1N; -.
DR PhylomeDB; Q01970; -.
DR BRENDA; 3.1.4.11; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_13685; Neuronal System.
DR GeneWiki; PLCB3; -.
DR GenomeRNAi; 5331; -.
DR NextBio; 20644; -.
DR PRO; PR:Q01970; -.
DR Bgee; Q01970; -.
DR CleanEx; HS_PLCB3; -.
DR Genevestigator; Q01970; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043234; C:protein complex; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IEA:UniProtKB-EC.
DR GO; GO:0004629; F:phospholipase C activity; TAS:ProtInc.
DR GO; GO:0004871; F:signal transducer activity; IEA:UniProtKB-KW.
DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0003073; P:regulation of systemic arterial blood pressure; IDA:MGI.
DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome.
DR Gene3D; 1.10.238.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.20.20.190; -; 2.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001192; PI-PLC_fam.
DR InterPro; IPR016280; PLC-beta.
DR InterPro; IPR028390; PLC-beta3.
DR InterPro; IPR014815; PLC-beta_C.
DR InterPro; IPR009535; PLC-beta_CS.
DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl.
DR InterPro; IPR015359; PLipase_C_EF-hand-like.
DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR PANTHER; PTHR10336; PTHR10336; 1.
DR PANTHER; PTHR10336:SF11; PTHR10336:SF11; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF06631; DUF1154; 1.
DR Pfam; PF09279; EF-hand_like; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR Pfam; PF08703; PLC-beta_C; 1.
DR PIRSF; PIRSF000956; PLC-beta; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR SMART; SM00239; C2; 1.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF51695; SSF51695; 2.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Complete proteome;
KW Hydrolase; Lipid degradation; Lipid metabolism; Membrane;
KW Phosphoprotein; Polymorphism; Reference proteome; Transducer.
FT CHAIN 1 1234 1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase beta-3.
FT /FTId=PRO_0000088491.
FT DOMAIN 318 468 PI-PLC X-box.
FT DOMAIN 590 706 PI-PLC Y-box.
FT DOMAIN 713 810 C2.
FT REGION 1231 1234 Interaction with SHANK2 (By similarity).
FT ACT_SITE 332 332 By similarity.
FT ACT_SITE 379 379 By similarity.
FT MOD_RES 474 474 Phosphoserine.
FT MOD_RES 537 537 Phosphoserine.
FT MOD_RES 1105 1105 Phosphoserine.
FT VAR_SEQ 33 99 Missing (in isoform 2).
FT /FTId=VSP_046054.
FT VARIANT 483 483 R -> H (in dbSNP:rs12146487).
FT /FTId=VAR_029229.
FT CONFLICT 845 845 S -> L (in Ref. 6; CAA78903).
FT CONFLICT 881 881 G -> E (in Ref. 2; CAA85776).
FT CONFLICT 1089 1119 REKKELQKILDRKRHNSISEAKMRDKHKKEA -> SWPSWP
FT RSVRSSGRGSPRRSAGACWARCRRG (in Ref. 2;
FT CAA85776).
