P19174 (PLCG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1
EC=3.1.4.11

Alternative name(s):
PLC-148
Phosphoinositide phospholipase C-gamma-1
Phospholipase C-II
Short name=PLC-II
Phospholipase C-gamma-1
Short name=PLC-gamma-1

Gene names

Name:	PLCG1
Synonyms:	PLC1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1290 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

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, FGFR1, FGFR2, FGFR3 and FGFR4. Plays a role in actin reorganization and cell migration. Ref.30
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
Cofactor	Calcium.
Enzyme regulation	Activated by phosphorylation on tyrosine residues.
Subunit structure	Interacts with AGAP2 via its SH3 domain. Interacts (via SH2 domain) with RET. Interacts with FLT1 (tyrosine-phosphorylated) By similarity. Interacts (via SH2 domain) with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated). Interacts with LAT (phosphorylated) upon TCR activation. Interacts (via SH3 domain) with the Pro-rich domain of TNK1. Associates with BLNK, VAV1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with CBLB in activated T-cells; which inhibits phosphorylation. Interacts with SHB. Interacts (via SH3 domain) with the Arg/Gly-rich-flanked Pro-rich domains of KHDRBS1/SAM68. This interaction is selectively regulated by arginine methylation of KHDRBS1/SAM68. Interacts with INPP5D/SHIP1, THEMIS and CLNK By similarity. Interacts with AXL, FLT4 and KIT. Interacts with RALGPS1. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts (via the SH2 domains) with VIL1 (phosphorylated at C-terminus tyrosine phosphorylation sites). Interacts (via SH2 domain) with PDGFRA and PDGFRB (tyrosine phosphorylated). Interacts with PIP5K1C By similarity. Interacts with NTRK1 and NTRK2 (phosphorylated upon ligand-binding). Interacts with SYK; activates PLCG1. Ref.6 Ref.7 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.16 Ref.20 Ref.22 Ref.23 Ref.29 Ref.30 Ref.33 Ref.38 Ref.41 Ref.43
Subcellular location	Cell projection › lamellipodium. Cell projection › ruffle. Note: Rapidly redistributed to ruffles and lamellipodia structures in response to epidermal growth factor (EGF) treatment. Ref.18 Ref.30
Domain	The SH3 domain mediates interaction with CLNK By similarity. The SH3 domain also mediates interaction with RALGPS1. Ref.45
Post-translational modification	Tyrosine phosphorylated in response to signaling via activated FLT3, KIT and PDGFRA By similarity. Tyrosine phosphorylated by activated FGFR1, FGFR2, FGFR3 and FGFR4. Tyrosine phosphorylated by activated FLT1 and KDR. Tyrosine phosphorylated by activated PDGFRB. The receptor-mediated activation of PLCG1 involves its phosphorylation by tyrosine kinases, in response to ligation of a variety of growth factor receptors and immune system receptors. For instance, SYK phosphorylates and activates PLCG1 in response to ligation of the B cell receptor. May be dephosphorylated by PTPRJ. Phosphorylated by ITK and TXK on Tyr-783 upon TCR activation in T-cells. Ref.1 Ref.13 Ref.17 Ref.18 Ref.19 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31 Ref.32 Ref.34 Ref.35 Ref.36 Ref.37 Ref.39 Ref.40 Ref.41 Ref.43 Ubiquitinated by CBLB in activated T-cells By similarity.
Sequence similarities	Contains 1 C2 domain. Contains 1 EF-hand domain. Contains 2 PH domains. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain. Contains 2 SH2 domains. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Host-virus interaction Lipid degradation
Cellular component	Cell projection
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH2 domain SH3 domain
Ligand	Calcium
Molecular function	Hydrolase Transducer
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell receptor signaling pathway Traceable author statement. Source: Reactome activation of phospholipase C activity Traceable author statement. Source: Reactome axon guidance Traceable author statement. Source: Reactome blood coagulation Traceable author statement. Source: Reactome cellular response to epidermal growth factor stimulus Inferred from direct assay Ref.30. Source: UniProtKB epidermal growth factor receptor signaling pathway Traceable author statement. Source: Reactome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from electronic annotation. Source: InterPro leukocyte migration Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome phospholipid catabolic process Inferred from electronic annotation. Source: InterPro positive regulation of angiogenesis Inferred from direct assay. Source: DFLAT positive regulation of blood vessel endothelial cell migration Inferred from direct assay. Source: DFLAT positive regulation of epithelial cell migration Inferred from mutant phenotype Ref.30. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB lamellipodium Inferred from direct assay Ref.30. Source: UniProtKB plasma membrane Inferred from direct assay. Source: UniProtKB ruffle Inferred from direct assay Ref.30. Source: UniProtKB
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro neurotrophin TRKA receptor binding Inferred from physical interaction Ref.20. Source: UniProtKB phosphatidylinositol phospholipase C activity Inferred from direct assay. Source: UniProtKB receptor signaling protein activity Non-traceable author statement Ref.45. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL2	P42684	4	EBI-79387,EBI-1102694
ASAP1	Q9ULH1	3	EBI-79387,EBI-346622
ASAP2	O43150	3	EBI-79387,EBI-310968
CD22	P20273	2	EBI-79387,EBI-78277
DUSP15	Q9H1R2	2	EBI-79387,EBI-1752795
FCGR2B	P31994	2	EBI-79387,EBI-724784
KHDRBS1	Q07666	2	EBI-79387,EBI-1364
LAT	O43561	2	EBI-79387,EBI-1222766
MAP4K1	Q92918	6	EBI-79387,EBI-881
RIN3	Q8TB24	3	EBI-79387,EBI-1570523
SHANK2	Q9UPX8	4	EBI-79387,EBI-1570571
SHANK3	Q9BYB0	2	EBI-79387,EBI-1752330
SNX17	Q15036	2	EBI-79387,EBI-1752620
SOS1	Q07889	2	EBI-79387,EBI-297487
SOS2	Q07890	4	EBI-79387,EBI-298181
VIL1	P09327	5	EBI-79387,EBI-1047253

