DB code: M00183

RLCP classification 1.15.72000.565 : Hydrolysis
CATH domain 2.30.29.30 : PH-domain like
1.10.238.10 : Recoverin; domain 1
1.10.238.10 : Recoverin; domain 1
3.20.20.190 : TIM Barrel Catalytic domain
2.30.29.30 : PH-domain like
3.30.505.10 : SHC Adaptor Protein
3.30.505.10 : SHC Adaptor Protein
2.30.30.40 : SH3 type barrels.
2.60.40.150 : Immunoglobulin-like
-.-.-.- :
E.C. 3.1.4.11
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.238.10 : Recoverin; domain 1 M00198 D00151 M00118
2.30.29.30 : PH-domain like M00125 M00344 M00118
2.30.30.40 : SH3 type barrels. M00043 M00130 T00256 M00304 M00335
2.60.40.150 : Immunoglobulin-like M00221 M00043 M00118
3.20.20.190 : TIM Barrel S00236 M00118
3.30.505.10 : SHC Adaptor Protein M00043 M00130 M00148 T00256 M00304 M00333 M00339 M00344 T00221

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9X0A5
Putative uncharacterized protein
NP_228818.1 (Protein)
NC_000853.1 (DNA/RNA sequence)
[Graphical View]
P08487 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1
EC 3.1.4.11
Phosphoinositide phospholipase C
Phospholipase C-gamma-1
PLC-gamma-1
PLC-II
PLC-148
NP_776850.1 (Protein)
NM_174425.3 (DNA/RNA sequence)
PF00168 (C2)
PF09279 (efhand_like)
PF00388 (PI-PLC-X)
PF00387 (PI-PLC-Y)
PF00017 (SH2)
PF00018 (SH3_1)
[Graphical View]
P19174 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma-1
EC 3.1.4.11
Phosphoinositide phospholipase C
Phospholipase C-gamma-1
PLC-gamma-1
PLC-II
PLC-148
NP_002651.2 (Protein)
NM_002660.2 (DNA/RNA sequence)
NP_877963.1 (Protein)
NM_182811.1 (DNA/RNA sequence)
PF00168 (C2)
PF09279 (efhand_like)
PF00388 (PI-PLC-X)
PF00387 (PI-PLC-Y)
PF00017 (SH2)
PF00018 (SH3_1)
[Graphical View]

KEGG enzyme name
phosphoinositide phospholipase C
triphosphoinositide phosphodiesterase
phosphoinositidase C
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase
monophosphatidylinositol phosphodiesterase
phosphatidylinositol phospholipase C
PI-PLC
1-phosphatidyl-D-myo-inositol-4,5-bisphosphateinositoltrisphosphohydrolase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q9X0A5 Q9X0A5_THEMA
P08487 PLCG1_BOVIN 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Interacts with CENTG1 via its SH3 domain. Interacts with phosphorylated LAT upon TCR activation. Interacts with the Pro- rich domain of TNK1 via its SH3 domain. 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 its 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 and MIST (By similarity). Interacts with RALGPS1 (By similarity). Calcium.
P19174 PLCG1_HUMAN 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol. Interacts with CENTG1 via its SH3 domain (By similarity). Interacts with phosphorylated LAT upon TCR activation. Interacts with the Pro-rich domain of TNK1 via its SH3 domain. 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 its 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 and MIST (By similarity). Interacts with RALGPS1. Interacts (via SH3 domain) with HEV ORF3 protein. Calcium.

