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Q8K3R3 (PLCD4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4

EC=3.1.4.11
Alternative name(s):
Phosphoinositide phospholipase C-delta-4
Phospholipase C-delta-4
Short name=PLC-delta-4
Gene names
Name:Plcd4
Synonyms:Plcd
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length807 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hydrolyzes the phosphatidylinositol 4,5-bisphosphate (PIP2) to generate 2 second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG mediates the activation of protein kinase C (PKC), while IP3 releases Ca2+ from intracellular stores. Required for acrosome reaction in sperm during fertilization, probably by acting as an important enzyme for intracellular Ca2+ mobilization in the zona pellucida-induced acrosome reaction. May play a role in cell growth. Modulates the liver regeneration in cooperation with nuclear PKC. Overexpression up-regulates the Erk signaling pathway and proliferation. Ref.5 Ref.6 Ref.8

Catalytic activity

1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate + H2O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.

Cofactor

Binds 3 calcium ions per subunit. Two of the calcium ions are bound to the C2 domain By similarity.

Subunit structure

Interacts with GRIP1. Ref.7

Subcellular location

Membrane; Peripheral membrane protein By similarity. Nucleus By similarity. Cytoplasm By similarity. Endoplasmic reticulum By similarity. Note: Localizes primarily to intracellular membranes mostly to the endoplasmic reticulum By similarity.

Induction

By treatment with growth factors such as bradykinin, lysophosphatidic acid, and Ca2+ ionophore in addition to serum. Ref.4

Domain

The PDZ-binding motif mediates the interaction with GRIP1.

The C2 domain mediates pre-localization to the membrane prior to Ca2+ import and non-selective Ca2+-mediated targeting to various cellular membranes By similarity.

The PH domain is not a critical determinant of the membrane localization By similarity.

Disruption phenotype

Mice are either sterile or produce few small litters. In these mice, fewer eggs become activated and the Ca2+ transients associated with fertilization are absent or delayed. Sperm are unable to initiate the acrosome reaction. Ref.5

Sequence similarities

Contains 1 C2 domain.

Contains 3 EF-hand domains.

Contains 1 PH domain.

Contains 1 PI-PLC X-box domain.

Contains 1 PI-PLC Y-box domain.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8K3R3-1)

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: Q8K3R3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     493-524: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8K3R3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     493-524: Missing.
     773-807: GYRHVSLLSRDGTSLNPASIFVYTCMQEDLDMDEP → EMALASIQLP...LKIQSQPKDQ
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8K3R3-4)

The sequence of this isoform differs from the canonical sequence as follows:
     494-496: MKC → SQD
     497-807: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 8078071-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4
PRO_0000306826

Regions

Domain16 – 124109PH
Domain134 – 16936EF-hand 1
Domain170 – 20536EF-hand 2
Domain203 – 23735EF-hand 3
Domain290 – 435146PI-PLC X-box
Domain538 – 654117PI-PLC Y-box
Domain659 – 764106C2
Calcium binding147 – 158121 Potential
Calcium binding183 – 194122 Potential
Region26 – 5328Substrate binding By similarity
Motif776 – 7794PDZ-binding
Compositional bias445 – 45612Poly-Glu

Sites

Active site3051 By similarity
Active site3501 By similarity
Metal binding3061Calcium 1; catalytic By similarity
Metal binding3351Calcium 1; catalytic By similarity
Metal binding3371Calcium 1; catalytic By similarity
Metal binding3841Calcium 1; catalytic By similarity
Metal binding6971Calcium 2 By similarity
Metal binding7211Calcium 2 By similarity
Metal binding7501Calcium 3 By similarity
Metal binding7511Calcium 3; via carbonyl oxygen By similarity
Binding site4331Substrate By similarity
Binding site4351Substrate By similarity
Binding site5671Substrate By similarity
Binding site5941Substrate By similarity

Natural variations

Alternative sequence493 – 52432Missing in isoform 2 and isoform 3.
VSP_028503
Alternative sequence494 – 4963MKC → SQD in isoform 4.
VSP_028504
Alternative sequence497 – 807311Missing in isoform 4.
VSP_028505
Alternative sequence773 – 80735GYRHV…DMDEP → EMALASIQLPSLYTPACRKT WIWMSPEKHREGLEEQSTDA QSFPTYNFLKIQSQPKDQ in isoform 3.
VSP_028506

Experimental info

Sequence conflict1801Q → R in BAE24292. Ref.2
Sequence conflict3101V → A in AAH66156. Ref.3
Sequence conflict3721F → L in AAH66156. Ref.3
Sequence conflict4451Missing in BAE24292. Ref.2
Sequence conflict4701L → F in AAK61537. Ref.1
Sequence conflict5941R → C in AAH66156. Ref.3
Sequence conflict6531L → V in AAK61537. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 2, 2007. Version 2.
Checksum: C109F6255CED45F7

