ID PLCB4_HUMAN Reviewed; 1175 AA. AC Q15147; B7ZLK6; E2QRH8; Q17R56; Q5JYS8; Q5JYS9; Q5JYT0; Q5JYT3; Q5JYT4; AC Q9BQW5; Q9BQW6; Q9BQW8; Q9UJQ2; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 05-DEC-2001, sequence version 3. DT 27-MAR-2024, entry version 224. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 {ECO:0000305}; DE EC=3.1.4.11 {ECO:0000250|UniProtKB:Q07722}; DE AltName: Full=Phosphoinositide phospholipase C-beta-4; DE AltName: Full=Phospholipase C-beta-4; DE Short=PLC-beta-4; GN Name=PLCB4 {ECO:0000312|HGNC:HGNC:9059}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Retina; RX PubMed=8530101; DOI=10.1006/geno.1995.1214; RA Alvarez R.A., Ghalayini A.J., Xu P., Hardcastle A., Bhattacharya S., RA Rao P.N., Pettenati M.J., Anderson R.E., Baehr W.; RT "cDNA sequence and gene locus of the human retinal phosphoinositide- RT specific phospholipase-C beta 4 (PLCB4)."; RL Genomics 29:53-61(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT THR-21. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PROTEIN SEQUENCE OF 2-11; 79-88; 154-163; 181-195; 220-227; 255-266; RP 366-377; 435-455; 516-528; 577-586; 606-717; 762-780; 786-797; 822-847; RP 854-871; 883-908; 910-918; 1023-1039 AND 1139-1149, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-886, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [6] RP VARIANTS ARCND2A THR-329; HIS-621; CYS-621; CYS-623 AND HIS-650. RX PubMed=22560091; DOI=10.1016/j.ajhg.2012.04.002; RA Rieder M.J., Green G.E., Park S.S., Stamper B.D., Gordon C.T., RA Johnson J.M., Cunniff C.M., Smith J.D., Emery S.B., Lyonnet S., Amiel J., RA Holder M., Heggie A.A., Bamshad M.J., Nickerson D.A., Cox T.C., Hing A.V., RA Horst J.A., Cunningham M.L.; RT "A human homeotic transformation resulting from mutations in PLCB4 and RT GNAI3 causes auriculocondylar syndrome."; RL Am. J. Hum. Genet. 90:907-914(2012). RN [7] RP ERRATUM OF PUBMED:22560091. RA Rieder M.J., Green G.E., Park S.S., Stamper B.D., Gordon C.T., RA Johnson J.M., Cunniff C.M., Smith J.D., Emery S.B., Lyonnet S., Amiel J., RA Holder M., Heggie A.A., Bamshad M.J., Nickerson D.A., Cox T.C., Hing A.V., RA Horst J.A., Cunningham M.L.; RL Am. J. Hum. Genet. 90:1116-1116(2012). RN [8] RP INVOLVEMENT IN ARCND2B. RX PubMed=23913798; DOI=10.1002/ajmg.a.36066; RA Kido Y., Gordon C.T., Sakazume S., Ben Bdira E., Dattani M., Wilson L.C., RA Lyonnet S., Murakami N., Cunningham M.L., Amiel J., Nagai T.; RT "Further characterization of atypical features in auriculocondylar syndrome RT caused by recessive PLCB4 mutations."; RL Am. J. Med. Genet. A 161A:2339-2346(2013). RN [9] RP VARIANTS ARCND2A VAL-358; ASN-360; VAL-360; CYS-621; LEU-621 AND HIS-621, RP INVOLVEMENT IN ARCND2A, AND INVOLVEMENT IN ARCND2B. RX PubMed=23315542; DOI=10.1136/jmedgenet-2012-101331; RA Gordon C.T., Vuillot A., Marlin S., Gerkes E., Henderson A., Al-Kindy A., RA Holder-Espinasse M., Park S.S., Omarjee A., Sanchis-Borja M., Bdira E.B., RA Oufadem M., Sikkema-Raddatz B., Stewart A., Palmer R., McGowan R., RA Petit F., Delobel B., Speicher M.R., Aurora P., Kilner D., Pellerin P., RA Simon M., Bonnefont J.P., Tobias E.S., Garcia-Minaur S., RA Bitner-Glindzicz M., Lindholm P., Meijer B.A., Abadie V., Denoyelle F., RA Vazquez M.P., Rotky-Fast C., Couloigner V., Pierrot S., Manach Y., RA Breton S., Hendriks Y.M., Munnich A., Jakobsen L., Kroisel P., Lin A., RA Kaban L.B., Basel-Vanagaite L., Wilson L., Cunningham M.L., Lyonnet S., RA Amiel J.; RT "Heterogeneity of mutational mechanisms and modes of inheritance in RT auriculocondylar syndrome."; RL J. Med. Genet. 