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P16885 (PLCG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:PLCG2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1265 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 activity

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

Cofactor

Calcium.

Subunit structure

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

Post-translational modification

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. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Sequence similarities

Contains 1 C2 domain.

Contains 1 PH domain.

Contains 1 PI-PLC X-box domain.

Contains 1 PI-PLC Y-box domain.

Contains 2 SH2 domains.

Contains 1 SH3 domain.

Sequence caution

The sequence AAA60112.1 differs from that shown. Reason: Frameshift at position 1242.

The sequence AAQ76815.1 differs from that shown. Reason: Frameshift at position 1242.

The sequence BAD92151.1 differs from that shown. Reason: Erroneous initiation.

The sequence CAA32194.1 differs from that shown. Reason: Frameshift at position 1242.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

EPORP192353EBI-617403,EBI-617321

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 126512651-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-2
PRO_0000088501

Regions

Domain20 – 131112PH
Domain312 – 456145PI-PLC X-box
Domain532 – 635104SH2 1
Domain646 – 73590SH2 2
Domain769 – 82961SH3
Domain930 – 1044115PI-PLC Y-box
Domain1059 – 115294C2

Sites

Active site3271 By similarity
Active site3721 By similarity

Amino acid modifications

Modified residue7331Phosphotyrosine Ref.10
Modified residue7531Phosphotyrosine; by BTK Ref.7 Ref.8 Ref.11
Modified residue7591Phosphotyrosine; by BTK Ref.7 Ref.8 Ref.11
Modified residue12171Phosphotyrosine Ref.11
Modified residue12451Phosphotyrosine Ref.9

Natural variations

Natural variant2441H → R. Ref.6
Corresponds to variant rs11548656 [ dbSNP | Ensembl ].
VAR_031560
Natural variant2681R → W.
Corresponds to variant rs17537869 [ dbSNP | Ensembl ].
VAR_031561
Natural variant5411T → A.
Corresponds to variant rs11548657 [ dbSNP | Ensembl ].
VAR_047427
Natural variant8831D → Y. Ref.6
Corresponds to variant rs17856213 [ dbSNP | Ensembl ].
VAR_047428

Experimental info

Sequence conflict606 – 6105TFSSI → RFRRM in CAA32194. Ref.1
Sequence conflict606 – 6105TFSSI → RFRRM in AAA60112. Ref.1
Sequence conflict606 – 6105TFSSI → RFRRM in AAQ76815. Ref.3
Sequence conflict6231R → P in AAA60112. Ref.1
Sequence conflict6231R → P in CAA32194. Ref.1
Sequence conflict6231R → P in AAQ76815. Ref.3
Sequence conflict7451M → T in AAA60112. Ref.1
Sequence conflict7451M → T in CAA32194. Ref.1
Sequence conflict7451M → T in AAQ76815. Ref.3
Sequence conflict8801Q → E in AAA60112. Ref.1
Sequence conflict8801Q → E in CAA32194. Ref.1
Sequence conflict8801Q → E in AAQ76815. Ref.3
Sequence conflict9121T → S in AAA60112. Ref.1
Sequence conflict9121T → S in CAA32194. Ref.1
Sequence conflict9121T → S in AAQ76815. Ref.3
Sequence conflict10951D → G in AAA60112. Ref.1
Sequence conflict10951D → G in CAA32194. Ref.1
Sequence conflict10951D → G in AAQ76815. Ref.3

Secondary structure

............. 1265
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P16885 [UniParc].

Last modified November 25, 2008. Version 4.
Checksum: 1D56BCBF51D7A0D3

FASTA1,265147,870
        10         20         30         40         50         60 
MSTTVNVDSL AEYEKSQIKR ALELGTVMTV FSFRKSTPER RTVQVIMETR QVAWSKTADK 

        70         80         90        100        110        120 
IEGFLDIMEI KEIRPGKNSK DFERAKAVRQ KEDCCFTILY GTQFVLSTLS LAADSKEDAV 

       130        140        150        160        170        180 
NWLSGLKILH QEAMNASTPT IIESWLRKQI YSVDQTRRNS ISLRELKTIL PLINFKVSSA 

       190        200        210        220        230        240 
KFLKDKFVEI GAHKDELSFE QFHLFYKKLM FEQQKSILDE FKKDSSVFIL GNTDRPDASA 

       250        260        270        280        290        300 
VYLHDFQRFL IHEQQEHWAQ DLNKVRERMT KFIDDTMRET AEPFLFVDEF LTYLFSRENS 