KEGG Pathways
Map code Pathways E.C.
MAP00562 Inositol phosphate metabolism
MAP04070 Phosphatidylinositol signaling system

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00076 C00001 C04021 C04637 C00165 C00641 C01245
E.C.
Compound Calcium H2O Phosphatidylinositol phosphate 1-Phosphatidyl-D-myo-inositol 4,5-bisphosphate Diacylglycerol 1,2-Diacyl-sn-glycerol D-myo-Inositol 1,4,5-trisphosphate
Type divalent metal (Ca2+, Mg2+) H2O carbohydrate,phosphate group/phosphate ion carbohydrate,lipid,phosphate group/phosphate ion carbohydrate,lipid carbohydrate,lipid carbohydrate,phosphate group/phosphate ion
ChEBI 29108
15377
16595
PubChem 271
22247451
962
439456
2fclA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2pldA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2pleA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1hspA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
1hsqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound
2hspA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2fclA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2pldA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2pleA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1hspA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1hsqA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2hspA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain

References for Catalytic Mechanism
References Sections No. of steps in catalysis

References
[1]
Resource
Comments PHOSPHORYLATION SITES.
Medline ID 90154080
PubMed ID 1689310
Journal J Biol Chem
Year 1990
Volume 265
Pages 3940-3
Authors Kim JW, Sim SS, Kim UH, Nishibe S, Wahl MI, Carpenter G, Rhee SG
Title Tyrosine residues in bovine phospholipase C-gamma phosphorylated by the epidermal growth factor receptor in vitro.
Related PDB
Related UniProtKB P08487
[2]
Resource
Comments PHOSPHORYLATION SITES.
Medline ID 90154081
PubMed ID 1689311
Journal J Biol Chem
Year 1990
Volume 265
Pages 3944-8
Authors Wahl MI, Nishibe S, Kim JW, Kim H, Rhee SG, Carpenter G
Title Identification of two epidermal growth factor-sensitive tyrosine phosphorylation sites of phospholipase C-gamma in intact HSC-1 cells.
Related PDB
Related UniProtKB P08487
[3]
Resource
Comments PHOSPHORYLATION SITES.
Medline ID 91208680
PubMed ID 1708307
Journal Cell
Year 1991
Volume 65
Pages 435-41
Authors Kim HK, Kim JW, Zilberstein A, Margolis B, Kim JG, Schlessinger J, Rhee SG
Title PDGF stimulation of inositol phospholipid hydrolysis requires PLC-gamma 1 phosphorylation on tyrosine residues 783 and 1254.
Related PDB
Related UniProtKB P08487
[4]
Resource
Comments STRUCTURE BY NMR OF SH3 DOMAIN.
Medline ID 93208890
PubMed ID 7681365
Journal Cell
Year 1993
Volume 72
Pages 953-60
Authors Kohda D, Hatanaka H, Odaka M, Mandiyan V, Ullrich A, Schlessinger J, Inagaki F
Title Solution structure of the SH3 domain of phospholipase C-gamma.
Related PDB 1hsp 1hsq 2hsp
Related UniProtKB P19174
[5]
Resource
Comments
Medline ID
PubMed ID 7993895
Journal Biochemistry
Year 1994
Volume 33
Pages 14671-8
Authors Gergel JR, McNamara DJ, Dobrusin EM, Zhu G, Saltiel AR, Miller WT
Title Identification of amino acids in the N-terminal SH2 domain of phospholipase C gamma 1 important in the interaction with epidermal growth factor receptor.
Related PDB
Related UniProtKB
[6]
Resource
Comments STRUCTURE BY NMR OF 663-759.
Medline ID 94236690
PubMed ID 8181064
Journal Cell
Year 1994
Volume 77
Pages 461-72
Authors Pascal SM, Singer AU, Gish G, Yamazaki T, Shoelson SE, Pawson T, Kay LE, Forman-Kay JD