FT HELIX 20 24
FT STRAND 26 31
FT STRAND 40 45
FT STRAND 51 55
FT HELIX 57 59
FT STRAND 61 65
FT HELIX 66 68
FT STRAND 69 74
FT TURN 75 77
FT HELIX 84 88
FT STRAND 103 108
FT HELIX 112 114
FT STRAND 116 126
FT HELIX 127 140
FT HELIX 142 145
FT HELIX 149 162
FT HELIX 172 177
FT HELIX 180 182
FT HELIX 183 191
FT TURN 192 194
FT HELIX 205 207
FT HELIX 210 220
FT HELIX 224 232
FT HELIX 243 253
FT TURN 261 263
FT HELIX 269 279
FT HELIX 283 287
FT HELIX 293 300
FT HELIX 310 313
FT HELIX 323 325
FT STRAND 326 328
FT STRAND 331 333
FT STRAND 336 338
FT STRAND 340 343
FT HELIX 348 355
FT STRAND 360 366
FT STRAND 370 372
FT STRAND 382 384
FT HELIX 389 399
FT STRAND 408 415
FT HELIX 421 433
FT HELIX 434 436
FT STRAND 447 450
FT TURN 456 461
FT STRAND 463 466
FT HELIX 578 580
FT HELIX 588 591
FT HELIX 605 611
FT STRAND 616 621
FT HELIX 622 631
FT HELIX 633 642
FT STRAND 645 648
FT HELIX 662 665
FT TURN 666 668
FT STRAND 670 672
FT HELIX 681 690
FT HELIX 693 695
FT STRAND 697 700
FT HELIX 703 705
FT STRAND 726 737
FT STRAND 745 754
FT TURN 755 757
FT STRAND 771 773
FT STRAND 781 787
FT HELIX 789 791
FT STRAND 793 800
FT TURN 801 803
FT STRAND 804 812
FT TURN 813 815
FT STRAND 819 826
FT STRAND 832 846
FT HELIX 850 852
FT HELIX 853 860
FT HELIX 862 875
FT HELIX 877 880
SQ SEQUENCE 1234 AA; 138799 MW; C5106EFBA8037788 CRC64;
MAGAQPGVHA LQLEPPTVVE TLRRGSKFIK WDEETSSRNL VTLRVDPNGF FLYWTGPNME
VDTLDISSIR DTRTGRYARL PKDPKIREVL GFGGPDARLE EKLMTVVSGP DPVNTVFLNF
MAVQDDTAKV WSEELFKLAM NILAQNASRN TFLRKAYTKL KLQVNQDGRI PVKNILKMFS
ADKKRVETAL ESCGLKFNRS ESIRPDEFSL EIFERFLNKL CLRPDIDKIL LEIGAKGKPY
LTLEQLMDFI NQKQRDPRLN EVLYPPLRPS QARLLIEKYE PNQQFLERDQ MSMEGFSRYL
GGEENGILPL EALDLSTDMT QPLSAYFINS SHNTYLTAGQ LAGTSSVEMY RQALLWGCRC
VELDVWKGRP PEEEPFITHG FTMTTEVPLR DVLEAIAETA FKTSPYPVIL SFENHVDSAK
QQAKMAEYCR SIFGDALLIE PLDKYPLAPG VPLPSPQDLM GRILVKNKKR HRPSAGGPDS
AGRKRPLEQS NSALSESSAA TEPSSPQLGS PSSDSCPGLS NGEEVGLEKP SLEPQKSLGD
EGLNRGPYVL GPADREDEEE DEEEEEQTDP KKPTTDEGTA SSEVNATEEM STLVNYIEPV
KFKSFEAARK RNKCFEMSSF VETKAMEQLT KSPMEFVEYN KQQLSRIYPK GTRVDSSNYM
PQLFWNVGCQ LVALNFQTLD VAMQLNAGVF EYNGRSGYLL KPEFMRRPDK SFDPFTEVIV
DGIVANALRV KVISGQFLSD RKVGIYVEVD MFGLPVDTRR KYRTRTSQGN SFNPVWDEEP
FDFPKVVLPT LASLRIAAFE EGGKFVGHRI LPVSAIRSGY HYVCLRNEAN QPLCLPALLI
YTEASDYIPD DHQDYAEALI NPIKHVSLMD QRARQLAALI GESEAQAGQE TCQDTQSQQL
GSQPSSNPTP SPLDASPRRP PGPTTSPAST SLSSPGQRDD LIASILSEVA PTPLDELRGH
KALVKLRSRQ ERDLRELRKK HQRKAVTLTR RLLDGLAQAQ AEGRCRLRPG ALGGAADVED
TKEGEDEAKR YQEFQNRQVQ SLLELREAQV DAEAQRRLEH LRQALQRLRE VVLDANTTQF
KRLKEMNERE KKELQKILDR KRHNSISEAK MRDKHKKEAE LTEINRRHIT ESVNSIRRLE
EAQKQRHDRL VAGQQQVLQQ LAEEEPKLLA QLAQECQEQR ARLPQEIRRS LLGEMPEGLG
DGPLVACASN GHAPGSSGHL SGADSESQEE NTQL
//
MIM
600230
*RECORD*
*FIELD* NO
600230
*FIELD* TI
*600230 PHOSPHOLIPASE C, BETA-3; PLCB3
*FIELD* TX
DESCRIPTION
PLCB3 plays an important role in initiating receptor-mediated signal
read moretransduction. Activation of PLC takes place in many cells as a response
to stimulation by hormones, growth factors, neurotransmitters, and other
ligands (Lagercrantz et al., 1995).