50:174-186(2013). RN [10] RP INVOLVEMENT IN ARCND2B. RX PubMed=27007857; DOI=10.1002/ajmg.a.37625; RA Leoni C., Gordon C.T., Della Marca G., Giorgio V., Onesimo R., Perrino F., RA Cianfoni A., Cerchiari A., Amiel J., Zampino G.; RT "Respiratory and gastrointestinal dysfunctions associated with auriculo- RT condylar syndrome and a homozygous PLCB4 loss-of-function mutation."; RL Am. J. Med. Genet. A 170:1471-1478(2016). RN [11] RP VARIANTS ARCND2A ARG-328 AND GLN-358. RX PubMed=28328130; DOI=10.1002/ajmg.a.38101; RA Romanelli Tavares V.L., Zechi-Ceide R.M., Bertola D.R., Gordon C.T., RA Ferreira S.G., Hsia G.S., Yamamoto G.L., Ezquina S.A., Kokitsu-Nakata N.M., RA Vendramini-Pittoli S., Freitas R.S., Souza J., Raposo-Amaral C.A., Zatz M., RA Amiel J., Guion-Almeida M.L., Passos-Bueno M.R.; RT "Targeted molecular investigation in patients within the clinical spectrum RT of Auriculocondylar syndrome."; RL Am. J. Med. Genet. A 173:938-945(2017). RN [12] RP VARIANT ARCND2A HIS-621. RX PubMed=32201334; DOI=10.1016/j.ejmg.2020.103917; RA Nabil A., El Shafei S., El Shakankiri N.M., Habib A., Morsy H., RA Maddirevula S., Alkuraya F.S.; RT "A familial PLCB4 mutation causing auriculocondylar syndrome 2 with RT variable severity."; RL Eur. J. Med. Genet. 63:103917-103917(2020). RN [13] RP CHARACTERIZATION OF VARIANTS ARCND2A VAL-358; VAL-360; HIS-621 AND CYS-623, RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=35284927; DOI=10.1242/dmm.049320; RA Kanai S.M., Heffner C., Cox T.C., Cunningham M.L., Perez F.A., Bauer A.M., RA Reigan P., Carter C., Murray S.A., Clouthier D.E.; RT "Auriculocondylar syndrome 2 results from the dominant-negative action of RT PLCB4 variants."; RL Dis. Model. Mech. 15:0-0(2022). RN [14] RP VARIANTS ARCND2A ARG-339; PHE-569; CYS-621 AND HIS-621, AND INVOLVEMENT IN RP ARCND2B. RX PubMed=35170830; DOI=10.1002/humu.24349; RA Vegas N., Demir Z., Gordon C.T., Breton S., Romanelli Tavares V.L., RA Moisset H., Zechi-Ceide R., Kokitsu-Nakata N.M., Kido Y., Marlin S., RA Gherbi Halem S., Meerschaut I., Callewaert B., Chung B., Revencu N., RA Lehalle D., Petit F., Propst E.J., Papsin B.C., Phillips J.H., Jakobsen L., RA Le Tanno P., Thevenon J., McGaughran J., Gerkes E.H., Leoni C., Kroisel P., RA Tan T.Y., Henderson A., Terhal P., Basel-Salmon L., Alkindy A., White S.M., RA Passos-Bueno M.R., Pingault V., De Pontual L., Amiel J.; RT "Further delineation of auriculocondylar syndrome based on 14 novel cases RT and reassessment of 25 published cases."; RL Hum. Mutat. 43:582-594(2022). CC -!- FUNCTION: Activated phosphatidylinositol-specific phospholipase C CC enzymes catalyze the production of the second messenger molecules CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) involved in CC G-protein coupled receptor signaling pathways. PLCB4 is a direct CC effector of the endothelin receptor signaling pathway that plays an CC essential role in lower jaw and middle ear structures development CC (PubMed:35284927). {ECO:0000250|UniProtKB:Q07722, CC ECO:0000269|PubMed:35284927}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5- CC bisphosphate) + H2O = 1D-myo-inositol 1,4,5-trisphosphate + a 1,2- CC diacyl-sn-glycerol + H(+); Xref=Rhea:RHEA:33179, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:58456, CC ChEBI:CHEBI:203600; EC=3.1.4.11; CC Evidence={ECO:0000250|UniProtKB:Q07722}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180; CC Evidence={ECO:0000250|UniProtKB:Q07722}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + H2O = CC 1D-myo-inositol 1-phosphate + a 1,2-diacyl-sn-glycerol + H(+); CC Xref=Rhea:RHEA:43484, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17815, ChEBI:CHEBI:57880, ChEBI:CHEBI:58433; CC Evidence={ECO:0000250|UniProtKB:Q07722}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43485; CC Evidence={ECO:0000250|UniProtKB:Q07722}; CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC -!- INTERACTION: CC Q15147; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-998637, EBI-16439278; CC Q15147; Q04864: REL; NbExp=3; IntAct=EBI-998637, EBI-307352; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35284927}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=2; CC IsoId=Q15147-1; Sequence=Displayed; CC Name=1; CC IsoId=Q15147-2; Sequence=VSP_004721, VSP_004722; CC Name=3; CC IsoId=Q15147-4; Sequence=VSP_037818; CC Name=4; CC IsoId=Q15147-5; Sequence=VSP_055182; CC -!- TISSUE SPECIFICITY: Preferentially expressed in the retina. CC -!- DISEASE: Auriculocondylar syndrome 2A (ARCND2A) [MIM:614669]: An CC autosomal dominant form of auriculocondylar syndrome, a craniofacial CC malformation syndrome characterized by variable mandibular anomalies, CC including mild to severe micrognathia, temporomandibular joint CC ankylosis, cleft palate, and a characteristic ear malformation that CC consists of separation of the lobule from the external ear, giving the CC appearance of a question mark (question-mark ear). Other frequently CC described features include prominent cheeks, cupped and posteriorly CC rotated ears, preauricular tags, and microstomia. Glossoptosis, CC masticatory abnormalities, orthodontic problems, and malocclusion occur CC in a majority of affected subjects. {ECO:0000269|PubMed:22560091, CC ECO:0000269|PubMed:23315542, ECO:0000269|PubMed:28328130, CC ECO:0000269|PubMed:32201334, ECO:0000269|PubMed:35170830, CC ECO:0000269|PubMed:35284927}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Auriculocondylar syndrome 2B (ARCND2B) [MIM:620458]: An CC autosomal recessive form of auriculocondylar syndrome, a craniofacial CC malformation syndrome characterized by variable mandibular anomalies, CC including mild to severe micrognathia, temporomandibular joint CC ankylosis, cleft palate, and a characteristic ear malformation that CC consists of separation of the lobule from the external ear, giving the CC appearance of a question mark (question-mark ear). Other frequently CC described features include prominent cheeks, cupped and posteriorly CC rotated ears, preauricular tags, and microstomia. Glossoptosis, CC masticatory abnormalities, orthodontic problems, and malocclusion occur CC in a majority of affected subjects. {ECO:0000269|PubMed:23315542, CC ECO:0000269|PubMed:23913798, ECO:0000269|PubMed:27007857, CC ECO:0000269|PubMed:35170830}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L41349; AAB02027.1; -; mRNA. DR EMBL; AL121898; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL121909; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL023805; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL031652; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC117458; AAI17459.1; -; mRNA. DR EMBL; BC143868; AAI43869.1; -; mRNA. DR CCDS; CCDS13104.1; -. [Q15147-4] DR CCDS; CCDS13105.1; -. [Q15147-1] DR CCDS; CCDS54447.1; -. [Q15147-5] DR RefSeq; NP_000924.3; NM_000933.3. [Q15147-4] DR RefSeq; NP_001166117.1; NM_001172646.1. [Q15147-5] DR RefSeq; NP_877949.2; NM_182797.2. [Q15147-1] DR RefSeq; XP_016883369.1; XM_017027880.1. DR RefSeq; XP_016883370.1; XM_017027881.1. DR AlphaFoldDB; Q15147; -. DR SMR; Q15147; -. DR BioGRID; 111348; 25. DR DIP; DIP-36735N; -. DR IntAct; Q15147; 6. DR STRING; 9606.ENSP00000367762; -. DR GlyGen; Q15147; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15147; -. DR PhosphoSitePlus; Q15147; -. DR SwissPalm; Q15147; -. DR BioMuta; PLCB4; -. DR EPD; Q15147; -. DR jPOST; Q15147; -. DR MassIVE; Q15147; -. DR MaxQB; Q15147; -. DR PaxDb; 9606-ENSP00000367762; -. DR PeptideAtlas; Q15147; -. DR ProteomicsDB; 15257; -. DR ProteomicsDB; 60459; -. [Q15147-1] DR ProteomicsDB; 60460; -. [Q15147-2] DR ProteomicsDB; 60461; -. [Q15147-4] DR ProteomicsDB; 63514; -. DR Pumba; Q15147; -. DR Antibodypedia; 24070; 42 antibodies from 17 providers. DR DNASU; 5332; -. DR Ensembl; ENST00000378493.6; ENSP00000367754.