Title Nuclear magnetic resonance structure of an SH2 domain of phospholipase C-gamma 1 complexed with a high affinity binding peptide.
Related PDB 2pld 2ple
Related UniProtKB P08487
[7]
Resource
Comments
Medline ID
PubMed ID 7843417
Journal FEBS Lett
Year 1995
Volume 358
Pages 287-92
Authors Huang PS, Davis L, Huber H, Goodhart PJ, Wegrzyn RE, Oliff A, Heimbrook DC
Title An SH3 domain is required for the mitogenic activity of microinjected phospholipase C-gamma 1.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 8524815
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 11618-22
Authors Huang X, Li Y, Tanaka K, Moore KG, Hayashi JI
Title Cloning and characterization of Lnk, a signal transduction protein that links T-cell receptor activation signal to phospholipase C gamma 1, Grb2, and phosphatidylinositol 3-kinase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 7773170
Journal Protein Sci
Year 1995
Volume 4
Pages 13-20
Authors MacLean D, Sefler AM, Zhu G, Decker SJ, Saltiel AR, Singh J, McNamara D, Dobrusin EM, Sawyer TK
Title Differentiation of peptide molecular recognition by phospholipase C gamma-1 Src homology-2 domain and a mutant Tyr phosphatase PTP1bC215S.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 8660853
Journal Cell Immunol
Year 1996
Volume 171
Pages 164-9
Authors Kanner SB
Title Focal adhesion kinase-related fakB is regulated by the integrin LFA-1 and interacts with the SH3 domain of phospholipase C gamma 1.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 8941357
Journal Biochem Biophys Res Commun
Year 1996
Volume 228
Pages 802-6
Authors Pei Z, Yang L, Williamson JR
Title Phospholipase C-gamma 1 binds to actin-cytoskeleton via its C-terminal SH2 domain in vitro.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8630067
Journal Biochem Biophys Res Commun
Year 1996
Volume 222
Pages 186-93
Authors Smith MR, Liu YL, Kim SR, Bae YS, Kim CG, Kwon KS, Rhee SG, Kung HF
Title PLC gamma 1 Src homology domain induces mitogenesis in quiescent NIH 3T3 fibroblasts.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8598208
Journal EMBO J
Year 1996
Volume 15
Pages 73-82
Authors Obermeier A, Tinhofer I, Grunicke HH, Ullrich A
Title Transforming potentials of epidermal growth factor and nerve growth factor receptors inversely correlate with their phospholipase C gamma affinity and signal activation.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8657103
Journal Mol Cell Biol
Year 1996
Volume 16
Pages 1305-15
Authors Law CL, Chandran KA, Sidorenko SP, Clark EA
Title Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 8649391
Journal Mol Cell Biol
Year 1996
Volume 16
Pages 2823-9
Authors Motto DG, Musci MA, Ross SE, Koretzky GA
Title Tyrosine phosphorylation of Grb2-associated proteins correlates with phospholipase C gamma 1 activation in T cells.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 9712732
Journal Biochem Biophys Res Commun
Year 1998
Volume 249
Pages 537-41
Authors Graham LJ, Stoica BA, Shapiro M, DeBell KE, Rellahan B, Laborda J, Bonvini E
Title Sequences surrounding the Src-homology 3 domain of phospholipase Cgamma-1 increase the domain's association with Cbl.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 9514887
Journal Biochem Biophys Res Commun
Year 1998
Volume 244
Pages 62-7
Authors Ahn SJ, Han SJ, Mo HJ, Chung JK, Hong SH, Park TK, Kim CG
Title Interaction of phospholipase C gamma 1 via its COOH-terminal SRC homology 2 domain with synaptojanin.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9468499
Journal J Biol Chem
Year 1998
Volume 273
Pages 4465-9