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P19174-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P19174-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1215-1215: K → KQ

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 1290

1289

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

PRO_0000088498

Regions

Domain

27 – 142

116

PH 1

Domain

152 – 187

36

EF-hand

Domain

320 – 464

145

PI-PLC X-box

Domain

489 – 523

35

PH 2; first part

Domain

550 – 657

108

SH2 1

Domain

668 – 756

89

SH2 2

Domain

791 – 851

61

SH3

Domain

895 – 931

37

PH 2; second part

Domain

953 – 1070

118

PI-PLC Y-box

Domain

1075 – 1177

103

C2

Calcium binding

165 – 176

12

Potential

Sites

Active site

335

1

By similarity

Active site

380

1

By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.37

Modified residue

6

1

Phosphoserine Ref.37

Modified residue

379

1

Phosphotyrosine By similarity

Modified residue

481

1

Phosphotyrosine By similarity

Modified residue

506

1

Phosphotyrosine By similarity

Modified residue

525

1

Phosphoserine Ref.37

Modified residue

771

1

Phosphotyrosine; by SYK

Modified residue

775

1

Phosphotyrosine Ref.26 Ref.27 Ref.39 Ref.40

Modified residue

783

1

Phosphotyrosine; by ITK, SYK and TXK

Modified residue

977

1

Phosphotyrosine Ref.32

Modified residue

1221

1

Phosphoserine Ref.36 Ref.40

Modified residue

1248

1

Phosphoserine By similarity

Modified residue

1253

1

Phosphotyrosine Ref.28 Ref.34 Ref.40

Modified residue

1263

1

Phosphoserine Ref.35 Ref.40

Natural variations

Alternative sequence

1215

1

K → KQ in isoform 2.

VSP_038692

Natural variant

209

1

T → N. Ref.2
Corresponds to variant rs2229348 [ dbSNP | Ensembl ].

VAR_025213

Natural variant

279

1

S → G. Ref.2
Corresponds to variant rs2228246 [ dbSNP | Ensembl ].