CLONING
Weber et al. (1994) mapped the gene for multiple endocrine neoplasia
type I (MEN1; 131100) to a region of less than 900 kb by deletion
mapping in 27 primary parathyroid tumors. One of the cDNA clones
isolated from this region showed expression of a 4.4-kb message in
multiple tissues, including those affected in MEN1, while in 5 endocrine
tumors from MEN1 patients no transcript was detected. Sequence
characterization showed that this gene encodes PLCB3, a key enzyme in
signal transduction.
Lagercrantz et al. (1995) determined that the full-length PLCB3 cDNA has
an open reading frame of 1,234 amino acids. Northern blot analysis
revealed a 4.4-kb transcript in all tissues tested.
Mazuruk et al. (1995) cloned the PLCB3 gene. It was highly expressed in
several human tissues, including retina, brain, and kidney. PLCB3 mRNA
was detected at a much lower level in liver.
GENE STRUCTURE
Lagercrantz et al. (1995) estimated that the size of the complete PLCB3
transcription unit is on the order of 15 kb. The gene contains 31 exons,
with all splice donor and acceptor sites conforming to the GT/AG rule.
No exon exceeds 571 bp in length, and the shortest exon spans only 36
bp. More than half of the introns are shorter than 200 bp, with the
shortest being only 79 bp.
Mazuruk et al. (1995) determined that the PLCB3 gene spans approximately
17 kb and contains 31 exons.
BIOCHEMICAL FEATURES
- Crystal Structure
Waldo et al. (2010) described how heterotrimeric guanine
nucleotide-binding proteins (G proteins) activate PLC-betas and in turn
are deactivated by the downstream effectors. The 2.7-angstrom structure
of PLC-beta-3 bound to activated G-alpha-q (600998) revealed a conserved
module found within PLC-betas and other effectors optimized for rapid
engagement of activated G proteins. The active site of PLC-beta-3 in the
complex is occluded by an intramolecular plug that is likely removed
upon G protein-dependent anchoring and orientation of the lipase at
membrane surfaces. A second domain of PLC-beta-3 subsequently
accelerates guanosine triphosphate hydrolysis by G-alpha-q, causing the
complex to dissociate and terminate signal propagation. Mutations within
this domain dramatically delay signal termination in vitro and in vivo.
Waldo et al. (2010) concluded that their work suggested a dynamic
catch-and-release mechanism used to sharpen spatiotemporal signals
mediated by diverse sensory inputs.
MAPPING
In the course of the molecular characterization of a human extragonadal
germ cell tumor (EGCT)-associated chromosomal translocation, Sinke and
Geurts van Kessel (1995) identified YACs and cosmids from the 11q13
region. The end clone of one of these YACs appeared to contain a stretch
of DNA homologous to part of the PLCB3 gene. They cloned the entire cDNA
and confirmed the location of the gene to 11q13. No aberrantly
hybridizing fragments were observed in EGCT DNAs. This result, together
with mRNA studies, excluded the PLCB3 gene as a candidate in the
development of EGCTs.
Courseaux et al. (1996) used a combination of methods to refine maps of
the approximately 5-Mb region of 11q13 that includes MEN1. They proposed
the following gene order:
cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM,
ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel.
Gobl et al. (1995) mapped the Plcb3 gene to mouse chromosome 19.
Because of its chromosomal localization and biologic function, Mazuruk
et al. (1995) considered PLCB3 to be a promising candidate for human
genetic disorders such as Bardet-Biedl syndrome type 1 (BBS1; see
209900), Best disease (153700), and 2 forms of vitreoretinopathy
(193235, 133780). Because of its map location on 11q13, its function in
the signal transduction cascade, and its expression pattern, PLCB3 was
considered an attractive candidate for the site of the mutation in
multiple endocrine neoplasia type I (131100) but was excluded as a
candidate for this disorder by failure to find mutations (Weber et al.,
1997; de Wit et al., 1997).
ANIMAL MODEL
Morphine and other mu opioids regulate a number of intracellular
signaling pathways, including the one mediated by PLC. By studying
Plcb3-deficient mice, Xie et al. (1999) established a strong link
between PLC and mu-opioid-mediated responses at both the behavioral and
the cellular levels. When compared with the wildtype, mice lacking Pclb3
exhibited up to a 10-fold decrease in the ED50 value for morphine in
producing antinociception. The reduced ED50 value was unlikely to be a
result of changes in opioid receptor number or affinity because no
differences were found in whole brain Bmax and Kd values for mu-,
kappa-, and delta-opioid receptors between wildtype and Plcb3 null mice.