Authors Bae YS, Cantley LG, Chen CS, Kim SR, Kwon KS, Rhee SG
Title Activation of phospholipase C-gamma by phosphatidylinositol 3,4,5-trisphosphate.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9570517
Journal J Immunol
Year 1998
Volume 160
Pages 1059-66
Authors Stoica B, DeBell KE, Graham L, Rellahan BL, Alava MA, Laborda J, Bonvini E
Title The amino-terminal Src homology 2 domain of phospholipase C gamma 1 is essential for TCR-induced tyrosine phosphorylation of phospholipase C gamma 1.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 9882440
Journal Arch Biochem Biophys
Year 1999
Volume 361
Pages 149-55
Authors Horstman DA, Chattopadhyay A, Carpenter G
Title The influence of deletion mutations on phospholipase C-gamma 1 activity.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 10360750
Journal Bioorg Med Chem Lett
Year 1999
Volume 9
Pages 1429-32
Authors Lee JS, Yang MY, Yeo H, Kim J, Lee HS, Ahn JS
Title Uncarinic acids: phospholipase Cgamma1 inhibitors from hooks of Uncaria rhynchophylla.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10202147
Journal EMBO J
Year 1999
Volume 18
Pages 1832-44
Authors Williams BL, Irvin BJ, Sutor SL, Chini CC, Yacyshyn E, Bubeck Wardenburg J, Dalton M, Chan AC, Abraham RT
Title Phosphorylation of Tyr319 in ZAP-70 is required for T-cell antigen receptor-dependent phospholipase C-gamma1 and Ras activation.
Related PDB
Related UniProtKB
[23]
Resource
Comments
Medline ID
PubMed ID 10350061
Journal FEBS Lett
Year 1999
Volume 450
Pages 77-83
Authors Pumphrey NJ, Taylor V, Freeman S, Douglas MR, Bradfield PF, Young SP, Lord JM, Wakelam MJ, Bird IN, Salmon M, Buckley CD
Title Differential association of cytoplasmic signalling molecules SHP-1, SHP-2, SHIP and phospholipase C-gamma1 with PECAM-1/CD31.
Related PDB
Related UniProtKB
[24]
Resource
Comments
Medline ID
PubMed ID 10586033
Journal J Immunol
Year 1999
Volume 163
Pages 6435-41
Authors Perez-Villar JJ, Kanner SB
Title Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 10672930
Journal Mol Cells
Year 1999
Volume 9
Pages 631-7
Authors Kim MJ, Si F, Kim SJ, Hong SB, Hwang JI, Lee HJ, Lee SJ, Chang JS, Lee YH, Ryu SH, Suh PG
Title The SH2-SH2-SH3 domain of phospholipase C-gamma1 directly binds to translational elongation factor-1alpha.
Related PDB
Related UniProtKB
[26]
Resource
Comments
Medline ID
PubMed ID 10438904
Journal J Immunol
Year 1999
Volume 163
Pages 1746-9
Authors Ishiai M, Sugawara H, Kurosaki M, Kurosaki T
Title Cutting edge: association of phospholipase C-gamma 2 Src homology 2 domains with BLNK is critical for B cell antigen receptor signaling.
Related PDB
Related UniProtKB
[27]
Resource
Comments
Medline ID
PubMed ID 10873601
Journal Biochem Biophys Res Commun
Year 2000
Volume 273
Pages 294-301
Authors Felschow DM, Civin CI, Hoehn GT
Title Characterization of the tyrosine kinase Tnk1 and its binding with phospholipase C-gamma1.
Related PDB
Related UniProtKB
[28]
Resource
Comments
Medline ID
PubMed ID 11094067
Journal Mol Cell Biol
Year 2000
Volume 20
Pages 9149-61
Authors Irvin BJ, Williams BL, Nilson AE, Maynor HO, Abraham RT
Title Pleiotropic contributions of phospholipase C-gamma1 (PLC-gamma1) to T-cell antigen receptor-mediated signaling: reconstitution studies of a PLC-gamma1-deficient Jurkat T-cell line.
Related PDB
Related UniProtKB
[29]
Resource
Comments
Medline ID
PubMed ID 11015615
Journal Physiol Rev
Year 2000
Volume 80
Pages 1291-335
Authors Rebecchi MJ, Pentyala SN
Title Structure, function, and control of phosphoinositide-specific phospholipase C.
Related PDB
