P10686 (PLCG1_RAT) 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):
Phosphoinositide phospholipase C-gamma-1
Phospholipase C-gamma-1
Short name=PLC-gamma-1

Gene names

Name:

Plcg1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1290 AA.
Sequence status	Complete.
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 By similarity.
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 By similarity.
Subunit structure	Interacts (via SH2 domain) with FGFR1, FGFR2, FGFR3 and FGFR4 (phosphorylated). Interacts (via SH3 domain) with AGAP2. 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 RALGPS1. Interacts (via the SH2 domains) with VIL1 (phosphorylated at C-terminus tyrosine phosphorylation sites). Interacts (via SH2 domain) with RET By similarity. Interacts with FLT1 (tyrosine-phosphorylated). Interacts with AXL, FLT4 and KIT. Interacts (via SH2 domain) with PDGFRA and PDGFRB (tyrosine phosphorylated) By similarity. Interacts with PIP5K1C By similarity. Interacts with NTRK1 and NTRK2 (phosphorylated upon ligand-binding) By similarity. Interacts with SYK; activates PLCG1 By similarity. Interacts with TESPA1 By similarity. Interacts with GRB2, LAT and THEMIS upon TCR activation in thymocytes By similarity. Ref.3 Ref.4
Subcellular location	Cell projection › lamellipodium By similarity. Cell projection › ruffle By similarity. Note: Rapidly redistributed to ruffles and lamellipodia structures in response to epidermal growth factor (EGF) treatment By similarity.
Domain	The SH3 domain mediates interaction with CLNK and RALGPS1 By similarity.
Post-translational modification	May be dephosphorylated by PTPRJ By similarity. Tyrosine phosphorylated by activated FGFR1, FGFR2, FGFR3 and FGFR4. 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. Tyrosine phosphorylated in response to signaling via activated FLT1, FLT3, KIT and PDGFRB. Phosphorylated by ITK and TXK on Tyr-783 upon TCR activation in T-cells By similarity. Ref.3 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	Lipid degradation Lipid metabolism
Cellular component	Cell projection
Domain	Repeat SH2 domain SH3 domain
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Transducer
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	calcium ion transport Inferred from mutant phenotype PubMed 12437926. Source: RGD cellular response to epidermal growth factor stimulus Inferred from sequence or structural similarity. Source: UniProtKB inositol trisphosphate biosynthetic process Inferred from mutant phenotype PubMed 16973916. Source: RGD intracellular signal transduction Inferred from electronic annotation. Source: InterPro phospholipid catabolic process Inferred from electronic annotation. Source: InterPro positive regulation of epithelial cell migration Inferred from mutant phenotype PubMed 16973916. Source: RGD protein secretion Inferred from mutant phenotype PubMed 12507498. Source: RGD regulation of store-operated calcium channel activity Inferred from mutant phenotype PubMed 17432954. Source: RGD response to gravity Inferred from expression pattern PubMed 17404041. Source: RGD response to hydrogen peroxide Inferred from expression pattern PubMed 17982259. Source: RGD response to morphine Inferred from expression pattern PubMed 17524370. Source: RGD signal transduction Traceable author statement PubMed 12009430. Source: RGD
Cellular_component	cytoplasm Traceable author statement PubMed 12009430. Source: RGD lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome ruffle Inferred from sequence or structural similarity. Source: UniProtKB signalosome Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro insulin receptor binding Inferred from direct assay PubMed 14568990. Source: RGD phosphatidylinositol phospholipase C activity Inferred from electronic annotation. Source: EC phospholipid binding Inferred from electronic annotation. Source: InterPro signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FGFR1	P11362	4	EBI-520788,EBI-1028277	From a different organism.
Fgfr1	Q04589	2	EBI-520788,EBI-2480918
TRPC3	Q13507	2	EBI-520788,EBI-520807	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1290

1290

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

PRO_0000088500

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

379

1

Phosphotyrosine By similarity

Modified residue

481

1

Phosphotyrosine By similarity

Modified residue

506

1

Phosphotyrosine By similarity

Modified residue

771

1

Phosphotyrosine; by SYK By similarity

Modified residue

775

1

Phosphotyrosine By similarity

Modified residue

783

1

Phosphotyrosine; by ITK, SYK and TXK By similarity

Modified residue

977

1

Phosphotyrosine By similarity

Modified residue

1221

1

Phosphoserine By similarity

Modified residue

1248

1

Phosphoserine By similarity

Modified residue

1253

1

Phosphotyrosine By similarity

Modified residue

1263

1

Phosphoserine By similarity

Experimental info

Mutagenesis

842

1

P → L: Inhibits interaction with AGAP2. Ref.4

Secondary structure

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1290

Helix Strand Turn

Details...

