PLCG1 (phospholipase C gamma 1)

Gene

• Entrez ID: 5335
• Gene name: Phospholipase C gamma 1
• Gene symbol: PLCG1
• Synonyms: NCKAP3, PLC-II, PLC1, PLC148, PLCgamma1
• Chromosome: 20
• Chromosome location: 20q12
• Summary: The protein encoded by this gene catalyzes the formation of inositol 1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. This reaction uses calcium as a cofactor and plays an important role in the intracellular transduction of receptor-mediated tyrosine kinase activators. For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RasGRP1 to translocate to the Golgi, where it activates Ras. Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025369	hsa-miR-34a-5p	Proteomics	21566225
MIRT035779	hsa-miR-1914-3p	CLASH	23622248
MIRT037381	hsa-miR-744-3p	CLASH	23622248
MIRT049488	hsa-miR-92a-3p	CLASH	23622248
MIRT448563	hsa-miR-3616-5p	PAR-CLIP	22100165
MIRT448564	hsa-miR-573	PAR-CLIP	22100165
MIRT448565	hsa-miR-6894-5p	PAR-CLIP	22100165
MIRT448566	hsa-miR-516b-5p	PAR-CLIP	22100165
MIRT448567	hsa-miR-765	PAR-CLIP	22100165
MIRT448568	hsa-miR-7154-3p	PAR-CLIP	22100165
MIRT448569	hsa-miR-766-5p	PAR-CLIP	22100165
MIRT448570	hsa-miR-4795-5p	PAR-CLIP	22100165
MIRT448571	hsa-miR-4635	PAR-CLIP	22100165
MIRT448572	hsa-miR-6885-3p	PAR-CLIP	22100165
MIRT448573	hsa-miR-4693-3p	PAR-CLIP	22100165
MIRT448574	hsa-miR-302d-5p	PAR-CLIP	22100165
MIRT448575	hsa-miR-302b-5p	PAR-CLIP	22100165
MIRT448576	hsa-miR-513c-3p	PAR-CLIP	22100165
MIRT448576	hsa-miR-513c-3p	PAR-CLIP	26701625
MIRT448577	hsa-miR-513a-3p	PAR-CLIP	22100165
MIRT448577	hsa-miR-513a-3p	PAR-CLIP	26701625
MIRT448578	hsa-miR-3606-3p	PAR-CLIP	22100165
MIRT448578	hsa-miR-3606-3p	PAR-CLIP	26701625
MIRT501586	hsa-miR-552-5p	PAR-CLIP	24398324
MIRT501587	hsa-miR-302c-5p	PAR-CLIP	24398324
MIRT501588	hsa-miR-6864-3p	PAR-CLIP	24398324
MIRT501589	hsa-miR-3672	PAR-CLIP	24398324
MIRT501590	hsa-miR-8084	PAR-CLIP	24398324
MIRT501591	hsa-miR-3143	PAR-CLIP	24398324
MIRT501592	hsa-miR-5692a	PAR-CLIP	24398324
MIRT501593	hsa-miR-369-3p	PAR-CLIP	24398324
MIRT501594	hsa-miR-200b-3p	PAR-CLIP	24398324
MIRT501595	hsa-miR-429	PAR-CLIP	24398324
MIRT501596	hsa-miR-200c-3p	PAR-CLIP	24398324
MIRT654990	hsa-miR-6777-5p	HITS-CLIP	23824327
MIRT654991	hsa-miR-335-3p	HITS-CLIP	23824327
MIRT654992	hsa-miR-670-3p	HITS-CLIP	23824327
MIRT654993	hsa-miR-211-5p	HITS-CLIP	23824327
MIRT654994	hsa-miR-204-5p	HITS-CLIP	23824327
MIRT654995	hsa-miR-1298-5p	HITS-CLIP	23824327
MIRT654996	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT654997	hsa-miR-6866-3p	HITS-CLIP	23824327
MIRT654998	hsa-miR-188-5p	HITS-CLIP	23824327
MIRT654999	hsa-miR-483-3p	HITS-CLIP	23824327
MIRT732779	hsa-miR-665	Microarray, qRT-PCR	25964059
MIRT735804	hsa-miR-103a-2-5p	PAR-CLIP	26701625
MIRT737906	hsa-miR-155-3p	PAR-CLIP	26701625
MIRT739038	hsa-miR-217	PAR-CLIP	26701625
MIRT739542	hsa-miR-298	PAR-CLIP	26701625
MIRT740479	hsa-miR-3158-5p	PAR-CLIP	26701625
MIRT740803	hsa-miR-3180-5p	PAR-CLIP	26701625
MIRT742212	hsa-miR-3685	PAR-CLIP	26701625
MIRT742813	hsa-miR-384	PAR-CLIP	26701625
MIRT744157	hsa-miR-4418	PAR-CLIP	26701625
MIRT749674	hsa-miR-509-3-5p	PAR-CLIP	26701625
MIRT749710	hsa-miR-509-5p	PAR-CLIP	26701625
MIRT750200	hsa-miR-520a-5p	PAR-CLIP	26701625
MIRT750307	hsa-miR-525-5p	PAR-CLIP	26701625
MIRT756508	hsa-miR-6807-3p	PAR-CLIP	26701625

