Reviewed, UniProtKB/Swiss-Prot Q00722 (PLCB2_HUMAN)

Names and origin

Protein names

Recommended name:
    1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2
    EC=3.1.4.11
Alternative name(s):
    Phosphoinositide phospholipase C-beta-2
    Phospholipase C-beta-2
      Short name=PLC-beta-2

Gene names

Name:

PLCB2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1185 AA.
Sequence status	Complete.
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	Binds 1 calcium ion per subunit.
Subunit structure	Interacts with RAC1.
Miscellaneous	The receptor-mediated activation of PLC-beta-2 is most effectively mediated by one G-protein alpha subunit, alpha-16.
Sequence similarities	Contains 1 C2 domain. Contains 1 PI-PLC X-box domain. Contains 1 PI-PLC Y-box domain.

Ontologies

Keywords
Biological process	Lipid degradation
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Ligand	Calcium Metal-binding
Molecular function	Hydrolase Transducer
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	activation of phospholipase C activity Traceable author statement. Source: ProtInc lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW phosphoinositide phospholipase C activity Ref.1 Traceable author statement. Source: ProtInc signal transducer activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q00722-1)

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: Q00722-2)

The sequence of this isoform differs from the canonical sequence as follows:
     492-495: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1185

1185

1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-2

PRO_0000088489

Regions

Domain

312 – 463

152

PI-PLC X-box

Domain

546 – 662

117

PI-PLC Y-box

Domain

669 – 767

99

C2

Coiled coil

988 – 1147

160

Potential

Compositional bias

500 – 545

46

Glu-rich

Sites

Active site

327

1

By similarity

Active site

374

1

By similarity

Metal binding

328

1

Calcium

Metal binding

357

1

Calcium

Metal binding

359

1

Calcium

Metal binding

408

1

Calcium

Natural variations

Alternative sequence

492 – 495

4

Missing in isoform 2.

VSP_035770

Natural variant

324

1

N → I: dbSNP rs45628633.

VAR_047509

Natural variant

598

1

R → H: dbSNP rs8025153.

VAR_047510

Natural variant

664

1

P → L: dbSNP rs9972332.

VAR_047511

Natural variant

712

1

G → R: dbSNP rs28395835.

VAR_047512

Natural variant

1095

1

E → G: dbSNP rs936212. Ref.2

VAR_047513

Experimental info

Mutagenesis

52

1

Q → A: Strongly reduces interaction with RAC1. Ref.4

Sequence conflict

119

1

K → R in BAF84346. Ref.2

Sequence conflict

1060

1

K → R in BAF84346. Ref.2

Secondary structure

1

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1185

Helix Strand Turn

Details...

