ID PLCZ1_HUMAN Reviewed; 608 AA.
AC Q86YW0; Q08AQ7; Q96J70;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 27-MAR-2024, entry version 162.
DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1;
DE EC=3.1.4.11;
DE AltName: Full=Phosphoinositide phospholipase C-zeta-1;
DE AltName: Full=Phospholipase C-zeta-1 {ECO:0000303|PubMed:12416999};
DE Short=PLC-zeta-1 {ECO:0000303|PubMed:12416999};
DE AltName: Full=Testis-development protein NYD-SP27;
GN Name=PLCZ1 {ECO:0000312|HGNC:HGNC:19218};
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] {ECO:0000305, ECO:0000312|EMBL:AAN71895.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Testis {ECO:0000312|EMBL:AAN71895.1};
RX PubMed=12416999; DOI=10.1530/rep.0.1240611;
RA Cox L.J., Larman M.G., Saunders C.M., Hashimoto K., Swann K., Lai F.A.;
RT "Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+
RT oscillations, activation and development of mouse oocytes.";
RL Reproduction 124:611-623(2002).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAK61372.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Testis {ECO:0000312|EMBL:AAK61372.1};
RX PubMed=14697805; DOI=10.1016/s0140-6736(03)15100-8;
RA Zhu H., Zhu J.X., Lo P.S., Li J., Leung K.M., Rowlands D.K., Tsang L.L.,
RA Yu M.K., Jiang J.L., Lam S.Y., Chung Y.W., Zhou Z., Sha J., Chang Chan H.;
RT "Rescue of defective pancreatic secretion in cystic-fibrosis cells by
RT suppression of a novel isoform of phospholipase C.";
RL Lancet 362:2059-2065(2003).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAF84968.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis {ECO:0000312|EMBL:BAF84968.1};
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4] {ECO:0000305, ECO:0000312|EMBL:AAI25068.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=15579586; DOI=10.1530/rep.1.00484;
RA Rogers N.T., Hobson E., Pickering S., Lai F.A., Braude P., Swann K.;
RT "Phospholipase Czeta causes Ca2+ oscillations and parthenogenetic
RT activation of human oocytes.";
RL Reproduction 128:697-702(2004).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN SPGF17, VARIANT SPGF17
RP PHE-489, AND CHARACTERIZATION OF VARIANT SPGF17 PHE-489.
RX PubMed=26721930; DOI=10.1093/hmg/ddv617;
RA Escoffier J., Lee H.C., Yassine S., Zouari R., Martinez G., Karaouzene T.,
RA Coutton C., Kherraf Z.E., Halouani L., Triki C., Nef S., Thierry-Mieg N.,
RA Savinov S.N., Fissore R., Ray P.F., Arnoult C.;
RT "Homozygous mutation of PLCZ1 leads to defective human oocyte activation
RT and infertility that is not rescued by the WW-binding protein PAWP.";
RL Hum. Mol. Genet. 25:878-891(2016).
CC -!- FUNCTION: The production of the second messenger molecules
CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated
CC by activated phosphatidylinositol-specific phospholipase C enzymes. In
CC vitro, hydrolyzes PtdIns(4,5)P2 in a Ca(2+)-dependent manner. Triggers
CC intracellular Ca(2+) oscillations in oocytes solely during M phase and
CC is involved in inducing oocyte activation and initiating embryonic
CC development up to the blastocyst stage. Is therefore a strong candidate
CC for the egg-activating soluble sperm factor that is transferred from
CC the sperm into the egg cytoplasm following gamete membrane fusion. May
CC exert an inhibitory effect on phospholipase-C-coupled processes that
CC depend on calcium ions and protein kinase C, including CFTR trafficking
CC and function. {ECO:0000250|UniProtKB:Q8K4D7,
CC ECO:0000269|PubMed:12416999, ECO:0000269|PubMed:14697805,
CC ECO:0000269|PubMed:15579586, ECO:0000269|PubMed:26721930, ECO:0000305}.
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:Q8K4D7};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33180;
CC Evidence={ECO:0000250|UniProtKB:Q8K4D7};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q8K4D7};
CC -!- SUBUNIT: Interacts via its C2 domain with PtdIns(3)P and, to a lesser
CC extent, PtdIns(5)P in vitro. {ECO:0000250|UniProtKB:Q8K4D7}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8K4D7}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q8K4D7}.
CC Note=Exhibits alternative cytoplasmic/nuclear localization during
CC development. Translocates from the pronucleus into cytoplasm upon
CC nuclear envelope breakdown for mitosis and localizes again to the
CC pronucleus at interphase following meiosis and mitosis (By similarity).
CC {ECO:0000250|UniProtKB:Q8K4D7}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1 {ECO:0000269|PubMed:12416999, ECO:0000269|PubMed:14697805,
CC ECO:0000269|PubMed:14702039};
CC IsoId=Q86YW0-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334};
CC IsoId=Q86YW0-2; Sequence=VSP_052862;
CC Name=3;
CC IsoId=Q86YW0-3; Sequence=VSP_035076;
CC -!- TISSUE SPECIFICITY: Expressed specifically in testis and sperm. Weakly
CC expressed in pancreatic-duct cells. Up-regulated in pancreatic-duct
CC cells from patients with cystic fibrosis. {ECO:0000269|PubMed:12416999,
CC ECO:0000269|PubMed:14697805, ECO:0000269|PubMed:26721930}.
CC -!- DOMAIN: The EF-hand and C2 domains are essential for triggering Ca(2+)
CC oscillating activity and the regulation of PLCZ1 enzyme activity.
CC {ECO:0000250|UniProtKB:Q8K4D7}.
CC -!- DOMAIN: The X-Y linker region between PI-PLC X-box and Y-box domains
CC may be a target for proteolysis and may play an important regulatory
CC role during fertilization. {ECO:0000250|UniProtKB:Q8K4D7}.
CC -!- DISEASE: Spermatogenic failure 17 (SPGF17) [MIM:617214]: An autosomal
CC recessive infertility disorder due to failure of oocyte activation and
CC fertilization by sperm that otherwise exhibits normal morphology.
CC {ECO:0000269|PubMed:26721930}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; AF532185; AAN71895.1; -; mRNA.
DR EMBL; AY035866; AAK61372.1; -; mRNA.
DR EMBL; AK292279; BAF84968.1; -; mRNA.
DR EMBL; BC125067; AAI25068.1; -; mRNA.
DR CCDS; CCDS81671.1; -. [Q86YW0-2]
DR CCDS; CCDS8680.1; -. [Q86YW0-1]
DR RefSeq; NP_001317698.1; NM_001330769.1. [Q86YW0-2]
DR RefSeq; NP_001317703.1; NM_001330774.1. [Q86YW0-3]
DR RefSeq; NP_149114.2; NM_033123.3. [Q86YW0-1]
DR AlphaFoldDB; Q86YW0; -.
DR SMR; Q86YW0; -.
DR BioGRID; 124625; 17.
DR IntAct; Q86YW0; 9.
DR STRING; 9606.ENSP00000266505; -.
DR iPTMnet; Q86YW0; -.
DR PhosphoSitePlus; Q86YW0; -.
DR BioMuta; PLCZ1; -.
DR DMDM; 74714209; -.
DR MassIVE; Q86YW0; -.
DR PaxDb; 9606-ENSP00000266505; -.
DR PeptideAtlas; Q86YW0; -.
DR ProteomicsDB; 70479; -. [Q86YW0-1]
DR ProteomicsDB; 70480; -. [Q86YW0-2]
DR ProteomicsDB; 70481; -. [Q86YW0-3]
DR Antibodypedia; 52401; 154 antibodies from 18 providers.
DR DNASU; 89869; -.
DR Ensembl; ENST00000266505.12; ENSP00000266505.7; ENSG00000139151.16. [Q86YW0-1]
DR Ensembl; ENST00000539875.5; ENSP00000445026.1; ENSG00000139151.16. [Q86YW0-2]
DR GeneID; 89869; -.
DR KEGG; hsa:89869; -.
DR MANE-Select; ENST00000266505.12; ENSP00000266505.7; NM_033123.4; NP_149114.2.
DR UCSC; uc058lrt.1; human. [Q86YW0-1]
DR AGR; HGNC:19218; -.
DR CTD; 89869; -.
DR DisGeNET; 89869; -.
DR GeneCards; PLCZ1; -.
DR HGNC; HGNC:19218; PLCZ1.
DR HPA; ENSG00000139151; Tissue enriched (testis).
DR MalaCards; PLCZ1; -.
DR MIM; 608075; gene.
DR MIM; 617214; phenotype.
DR neXtProt; NX_Q86YW0; -.
DR OpenTargets; ENSG00000139151; -.
DR PharmGKB; PA134875646; -.
DR VEuPathDB; HostDB:ENSG00000139151; -.
DR eggNOG; KOG0169; Eukaryota.
DR GeneTree; ENSGT00940000159950; -.
DR HOGENOM; CLU_002738_0_3_1; -.
DR InParanoid; Q86YW0; -.
DR OrthoDB; 2900494at2759; -.
DR PhylomeDB; Q86YW0; -.
DR TreeFam; TF313216; -.
DR PathwayCommons; Q86YW0; -.
DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol.
DR SignaLink; Q86YW0; -.
DR BioGRID-ORCS; 89869; 11 hits in 1152 CRISPR screens.
DR ChiTaRS; PLCZ1; human.
DR GenomeRNAi; 89869; -.
DR Pharos; Q86YW0; Tbio.
DR PRO; PR:Q86YW0; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q86YW0; Protein.
DR Bgee; ENSG00000139151; Expressed in sperm and 107 other cell types or tissues.