Related UniProtKB
[30]
Resource
Comments
Medline ID
PubMed ID 11502583
Journal Am J Physiol Cell Physiol
Year 2001
Volume 281
Pages C1046-58
Authors Panebra A, Ma SX, Zhai LW, Wang XT, Rhee SG, Khurana S
Title Regulation of phospholipase C-gamma(1) by the actin-regulatory protein villin.
Related PDB
Related UniProtKB
[31]
Resource
Comments
Medline ID
PubMed ID 11331309
Journal J Cell Biol
Year 2001
Volume 153
Pages 599-612
Authors Matsuda M, Paterson HF, Rodriguez R, Fensome AC, Ellis MV, Swann K, Katan M
Title Real time fluorescence imaging of PLC gamma translocation and its interaction with the epidermal growth factor receptor.
Related PDB
Related UniProtKB
[32]
Resource
Comments
Medline ID
PubMed ID 11390650
Journal Mol Cell Biol
Year 2001
Volume 21
Pages 4208-18
Authors Yablonski D, Kadlecek T, Weiss A
Title Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.
Related PDB
Related UniProtKB
[33]
Resource
Comments
Medline ID
PubMed ID 12061819
Journal Exp Cell Res
Year 2002
Volume 277
Pages 86-94
Authors Tvorogov D, Carpenter G
Title EGF-dependent association of phospholipase C-gamma1 with c-Cbl.
Related PDB
Related UniProtKB
[34]
Resource
Comments
Medline ID
PubMed ID 12374773
Journal FASEB J
Year 2002
Volume 16
Pages 1504-14
Authors Shin SY, Ko J, Chang JS, Min do S, Choi C, Bae SS, Kim MJ, Hyun DS, Kim JH, Han MY, Kim YH, Kim YS, Na DS, Suh PG, Lee YH
Title Negative regulatory role of overexpression of PLC gamma 1 in the expression of early growth response 1 gene in rat 3Y1 fibroblasts.
Related PDB
Related UniProtKB
[35]
Resource
Comments
Medline ID
PubMed ID 11886851
Journal J Biol Chem
Year 2002
Volume 277
Pages 19697-702
Authors Chang JS, Seok H, Kwon TK, Min do S, Ahn BH, Lee YH, Suh JW, Kim JW, Iwashita S, Omori A, Ichinose S, Numata O, Seo JK, Oh YS, Suh PG
Title Interaction of elongation factor-1alpha and pleckstrin homology domain of phospholipase C-gamma 1 with activating its activity.
Related PDB
Related UniProtKB
[36]
Resource
Comments
Medline ID
PubMed ID 14993410
Journal Mol Interv
Year 2002
Volume 2
Pages 352-5;338
Authors Wang Z, Moran MF
Title Phospholipase C-gamma1: a phospholipase and guanine nucleotide exchange factor.
Related PDB
Related UniProtKB
[37]
Resource
Comments
Medline ID
PubMed ID 12226755
Journal Oncogene
Year 2002
Volume 21
Pages 6520-9
Authors Piccolo E, Innominato PF, Mariggio MA, Maffucci T, Iacobelli S, Falasca M
Title The mechanism involved in the regulation of phospholipase Cgamma1 activity in cell migration.
Related PDB
Related UniProtKB
[38]
Resource
Comments
Medline ID
PubMed ID 11796522
Journal Endocrinology
Year 2002
Volume 143
Pages 655-64
Authors Eichhorn J, Kayali AG, Resor L, Austin DA, Rose DW, Webster NJ
Title PLC-gamma1 enzyme activity is required for insulin-induced DNA synthesis.
Related PDB
Related UniProtKB

Comments
Although this enzyme is partially homologous to 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase from rat and human (Swiss-prot;P10688, M00118), the tertiary structure of catalytic domain has not been sulved yet. Comparison of sequence data suggests that this enzyme should have a similar catalytic site.
This enzyme must be composed of the following domains:
the N-terminal PH domain (CATH 2.30.29.30),
two EF-hand domains (CATH 1.10.238.10),
a catalytic domain (CATH 3.20.20.190), which is split into two regions,
another PH domain, which is also split into two regions,
two SH2 domains (CATH 3.30.505.10),
SH3 domain (CATH 2.30.30.40),
C2 domain (CATH 2.60.40.150),
and the C-terminal domain.

Created Updated
2003-08-28 2009-02-26