Helix

15 – 18

4

Beta strand

22 – 26

5

Turn

28 – 30

3

Beta strand

33 – 40

8

Beta strand

46 – 51

6

Beta strand

56 – 60

5

Helix

61 – 63

3

Beta strand

66 – 68

3

Helix

79 – 84

6

Helix

94 – 96

3

Beta strand

98 – 103

6

Beta strand

107 – 109

3

Beta strand

111 – 120

10

Helix

125 – 135

11

Helix

139 – 141

3

Helix

144 – 157

14

Helix

167 – 173

7

Helix

178 – 187

10

Helix

200 – 202

3

Helix

205 – 215

11

Helix

219 – 222

4

Helix

238 – 247

10

Helix

271 – 274

4

Helix

292 – 295

4

Helix

305 – 308

4

Helix

318 – 320

3

Beta strand

321 – 323

3

Beta strand

325 – 328

4

Helix

343 – 350

8

Beta strand

355 – 361

7

Helix

384 – 394

11

Beta strand

403 – 409

7

Helix

414 – 427

14

Turn

451 – 454

4

Beta strand

458 – 461

4

Helix

523 – 531

9

Helix

544 – 547

4

Helix

561 – 567

7

Beta strand

572 – 577

6

Helix

578 – 587

10

Helix

589 – 598

10

Beta strand

599 – 604

6

Helix

618 – 622

5

Helix

637 – 645

9

Helix

659 – 661

3

Turn

675 – 680

6

Beta strand

682 – 690

9

Beta strand

701 – 708

8

Beta strand

724 – 726

3

Beta strand

738 – 745

8

Helix

746 – 748

3

Beta strand

750 – 757

8

Beta strand

766 – 769

4

Helix

770 – 772

3

Beta strand

778 – 783

6

Beta strand

789 – 799

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 25, 2008. Version 2. Checksum: A0397309D943672A	FASTA	1,185	134,024
	10 20 30 40 50 60 MSLLNPVLLP PKVKAYLSQG ERFIKWDDET TVASPVILRV DPKGYYLYWT YQSKEMEFLD 70 80 90 100 110 120 ITSIRDTRFG KFAKMPKSQK LRDVFNMDFP DNSFLLKTLT VVSGPDMVDL TFHNFVSYKE 130 140 150 160 170 180 NVGKAWAEDV LALVKHPLTA NASRSTFLDK ILVKLKMQLN SEGKIPVKNF FQMFPADRKR 190 200 210 220 230 240 VEAALSACHL PKGKNDAINP EDFPEPVYKS FLMSLCPRPE IDEIFTSYHA KAKPYMTKEH 250 260 270 280 290 300 LTKFINQKQR DSRLNSLLFP PARPDQVQGL IDKYEPSGIN AQRGQLSPEG MVWFLCGPEN 310 320 330 340 350 360 SVLAQDKLLL HHDMTQPLNH YFINSSHNTY LTAGQFSGLS SAEMYRQVLL SGCRCVELDC 370 380 390 400 410 420 WKGKPPDEEP IITHGFTMTT DIFFKEAIEA IAESAFKTSP YPIILSFENH VDSPRQQAKM 430 440 450 460 470 480 AEYCRTIFGD MLLTEPLEKF PLKPGVPLPS PEDLRGKILI KNKKNQFSGP TSSSKDTGGE 490 500 510 520 530 540 AEGSSPPSAP AGEGTVWAGE EGTELEEEEV EEEEEEESGN LDEEEIKKMQ SDEGTAGLEV 550 560 570 580 590 600 TAYEEMSSLV NYIQPTKFVS FEFSAQKNRS YVISSFTELK AYDLLSKASV QFVDYNKRQM 610 620 630 640 650 660 SRIYPKGTRM DSSNYMPQMF WNAGCQMVAL NFQTMDLPMQ QNMAVFEFNG QSGYLLKHEF 670 680 690 700 710 720 MRRPDKQFNP FSVDRIDVVV ATTLSITVIS GQFLSERSVR TYVEVELFGL PGDPKRRYRT 730 740 750 760 770 780 KLSPSTNSIN PVWKEEPFVF EKILMPELAS LRVAVMEEGN KFLGHRIIPI NALNSGYHHL 790 800 810 820 830 840 CLHSESNMPL TMPALFIFLE MKDYIPGAWA DLTVALANPI KFFSAHDTKS VKLKEAMGGL 850 860 870 880 890 900 PEKPFPLASP VASQVNGALA PTSNGSPAAR AGAREEAMKE AAEPRTASLE ELRELKGVVK 910 920 930 940 950 960 LQRRHEKELR ELERRGARRW EELLQRGAAQ LAELGPPGVG GVGACKLGPG KGSRKKRSLP 970 980 990 1000 1010 1020 REESAGAAPG EGPEGVDGRV RELKDRLELE LLRQGEEQYE CVLKRKEQHV AEQISKMMEL 1030 1040 1050 1060 1070 1080 AREKQAAELK ALKETSENDT KEMKKKLETK RLERIQGMTK VTTDKMAQER LKREINNSHI 1090 1100 1110 1120 1130 1140 QEVVQVIKQM TENLERHQEK LEEKQAACLE QIREMEKQFQ KEALAEYEAR MKGLEAEVKE 1150 1160 1170 1180 SVRACLRTCF PSEAKDKPER ACECPPELCE QDPLIAKADA QESRL
	Isoform 2. Checksum: 7A6889F204D17FA4	FASTA	1,181	133,680
	10 20 30 40 50 60 MSLLNPVLLP PKVKAYLSQG ERFIKWDDET TVASPVILRV DPKGYYLYWT YQSKEMEFLD 70 80 90 100 110 120 ITSIRDTRFG KFAKMPKSQK LRDVFNMDFP DNSFLLKTLT VVSGPDMVDL TFHNFVSYKE 130 140 150 160 170 180 NVGKAWAEDV LALVKHPLTA NASRSTFLDK ILVKLKMQLN SEGKIPVKNF FQMFPADRKR 190 200 210 220 230 240 VEAALSACHL PKGKNDAINP EDFPEPVYKS FLMSLCPRPE IDEIFTSYHA KAKPYMTKEH 250 260 270 280 290 300 LTKFINQKQR DSRLNSLLFP PARPDQVQGL IDKYEPSGIN AQRGQLSPEG MVWFLCGPEN 310 320 330 340 350 360 SVLAQDKLLL HHDMTQPLNH YFINSSHNTY LTAGQFSGLS SAEMYRQVLL SGCRCVELDC 370 380 390 400 410 420 WKGKPPDEEP IITHGFTMTT DIFFKEAIEA IAESAFKTSP YPIILSFENH VDSPRQQAKM 430 440 450 460 470 480 AEYCRTIFGD MLLTEPLEKF PLKPGVPLPS PEDLRGKILI KNKKNQFSGP TSSSKDTGGE 490 500 510 520 530 540 AEGSSPPSAP AVWAGEEGTE LEEEEVEEEE EEESGNLDEE EIKKMQSDEG TAGLEVTAYE 550 560 570 580 590 600 EMSSLVNYIQ PTKFVSFEFS AQKNRSYVIS SFTELKAYDL LSKASVQFVD YNKRQMSRIY 610 620 630 640 650 660 PKGTRMDSSN YMPQMFWNAG CQMVALNFQT MDLPMQQNMA VFEFNGQSGY LLKHEFMRRP 670 680 690 700 710 720 DKQFNPFSVD RIDVVVATTL SITVISGQFL SERSVRTYVE VELFGLPGDP KRRYRTKLSP 730 740 750 760 770 780 STNSINPVWK EEPFVFEKIL MPELASLRVA VMEEGNKFLG HRIIPINALN SGYHHLCLHS 790 800 810 820 830 840 ESNMPLTMPA LFIFLEMKDY IPGAWADLTV ALANPIKFFS AHDTKSVKLK EAMGGLPEKP 850 860 870 880 890 900 FPLASPVASQ VNGALAPTSN GSPAARAGAR EEAMKEAAEP RTASLEELRE LKGVVKLQRR 910 920 930 940 950 960 HEKELRELER RGARRWEELL QRGAAQLAEL GPPGVGGVGA CKLGPGKGSR KKRSLPREES 970 980 990 1000 1010 1020 AGAAPGEGPE GVDGRVRELK DRLELELLRQ GEEQYECVLK RKEQHVAEQI SKMMELAREK 1030 1040 1050 1060 1070 1080 QAAELKALKE TSENDTKEMK KKLETKRLER IQGMTKVTTD KMAQERLKRE INNSHIQEVV 1090 1100 1110 1120 1130 1140 QVIKQMTENL ERHQEKLEEK QAACLEQIRE MEKQFQKEAL AEYEARMKGL EAEVKESVRA 1150 1160 1170 1180 CLRTCFPSEA KDKPERACEC PPELCEQDPL IAKADAQESR L