Beta strand

491 – 499

9

Turn

500 – 503

4

Beta strand

504 – 513

10

Beta strand

516 – 519

4

Beta strand

551 – 553

3

Helix

556 – 558

3

Helix

561 – 576

16

Beta strand

583 – 587

5

Beta strand

589 – 591

3

Beta strand

594 – 600

7

Beta strand

605 – 613

9

Beta strand

616 – 618

3

Beta strand

620 – 624

5

Beta strand

627 – 631

5

Helix

632 – 641

10

Helix

662 – 665

4

Beta strand

666 – 672

7

Helix

675 – 683

9

Beta strand

687 – 695

9

Beta strand

697 – 708

12

Beta strand

711 – 720

10

Beta strand

723 – 726

4

Beta strand

729 – 733

5

Helix

734 – 741

8

Helix

758 – 761

4

Beta strand

796 – 800

5

Beta strand

817 – 822

6

Beta strand

825 – 833

9

Beta strand

836 – 842

7

Helix

843 – 845

3

Beta strand

846 – 848

3

Beta strand

860 – 862

3

Turn

864 – 870

7

Beta strand

874 – 876

3

Beta strand

882 – 886

5

Beta strand

890 – 892

3

Beta strand

896 – 900

5

Beta strand

904 – 906

3

Beta strand

909 – 912

4

Helix

916 – 930

15

Sequences

	Sequence		Length	Mass (Da)
	P10686 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: BB3240C27972CE3B	FASTA	1,290	148,548
	10 20 30 40 50 60 MAGVGTPCAN GCGPSAPSEA EVLHLCRSLE VGTVMTLFYS KKSQRPERKT FQVKLETRQI 70 80 90 100 110 120 TWSRGADKIE GSIDIREIKE IRPGKTSRDF DRYQEDPAFR PDQSHCFVIL YGMEFRLKTL 130 140 150 160 170 180 SLQATSEDEV NMWIKGLTWL MEDTLQAATP LQIERWLRKQ FYSVDRNRED RISAKDLKNM 190 200 210 220 230 240 LSQVNYRVPN MRFLRERLTD FEQRSGDITY GQFAQLYRSL MYSAQKTMDL PFLETNTLRT 250 260 270 280 290 300 GERPELCQVS LSEFQQFLLE YQGELWAVDR LQVQEFMLSF LRDPLREIEE PYFFLDELVT 310 320 330 340 350 360 FLFSKENSVW NSQLDAVCPE TMNNPLSHYW ISSSHNTYLT GDQFSSESSL EAYARCLRMG 370 380 390 400 410 420 CRCIELDCWD GPDGMPVIYH GHTLTTKIKF SDVLHTIKEH AFVASEYPVI LSIEDHCSIA 430 440 450 460 470 480 QQRNMAQHFR KVLGDTLLTK PVDIAADGLP SPNQLKRKIL IKHKKLAEGS AYEEVPTSVM 490 500 510 520 530 540 YSENDISNSI KNGILYLEDP VNHEWYPHYF VLTSSKIYYS EETSSDQGNE DEEEPKEASG 550 560 570 580 590 600 STELHSSEKW 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 TFTKSAIIQN VEKQDGGWWR GDYGGKKQLW 850 860 870 880 890 900 FPSNYVEEMI NPAILEPERE HLDENSPLGD LLRGVLDVPA CQIAIRPEGK NNRLFVFSIS 910 920 930 940 950 960 MPSVAQWSLD VAADSQEELQ DWVKKIREVA QTADARLTEG KMMERRKKIA LELSELVVYC 970 980 990 1000 1010 1020 RPVPFDEEKI GTERACYRDM SSFPETKAEK YVNKAKGKKF LQYNRLQLSR IYPKGQRLDS 1030 1040 1050 1060 1070 1080 SNYDPLPMWI CGSQLVALNF QTPDKPMQMN QALFMAGGHC GYVLQPSTMR DEAFDPFDKS 1090 1100 1110 1120 1130 1140 SLRGLEPCVI CIEVLGARHL 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 RASDASSQLF HVRAREGSFE ARYQQPFEDF 1270 1280 1290 RISQEHLADH FDSRERRAPR RTRVNGDNRL