Xie et al. (1999) demonstrated that PLCB3 constitutes a significant
pathway involved in negative modulation of mu-opioid responses, perhaps
via protein kinase C (see 176982), and suggested that differences in
opioid sensitivity among individuals could be, in part, because of
genetic factors. They noted that Wang et al. (1998) had reported that a
targeted disruption of the Plcb3 gene caused embryonic lethality. The
fact that their construct deleted exons 11 to 17, whereas the construct
used by Xie et al. (1999) partially deleted 1 exon, may account for the
absence of lethality in the animals studied by Xie et al. (1999).
Li et al. (2000) studied mice lacking Plcb3. These mice developed
spontaneous multifocal skin ulcers usually starting at the age of 6
months or older. The lesions were localized mainly behind ears or on the
neck, but sometimes also appeared on the face. A similar phenotype was
observed in mice lacking both Plcb2 (604114) and Plcb3. Histologic
examination of the lesion tissues revealed hyperinfiltration of
leukocytes in the lesion tissues. Most leukocytes were macrophages or
lymphocytes.
Using mice lacking either Plcb2, Plcb3, or both Plcb2 and Plcb3, Wang et
al. (2008) identified Plcb3 as the major functional isoform in mouse
macrophages. Plcb3 deficiency did not affect macrophage migration,
adhesion, or phagocytosis, but it resulted in hypersensitivity to
several inducers of apoptosis via upregulation of Pkc (see
176960)-dependent upregulation of Bclxl (600039). In the apoE
(107741)-deficient mouse model of atherosclerosis, mice lacking both
apoE and Plcb3 exhibited fewer total macrophages and increased
macrophage apoptosis in atherosclerotic lesions and reduced lesion size
compared with mice lacking only apoE. Wang et al. (2008) concluded that
PLC activity is critical for promoting macrophage survival in
atherosclerotic plaques.
*FIELD* RF
1. Courseaux, A.; Grosgeorge, J.; Gaudray, P.; Pannett, A. A. J.;
Forbes, S. A.; Williamson, C.; Bassett, D.; Thakker, R. V.; Teh, B.
T.; Farnebo, F.; Shepherd, J.; Skogseid, B.; Larsson, C.; Giraud,
S.; Zhang, C. X.; Salandre, J.; Calender, A.: Definition of the minimal
MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. Genomics 37:
354-365, 1996.
2. de Wit, M. J.; Landsvater, R. M.; Sinke, R. J.; Geurts van Kessel,
A.; Lips, C. J. M.; Hoppener, J. W. M.: Exclusion of the phosphatidylinositol-specific
phospholipase C beta-3 (PLC beta-3) gene as candidate for the multiple
endocrine neoplasia type 1 (MEN 1) gene. Hum. Genet. 99: 133-137,
1997.
3. Gobl, A. E.; Chwdhary, B. P.; Shu, W.; Eriksson, L.; Larsson, C.;
Weber, G.; Oberg, K.; Skogseid, B.: Assignment of the mouse homologue
of a human MEN1 candidate gene, phospholipase C-beta-3 (Plcb3), to
chromosome region 19B by FISH. Cytogenet. Cell Genet. 71: 257-259,
1995.
4. Lagercrantz, J.; Carson, E.; Phelan, C.; Grimmond, S.; Rosen, A.;
Dare, E.; Nordenskjold, M.; Hayward, N. K.; Larsson, C.; Weber, G.
: Genomic organization and complete cDNA sequence of the human phosphoinositide-specific
phospholipase C beta-3 gene (PLCB3). Genomics 26: 467-472, 1995.
5. Li, Z.; Jiang, H.; Xie, W.; Zhang, Z.; Smrcka, A. V.; Wu, D.:
Roles of PLC-beta-2 and -beta-3 and PI3K-gamma in chemoattractant-mediated
signal transduction. Science 287: 1046-1049, 2000.
6. Mazuruk, K.; Schoen, T. J.; Chader, G. J.; Rodriguez, I. R.: Structural
organization and expression of the human phosphatidylinositol-specific
phospholipase C beta-3 gene. Biochem. Biophys. Res. Commun. 212:
190-195, 1995.