VAR_022130

Natural variant

739

1

S → T. Ref.2

VAR_025214

Natural variant

813

1

I → T. Ref.2 Ref.5
Corresponds to variant rs753381 [ dbSNP | Ensembl ].

VAR_011908

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

1290

Helix Strand Turn

Details...

Beta strand

792 – 794

3

Beta strand

805 – 809

5

Turn

825 – 827

3

Beta strand

834 – 836

3

Turn

843 – 845

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: AE05ABE2A18EDDAC	FASTA	1,290	148,532
	10 20 30 40 50 60 MAGAASPCAN GCGPGAPSDA EVLHLCRSLE VGTVMTLFYS KKSQRPERKT FQVKLETRQI 70 80 90 100 110 120 TWSRGADKIE GAIDIREIKE IRPGKTSRDF DRYQEDPAFR PDQSHCFVIL YGMEFRLKTL 130 140 150 160 170 180 SLQATSEDEV NMWIKGLTWL MEDTLQAPTP LQIERWLRKQ FYSVDRNRED RISAKDLKNM 190 200 210 220 230 240 LSQVNYRVPN MRFLRERLTD LEQRSGDITY GQFAQLYRSL MYSAQKTMDL PFLEASTLRA 250 260 270 280 290 300 GERPELCRVS LPEFQQFLLD YQGELWAVDR LQVQEFMLSF LRDPLREIEE PYFFLDEFVT 310 320 330 340 350 360 FLFSKENSVW NSQLDAVCPD TMNNPLSHYW ISSSHNTYLT GDQFSSESSL EAYARCLRMG 370 380 390 400 410 420 CRCIELDCWD GPDGMPVIYH GHTLTTKIKF SDVLHTIKEH AFVASEYPVI LSIEDHCSIA 430 440 450 460 470 480 QQRNMAQYFK KVLGDTLLTK PVEISADGLP SPNQLKRKIL IKHKKLAEGS AYEEVPTSMM 490 500 510 520 530 540 YSENDISNSI KNGILYLEDP VNHEWYPHYF VLTSSKIYYS EETSSDQGNE DEEEPKEVSS 550 560 570 580 590 600 STELHSNEKW FHGKLGAGRD GRHIAERLLT EYCIETGAPD GSFLVRESET FVGDYTLSFW 610 620 630 640 650 660 RNGKVQHCRI HSRQDAGTPK FFLTDNLVFD SLYDLITHYQ QVPLRCNEFE MRLSEPVPQT 670 680 690 700 710 720 NAHESKEWYH ASLTRAQAEH MLMRVPRDGA FLVRKRNEPN SYAISFRAEG KIKHCRVQQE 730 740 750 760 770 780 GQTVMLGNSE FDSLVDLISY YEKHPLYRKM KLRYPINEEA LEKIGTAEPD YGALYEGRNP 790 800 810 820 830 840 GFYVEANPMP TFKCAVKALF DYKAQREDEL TFIKSAIIQN VEKQEGGWWR GDYGGKKQLW 850 860 870 880 890 900 FPSNYVEEMV NPVALEPERE HLDENSPLGD LLRGVLDVPA CQIAIRPEGK NNRLFVFSIS 910 920 930 940 950 960 MASVAHWSLD VAADSQEELQ DWVKKIREVA QTADARLTEG KIMERRKKIA LELSELVVYC 970 980 990 1000 1010 1020 RPVPFDEEKI GTERACYRDM SSFPETKAEK YVNKAKGKKF LQYNRLQLSR IYPKGQRLDS 1030 1040 1050 1060 1070 1080 SNYDPLPMWI CGSQLVALNF QTPDKPMQMN QALFMTGRHC GYVLQPSTMR DEAFDPFDKS 1090 1100 1110 1120 1130 1140 SLRGLEPCAI SIEVLGARHL PKNGRGIVCP FVEIEVAGAE YDSTKQKTEF VVDNGLNPVW 1150 1160 1170 1180 1190 1200 PAKPFHFQIS NPEFAFLRFV VYEEDMFSDQ NFLAQATFPV KGLKTGYRAV PLKNNYSEDL 1210 1220 1230 1240 1250 1260 ELASLLIKID IFPAKENGDL SPFSGTSLRE RGSDASGQLF HGRAREGSFE SRYQQPFEDF 1270 1280 1290 RISQEHLADH FDSRERRAPR RTRVNGDNRL
	Isoform 2 [UniParc]. Checksum: EDDBB8D4E49B2F3E	FASTA	1,291	148,660
	10 20 30 40 50 60 MAGAASPCAN GCGPGAPSDA EVLHLCRSLE VGTVMTLFYS KKSQRPERKT FQVKLETRQI 70 80 90 100 110 120 TWSRGADKIE GAIDIREIKE IRPGKTSRDF DRYQEDPAFR PDQSHCFVIL YGMEFRLKTL 130 140 150 160 170 180 SLQATSEDEV NMWIKGLTWL MEDTLQAPTP LQIERWLRKQ FYSVDRNRED RISAKDLKNM 190 200 210 220 230 240 LSQVNYRVPN MRFLRERLTD LEQRSGDITY GQFAQLYRSL MYSAQKTMDL PFLEASTLRA 250 260 270 280 290 300 GERPELCRVS LPEFQQFLLD YQGELWAVDR LQVQEFMLSF LRDPLREIEE PYFFLDEFVT 310 320 330 340 350 360 FLFSKENSVW NSQLDAVCPD TMNNPLSHYW ISSSHNTYLT GDQFSSESSL EAYARCLRMG 370 380 390 400 410 420 CRCIELDCWD GPDGMPVIYH GHTLTTKIKF SDVLHTIKEH AFVASEYPVI LSIEDHCSIA 430 440 450 460 470 480 QQRNMAQYFK KVLGDTLLTK PVEISADGLP SPNQLKRKIL