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000378501.3; ENSP00000367762.2; ENSG00000101333.19. [Q15147-4] DR Ensembl; ENST00000685110.1; ENSP00000510632.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000685310.1; ENSP00000510124.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000685823.1; ENSP00000508676.1; ENSG00000101333.19. [Q15147-5] DR Ensembl; ENST00000685859.1; ENSP00000510302.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000686313.1; ENSP00000508595.1; ENSG00000101333.19. [Q15147-4] DR Ensembl; ENST00000686871.1; ENSP00000510118.1; ENSG00000101333.19. [Q15147-4] DR Ensembl; ENST00000686976.1; ENSP00000508600.1; ENSG00000101333.19. [Q15147-4] DR Ensembl; ENST00000688656.1; ENSP00000509912.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000689910.1; ENSP00000508650.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000693005.1; ENSP00000509597.1; ENSG00000101333.19. [Q15147-1] DR Ensembl; ENST00000693752.1; ENSP00000508677.1; ENSG00000101333.19. [Q15147-4] DR GeneID; 5332; -. DR KEGG; hsa:5332; -. DR UCSC; uc010gbx.4; human. [Q15147-1] DR AGR; HGNC:9059; -. DR CTD; 5332; -. DR DisGeNET; 5332; -. DR GeneCards; PLCB4; -. DR HGNC; HGNC:9059; PLCB4. DR HPA; ENSG00000101333; Tissue enhanced (brain, salivary gland). DR MalaCards; PLCB4; -. DR MIM; 600810; gene. DR MIM; 614669; phenotype. DR MIM; 620458; phenotype. DR neXtProt; NX_Q15147; -. DR OpenTargets; ENSG00000101333; -. DR Orphanet; 137888; Auriculocondylar syndrome. DR PharmGKB; PA33387; -. DR VEuPathDB; HostDB:ENSG00000101333; -. DR eggNOG; KOG1265; Eukaryota. DR GeneTree; ENSGT00940000156426; -. DR HOGENOM; CLU_002738_2_1_1; -. DR InParanoid; Q15147; -. DR OMA; AMQKAHC; -. DR OrthoDB; 2900494at2759; -. DR PhylomeDB; Q15147; -. DR TreeFam; TF352235; -. DR BRENDA; 3.1.4.11; 2681. DR PathwayCommons; Q15147; -. DR Reactome; R-HSA-112043; PLC beta mediated events. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; Q15147; -. DR BioGRID-ORCS; 5332; 7 hits in 1150 CRISPR screens. DR ChiTaRS; PLCB4; human. DR GeneWiki; PLCB4; -. DR GenomeRNAi; 5332; -. DR Pharos; Q15147; Tbio. DR PRO; PR:Q15147; -. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; Q15147; Protein. DR Bgee; ENSG00000101333; Expressed in parotid gland and 196 other cell types or tissues. DR ExpressionAtlas; Q15147; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IBA:GO_Central. DR GO; GO:0004629; F:phospholipase C activity; TAS:Reactome. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IBA:GO_Central. DR CDD; cd00275; C2_PLC_like; 1. DR CDD; cd16211; EFh_PI-PLCbeta4; 1. DR CDD; cd13361; PH_PLC_beta; 1. DR CDD; cd08591; PI-PLCc_beta; 1. DR Gene3D; 2.30.29.240; -; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR Gene3D; 3.20.20.190; Phosphatidylinositol (PI) phosphodiesterase; 1. DR Gene3D; 1.20.1230.10; Phospholipase C beta, distal C-terminal domain; 1. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR001192; PI-PLC_fam. DR InterPro; IPR016280; PLC-beta. DR InterPro; IPR042531; PLC-beta_C_sf. DR InterPro; IPR009535; PLC-beta_CS. DR InterPro; IPR037862; PLC-beta_PH. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR015359; PLC_EF-hand-like. DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom. DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y. DR PANTHER; PTHR10336:SF211; 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE BETA-4; 1. DR PANTHER; PTHR10336; PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF06631; DUF1154; 1. DR Pfam; PF09279; EF-hand_like; 1. DR Pfam; PF17787; PH_14; 1. DR Pfam; PF00388; PI-PLC-X; 1. DR Pfam; PF00387; PI-PLC-Y; 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; SSF69989; C-terminal domain of PLC-beta; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF47473; EF-hand; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF51695; PLC-like phosphodiesterases; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1. DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1. DR Genevisible; Q15147; HS. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Calcium; Cell membrane; KW Direct protein sequencing; Disease variant; Hydrolase; Lipid degradation; KW Lipid metabolism; Membrane; Phosphoprotein; Reference proteome; Transducer. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.4" FT CHAIN 2..1175 FT /note="1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase beta-4" FT /id="PRO_0000088495" FT DOMAIN 313..463 FT /note="PI-PLC X-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT DOMAIN 565..681 FT /note="PI-PLC Y-box" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271" FT DOMAIN 684..809 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT REGION 482..511 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 863..895 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1082..1110 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 492..507 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 879..895 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1093..1110 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 328 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT ACT_SITE 375 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.4" FT MOD_RES 886 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692" FT VAR_SEQ 1..153 FT /note="Missing (in isoform 1)" FT /evidence="ECO:0000303|PubMed:8530101" FT /id="VSP_004721" FT VAR_SEQ 154..167 FT /note="LAFMTNTNGKIPVR -> MNNNWNVCFFLFCP (in isoform 1)" FT /evidence="ECO:0000303|PubMed:8530101" FT /id="VSP_004722" FT VAR_SEQ 535 FT /note="V -> VKKASDDLEHENN (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_055182" FT VAR_SEQ 1154..1175 FT /note="AKEMQQMVKLEAEMDRRPATVV -> LLKSCHAVSQTQGEGDAADGEIGSRD FT GPQTSNSSMKLQNAN (in isoform 3)" FT /evidence="ECO:0000305" FT /id="VSP_037818" FT VARIANT 21 FT /note="A -> T (in dbSNP:rs6077510)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_056694" FT VARIANT 328 FT /note="H -> R (in ARCND2A; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:28328130" FT /id="VAR_088767" FT VARIANT 329 FT /note="N -> T (in ARCND2A; likely pathogenic; FT dbSNP:rs387907179)" FT /evidence="ECO:0000269|PubMed:22560091" FT /id="VAR_068559" FT VARIANT 339 FT /note="G -> R (in ARCND2A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35170830" FT /id="VAR_088768" FT VARIANT 358 FT /note="E -> Q (in ARCND2A; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:28328130" FT /id="VAR_088769" FT VARIANT 358 FT /note="E -> V (in ARCND2A; likely pathogenic; decreased FT function in phospholipase C-activating endothelin receptor FT signaling pathway; dominant negative effect; no effect on FT localization to cell membrane)" FT /evidence="ECO:0000269|PubMed:23315542, FT ECO:0000269|PubMed:35284927" FT /id="VAR_088770" FT VARIANT 360 FT /note="D -> N (in