FASTA80792,694
        10         20         30         40         50         60 
MTSQIQDLLA TDQDLLLMQE GTMMRKVRTK SWKKLRYFRL QNDGMTVWHG SQPESMPKPT 

        70         80         90        100        110        120 
FSISDVERIR KGQDSELLRY LVEEFPLEQG FTVVFHGRRP NLDLVANSVE EAQIWMRGLQ 

       130        140        150        160        170        180 
LLVDLVASMD HQEQMDQMLN EWFQQADRNQ DGRMSFREAQ RLLLLMNVEM DEEYAFSLFQ 

       190        200        210        220        230        240 
EADVTQSDDL GSEEFVQFYK ALTKRTEIEE IFEDFSSDKQ KLTLLEFVDF LRKEQKEKDH 

       250        260        270        280        290        300 
APDLALELID RYEPSENGRL LHVLSKDGFL KYLCSKDGNI FNSDCLPIYQ DMTQPLSHYY 

       310        320        330        340        350        360 
INSSHNTYLV GDQLCGQSSV EGYIRALKRG CRCVEVDTWD GPDGEPVVYH GHTLTSRILF 

       370        380        390        400        410        420 
KDVLATLAQY AFQSSDYPLI LSLENHCTWE QQRTMAHHLT EILGEQLLRN TLEGLLVDSM 

       430        440        450        460        470        480 
PSPEQLRGKI LVKGKKLRTI EVDKEEEEEE EEEELEKDEG PDLDPASPEL DTQPQPETQG 

       490        500        510        520        530        540 
QAAGNKKERK KKVMKCPMSC LLICGHVMAQ APSSIPESIL LSKQFLLLSS TTIMCPDLSA 

       550        560        570        580        590        600 
LVVYLRTVPF CSFTHSKENY HIYDISSFSE SKAKNLIKEA GNEFVQHNAR QLCRVYPSGL 

       610        620        630        640        650        660 
RTDSSNFNPQ EHWNVGCQMV AMNMQTAGSA MDICDGLFRQ NGGSGYVLKP EFLRDTQSSF 

       670        680        690        700        710        720 
NPERPISLYK AQILVVQVIS GQQLPKVDKT KETTVVDPLV KVELYGVPED TKEQETSHVE 

       730        740        750        760        770        780 
NNGINPYWGE TFYFRLQVPE LAMLRFVVKD YSRKSRNNFI GQYTLPWTCM KQGYRHVSLL 

       790        800 
SRDGTSLNPA SIFVYTCMQE DLDMDEP 

« Hide

Isoform 2 [UniParc].

Checksum: EFA6651F8635BBF7
Show »

FASTA77589,296
Isoform 3 [UniParc].

Checksum: 5D5EEC1B9028824D
Show »

FASTA79892,091
Isoform 4 [UniParc].

Checksum: 85050CCD6471FB72
Show »

FASTA49657,480

References

« Hide 'large scale' references
[1]"Molecular cloning of PLC delta4."
Kim J., Kim H., Lee K.-H.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Testis.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
Strain: C57BL/6J.
Tissue: Corpora quadrigemina, Hypothalamus and Testis.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: CD-1.
Tissue: Neural stem cell.
[4]"Growth factor-induced promoter activation of murine phospholipase C delta4 gene."
Fukami K., Takenaka K., Nagano K., Takenawa T.
Eur. J. Biochem. 267:28-36(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[5]"Requirement of phospholipase Cdelta4 for the zona pellucida-induced acrosome reaction."
Fukami K., Nakao K., Inoue T., Kataoka Y., Kurokawa M., Fissore R.A., Nakamura K., Katsuki M., Mikoshiba K., Yoshida N., Takenawa T.
Science 292:920-923(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[6]"Phospholipase Cdelta4 is required for Ca2+ mobilization essential for acrosome reaction in sperm."
Fukami K., Yoshida M., Inoue T., Kurokawa M., Fissore R.A., Yoshida N., Mikoshiba K., Takenawa T.
J. Cell Biol. 161:79-88(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Phospholipase Cdelta4 associates with glutamate receptor interacting protein 1 in testis."
Irino Y., Ichinohe M., Nakamura Y., Nakahara M., Fukami K.
J. Biochem. 138:451-456(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRIP1.
[8]"Disruption of phospholipase Cdelta4 gene modulates the liver regeneration in cooperation with nuclear protein kinase C."
Akutagawa A., Fukami K., Banno Y., Takenawa T., Kannagi R., Yokoyama Y., Oda K., Nagino M., Nimura Y., Yoshida S., Tamiya-Koizumi K.
J. Biochem. 140:619-625(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY033991 mRNA. Translation: AAK61537.1.
AK016945 mRNA. Translation: BAB30513.1.
AK039149 mRNA. Translation: BAC30256.1.
AK140231 mRNA. Translation: BAE24292.1.
BC066156 mRNA. Translation: AAH66156.1.
CCDSCCDS35616.1. [Q8K3R3-1]
CCDS35617.1. [Q8K3R3-2]
RefSeqNP_001074925.1. NM_001081456.1. [Q8K3R3-2]
NP_683739.2. NM_148937.2. [Q8K3R3-1]
XP_006495851.1. XM_006495788.1. [Q8K3R3-1]
UniGeneMm.290731.