IKHKKLAEGS AYEEVPTSMM 490 500 510 520 530 540 YSENDISNSI KNGILYLEDP VNHEWYPHYF VLTSSKIYYS EETSSDQGNE DEEEPKEVSS 550 560 570 580 590 600 STELHSNEKW FHGKLGAGRD GRHIAERLLT EYCIETGAPD GSFLVRESET FVGDYTLSFW 610 620 630 640 650 660 RNGKVQHCRI HSRQDAGTPK FFLTDNLVFD SLYDLITHYQ QVPLRCNEFE MRLSEPVPQT 670 680 690 700 710 720 NAHESKEWYH ASLTRAQAEH MLMRVPRDGA FLVRKRNEPN SYAISFRAEG KIKHCRVQQE 730 740 750 760 770 780 GQTVMLGNSE FDSLVDLISY YEKHPLYRKM KLRYPINEEA LEKIGTAEPD YGALYEGRNP 790 800 810 820 830 840 GFYVEANPMP TFKCAVKALF DYKAQREDEL TFIKSAIIQN VEKQEGGWWR GDYGGKKQLW 850 860 870 880 890 900 FPSNYVEEMV NPVALEPERE HLDENSPLGD LLRGVLDVPA CQIAIRPEGK NNRLFVFSIS 910 920 930 940 950 960 MASVAHWSLD VAADSQEELQ DWVKKIREVA QTADARLTEG KIMERRKKIA LELSELVVYC 970 980 990 1000 1010 1020 RPVPFDEEKI GTERACYRDM SSFPETKAEK YVNKAKGKKF LQYNRLQLSR IYPKGQRLDS 1030 1040 1050 1060 1070 1080 SNYDPLPMWI CGSQLVALNF QTPDKPMQMN QALFMTGRHC GYVLQPSTMR DEAFDPFDKS 1090 1100 1110 1120 1130 1140 SLRGLEPCAI SIEVLGARHL PKNGRGIVCP FVEIEVAGAE YDSTKQKTEF VVDNGLNPVW 1150 1160 1170 1180 1190 1200 PAKPFHFQIS NPEFAFLRFV VYEEDMFSDQ NFLAQATFPV KGLKTGYRAV PLKNNYSEDL 1210 1220 1230 1240 1250 1260 ELASLLIKID IFPAKQENGD LSPFSGTSLR ERGSDASGQL FHGRAREGSF ESRYQQPFED 1270 1280 1290 FRISQEHLAD HFDSRERRAP RRTRVNGDNR L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization and cDNA cloning of phospholipase C-gamma, a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase." Burgess W.H., Dionne C.A., Kaplow J.M., Mudd R., Friesel R., Zilberstein A., Schlessinger J., Jaye M. Mol. Cell. Biol. 10:4770-4777(1990) [PubMed: 2167438] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION. Tissue: Brain and Vein.
[2]	NIEHS SNPs program Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASN-209; GLY-279; THR-739 AND THR-813.
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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. , 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].
[5]	"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] (ISOFORMS 1 AND 2), VARIANT THR-813. Tissue: Brain and Testis.
[6]	"A tyrosine-phosphorylated carboxy-terminal peptide of the fibroblast growth factor receptor (Flg) is a binding site for the SH2 domain of phospholipase C-gamma 1." Mohammadi M., Honegger A.M., Rotin D., Fischer R., Bellot F., Li W., Dionne C.A., Jaye M., Rubinstein M., Schlessinger J. Mol. Cell. Biol. 11:5068-5078(1991) [PubMed: 1656221] [Abstract] Cited for: INTERACTION WITH FGFR1.
[7]	"Signal transduction by fibroblast growth factor receptor-4 (FGFR-4). Comparison with FGFR-1." Vainikka S., Joukov V., Wennstrom S., Bergman M., Pelicci P.G., Alitalo K. J. Biol. Chem. 269:18320-18326(1994) [PubMed: 7518429] [Abstract] Cited for: INTERACTION WITH FGFR4.
[8]	"Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk." Law C.L., Chandran K.A., Sidorenko S.P., Clark E.A. Mol. Cell. Biol. 16:1305-1315(1996) [PubMed: 8657103] [Abstract] Cited for: PHOSPHORYLATION AT TYR-771 AND TYR-783 BY SYK, INTERACTION WITH SYK.
[9]	"Direct association of Csk homologous kinase (CHK) with the diphosphorylated site Tyr568/570 of the activated c-KIT in megakaryocytes." Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H. J. Biol. Chem. 272:5915-5920(1997) [PubMed: 9038210] [Abstract] Cited for: INTERACTION WITH KIT.