DR ExpressionAtlas; Q86YW0; baseline and differential.
DR Genevisible; Q86YW0; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0045120; C:pronucleus; IEA:Ensembl.
DR GO; GO:0061827; C:sperm head; IMP:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IDA:UniProtKB.
DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IMP:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB.
DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IMP:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl.
DR GO; GO:0007343; P:egg activation; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:UniProtKB.
DR GO; GO:0060470; P:positive regulation of cytosolic calcium ion concentration involved in egg activation; IDA:UniProtKB.
DR CDD; cd00275; C2_PLC_like; 1.
DR CDD; cd16204; EFh_PI-PLCzeta; 1.
DR CDD; cd08595; PI-PLCc_zeta; 1.
DR Gene3D; 2.60.40.150; C2 domain; 1.
DR Gene3D; 1.10.238.10; EF-hand; 2.
DR Gene3D; 3.20.20.190; Phosphatidylinositol (PI) phosphodiesterase; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR001192; PI-PLC_fam.
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:SF29; 1-PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE PHOSPHODIESTERASE ZETA-1; 1.
DR PANTHER; PTHR10336; PHOSPHOINOSITIDE-SPECIFIC PHOSPHOLIPASE C FAMILY PROTEIN; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF09279; EF-hand_like; 1.
DR Pfam; PF00388; PI-PLC-X; 1.
DR Pfam; PF00387; PI-PLC-Y; 1.
DR PRINTS; PR00390; PHPHLIPASEC.
DR SMART; SM00239; C2; 1.
DR SMART; SM00148; PLCXc; 1.
DR SMART; SM00149; PLCYc; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR SUPFAM; SSF47473; EF-hand; 1.
DR SUPFAM; SSF51695; PLC-like phosphodiesterases; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1.
DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cytoplasm; Developmental protein;
KW Disease variant; Fertilization; Hydrolase; Lipid degradation;
KW Lipid metabolism; Nucleus; Reference proteome; Transducer.
FT CHAIN 1..608
FT /note="1-phosphatidylinositol 4,5-bisphosphate
FT phosphodiesterase zeta-1"
FT /id="PRO_0000347244"
FT DOMAIN 35..70
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 155..299
FT /note="PI-PLC X-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00270"
FT DOMAIN 349..465
FT /note="PI-PLC Y-box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00271"
FT DOMAIN 465..589
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT REGION 305..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 170
FT /evidence="ECO:0000250|UniProtKB:P10688,
FT ECO:0000255|PROSITE-ProRule:PRU00270"
FT ACT_SITE 215
FT /evidence="ECO:0000250|UniProtKB:P10688,
FT ECO:0000255|PROSITE-ProRule:PRU00270"
FT VAR_SEQ 1..104
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14697805"
FT /id="VSP_035076"
FT VAR_SEQ 46..238
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_052862"
FT VARIANT 489
FT /note="I -> F (in SPGF17; loss of function in egg
FT activation; dbSNP:rs757326350)"
FT /evidence="ECO:0000269|PubMed:26721930"
FT /id="VAR_077876"
FT VARIANT 500
FT /note="S -> L (in dbSNP:rs10505830)"
FT /id="VAR_050542"
FT CONFLICT 294
FT /note="I -> V (in Ref. 2; AAK61372)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="I -> T (in Ref. 2; AAK61372)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 608 AA; 70411 MW; 540A81A2DDB9537B CRC64;
MEMRWFLSKI QDDFRGGKIN LEKTQRLLEK LDIRCSYIHV KQIFKDNDRL KQGRITIEEF
RAIYRIITHR EEIIEIFNTY SENRKILLAS NLAQFLTQEQ YAAEMSKAIA FEIIQKYEPI
EEVRKAHQMS LEGFTRYMDS RECLLFKNEC RKVYQDMTHP LNDYFISSSH NTYLVSDQLL
GPSDLWGYVS ALVKGCRCLE IDCWDGAQNE PVVYHGYTLT SKLLFKTVIQ AIHKYAFMTS
DYPVVLSLEN HCSTAQQEVM ADNLQATFGE SLLSDMLDDF PDTLPSPEAL KFKILVKNKK
IGTLKETHER KGSDKRGDNQ DKETGVKKLP GVMLFKKKKT RKLKIALALS DLVIYTKAEK
FKSFQHSRLY QQFNENNSIG ETQARKLSKL RVHEFIFHTR KFITRIYPKA TRADSSNFNP
QEFWNIGCQM VALNFQTPGL PMDLQNGKFL DNGGSGYILK PHFLRESKSY FNPSNIKEGM
PITLTIRLIS GIQLPLTHSS SNKGDSLVII EVFGVPNDQM KQQTRVIKKN AFSPRWNETF
TFIIHVPELA LIRFVVEGQG LIAGNEFLGQ YTLPLLCMNK GYRRIPLFSR MGESLEPASL
FVYVWYVR
//