7. Sinke, R. J.; Geurts van Kessel, A.: Localization of the human
phosphatidylinositol-specific phospholipase C beta-3 gene (PLCB3)
within chromosome band 11q13. Genomics 25: 568-569, 1995.
8. Waldo, G. L.; Ricks, T. K.; Hicks, S. N.; Cheever, M. L.; Kawano,
T.; Tsuboi, K.; Wang, X.; Montell, C.; Kozasa, T.; Sondek, J.; Harden,
T. K.: Kinetic scaffolding mediated by a phospholipase C-beta and
G-q signaling complex. Science 330: 974-980, 2010.
9. Wang, S.; Gebre-Medhin, S.; Betsholtz, C.; Stalberg, P.; Zhou,
Y.; Larsson, C.; Weber, G.; Feinstein, R.; Oberg, K.; Gobl, A.; Skogseid,
B.: Targeted disruption of the mouse phospholipase C beta-3 gene
results in early embryonic lethality. FEBS Lett. 441: 261-265, 1998.
10. Wang, Z.; Liu, B.; Wang, P.; Dong, X.; Fernandez-Hernando, C.;
Li, Z.; Hla, T.; Li, Z.; Claffey, K.; Smith, J. D.; Wu, D.: Phospholipase
C beta-3 deficiency leads to macrophage hypersensitivity to apoptotic
induction and reduction of atherosclerosis in mice. J. Clin. Invest. 118:
195-204, 2008.
11. Weber, G.; Friedman, E.; Grimmond, S.; Hayward, N. K.; Phelan,
C.; Skogseid, B.; Gobl, A.; Zedenius, J.; Sandelin, K.; Teh, B. T.;
Carson, E.; White, I.; Oberg, K.; Shepherd, J.; Nordenskjold, M.;
Larsson, C.: The phospholipase C beta-3 gene located in the MEN1
region shows loss of expression in endocrine tumours. Hum. Molec.
Genet. 3: 1775-1781, 1994.
12. Weber, G.; Grimmond, S.; Lagercrantz, J.; Friedman, E.; Phelan,
C.; Carson, E.; Hayward, N.; Jacobvitz, O.; Nordenskjold, M.; Larsson,
C.: Exclusion of the phosphoinositide-specific phospholipase C-beta-3
(PLCB3) gene as a candidate for multiple endocrine neoplasia type
1. Hum. Genet. 99: 130-132, 1997.
13. Xie, W.; Samoriski, G. M.; McLaughlin, J. P.; Romoser, V. A.;
Smrcka, A.; Hinkle, P. M.; Bidlack, J. M.; Gross, R. A.; Jiang, H.;
Wu, D.: Genetic alteration of phospholipase C beta-3 expression modulates
behavioral and cellular responses to mu opioids. Proc. Nat. Acad.
Sci. 96: 10385-10390, 1999.
*FIELD* CN
Ada Hamosh - updated: 6/23/2011
Paul J. Converse - updated: 3/13/2008
Ada Hamosh - updated: 2/10/2000
Victor A. McKusick - updated: 10/21/1999
Alan F. Scott - updated: 8/5/1997
*FIELD* CD
Victor A. McKusick: 12/13/1994
*FIELD* ED
alopez: 06/23/2011
terry: 6/23/2011
mgross: 3/18/2008
terry: 3/13/2008
carol: 5/3/2007
alopez: 2/10/2000
alopez: 11/15/1999
mgross: 10/29/1999
terry: 10/21/1999
psherman: 8/10/1999
alopez: 12/15/1997
terry: 8/5/1997
terry: 7/10/1997
alopez: 6/13/1997
jamie: 6/3/1997
jenny: 1/10/1997
terry: 12/30/1996
mark: 1/23/1996
mark: 1/22/1996
mark: 9/10/1995
terry: 6/3/1995
mark: 5/16/1995
terry: 3/7/1995
carol: 12/13/1994
*RECORD*
*FIELD* NO
600230
*FIELD* TI
*600230 PHOSPHOLIPASE C, BETA-3; PLCB3
*FIELD* TX
DESCRIPTION
PLCB3 plays an important role in initiating receptor-mediated signal
read moretransduction. Activation of PLC takes place in many cells as a response
to stimulation by hormones, growth factors, neurotransmitters, and other
ligands (Lagercrantz et al., 1995).