[10]	"Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site." Braunger J., Schleithoff L., Schulz A.S., Kessler H., Lammers R., Ullrich A., Bartram C.R., Janssen J.W. Oncogene 14:2619-2631(1997) [PubMed: 9178760] [Abstract] Cited for: INTERACTION WITH AXL.
[11]	"LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation." Zhang W., Sloan-Lancaster J., Kitchen J., Trible R.P., Samelson L.E. Cell 92:83-92(1998) [PubMed: 9489702] [Abstract] Cited for: INTERACTION WITH LAT.
[12]	"Requirement of the Src homology 2 domain protein Shb for T cell receptor-dependent activation of the interleukin-2 gene nuclear factor for activation of T cells element in Jurkat T cells." Lindholm C.K., Gylfe E., Zhang W., Samelson L.E., Welsh M. J. Biol. Chem. 274:28050-28057(1999) [PubMed: 10488157] [Abstract] Cited for: INTERACTION WITH SHB.
[13]	"Autophosphorylation of KDR in the kinase domain is required for maximal VEGF-stimulated kinase activity and receptor internalization." Dougher M., Terman B.I. Oncogene 18:1619-1627(1999) [PubMed: 10102632] [Abstract] Cited for: PHOSPHORYLATION BY KDR.
[14]	"Characterization of the tyrosine kinase Tnk1 and its binding with phospholipase C-gamma1." Felschow D.M., Civin C.I., Hoehn G.T. Biochem. Biophys. Res. Commun. 273:294-301(2000) [PubMed: 10873601] [Abstract] Cited for: INTERACTION WITH TNK1.
[15]	"The ORF3 protein of hepatitis E virus binds to Src homology 3 domains and activates MAPK." Korkaya H., Jameel S., Gupta D., Tyagi S., Kumar R., Zafrullah M., Mazumdar M., Lal S.K., Xiaofang L., Sehgal D., Das S.R., Sahal D. J. Biol. Chem. 276:42389-42400(2001) [PubMed: 11518702] [Abstract] Cited for: INTERACTION WITH HEV ORF3 PROTEIN.
[16]	"Identification and characterization of a new family of guanine nucleotide exchange factors for the ras-related GTPase Ral." Rebhun J.F., Chen H., Quilliam L.A. J. Biol. Chem. 275:13406-13410(2000) [PubMed: 10747847] [Abstract] Cited for: INTERACTION WITH RALGPS1.
[17]	"Protein tyrosine phosphatase CD148-mediated inhibition of T-cell receptor signal transduction is associated with reduced LAT and phospholipase Cgamma1 phosphorylation." Baker J.E., Majeti R., Tangye S.G., Weiss A. Mol. Cell. Biol. 21:2393-2403(2001) [PubMed: 11259588] [Abstract] Cited for: PROBABLE DEPHOSPHORYLATION BY PTPRJ.
[18]	"Membrane raft-dependent regulation of phospholipase Cgamma-1 activation in T lymphocytes." Veri M.C., DeBell K.E., Seminario M.C., DiBaldassarre A., Reischl I., Rawat R., Graham L., Noviello C., Rellahan B.L., Miscia S., Wange R.L., Bonvini E. Mol. Cell. Biol. 21:6939-6950(2001) [PubMed: 11564877] [Abstract] Cited for: PHOSPHORYLATION AT TYR-783, SUBCELLULAR LOCATION.
[19]	"The tyrosine phosphatase CD148 is excluded from the immunologic synapse and down-regulates prolonged T cell signaling." Lin J., Weiss A. J. Cell Biol. 162:673-682(2003) [PubMed: 12913111] [Abstract] Cited for: PROBABLE DEPHOSPHORYLATION BY PTPRJ.
[20]	"TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma." Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A., Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A., Mackay A.R. Cancer Cell 6:347-360(2004) [PubMed: 15488758] [Abstract] Cited for: INTERACTION WITH NTRK1.