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001701	Process	In utero embryonic development	IEA
GO:0001726	Component	Ruffle	IDA	17229814
GO:0004435	Function	Phosphatidylinositol phospholipase C activity	IDA	2550068
GO:0004435	Function	Phosphatidylinositol phospholipase C activity	TAS
GO:0004629	Function	Phospholipase C activity	TAS
GO:0005168	Function	Neurotrophin TRKA receptor binding	IPI	15488758
GO:0005509	Function	Calcium ion binding	IEA
GO:0005515	Function	Protein binding	IPI	1396585, 1656221, 7537096, 7537265, 7693694, 7993895, 8321198, 8627166, 8628282, 8657103, 8892607, 9020117, 9045636, 9489702, 9593725, 9697839, 10811803, 10873601, 11796522, 11896612, 14568990, 14570588, 14722116, 15641795, 15929943, 16273093, 16525023, 16921170, 16938345, 17229814, 1
GO:0005737	Component	Cytoplasm	IDA	15702972
GO:0005829	Component	Cytosol	IDA	2550068
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	2550068, 22454520
GO:0005886	Component	Plasma membrane	TAS
GO:0005911	Component	Cell-cell junction	IEA
GO:0007165	Process	Signal transduction	TAS
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	IMP	22454520
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	ISS
GO:0007202	Process	Activation of phospholipase C activity	TAS
GO:0007411	Process	Axon guidance	TAS
GO:0008180	Component	COP9 signalosome	IDA	22561606
GO:0009395	Process	Phospholipid catabolic process	IEA
GO:0010634	Process	Positive regulation of epithelial cell migration	IBA	21873635
GO:0010634	Process	Positive regulation of epithelial cell migration	IMP	17229814
GO:0010863	Process	Positive regulation of phospholipase C activity	TAS
GO:0016032	Process	Viral process	IEA
GO:0016477	Process	Cell migration	IMP	22454520
GO:0019722	Process	Calcium-mediated signaling	IMP	22454520
GO:0019901	Function	Protein kinase binding	IPI	22454520
GO:0030027	Component	Lamellipodium	IDA	17229814
GO:0030971	Function	Receptor tyrosine kinase binding	IEA
GO:0035254	Function	Glutamate receptor binding	IEA
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0042995	Component	Cell projection	IDA	22454520
GO:0043536	Process	Positive regulation of blood vessel endothelial cell migration	IDA	20011604
GO:0043647	Process	Inositol phosphate metabolic process	TAS
GO:0045766	Process	Positive regulation of angiogenesis	IDA	20011604
GO:0046488	Process	Phosphatidylinositol metabolic process	ISS
GO:0050429	Function	Calcium-dependent phospholipase C activity	ISS
GO:0050804	Process	Modulation of chemical synaptic transmission	IEA
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0050900	Process	Leukocyte migration	TAS
GO:0051281	Process	Positive regulation of release of sequestered calcium ion into cytosol	IMP	22454520
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IDA	17229814
GO:0071364	Process	Cellular response to epidermal growth factor stimulus	IMP	22454520
GO:0098685	Component	Schaffer collateral - CA1 synapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:1905564	Process	Positive regulation of vascular endothelial cell proliferation	IMP	27464494
GO:2000353	Process	Positive regulation of endothelial cell apoptotic process	IMP	27464494