CLONING
Weber et al. (1994) mapped the gene for multiple endocrine neoplasia
type I (MEN1; 131100) to a region of less than 900 kb by deletion
mapping in 27 primary parathyroid tumors. One of the cDNA clones
isolated from this region showed expression of a 4.4-kb message in
multiple tissues, including those affected in MEN1, while in 5 endocrine
tumors from MEN1 patients no transcript was detected. Sequence
characterization showed that this gene encodes PLCB3, a key enzyme in
signal transduction.
Lagercrantz et al. (1995) determined that the full-length PLCB3 cDNA has
an open reading frame of 1,234 amino acids. Northern blot analysis
revealed a 4.4-kb transcript in all tissues tested.
Mazuruk et al. (1995) cloned the PLCB3 gene. It was highly expressed in
several human tissues, including retina, brain, and kidney. PLCB3 mRNA
was detected at a much lower level in liver.
GENE STRUCTURE
Lagercrantz et al. (1995) estimated that the size of the complete PLCB3
transcription unit is on the order of 15 kb. The gene contains 31 exons,
with all splice donor and acceptor sites conforming to the GT/AG rule.
No exon exceeds 571 bp in length, and the shortest exon spans only 36
bp. More than half of the introns are shorter than 200 bp, with the
shortest being only 79 bp.
Mazuruk et al. (1995) determined that the PLCB3 gene spans approximately
17 kb and contains 31 exons.
BIOCHEMICAL FEATURES
- Crystal Structure
Waldo et al. (2010) described how heterotrimeric guanine
nucleotide-binding proteins (G proteins) activate PLC-betas and in turn
are deactivated by the downstream effectors. The 2.7-angstrom structure
of PLC-beta-3 bound to activated G-alpha-q (600998) revealed a conserved
module found within PLC-betas and other effectors optimized for rapid
engagement of activated G proteins. The active site of PLC-beta-3 in the
complex is occluded by an intramolecular plug that is likely removed
upon G protein-dependent anchoring and orientation of the lipase at
membrane surfaces. A second domain of PLC-beta-3 subsequently
accelerates guanosine triphosphate hydrolysis by G-alpha-q, causing the
complex to dissociate and terminate signal propagation. Mutations within
this domain dramatically delay signal termination in vitro and in vivo.
Waldo et al. (2010) concluded that their work suggested a dynamic
catch-and-release mechanism used to sharpen spatiotemporal signals
mediated by diverse sensory inputs.
MAPPING
In the course of the molecular characterization of a human extragonadal
germ cell tumor (EGCT)-associated chromosomal translocation, Sinke and
Geurts van Kessel (1995) identified YACs and cosmids from the 11q13
region. The end clone of one of these YACs appeared to contain a stretch
of DNA homologous to part of the PLCB3 gene. They cloned the entire cDNA
and confirmed the location of the gene to 11q13. No aberrantly
hybridizing fragments were observed in EGCT DNAs. This result, together
with mRNA studies, excluded the PLCB3 gene as a candidate in the
development of EGCTs.
Courseaux et al. (1996) used a combination of methods to refine maps of
the approximately 5-Mb region of 11q13 that includes MEN1. They proposed
the following gene order:
cen--PGA--FTH1--UGB--AHNAK--ROM1--MDU1--CHRM1--COX8--EMK1--FKBP2--PLCB3--[PYGM,
ZFM1]--FAU--CAPN1--[MLK3, RELA]--FOSL1--SEA--CFL1--tel.
Gobl et al. (1995) mapped the Plcb3 gene to mouse chromosome 19.
Because of its chromosomal localization and biologic function, Mazuruk
et al. (1995) considered PLCB3 to be a promising candidate for human
genetic disorders such as Bardet-Biedl syndrome type 1 (BBS1; see
209900), Best disease (153700), and 2 forms of vitreoretinopathy
(193235, 133780). Because of its map location on 11q13, its function in
the signal transduction cascade, and its expression pattern, PLCB3 was
considered an attractive candidate for the site of the mutation in
multiple endocrine neoplasia type I (131100) but was excluded as a
candidate for this disorder by failure to find mutations (Weber et al.,
1997; de Wit et al., 1997).