References

[1]	"Inositol phospholipid-specific phospholipase C: complete cDNA and protein sequences and sequence homology to tyrosine kinase-related oncogene products." Suh P.-G., Ryu S.H., Moon K.H., Suh H.W., Rhee S.G. Proc. Natl. Acad. Sci. U.S.A. 85:5419-5423(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Promoter region of the rat phospholipase C-gamma 1 gene." Lee S.J., Ryu S.H., Suh P.G. Biochem. Biophys. Res. Commun. 194:294-300(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
[3]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FGFR4, PHOSPHORYLATION.
[4]	"Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE." Ye K., Aghdasi B., Luo H.R., Moriarity J.L., Wu F.Y., Hong J.J., Hurt K.J., Bae S.S., Suh P.-G., Snyder S.H. Nature 415:541-544(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AGAP2, MUTAGENESIS OF PRO-842.
[5]	"Structural characterization of the split pleckstrin homology domain in phospholipase C-gamma1 and its interaction with TRPC3." Wen W., Yan J., Zhang M. J. Biol. Chem. 281:12060-12068(2006) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 489-553 AND 663-759.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03806 mRNA. Translation: AAA41921.1.
L14476 Genomic DNA. No translation available.

IPI

IPI00192532.

PIR

A31317.

RefSeq

NP_037319.1. NM_013187.1.

UniGene

Rn.11243.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Y0M	X-ray	1.20	A	791-851	[»]
1YWO	X-ray	1.81	A	790-851	[»]
1YWP	X-ray	1.60	A	790-851	[»]
2FJL	NMR	-	A	489-933	[»]
3GQI	X-ray	2.50	B	545-770	[»]

ProteinModelPortal

P10686.

SMR

P10686. Positions 320-454, 489-658, 663-759, 795-848, 851-933.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2863N.

IntAct

P10686. 3 interactions.

MINT

MINT-231720.

STRING

10116.ENSRNOP00000022276.

PTM databases

PhosphoSite

P10686.

Proteomic databases

PaxDb

P10686.

PRIDE

P10686.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

25738.

KEGG

rno:25738.

UCSC

RGD:3347. rat.

Organism-specific databases

CTD

5335.

RGD

3347. Plcg1.

Phylogenomic databases

eggNOG

NOG268751.

HOGENOM

HOG000230864.

HOVERGEN

HBG053611.

KO

K01116.

OrthoDB

EOG4320X7.

Enzyme and pathway databases

BRENDA

3.1.4.11. 5301.

Reactome

REACT_109781. Immune System.
REACT_110573. Disease.
REACT_111984. Signal Transduction.
REACT_96538. Developmental Biology.

Gene expression databases

Genevestigator

P10686.

GermOnline

ENSRNOG00000016340. Rattus norvegicus.

Family and domain databases

Gene3D

1.10.238.10. 1 hit.
2.30.29.30. 3 hits.
3.20.20.190. 2 hits.
3.30.505.10. 2 hits.

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.
IPR002048. EF_hand_dom.
IPR011993. PH_like_dom.
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]

PANTHER

PTHR10336. PTHR10336. 1 hit.

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.
PR00452. SH3DOMAIN.

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

BindingDB

P10686.

ChEMBL

CHEMBL5188.

EvolutionaryTrace

P10686.

NextBio

607883.

PMAP-CutDB

P10686.

Entry information

Entry name

PLCG1_RAT

Accession

Primary (citable) accession number: P10686

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	May 1, 2013
This is version 153 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program