Reviewed, UniProtKB/Swiss-Prot P10686 (PLCG1_RAT)

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
    Phospholipase C-gamma-1
      Short name=PLC-gamma-1
    PLC-II
    PLC-148

Gene names

Name:

Plcg1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1290 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.
Catalytic activity	1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
Cofactor	Calcium.
Subunit structure	Interacts with AGAP2 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, THEMIS and CLNK By similarity. Interacts with RALGPS1 By similarity.
Domain	The SH3 domain mediates interaction with CLNK and RALGPS1 By similarity.
Post-translational modification	The receptor-mediated activation of PLC-gamma-1 and PLC-gamma-2 involves their phosphorylation by tyrosine kinases in response to ligation of a variety of growth factor receptors and immune system receptors. 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
Domain	Repeat SH2 domain SH3 domain
Ligand	Calcium
Molecular function	Hydrolase Transducer
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	calcium ion transport Inferred from mutant phenotype. Source: RGD inositol trisphosphate biosynthetic process Inferred from mutant phenotype. Source: RGD intracellular signaling cascade Inferred from electronic annotation. Source: InterPro phospholipid catabolic process Inferred from electronic annotation. Source: InterPro positive regulation of calcium ion transport via store-operated calcium channel activity Inferred from mutant phenotype. Source: RGD positive regulation of epithelial cell migration Inferred from mutant phenotype. Source: RGD response to gravity Inferred from expression pattern. Source: RGD response to hydrogen peroxide Inferred from expression pattern. Source: RGD response to morphine Inferred from expression pattern. Source: RGD response to organic nitrogen Inferred from expression pattern. Source: RGD vesicle-mediated transport Inferred from physical interaction. Source: RGD
Cellular component	cytoplasm Traceable author statement. Source: RGD
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW insulin receptor binding Inferred from direct assay. Source: RGD phosphoinositide phospholipase C activity Inferred from electronic annotation. Source: EC phosphoprotein binding Inferred from physical interaction. Source: RGD signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRPC3	Q13507	1	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 similarity

Modified residue

775

1

Phosphotyrosine By similarity

Modified residue

783

1

Phosphotyrosine 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.3

Secondary structure

1

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1290

Helix Strand Turn

Details...

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)
	P10686-1 [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: 2840660] [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: 8392838] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
[3]	"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: 11823862] [Abstract] Cited for: INTERACTION WITH AGAP2, MUTAGENESIS OF PRO-842.
[4]	"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: 16500902] [Abstract] Cited for: STRUCTURE BY NMR OF 489-553 AND 663-759.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

IPI

IPI00192532.

PIR

A31317.

RefSeq

NP_037319.1.

UniGene

Rn.11243

3D structure databases

PDBPDBe

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	[»]

SMR

P10686. Positions 489-553, 663-759.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:2863N.

IntAct

P10686. 1 interaction.

STRING

P10686.

PTM databases

PhosphoSite

P10686.

Proteomic databases

PRIDE

P10686.

Genome annotation databases

Ensembl

ENSRNOT00000021872; ENSRNOP00000021872; ENSRNOG00000016340; Rattus norvegicus. [Genome view]
ENSRNOT00000022276; ENSRNOP00000022276; ENSRNOG00000016340; Rattus norvegicus. [Genome view]

GeneID

25738.

KEGG

rno:25738.

UCSC

NM_013187. rat.

Organism-specific databases

CTD

25738.

RGD

3347. Plcg1.

Phylogenomic databases

HOVERGEN

P10686.

Enzyme and pathway databases

BRENDA

3.1.4.11. 248.

Gene expression databases

Genevestigator

P10686.

GermOnline

ENSRNOG00000016340. Rattus norvegicus.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR018029. C2_membr_targeting.
IPR018247. EF_HAND_1_Ca_BS.
IPR018249. EF_HAND_2.
IPR011993. PH_type.
IPR001192. Phospholipase_C_Pinositol-sp_C.
IPR000909. Phospholipase_C_Pinositol-sp_X.
IPR001711. Phospholipase_C_Pinositol-sp_Y.
IPR016279. PLC-gamma.
IPR017946. PLC-like_Pdiesterase_TIM-brl.
IPR001849. Pleckstrin_homology.
IPR000980. SH2.
IPR001452. SH3_domain.
IPR020473. SH3_region.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:3.20.20.190. PLC-like_Pdiesterase_TIM-brl. 1 hit.

Pfam

PF00168. C2. 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.

ProDom

PD001202. PI_PLC_Y. 2 hits.
PD000093. SH2. 2 hits.
PD000066. SH3. 1 hit.
[Graphical view] [Entries sharing at least one domain]

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]

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 Resources

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:	November 3, 2009
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)