ANIMAL MODEL
Morphine and other mu opioids regulate a number of intracellular
signaling pathways, including the one mediated by PLC. By studying
Plcb3-deficient mice, Xie et al. (1999) established a strong link
between PLC and mu-opioid-mediated responses at both the behavioral and
the cellular levels. When compared with the wildtype, mice lacking Pclb3
exhibited up to a 10-fold decrease in the ED50 value for morphine in
producing antinociception. The reduced ED50 value was unlikely to be a
result of changes in opioid receptor number or affinity because no
differences were found in whole brain Bmax and Kd values for mu-,
kappa-, and delta-opioid receptors between wildtype and Plcb3 null mice.
Xie et al. (1999) demonstrated that PLCB3 constitutes a significant
pathway involved in negative modulation of mu-opioid responses, perhaps
via protein kinase C (see 176982), and suggested that differences in
opioid sensitivity among individuals could be, in part, because of
genetic factors. They noted that Wang et al. (1998) had reported that a
targeted disruption of the Plcb3 gene caused embryonic lethality. The
fact that their construct deleted exons 11 to 17, whereas the construct
used by Xie et al. (1999) partially deleted 1 exon, may account for the
absence of lethality in the animals studied by Xie et al. (1999).
Li et al. (2000) studied mice lacking Plcb3. These mice developed
spontaneous multifocal skin ulcers usually starting at the age of 6
months or older. The lesions were localized mainly behind ears or on the
neck, but sometimes also appeared on the face. A similar phenotype was
observed in mice lacking both Plcb2 (604114) and Plcb3. Histologic
examination of the lesion tissues revealed hyperinfiltration of
leukocytes in the lesion tissues. Most leukocytes were macrophages or
lymphocytes.
Using mice lacking either Plcb2, Plcb3, or both Plcb2 and Plcb3, Wang et
al. (2008) identified Plcb3 as the major functional isoform in mouse
macrophages. Plcb3 deficiency did not affect macrophage migration,
adhesion, or phagocytosis, but it resulted in hypersensitivity to
several inducers of apoptosis via upregulation of Pkc (see
176960)-dependent upregulation of Bclxl (600039). In the apoE
(107741)-deficient mouse model of atherosclerosis, mice lacking both
apoE and Plcb3 exhibited fewer total macrophages and increased
macrophage apoptosis in atherosclerotic lesions and reduced lesion size
compared with mice lacking only apoE. Wang et al. (2008) concluded that
PLC activity is critical for promoting macrophage survival in
atherosclerotic plaques.
*FIELD* RF
1. Courseaux, A.; Grosgeorge, J.; Gaudray, P.; Pannett, A. A. J.;
Forbes, S. A.; Williamson, C.; Bassett, D.; Thakker, R. V.; Teh, B.
T.; Farnebo, F.; Shepherd, J.; Skogseid, B.; Larsson, C.; Giraud,
S.; Zhang, C. X.; Salandre, J.; Calender, A.: Definition of the minimal
MEN1 candidate area based on a 5-Mb integrated map of proximal 11q13. Genomics 37:
354-365, 1996.
2. de Wit, M. J.; Landsvater, R. M.; Sinke, R. J.; Geurts van Kessel,
A.; Lips, C. J. M.; Hoppener, J. W. M.: Exclusion of the phosphatidylinositol-specific
phospholipase C beta-3 (PLC beta-3) gene as candidate for the multiple
endocrine neoplasia type 1 (MEN 1) gene. Hum. Genet. 99: 133-137,
1997.
3. Gobl, A. E.; Chwdhary, B. P.; Shu, W.; Eriksson, L.; Larsson, C.;
Weber, G.; Oberg, K.; Skogseid, B.: Assignment of the mouse homologue
of a human MEN1 candidate gene, phospholipase C-beta-3 (Plcb3), to
chromosome region 19B by FISH. Cytogenet. Cell Genet. 71: 257-259,
1995.
4. Lagercrantz, J.; Carson, E.; Phelan, C.; Grimmond, S.; Rosen, A.;
Dare, E.; Nordenskjold, M.; Hayward, N. K.; Larsson, C.; Weber, G.
: Genomic organization and complete cDNA sequence of the human phosphoinositide-specific
phospholipase C beta-3 gene (PLCB3). Genomics 26: 467-472, 1995.