3D structure databases

ProteinModelPortalQ8K3R3.
SMRQ8K3R3. Positions 9-453, 536-800.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ8K3R3.

Proteomic databases

MaxQBQ8K3R3.
PaxDbQ8K3R3.
PRIDEQ8K3R3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000027362; ENSMUSP00000027362; ENSMUSG00000026173. [Q8K3R3-1]
ENSMUST00000067916; ENSMUSP00000064413; ENSMUSG00000026173. [Q8K3R3-2]
ENSMUST00000113745; ENSMUSP00000109374; ENSMUSG00000026173. [Q8K3R3-4]
ENSMUST00000113747; ENSMUSP00000109376; ENSMUSG00000026173. [Q8K3R3-2]
ENSMUST00000113749; ENSMUSP00000109378; ENSMUSG00000026173. [Q8K3R3-1]
ENSMUST00000113750; ENSMUSP00000109379; ENSMUSG00000026173. [Q8K3R3-3]
GeneID18802.
KEGGmmu:18802.
UCSCuc007bmg.1. mouse. [Q8K3R3-2]
uc007bmh.1. mouse. [Q8K3R3-1]
uc007bmi.1. mouse. [Q8K3R3-4]
uc011wnb.1. mouse. [Q8K3R3-3]

Organism-specific databases

CTD84812.
MGIMGI:107469. Plcd4.

Phylogenomic databases

eggNOGNOG149692.
GeneTreeENSGT00740000114979.
HOGENOMHOG000006871.
HOVERGENHBG053610.
InParanoidQ8K3R3.
KOK05857.
OMARDYAFSS.
OrthoDBEOG7V49XT.
PhylomeDBQ8K3R3.
TreeFamTF313216.

Gene expression databases

ArrayExpressQ8K3R3.
BgeeQ8K3R3.
CleanExMM_PLCD4.
GenevestigatorQ8K3R3.

Family and domain databases

Gene3D1.10.238.10. 2 hits.
2.30.29.30. 1 hit.
2.60.40.150. 1 hit.
3.20.20.190. 2 hits.
InterProIPR000008. C2_dom.
IPR011992. EF-hand-dom_pair.
IPR002048. EF_hand_dom.
IPR011993. PH_like_dom.
IPR001192. PI-PLC_fam.
IPR028387. PLC-delta4.
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.
[Graphical view]
PANTHERPTHR10336. PTHR10336. 1 hit.
PTHR10336:SF31. PTHR10336:SF31. 1 hit.
PfamPF00168. C2. 1 hit.
PF09279. EF-hand_like. 1 hit.
PF00169. PH. 1 hit.
PF00388. PI-PLC-X. 1 hit.
PF00387. PI-PLC-Y. 1 hit.
[Graphical view]
PRINTSPR00390. PHPHLIPASEC.
SMARTSM00239. C2. 1 hit.
SM00054. EFh. 3 hits.
SM00233. PH. 1 hit.
SM00148. PLCXc. 1 hit.
SM00149. PLCYc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF51695. SSF51695. 2 hits.
PROSITEPS50004. C2. 1 hit.
PS50222. EF_HAND_2. 3 hits.
PS50003. PH_DOMAIN. 1 hit.
PS50007. PIPLC_X_DOMAIN. 1 hit.
PS50008. PIPLC_Y_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio295100.
PROQ8K3R3.
SOURCESearch...

Entry information

Entry namePLCD4_MOUSE
AccessionPrimary (citable) accession number: Q8K3R3
Secondary accession number(s): Q3USN9 expand/collapse secondary AC list , Q6NZF7, Q8CAB1, Q9CUC1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 2, 2007
Last sequence update: October 2, 2007
Last modified: July 9, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot