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Protein

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2

Gene

PLCG2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. It is a crucial enzyme in transmembrane signaling.

Catalytic activityi

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei327PROSITE-ProRule annotation1
Active sitei372PROSITE-ProRule annotation1

GO - Molecular functioni

  • phosphatidylinositol phospholipase C activity Source: UniProtKB
  • phospholipase C activity Source: Reactome
  • phosphotyrosine residue binding Source: CAFA

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Transducer
Biological processLipid degradation, Lipid metabolism
LigandCalcium

Enzyme and pathway databases

BioCyciMetaCyc:HS06773-MONOMER
BRENDAi3.1.4.11 2681
ReactomeiR-HSA-114604 GPVI-mediated activation cascade
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-2424491 DAP12 signaling
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5621480 Dectin-2 family
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
SignaLinkiP16885
SIGNORiP16885

Protein family/group databases

MoonDBiP16885 Predicted

Chemistry databases

SwissLipidsiSLP:000000647

Names & Taxonomyi

Protein namesi
Recommended name:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 (EC:3.1.4.11)
Alternative name(s):
Phosphoinositide phospholipase C-gamma-2
Phospholipase C-IV
Short name:
PLC-IV
Phospholipase C-gamma-2
Short name:
PLC-gamma-2
Gene namesi
Name:PLCG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000197943.9
HGNCiHGNC:9066 PLCG2
MIMi600220 gene
neXtProtiNX_P16885

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Familial cold autoinflammatory syndrome 3 (FCAS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B-cells, defective B-cells, increased susceptibility to infection, and increased risk of autoimmune disorders.
See also OMIM:614468
Autoinflammation, antibody deficiency, and immune dysregulation PLCG2-associated (APLAID)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant systemic disorder characterized by recurrent blistering skin lesions with a dense inflammatory infiltrate and variable involvement of other tissues, including joints, the eye, and the gastrointestinal tract. Affected individuals have a mild humoral immune deficiency associated with recurrent sinopulmonary infections, but no evidence of circulating autoantibodies.
See also OMIM:614878
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069211707S → Y in APLAID; results in increased epidermal growth factor-stimulated production of intracellular IP3 and increased intracellular calcium release; is a hypermorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs397514562EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5336
MalaCardsiPLCG2
MIMi614468 phenotype
614878 phenotype
OpenTargetsiENSG00000197943
Orphaneti324530 Autoinflammation-PLCG2-associated antibody deficiency-immune dysregulation
300359 PLCG2-associated antibody deficiency and immune dysregulation
PharmGKBiPA33393

Chemistry databases

ChEMBLiCHEMBL4100
GuidetoPHARMACOLOGYi1408

Polymorphism and mutation databases

BioMutaiPLCG2
DMDMi215274231

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000885011 – 12651-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2Add BLAST1265

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei753Phosphotyrosine; by BTKCombined sources2 Publications1
Modified residuei759Phosphotyrosine; by BTKCombined sources2 Publications1
Modified residuei1197Phosphotyrosine; by BTKBy similarity1
Modified residuei1217PhosphotyrosineCombined sources1
Modified residuei1245PhosphotyrosineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues by CSF1R (By similarity). Phosphorylated on tyrosine residues by BTK and SYK; upon ligand-induced activation of a variety of growth factor receptors and immune system receptors. Phosphorylation leads to increased phospholipase activity.By similarity2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP16885
MaxQBiP16885
PaxDbiP16885
PeptideAtlasiP16885
PRIDEiP16885
ProteomicsDBi53400

PTM databases

iPTMnetiP16885
PhosphoSitePlusiP16885

Expressioni

Gene expression databases

BgeeiENSG00000197943
CleanExiHS_PLCG2
ExpressionAtlasiP16885 baseline and differential
GenevisibleiP16885 HS

Organism-specific databases

HPAiCAB004280
HPA020099
HPA020100

Interactioni

Subunit structurei

Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • phosphotyrosine residue binding Source: CAFA

Protein-protein interaction databases

BioGridi111352, 44 interactors
CORUMiP16885
IntActiP16885, 37 interactors
MINTiP16885
STRINGi9606.ENSP00000352336

Chemistry databases

BindingDBiP16885

Structurei

Secondary structure

11265
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni815 – 817Combined sources3
Beta strandi818 – 825Combined sources8
Beta strandi828 – 831Combined sources4
Helixi835 – 840Combined sources6
Beta strandi850 – 854Combined sources5
Helixi855 – 857Combined sources3
Beta strandi858 – 862Combined sources5
Beta strandi867 – 869Combined sources3
Beta strandi870 – 882Combined sources13
Beta strandi886 – 892Combined sources7
Helixi893 – 907Combined sources15

3D structure databases

ProteinModelPortaliP16885
SMRiP16885
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16885

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 131PHPROSITE-ProRule annotationAdd BLAST112
Domaini312 – 456PI-PLC X-boxPROSITE-ProRule annotationAdd BLAST145
Domaini532 – 635SH2 1PROSITE-ProRule annotationAdd BLAST104
Domaini646 – 735SH2 2PROSITE-ProRule annotationAdd BLAST90
Domaini769 – 829SH3PROSITE-ProRule annotationAdd BLAST61
Domaini930 – 1044PI-PLC Y-boxPROSITE-ProRule annotationAdd BLAST115
Domaini1059 – 1152C2PROSITE-ProRule annotationAdd BLAST94

Keywords - Domaini

Repeat, SH2 domain, SH3 domain

Phylogenomic databases

eggNOGiKOG1264 Eukaryota
ENOG410XPXE LUCA
GeneTreeiENSGT00730000110782
HOGENOMiHOG000230864
HOVERGENiHBG053611
InParanoidiP16885
KOiK05859
OMAiMLMRIPR
OrthoDBiEOG091G07R3
PhylomeDBiP16885
TreeFamiTF313216

Family and domain databases

CDDicd09932 SH2_C-SH2_PLC_gamma_like, 1 hit
cd10341 SH2_N-SH2_PLC_gamma_like, 1 hit
cd11969 SH3_PLCgamma2, 1 hit
Gene3Di2.30.29.30, 2 hits
2.60.40.150, 1 hit
3.20.20.190, 2 hits
3.30.505.10, 2 hits
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR011992 EF-hand-dom_pair
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR001192 PI-PLC_fam
IPR016279 PLC-gamma
IPR028381 PLC-gamma2
IPR035023 PLC-gamma_C-SH2
IPR035024 PLC-gamma_N-SH2
IPR017946 PLC-like_Pdiesterase_TIM-brl
IPR035723 PLCgamma2_SH3
IPR000909 PLipase_C_PInositol-sp_X_dom
IPR001711 PLipase_C_Pinositol-sp_Y
IPR000980 SH2
IPR036860 SH2_dom_sf
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PANTHERiPTHR10336 PTHR10336, 1 hit
PTHR10336:SF25 PTHR10336:SF25, 1 hit
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF00388 PI-PLC-X, 1 hit
PF00387 PI-PLC-Y, 1 hit
PF00017 SH2, 2 hits
PF00018 SH3_1, 1 hit
PIRSFiPIRSF000952 PLC-gamma, 1 hit
PRINTSiPR00390 PHPHLIPASEC
PR00401 SH2DOMAIN
PR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00233 PH, 2 hits
SM00148 PLCXc, 1 hit
SM00149 PLCYc, 1 hit
SM00252 SH2, 2 hits
SM00326 SH3, 1 hit
SUPFAMiSSF47473 SSF47473, 1 hit
SSF50044 SSF50044, 1 hit
SSF51695 SSF51695, 2 hits
SSF55550 SSF55550, 2 hits
PROSITEiView protein in PROSITE
PS50004 C2, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS50007 PIPLC_X_DOMAIN, 1 hit
PS50008 PIPLC_Y_DOMAIN, 1 hit
PS50001 SH2, 2 hits
PS50002 SH3, 1 hit

Sequencei

Sequence statusi: Complete.

P16885-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSTTVNVDSL AEYEKSQIKR ALELGTVMTV FSFRKSTPER RTVQVIMETR
60 70 80 90 100
QVAWSKTADK IEGFLDIMEI KEIRPGKNSK DFERAKAVRQ KEDCCFTILY
110 120 130 140 150
GTQFVLSTLS LAADSKEDAV NWLSGLKILH QEAMNASTPT IIESWLRKQI
160 170 180 190 200
YSVDQTRRNS ISLRELKTIL PLINFKVSSA KFLKDKFVEI GAHKDELSFE
210 220 230 240 250
QFHLFYKKLM FEQQKSILDE FKKDSSVFIL GNTDRPDASA VYLHDFQRFL
260 270 280 290 300
IHEQQEHWAQ DLNKVRERMT KFIDDTMRET AEPFLFVDEF LTYLFSRENS
310 320 330 340 350
IWDEKYDAVD MQDMNNPLSH YWISSSHNTY LTGDQLRSES SPEAYIRCLR
360 370 380 390 400
MGCRCIELDC WDGPDGKPVI YHGWTRTTKI KFDDVVQAIK DHAFVTSSFP
410 420 430 440 450
VILSIEEHCS VEQQRHMAKA FKEVFGDLLL TKPTEASADQ LPSPSQLREK
460 470 480 490 500
IIIKHKKLGP RGDVDVNMED KKDEHKQQGE LYMWDSIDQK WTRHYCAIAD
510 520 530 540 550
AKLSFSDDIE QTMEEEVPQD IPPTELHFGE KWFHKKVEKR TSAEKLLQEY
560 570 580 590 600
CMETGGKDGT FLVRESETFP NDYTLSFWRS GRVQHCRIRS TMEGGTLKYY
610 620 630 640 650
LTDNLTFSSI YALIQHYRET HLRCAEFELR LTDPVPNPNP HESKPWYYDS
660 670 680 690 700
LSRGEAEDML MRIPRDGAFL IRKREGSDSY AITFRARGKV KHCRINRDGR
710 720 730 740 750
HFVLGTSAYF ESLVELVSYY EKHSLYRKMR LRYPVTPELL ERYNMERDIN
760 770 780 790 800
SLYDVSRMYV DPSEINPSMP QRTVKALYDY KAKRSDELSF CRGALIHNVS
810 820 830 840 850
KEPGGWWKGD YGTRIQQYFP SNYVEDISTA DFEELEKQII EDNPLGSLCR
860 870 880 890 900
GILDLNTYNV VKAPQGKNQK SFVFILEPKQ QGDPPVEFAT DRVEELFEWF
910 920 930 940 950
QSIREITWKI DTKENNMKYW EKNQSIAIEL SDLVVYCKPT SKTKDNLENP
960 970 980 990 1000
DFREIRSFVE TKADSIIRQK PVDLLKYNQK GLTRVYPKGQ RVDSSNYDPF
1010 1020 1030 1040 1050
RLWLCGSQMV ALNFQTADKY MQMNHALFSL NGRTGYVLQP ESMRTEKYDP
1060 1070 1080 1090 1100
MPPESQRKIL MTLTVKVLGA RHLPKLGRSI ACPFVEVEIC GAEYDNNKFK
1110 1120 1130 1140 1150
TTVVNDNGLS PIWAPTQEKV TFEIYDPNLA FLRFVVYEED MFSDPNFLAH
1160 1170 1180 1190 1200
ATYPIKAVKS GFRSVPLKNG YSEDIELASL LVFCEMRPVL ESEEELYSSC
1210 1220 1230 1240 1250
RQLRRRQEEL NNQLFLYDTH QNLRNANRDA LVKEFSVNEN QLQLYQEKCN
1260
KRLREKRVSN SKFYS
Length:1,265
Mass (Da):147,870
Last modified:November 25, 2008 - v4
Checksum:i1D56BCBF51D7A0D3
GO

