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
    Phospholipase C-beta-2
      Short name=PLC-beta-2

Gene names

Name:

PLCB2

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	1185 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	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
Gene Ontology (GO)
Biological process	activation of phospholipase C activity Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from electronic annotation. Source: InterPro lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Ref.1 Traceable author statement. Source: ProtInc
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

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

EMBLGenBankDDBJ

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

PDBPDBe

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

SMR

Q00722. Positions 11-799.

ModBase

Search...

PTM databases

PhosphoSite

Q00722.

Proteomic databases

PRIDE

Q00722.

Genome annotation databases

Ensembl

ENSG00000137841. Homo sapiens. [Contig view]

GeneID

5330.

KEGG

hsa:5330.

Organism-specific databases

GeneCards

GC15M038367.

H-InvDB

HIX0012125.

HGNC

HGNC:9055. PLCB2.

HPA

CAB009443.

MIM

604114. gene.

PharmGKB

PA33385.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q00722.

OMA

Q00722. VKAYLSQ.

Enzyme and pathway databases

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.

Gene expression databases

ArrayExpress

Q00722.

Bgee

Q00722.

CleanEx

HS_PLCB2.

GermOnline

ENSG00000137841. Homo sapiens.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR018029. C2_membr_targeting.
IPR011992. EF-Hand_type.
IPR015359. Phospholipase_C_EF-hand-like.
IPR001192. Phospholipase_C_Pinositol-sp_C.
IPR000909. Phospholipase_C_Pinositol-sp_X.
IPR001711. Phospholipase_C_Pinositol-sp_Y.
IPR014815. PLC-beta_C.
[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.
PF08703. PLC-beta_C. 1 hit.
[Graphical view]

PRINTS

PR00390. PHPHLIPASEC.

ProDom

PD001202. PI_PLC_Y. 2 hits.
[Graphical view] [Entries sharing at least one domain]

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:	June 16, 2009
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)