[21]	"Signal transduction via the stem cell factor receptor/c-Kit." Ronnstrand L. Cell. Mol. Life Sci. 61:2535-2548(2004) [PubMed: 15526160] [Abstract] Cited for: REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
[22]	"Deficiency of BLNK hampers PLC-gamma2 phosphorylation and Ca2+ influx induced by the pre-B-cell receptor in human pre-B cells." Taguchi T., Kiyokawa N., Takenouch H., Matsui J., Tang W.-R., Nakajima H., Suzuki K., Shiozawa Y., Saito M., Katagiri Y.U., Takahashi T., Karasuyama H., Matsuo Y., Okita H., Fujimoto J. Immunology 112:575-582(2004) [PubMed: 15270728] [Abstract] Cited for: INTERACTION WITH BLNK; VAV1; GRB2 AND NCK1.
[23]	"Activation of vascular endothelial growth factor receptor-3 and its downstream signaling promote cell survival under oxidative stress." Wang J.F., Zhang X., Groopman J.E. J. Biol. Chem. 279:27088-27097(2004) [PubMed: 15102829] [Abstract] Cited for: INTERACTION WITH FLT4.
[24]	"Vascular endothelial growth factor (VEGF)-D and VEGF-A differentially regulate KDR-mediated signaling and biological function in vascular endothelial cells." Jia H., Bagherzadeh A., Bicknell R., Duchen M.R., Liu D., Zachary I. J. Biol. Chem. 279:36148-36157(2004) [PubMed: 15215251] [Abstract] Cited for: PHOSPHORYLATION AT TYR-783 IN RESPONSE TO KDR ACTIVATION.
[25]	"Early phosphorylation kinetics of proteins involved in proximal TCR-mediated signaling pathways." Houtman J.C., Houghtling R.A., Barda-Saad M., Toda Y., Samelson L.E. J. Immunol. 175:2449-2458(2005) [PubMed: 16081816] [Abstract] Cited for: PHOSPHORYLATION BY ITK.
[26]	"Time-resolved mass spectrometry of tyrosine phosphorylation sites in the epidermal growth factor receptor signaling network reveals dynamic modules." Zhang Y., Wolf-Yadlin A., Ross P.L., Pappin D.J., Rush J., Lauffenburger D.A., White F.M. Mol. Cell. Proteomics 4:1240-1250(2005) [PubMed: 15951569] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-775 AND TYR-783, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[27]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-771 AND TYR-775, MASS SPECTROMETRY.
[28]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-771 AND TYR-1253, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[29]	"Intracellular retention, degradation, and signaling of glycosylation-deficient FGFR2 and craniosynostosis syndrome-associated FGFR2C278F." Hatch N.E., Hudson M., Seto M.L., Cunningham M.L., Bothwell M. J. Biol. Chem. 281:27292-27305(2006) [PubMed: 16844695] [Abstract] Cited for: INTERACTION WITH FGFR2, PHOSPHORYLATION.
[30]	"Obligatory role for phospholipase C-gamma(1) in villin-induced epithelial cell migration." Wang Y., Tomar A., George S.P., Khurana S. Am. J. Physiol. 292:C1775-C1786(2007) [PubMed: 17229814] [Abstract] Cited for: FUNCTION, INTERACTION WITH VIL1, SUBCELLULAR LOCATION.
[31]	"Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCgamma-activated STAT1." Harada D., Yamanaka Y., Ueda K., Nishimura R., Morishima T., Seino Y., Tanaka H. Bone 41:273-281(2007) [PubMed: 17561467] [Abstract] Cited for: PHOSPHORYLATION BY FGFR3.