Sequence cautioni

The sequence AAA60112 differs from that shown. Reason: Frameshift at position 1242.Curated
The sequence AAQ76815 differs from that shown. Reason: Frameshift at position 1242.Curated
The sequence BAD92151 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAA32194 differs from that shown. Reason: Frameshift at position 1242.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti606 – 610TFSSI → RFRRM in CAA32194 (PubMed:2849563).Curated5
Sequence conflicti606 – 610TFSSI → RFRRM in AAA60112 (PubMed:2849563).Curated5
Sequence conflicti606 – 610TFSSI → RFRRM in AAQ76815 (PubMed:16533400).Curated5
Sequence conflicti623R → P in AAA60112 (PubMed:2849563).Curated1
Sequence conflicti623R → P in CAA32194 (PubMed:2849563).Curated1
Sequence conflicti623R → P in AAQ76815 (PubMed:16533400).Curated1
Sequence conflicti745M → T in AAA60112 (PubMed:2849563).Curated1
Sequence conflicti745M → T in CAA32194 (PubMed:2849563).Curated1
Sequence conflicti745M → T in AAQ76815 (PubMed:16533400).Curated1
Sequence conflicti880Q → E in AAA60112 (PubMed:2849563).Curated1
Sequence conflicti880Q → E in CAA32194 (PubMed:2849563).Curated1
Sequence conflicti880Q → E in AAQ76815 (PubMed:16533400).Curated1
Sequence conflicti912T → S in AAA60112 (PubMed:2849563).Curated1
Sequence conflicti912T → S in CAA32194 (PubMed:2849563).Curated1
Sequence conflicti912T → S in AAQ76815 (PubMed:16533400).Curated1
Sequence conflicti1095D → G in AAA60112 (PubMed:2849563).Curated1
Sequence conflicti1095D → G in CAA32194 (PubMed:2849563).Curated1
Sequence conflicti1095D → G in AAQ76815 (PubMed:16533400).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_031560244H → R1 PublicationCorresponds to variant dbSNP:rs11548656EnsemblClinVar.1
Natural variantiVAR_031561268R → W. Corresponds to variant dbSNP:rs1143687EnsemblClinVar.1
Natural variantiVAR_047427541T → A. Corresponds to variant dbSNP:rs11548657Ensembl.1
Natural variantiVAR_074310665R → W Found in patients with chronic lymphocytic leukemia; associated with BTK mutation S-481; unknown pathological significance; results in resistance to ibrutinib therapy. 1 PublicationCorresponds to variant dbSNP:rs1057519831Ensembl.1
Natural variantiVAR_069211707S → Y in APLAID; results in increased epidermal growth factor-stimulated production of intracellular IP3 and increased intracellular calcium release; is a hypermorphic mutation. 1 PublicationCorresponds to variant dbSNP:rs397514562EnsemblClinVar.1
Natural variantiVAR_074311845L → F Found in patients with chronic lymphocytic leukemia; associated with BTK mutation S-481; unknown pathological significance; results in resistance to ibrutinib therapy. 1 PublicationCorresponds to variant dbSNP:rs1057519832Ensembl.1
Natural variantiVAR_047428883D → Y1 PublicationCorresponds to variant dbSNP:rs17856213Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M37238 mRNA Translation: AAA60112.1 Frameshift.
X14034 mRNA Translation: CAA32194.1 Frameshift.
AB208914 mRNA Translation: BAD92151.1 Different initiation.
AY364256 mRNA Translation: AAQ76815.1 Frameshift.
AC092142 Genomic DNA No translation available.
AC098966 Genomic DNA No translation available.
AC099524 Genomic DNA No translation available.
CH471114 Genomic DNA Translation: EAW95524.1
CH471114 Genomic DNA Translation: EAW95525.1
BC007565 mRNA Translation: AAH07565.1
BC011772 mRNA Translation: AAH11772.1
BC014561 mRNA Translation: AAH14561.1
BC018646 mRNA Translation: AAH18646.1
CCDSiCCDS42204.1
PIRiS02004
RefSeqiNP_002652.2, NM_002661.4
UniGeneiHs.372303
Hs.413111
Hs.586906

Genome annotation databases

EnsembliENST00000564138; ENSP00000482457; ENSG00000197943
GeneIDi5336
KEGGihsa:5336
UCSCiuc002fgt.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPLCG2_HUMAN
AccessioniPrimary (citable) accession number: P16885
Secondary accession number(s): D3DUL3
, Q3ZTS2, Q59H45, Q969T5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 25, 2008
Last modified: July 18, 2018
This is version 213 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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