5. Li, Z.; Jiang, H.; Xie, W.; Zhang, Z.; Smrcka, A. V.; Wu, D.:
Roles of PLC-beta-2 and -beta-3 and PI3K-gamma in chemoattractant-mediated
signal transduction. Science 287: 1046-1049, 2000.
6. Mazuruk, K.; Schoen, T. J.; Chader, G. J.; Rodriguez, I. R.: Structural
organization and expression of the human phosphatidylinositol-specific
phospholipase C beta-3 gene. Biochem. Biophys. Res. Commun. 212:
190-195, 1995.
7. Sinke, R. J.; Geurts van Kessel, A.: Localization of the human
phosphatidylinositol-specific phospholipase C beta-3 gene (PLCB3)
within chromosome band 11q13. Genomics 25: 568-569, 1995.
8. Waldo, G. L.; Ricks, T. K.; Hicks, S. N.; Cheever, M. L.; Kawano,
T.; Tsuboi, K.; Wang, X.; Montell, C.; Kozasa, T.; Sondek, J.; Harden,
T. K.: Kinetic scaffolding mediated by a phospholipase C-beta and
G-q signaling complex. Science 330: 974-980, 2010.
9. Wang, S.; Gebre-Medhin, S.; Betsholtz, C.; Stalberg, P.; Zhou,
Y.; Larsson, C.; Weber, G.; Feinstein, R.; Oberg, K.; Gobl, A.; Skogseid,
B.: Targeted disruption of the mouse phospholipase C beta-3 gene
results in early embryonic lethality. FEBS Lett. 441: 261-265, 1998.
10. Wang, Z.; Liu, B.; Wang, P.; Dong, X.; Fernandez-Hernando, C.;
Li, Z.; Hla, T.; Li, Z.; Claffey, K.; Smith, J. D.; Wu, D.: Phospholipase
C beta-3 deficiency leads to macrophage hypersensitivity to apoptotic
induction and reduction of atherosclerosis in mice. J. Clin. Invest. 118:
195-204, 2008.
11. Weber, G.; Friedman, E.; Grimmond, S.; Hayward, N. K.; Phelan,
C.; Skogseid, B.; Gobl, A.; Zedenius, J.; Sandelin, K.; Teh, B. T.;
Carson, E.; White, I.; Oberg, K.; Shepherd, J.; Nordenskjold, M.;
Larsson, C.: The phospholipase C beta-3 gene located in the MEN1
region shows loss of expression in endocrine tumours. Hum. Molec.
Genet. 3: 1775-1781, 1994.
12. Weber, G.; Grimmond, S.; Lagercrantz, J.; Friedman, E.; Phelan,
C.; Carson, E.; Hayward, N.; Jacobvitz, O.; Nordenskjold, M.; Larsson,
C.: Exclusion of the phosphoinositide-specific phospholipase C-beta-3
(PLCB3) gene as a candidate for multiple endocrine neoplasia type
1. Hum. Genet. 99: 130-132, 1997.
13. Xie, W.; Samoriski, G. M.; McLaughlin, J. P.; Romoser, V. A.;
Smrcka, A.; Hinkle, P. M.; Bidlack, J. M.; Gross, R. A.; Jiang, H.;
Wu, D.: Genetic alteration of phospholipase C beta-3 expression modulates
behavioral and cellular responses to mu opioids. Proc. Nat. Acad.
Sci. 96: 10385-10390, 1999.
*FIELD* CN
Ada Hamosh - updated: 6/23/2011
Paul J. Converse - updated: 3/13/2008
Ada Hamosh - updated: 2/10/2000
Victor A. McKusick - updated: 10/21/1999
Alan F. Scott - updated: 8/5/1997
*FIELD* CD
Victor A. McKusick: 12/13/1994
*FIELD* ED
alopez: 06/23/2011
terry: 6/23/2011
mgross: 3/18/2008
terry: 3/13/2008
carol: 5/3/2007
alopez: 2/10/2000
alopez: 11/15/1999
mgross: 10/29/1999
terry: 10/21/1999
psherman: 8/10/1999
alopez: 12/15/1997
terry: 8/5/1997
terry: 7/10/1997
alopez: 6/13/1997
jamie: 6/3/1997
jenny: 1/10/1997
terry: 12/30/1996
mark: 1/23/1996
mark: 1/22/1996
mark: 9/10/1995
terry: 6/3/1995
mark: 5/16/1995
terry: 3/7/1995
carol: 12/13/1994