[32]	"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. , 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-977, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[33]	"Binding of Cbl to a phospholipase Cgamma1-docking site on platelet-derived growth factor receptor beta provides a dual mechanism of negative regulation." Reddi A.L., Ying G., Duan L., Chen G., Dimri M., Douillard P., Druker B.J., Naramura M., Band V., Band H. J. Biol. Chem. 282:29336-29347(2007) [PubMed: 17620338] [Abstract] Cited for: INTERACTION WITH PDGFRB.
[34]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-771; TYR-783 AND TYR-1253, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[35]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1263, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[36]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1221, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[37]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-525, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[38]	"A novel interaction between fibroblast growth factor receptor 3 and the p85 subunit of phosphoinositide 3-kinase: activation-dependent regulation of ERK by p85 in multiple myeloma cells." Salazar L., Kashiwada T., Krejci P., Muchowski P., Donoghue D., Wilcox W.R., Thompson L.M. Hum. Mol. Genet. 18:1951-1961(2009) [PubMed: 19286672] [Abstract] Cited for: INTERACTION WITH FGFR3.
[39]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-771; TYR-775 AND TYR-783, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[40]	"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-771; TYR-775; TYR-783; SER-1221; TYR-1253 AND SER-1263, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[41]	"Mutation of tyrosine residue 857 in the PDGF beta-receptor affects cell proliferation but not migration." Wardega P., Heldin C.H., Lennartsson J. Cell. Signal. 22:1363-1368(2010) [PubMed: 20494825] [Abstract] Cited for: INTERACTION WITH PDGFRB, PHOSPHORYLATION.
[42]	"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].
[43]	"Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function." Persaud A., Alberts P., Hayes M., Guettler S., Clarke I., Sicheri F., Dirks P., Ciruna B., Rotin D. EMBO J. 30:3259-3273(2011) [PubMed: 21765395] [Abstract] Cited for: INTERACTION WITH FGFR1, PHOSPHORYLATION BY FGFR1.
[44]	"Cellular signaling by fibroblast growth factor receptors." Eswarakumar V.P., Lax I., Schlessinger J. Cytokine Growth Factor Rev. 16:139-149(2005) [PubMed: 15863030] [Abstract] Cited for: REVIEW ON ROLE IN FGF-ACTIVATED SIGNALING PATHWAYS.
[45]	"Solution structure of the SH3 domain of phospholipase C-gamma." Kohda D., Hatanaka H., Odaka M., Mandiyan V., Ullrich A., Schlessinger J., Inagaki F. Cell 72:953-960(1993) [PubMed: 7681365] [Abstract] Cited for: STRUCTURE BY NMR OF SH3 DOMAIN.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M34667 mRNA. Translation: AAA36452.1.
DQ297143 Genomic DNA. Translation: ABB84466.1.
AL022394 Genomic DNA. Translation: CAA18537.1.
CH471077 Genomic DNA. Translation: EAW75991.1.
CH471077 Genomic DNA. Translation: EAW75992.1.
BC136466 mRNA. Translation: AAI36467.1.
BC144136 mRNA. Translation: AAI44137.1.