       310        320        330        340        350        360 
IWDEKYDAVD MQDMNNPLSH YWISSSHNTY LTGDQLRSES SPEAYIRCLR MGCRCIELDC 

       370        380        390        400        410        420 
WDGPDGKPVI YHGWTRTTKI KFDDVVQAIK DHAFVTSSFP VILSIEEHCS VEQQRHMAKA 

       430        440        450        460        470        480 
FKEVFGDLLL TKPTEASADQ LPSPSQLREK IIIKHKKLGP RGDVDVNMED KKDEHKQQGE 

       490        500        510        520        530        540 
LYMWDSIDQK WTRHYCAIAD AKLSFSDDIE QTMEEEVPQD IPPTELHFGE KWFHKKVEKR 

       550        560        570        580        590        600 
TSAEKLLQEY CMETGGKDGT FLVRESETFP NDYTLSFWRS GRVQHCRIRS TMEGGTLKYY 

       610        620        630        640        650        660 
LTDNLTFSSI YALIQHYRET HLRCAEFELR LTDPVPNPNP HESKPWYYDS LSRGEAEDML 

       670        680        690        700        710        720 
MRIPRDGAFL IRKREGSDSY AITFRARGKV KHCRINRDGR HFVLGTSAYF ESLVELVSYY 

       730        740        750        760        770        780 
EKHSLYRKMR LRYPVTPELL ERYNMERDIN SLYDVSRMYV DPSEINPSMP QRTVKALYDY 

       790        800        810        820        830        840 
KAKRSDELSF CRGALIHNVS KEPGGWWKGD YGTRIQQYFP SNYVEDISTA DFEELEKQII 

       850        860        870        880        890        900 
EDNPLGSLCR GILDLNTYNV VKAPQGKNQK SFVFILEPKQ QGDPPVEFAT DRVEELFEWF 

       910        920        930        940        950        960 
QSIREITWKI DTKENNMKYW EKNQSIAIEL SDLVVYCKPT SKTKDNLENP DFREIRSFVE 

       970        980        990       1000       1010       1020 
TKADSIIRQK PVDLLKYNQK GLTRVYPKGQ RVDSSNYDPF RLWLCGSQMV ALNFQTADKY 

      1030       1040       1050       1060       1070       1080 
MQMNHALFSL NGRTGYVLQP ESMRTEKYDP MPPESQRKIL MTLTVKVLGA RHLPKLGRSI 

      1090       1100       1110       1120       1130       1140 
ACPFVEVEIC GAEYDNNKFK TTVVNDNGLS PIWAPTQEKV TFEIYDPNLA FLRFVVYEED 

      1150       1160       1170       1180       1190       1200 
MFSDPNFLAH ATYPIKAVKS GFRSVPLKNG YSEDIELASL LVFCEMRPVL ESEEELYSSC 

      1210       1220       1230       1240       1250       1260 
RQLRRRQEEL NNQLFLYDTH QNLRNANRDA LVKEFSVNEN QLQLYQEKCN KRLREKRVSN 


SKFYS 

« Hide

References

« Hide 'large scale' references
[1]"Complete cDNA encoding a putative phospholipase C from transformed human lymphocytes."
Ohta S., Matsui A., Nazawa Y., Kagawa Y.
FEBS Lett. 242:31-35(1988) [PubMed: 2849563] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lymphoblast.
[2]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Spleen.
[3]"NovelFam3000 -- uncharacterized human protein domains conserved across model organisms."
Kemmer D., Podowski R.M., Arenillas D., Lim J., Hodges E., Roth P., Sonnhammer E.L.L., Hoeoeg C., Wasserman W.W.
BMC Genomics 7:48-48(2006) [PubMed: 16533400] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The sequence and analysis of duplication-rich human chromosome 16."
Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. expand/collapse author list , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
Nature 432:988-994(2004) [PubMed: 15616553] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-244 AND TYR-883.
Tissue: Lymph.
[7]"Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling."
Rodriguez R., Matsuda M., Perisic O., Bravo J., Paul A., Jones N.P., Light Y., Swann K., Williams R.L., Katan M.
J. Biol. Chem. 276:47982-47992(2001) [PubMed: 11606584] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-753 AND TYR-759.
[8]"Activation of phospholipase Cgamma2 by tyrosine phosphorylation."
Ozdener F., Dangelmaier C., Ashby B., Kunapuli S.P., Daniel J.L.
Mol. Pharmacol. 62:672-679(2002) [PubMed: 12181444] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-753 AND TYR-759.
[9]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1245, MASS SPECTROMETRY.
Tissue: Leukemic T-cell.
[10]"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer."
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. expand/collapse author list , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.
Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-733, MASS SPECTROMETRY.
Tissue: Lung carcinoma.
[11]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-753; TYR-759 AND TYR-1217, MASS SPECTROMETRY.
Tissue: Leukemic T-cell.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
IPIIPI00329185.
PIRS02004.
RefSeqNP_002652.2. NM_002661.3.
UniGeneHs.413111.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2K2JNMR-A471-913[»]
2W2WX-ray3.30A/B/C/D/E/F/G/H/I/J/K/L471-913[»]
2W2XX-ray2.30C/D471-913[»]
ProteinModelPortalP16885.
SMRP16885. Positions 14-130, 336-378, 476-514, 520-913, 1062-1186.
ModBaseSearch...