ARCND2A; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:23315542" FT /id="VAR_088771" FT VARIANT 360 FT /note="D -> V (in ARCND2A; likely pathogenic; decreased FT function in phospholipase C-activating endothelin receptor FT signaling pathway; dominant negative effect; no effect on FT localization to cell membrane)" FT /evidence="ECO:0000269|PubMed:23315542, FT ECO:0000269|PubMed:35284927" FT /id="VAR_088772" FT VARIANT 569 FT /note="I -> F (in ARCND2A; uncertain significance)" FT /evidence="ECO:0000269|PubMed:35170830" FT /id="VAR_088773" FT VARIANT 621 FT /note="R -> C (in ARCND2A; pathogenic; dbSNP:rs397514482)" FT /evidence="ECO:0000269|PubMed:22560091, FT ECO:0000269|PubMed:23315542, ECO:0000269|PubMed:35170830" FT /id="VAR_068560" FT VARIANT 621 FT /note="R -> H (in ARCND2A; pathogenic; decreased function FT in phospholipase C-activating endothelin receptor signaling FT pathway; dominant negative effect; no effect on FT localization to cell membrane; dbSNP:rs397514481)" FT /evidence="ECO:0000269|PubMed:22560091, FT ECO:0000269|PubMed:23315542, ECO:0000269|PubMed:32201334, FT ECO:0000269|PubMed:35170830, ECO:0000269|PubMed:35284927" FT /id="VAR_068561" FT VARIANT 621 FT /note="R -> L (in ARCND2A; likely pathogenic)" FT /evidence="ECO:0000269|PubMed:23315542" FT /id="VAR_088774" FT VARIANT 623 FT /note="Y -> C (in ARCND2A; likely pathogenic; decreased FT function in phospholipase C-activating endothelin receptor FT signaling pathway; dominant negative effect; no effect on FT localization to cell membrane; dbSNP:rs397514480)" FT /evidence="ECO:0000269|PubMed:22560091, FT ECO:0000269|PubMed:35284927" FT /id="VAR_068562" FT VARIANT 650 FT /note="N -> H (in ARCND2A; likely pathogenic; FT dbSNP:rs397514483)" FT /evidence="ECO:0000269|PubMed:22560091" FT /id="VAR_068563" FT VARIANT 710 FT /note="G -> S (in dbSNP:rs6118603)" FT /id="VAR_056695" FT CONFLICT 447 FT /note="A -> P (in Ref. 1; AAB02027)" FT /evidence="ECO:0000305" FT CONFLICT 757 FT /note="F -> L (in Ref. 1; AAB02027)" FT /evidence="ECO:0000305" FT CONFLICT 787 FT /note="L -> P (in Ref. 1; AAB02027)" FT /evidence="ECO:0000305" FT CONFLICT 840 FT /note="K -> T (in Ref. 1; AAB02027)" FT /evidence="ECO:0000305" FT CONFLICT 902 FT /note="A -> P (in Ref. 1; AAB02027)" FT /evidence="ECO:0000305" SQ SEQUENCE 1175 AA; 134464 MW; AB2C8EB99EF57357 CRC64; MAKPYEFNWQ KEVPSFLQEG AVFDRYEEES FVFEPNCLFK VDEFGFFLTW RSEGKEGQVL ECSLINSIRS GAIPKDPKIL AALEAVGKSE NDLEGRIVCV CSGTDLVNIS FTYMVAENPE VTKQWVEGLR SIIHNFRANN VSPMTCLKKH WMKLAFMTNT NGKIPVRSIT RTFASGKTEK VIFQALKELG LPSGKNDEIE PTAFSYEKFY ELTQKICPRT DIEDLFKKIN GDKTDYLTVD QLVSFLNEHQ RDPRLNEILF PFYDAKRAMQ IIEMYEPDED LKKKGLISSD GFCRYLMSDE NAPVFLDRLE LYQEMDHPLA HYFISSSHNT YLTGRQFGGK SSVEMYRQVL LAGCRCVELD CWDGKGEDQE PIITHGKAMC TDILFKDVIQ AIKETAFVTS EYPVILSFEN HCSKYQQYKM SKYCEDLFGD LLLKQALESH PLEPGRALPS PNDLKRKILI KNKRLKPEVE KKQLEALRSM MEAGESASPA NILEDDNEEE IESADQEEEA HPEFKFGNEL SADDLGHKEA VANSVKKGLV TVEDEQAWMA SYKYVGATTN IHPYLSTMIN YAQPVKFQGF HVAEERNIHY NMSSFNESVG LGYLKTHAIE FVNYNKRQMS RIYPKGGRVD SSNYMPQIFW NAGCQMVSLN YQTPDLAMQL NQGKFEYNGS CGYLLKPDFM RRPDRTFDPF SETPVDGVIA ATCSVQVISG QFLSDKKIGT YVEVDMYGLP TDTIRKEFRT RMVMNNGLNP VYNEESFVFR KVILPDLAVL RIAVYDDNNK LIGQRILPLD GLQAGYRHIS LRNEGNKPLS LPTIFCNIVL KTYVPDGFGD IVDALSDPKK FLSITEKRAD QMRAMGIETS DIADVPSDTS KNDKKGKANT AKANVTPQSS SELRPTTTAA LASGVEAKKG IELIPQVRIE DLKQMKAYLK HLKKQQKELN SLKKKHAKEH STMQKLHCTQ VDKIVAQYDK EKSTHEKILE KAMKKKGGSN CLEMKKETEI KIQTLTSDHK SKVKEIVAQH TKEWSEMINT HSAEEQEIRD LHLSQQCELL KKLLINAHEQ QTQQLKLSHD RESKEMRAHQ AKISMENSKA ISQDKSIKNK AERERRVREL NSSNTKKFLE ERKRLAMKQS KEMDQLKKVQ LEHLEFLEKQ NEQAKEMQQM VKLEAEMDRR PATVV //