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, sequencing, expression, and Gq-independent activation of phospholipase C-beta 2." Park D., Jhon D.-Y., Kriz R., Knopf J., Rhee S.G. J. Biol. Chem. 267:16048-16055(1992) [PubMed: 1644792] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLY-1095. Tissue: Placenta.
[3]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed: 16572171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Crystal structure of Rac1 bound to its effector phospholipase C-beta2." Jezyk M.R., Snyder J.T., Gershberg S., Worthylake D.K., Harden T.K., Sondek J. Nat. Struct. Mol. Biol. 13:1135-1140(2006) [PubMed: 17115053] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-803 (ISOFORM 2) IN COMPLEX WITH RAC1, MUTAGENESIS OF GLN-52.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M95678 mRNA. Translation: AAA36453.1.
AK291657 mRNA. Translation: BAF84346.1.
AC020658 Genomic DNA. No translation available.

IPI

IPI00784327.
IPI00914935.

PIR

A43346.

RefSeq

NP_004564.2.

UniGene

Hs.355888

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2FJU	X-ray	2.20	B	1-803	[»]
2ZKM	X-ray	1.62	X	1-799	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29259N.

STRING

Q00722.

PTM databases

PhosphoSite

Q00722.

Proteomic databases

PRIDE

Q00722.

Genome annotation databases

Ensembl

ENST00000260402; ENSP00000260402; ENSG00000137841; Homo sapiens. [Genome view]

GeneID

5330.

KEGG

hsa:5330.

UCSC

uc010bbo.1. human.

Organism-specific databases

CTD

5330.

GeneCards

GC15M038367.

H-InvDB

HIX0012125.

HGNC

HGNC:9055. PLCB2.

HPA

CAB009443.

MIM

604114. gene.

PharmGKB

PA33385.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG11373.

HOGENOM

HBG315986.

HOVERGEN

Q00722.

InParanoid

Q00722.

OMA

VKAYLSQ.

OrthoDB

EOG9HQH4M.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000137841-MONOMER.

BRENDA

3.1.4.11. 247.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
endothelinpathway. Endothelins.
er_nongenomic_pathway. Plasma membrane estrogen receptor signaling.
s1p_s1p1_pathway. S1P1 pathway.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_14797. Signaling by GPCR.
REACT_15295. Opioid Signalling.
REACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpress

Q00722.

Bgee

Q00722.

CleanEx

HS_PLCB2.

Genevestigator

Q00722.

GermOnline

ENSG00000137841. 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.
IPR015359. Phospholipase_C_EF-hand-like.
IPR001192. Phospholipase_C_Pinositol-sp_C.
IPR001711. Phospholipase_C_Pinositol-sp_Y.
IPR017946. PLC-like_Pdiesterase_TIM-brl.
IPR000909. PLipase_C_PInositol-sp_X_dom.
[Graphical view]

Gene3D

G3DSA:1.10.238.10. EF-Hand_type. 1 hit.

Pfam

PF00168. C2. 1 hit.
PF09279. efhand_like. 1 hit.
PF00388. PI-PLC-X. 1 hit.
PF00387. PI-PLC-Y. 1 hit.
[Graphical view]

PRINTS

PR00390. PHPHLIPASEC.

SMART

SM00239. C2. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]

PROSITE

PS50004. C2. 1 hit.
PS50007. PIPLC_X_DOMAIN. 1 hit.
PS50008. PIPLC_Y_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

PLCB2_HUMAN

Accession

Primary (citable) accession number: Q00722
Secondary accession number(s): A8K6J2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	November 25, 2008
Last modified:	February 9, 2010
This is version 99 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.