Protein-protein interaction databases

IntActP16885. 4 interactions.
MINTMINT-1199011.
STRINGP16885.

PTM databases

PhosphoSiteP16885.

Polymorphism databases

DMDM215274231.

Proteomic databases

PRIDEP16885.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359376; ENSP00000352336; ENSG00000197943.
GeneID5336.
KEGGhsa:5336.
UCSCuc002fgt.1. human.

Organism-specific databases

CTD5336.
GeneCardsGC16P081812.
H-InvDBHIX0013277.
HGNCHGNC:9066. PLCG2.
HPACAB004280.
HPA020099.
HPA020100.
MIM600220. gene.
neXtProtNX_P16885.
PharmGKBPA33393.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG19143.
GeneTreeENSGT00600000084266.
HOGENOMHBG402919.
HOVERGENHBG053611.
InParanoidP16885.
OMAYPKGQRV.
OrthoDBEOG4VDPXP.
PhylomeDBP16885.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000140917-MONOMER.
BRENDA3.1.4.11. 2681.
Pathway_Interaction_DBbcr_5pathway. BCR signaling pathway.
pi3kcipathway. Class I PI3K signaling events.
epopathway. EPO signaling pathway.
ReactomeREACT_2080. PLC-mediated hydrolysis of PIP2.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP16885.
BgeeP16885.
CleanExHS_PLCG2.
GenevestigatorP16885.
GermOnlineENSG00000197943. Homo sapiens.

Family and domain databases

InterProIPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR011993. PH_type.
IPR001192. Pinositol_PLipase_C.
IPR016279. PLC-gamma.
IPR017946. PLC-like_Pdiesterase_TIM-brl.
IPR001849. Pleckstrin_homology.
IPR015359. PLipase_C_EF-hand-like.
IPR000909. PLipase_C_PInositol-sp_X_dom.
IPR001711. PLipase_C_Pinositol-sp_Y.
IPR000980. SH2.
IPR001452. SH3_domain.
[Graphical view]
Gene3DG3DSA:2.30.29.30. PH_type. 3 hits.
G3DSA:3.20.20.190. PLC-like_Pdiesterase_TIM-brl. 2 hits.
G3DSA:3.30.505.10. SH2. 2 hits.
KOK05859.
PfamPF00168. C2. 1 hit.
PF09279. efhand_like. 1 hit.
PF00388. PI-PLC-X. 1 hit.
PF00387. PI-PLC-Y. 1 hit.
PF00017. SH2. 2 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]
PIRSFPIRSF000952. PLC-gamma. 1 hit.
PRINTSPR00390. PHPHLIPASEC.
PR00401. SH2DOMAIN.
PR00452. SH3DOMAIN.
SMARTSM00239. C2. 1 hit.
SM00233. PH. 2 hits.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF49562. C2_CaLB. 1 hit.
SSF51695. PLC-like_Pdiesterase_TIM-brl. 1 hit.
SSF50044. SH3. 1 hit.
PROSITEPS50004. 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.
[Graphical view]
ProtoNetSearch...

Other

NextBio20668.
SOURCESearch...

Entry information

Entry namePLCG2_HUMAN
AccessionPrimary (citable) accession number: P16885
Secondary accession number(s): D3DUL3 expand/collapse secondary AC list , Q3ZTS2, Q59H45, Q969T5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: November 25, 2008
Last modified: January 25, 2012
This is version 146 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families