Other IDs

• MIM: 172420
• HGNC: 9065
• e!Ensembl: ENSG00000124181

Protein

• UniProt ID: P19174
• Protein name: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (EC 3.1.4.11) (PLC-148) (Phosphoinositide phospholipase C-gamma-1) (Phospholipase C-II) (PLC-II) (Phospholipase C-gamma-1) (PLC-gamma-1)
• Protein function: Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades. Becomes activated in response to ligand-mediated activation of receptor-type tyrosine kinases, such as PDGFRA, PDGFRB, EGFR, FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Plays a role in actin reorganization and cell migration (PubMed:17229814).
• PDB: 1HSQ, 2HSP, 4EY0, 4FBN
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00388	PI-PLC-X	322 → 465	Phosphatidylinositol-specific phospholipase C, X domain	Family
  PF00017	SH2	550 → 639	SH2 domain	Domain
  PF00017	SH2	668 → 741	SH2 domain	Domain
  PF00018	SH3_1	797 → 843	SH3 domain	Domain
  PF00387	PI-PLC-Y	953 → 1068	Phosphatidylinositol-specific phospholipase C, Y domain	Family
  PF00168	C2	1088 → 1193	C2 domain	Domain

• Sequence:

  MAGAASPCANGCGPGAPSDAEVLHLCRSLEVGTVMTLFYSKKSQRPERKTFQVKLETRQI
  TWSRGADKIEGAIDIREIKEIRPGKTSRDFDRYQEDPAFRPDQSHCFVILYGMEFRLKTL
  SLQATSEDEVNMWIKGLTWLMEDTLQAPTPLQIERWLRKQFYSVDRNREDRISAKDLKNM
  LSQVNYRVPNMRFLRERLTDLEQRSGDITYGQFAQLYRSLMYSAQKTMDLPFLEASTLRA
  GERPELCRVSLPEFQQFLLDYQGELWAVDRLQVQEFMLSFLRDPLREIEEPYFFLDEFVT
  FLFSKENSVWNSQLDAVCPDTMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMG
  CRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKEHAFVASEYPVILSIEDHCSIA
  QQRNMAQYFKKVLGDTLLTKPVEISADGLPSPNQLKRKILIKHKKLAEGSAYEEVPTSMM
  YSENDISNSIKNGILYLEDPVNHEWYPHYFVLTSSKIYYSEETSSDQGNEDEEEPKEVSS
  STELHSNEKWFHGKLGAGRDGRHIAERLLTEYCIETGAPDGSFLVRESETFVGDYTLSFW
  RNGKVQHCRIHSRQDAGTPKFFLTDNLVFDSLYDLITHYQQVPLRCNEFEMRLSEPVPQT
  NAHESKEWYHASLTRAQAEHMLMRVPRDGAFLVRKRNEPNSYAISFRAEGKIKHCRVQQE
  GQTVMLGNSEFDSLVDLISYYEKHPLYRKMKLRYPINEEALEKIGTAEPDYGALYEGRNP
  GFYVEANPMPTFKCAVKALFDYKAQREDELTFIKSAIIQNVEKQEGGWWRGDYGGKKQLW
  FPSNYVEEMVNPVALEPEREHLDENSPLGDLLRGVLDVPACQIAIRPEGKNNRLFVFSIS
  MASVAHWSLDVAADSQEELQDWVKKIREVAQTADARLTEGKIMERRKKIALELSELVVYC
  RPVPFDEEKIGTERACYRDMSSFPETKAEKYVNKAKGKKFLQYNRLQLSRIYPKGQRLDS
  SNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMTGRHCGYVLQPSTMRDEAFDPFDKS
  SLRGLEPCAISIEVLGARHLPKNGRGIVCPFVEIEVAGAEYDSTKQKTEFVVDNGLNPVW
  PAKPFHFQISNPEFAFLRFVVYEEDMFSDQNFLAQATFPVKGLKTGYRAVPLKNNYSEDL
  ELASLLIKIDIFPAKENGDLSPFSGTSLRERGSDASGQLFHGRAREGSFESRYQQPFEDF
  RISQEHLADHFDSRERRAPRRTRVNGDNRL

• Sequence length: 1290

Pathways

KEGG:

Inositol phosphate metabolism
Metabolic pathways
EGFR tyrosine kinase inhibitor resistance
ErbB signaling pathway
Ras signaling pathway
Rap1 signaling pathway
Calcium signaling pathway
Chemokine signaling pathway
NF-kappa B signaling pathway
HIF-1 signaling pathway
Phosphatidylinositol signaling system
Phospholipase D signaling pathway
Axon guidance
VEGF signaling pathway
Neutrophil extracellular trap formation
Natural killer cell mediated cytotoxicity
Th1 and Th2 cell differentiation
Th17 cell differentiation
T cell receptor signaling pathway
Fc epsilon RI signaling pathway
Fc gamma R-mediated phagocytosis
Leukocyte transendothelial migration
Neurotrophin signaling pathway
Inflammatory mediator regulation of TRP channels
Thyroid hormone signaling pathway
AGE-RAGE signaling pathway in diabetic complications
Growth hormone synthesis, secretion and action
Parkinson disease
Pathways of neurodegeneration - multiple diseases
Vibrio cholerae infection
Epithelial cell signaling in Helicobacter pylori infection
Shigellosis
Yersinia infection
Kaposi sarcoma-associated herpesvirus infection
Human immunodeficiency virus 1 infection
Coronavirus disease - COVID-19
Pathways in cancer
Proteoglycans in cancer
MicroRNAs in cancer
Glioma
Non-small cell lung cancer
Hepatocellular carcinoma
Choline metabolism in cancer
PD-L1 expression and PD-1 checkpoint pathway in cancer
Lipid and atherosclerosis

Reactome:

ISG15 antiviral mechanism
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants
Synthesis of IP3 and IP4 in the cytosol
Downstream signal transduction
Generation of second messenger molecules
Role of phospholipids in phagocytosis
PECAM1 interactions
EGFR interacts with phospholipase C-gamma
DAP12 signaling
FCERI mediated MAPK activation
FCERI mediated Ca+2 mobilization
VEGFR2 mediated cell proliferation
Constitutive Signaling by EGFRvIII
Phospholipase C-mediated cascade: FGFR1
Phospholipase C-mediated cascade; FGFR2
Phospholipase C-mediated cascade; FGFR3
Phospholipase C-mediated cascade; FGFR4
Signaling by FGFR2 in disease
Signaling by FGFR4 in disease
Signaling by FGFR1 in disease
Signaling by FGFR3 point mutants in cancer
RET signaling
Activated NTRK2 signals through PLCG1
Activated NTRK3 signals through PLCG1
FCGR3A-mediated IL10 synthesis
Signaling by ERBB2 KD Mutants
Signaling by ERBB2 ECD mutants
Signaling by ERBB2 TMD/JMD mutants

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	Diabetes Mellitus	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs-1, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs371977235, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	27790247
Atrial fibrillation	Atrial Fibrillation	rs120074192, rs121908590, rs121908593, rs121434558, rs587776851, rs387906612, rs387906613, rs387906614, rs387906615, rs199472687, rs199472705, rs199473324, rs587777336, rs587777339, rs587777557, rs587777558, rs587777559, rs587777560, rs886037778, rs769405762, rs-1, rs770372675	27790247
Coronary artery disease	Coronary Artery Disease	rs137852988, rs121918313, rs-1, rs121918529, rs121918531, rs137852340, rs405509, rs1555800701, rs1215189537	29212778
Coronary heart disease	Coronary heart disease	rs-1	27790247
Sezary syndrome	Sezary Syndrome	rs587776632	26551670
Lymphoma	Lymphoma, T-Cell, Cutaneous	rs11540652, rs1592119138, rs1592123162, rs1599367044	26192916
Diabetes	Diabetes	rs80356611	27790247

Unknown
Disease name	Disease term	dbSNP ID	References
Heart failure	Heart failure	rs121918074, rs142027794, rs148791216, rs72648927, rs71578935, rs142416150, rs199830512, rs755445214, rs150102469, rs779568205, rs907992794, rs1202130741	27790247
Mental depression	Major Depressive Disorder	rs587778876, rs587778877	27479909
Hemangiosarcoma	Hemangiosarcoma	rs199469669	24633157
Bipolar disorder	Bipolar Disorder		11409699
Granulomatous slack skin	Granulomatous Slack Skin		26192916
Malignant neoplasm	Malignant Neoplasms		27790247
Stroke	Cerebrovascular accident		27790247
T-cell lymphoma/leukemia	Adult T-Cell Lymphoma/Leukemia		26437031