IPI

IPI00016736.
IPI00383849.

PIR

A36466.

RefSeq

NP_002651.2. NM_002660.2.
NP_877963.1. NM_182811.1.

UniGene

Hs.268177.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1HSQ	NMR	-	A	790-852	[»]
2HSP	NMR	-	A	790-852	[»]

ProteinModelPortal

P19174.

SMR

P19174. Positions 157-218, 345-384, 489-933, 1088-1195.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-100N.

IntAct

P19174. 67 interactions.

MINT

MINT-102915.

STRING

P19174.

PTM databases

PhosphoSite

P19174.

Polymorphism databases

DMDM

130225.

Proteomic databases

PRIDE

P19174.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373271; ENSP00000362368; ENSG00000124181.

GeneID

5335.

KEGG

hsa:5335.

UCSC

uc002xjp.1. human.

Organism-specific databases

CTD

5335.

GeneCards

GC20P039765.

H-InvDB

HIX0015819.
HIX0040702.

HGNC

HGNC:9065. PLCG1.

HPA

CAB004277.

MIM

172420. gene.

neXtProt

NX_P19174.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

HBG053611.

OMA

YRSLMYS.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
epha_fwdpathway. EPHA forward signaling.
epopathway. EPO signaling pathway.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
fgf_pathway. FGF signaling pathway.
lysophospholipid_pathway. LPA receptor mediated events.
trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
wnt_calcium_pathway. Noncanonical Wnt signaling pathway.
pdgfrapathway. PDGFR-alpha signaling pathway.
pdgfrbpathway. PDGFR-beta signaling pathway.
s1p_s1p1_pathway. S1P1 pathway.
s1p_s1p4_pathway. S1P4 pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2.
tcrpathway. TCR signaling in naive CD4+ T cells.
cd8tcrpathway. TCR signaling in naive CD8+ T cells.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
vegfr1_pathway. VEGFR1 specific signals.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P19174.

Bgee

P19174.

CleanEx

HS_PLCG1.

Genevestigator

P19174.

GermOnline

ENSG00000124181. Homo sapiens.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR018249. EF_HAND_2.
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]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.
G3DSA: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.

KO

K05859.

Pfam

PF00168. C2. 1 hit.
PF09279. efhand_like. 1 hit.
PF00169. PH. 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]

PIRSF

PIRSF000952. PLC-gamma. 1 hit.

PRINTS

PR00390. PHPHLIPASEC.
PR00401. SH2DOMAIN.

SMART

SM00239. C2. 1 hit.
SM00233. PH. 3 hits.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
SM00252. SH2. 2 hits.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF51695. PLC-like_Pdiesterase_TIM-brl. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS50004. C2. 1 hit.
PS00018. EF_HAND_1. 1 hit.
PS50222. EF_HAND_2. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS50007. PIPLC_X_DOMAIN. 1 hit.
PS50008. PIPLC_Y_DOMAIN. 1 hit.
PS50001. SH2. 2 hits.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

20662.

SOURCE

Search...

Entry information

Entry name

PLCG1_HUMAN

Accession

Primary (citable) accession number: P19174
Secondary accession number(s): B7ZLY7 , B9EGH4, E1P5W4, Q2V575

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	January 25, 2012
This is version 159 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.