Reviewed, UniProtKB/Swiss-Prot Q62101 (KPCD1_MOUSE)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase D1
    EC=2.7.11.13
Alternative name(s):
    nPKC-D1
    Protein kinase D
    Protein kinase C mu type
    nPKC-mu

Gene names

Name:	Prkd1
Synonyms:	Pkcm, Pkd, Prkcm

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	918 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress through activation of NF-kappa-B. Ref.4
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-748 and phosphorylation of Ser-744 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-469 by the Src/Abl pathway in response to oxidative stress, is also required for activation. Ref.4
Subunit structure	Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with Src By similarity.
Subcellular location	Cytoplasm By similarity. Membrane By similarity. Note: Translocation to the cell membrane is required for kinase activation By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily. Contains 1 PH domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Domain	Phorbol-ester binding Repeat Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 918	918	Serine/threonine-protein kinase D1		PRO_0000055715
Regions
	Domain	428 – 547	120	PH
	Domain	589 – 845	257	Protein kinase
	Zinc finger	144 – 194	51	Phorbol-ester/DAG-type 1
	Zinc finger	276 – 326	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	595 – 603	9	ATP By similarity
	Compositional bias	16 – 26	11	Poly-Ala
	Compositional bias	198 – 201	4	Poly-Arg
Sites
	Active site	712	1	Proton acceptor By similarity
	Binding site	618	1	ATP By similarity
Amino acid modifications
	Modified residue	93	1	Phosphotyrosine By similarity
	Modified residue	203	1	Phosphoserine Ref.5 Ref.6
	Modified residue	208	1	Phosphothreonine By similarity
	Modified residue	253	1	Phosphoserine Ref.6
	Modified residue	438	1	Phosphotyrosine By similarity
	Modified residue	469	1	Phosphotyrosine By similarity
	Modified residue	508	1	Phosphotyrosine By similarity
	Modified residue	744	1	Phosphoserine; by PKC Ref.4 Ref.3
	Modified residue	748	1	Phosphoserine; by autocatalysis Ref.4 Ref.3
	Modified residue	916	1	Phosphoserine; by autocatalysis Ref.2
Experimental info
	Mutagenesis	744	1	S → A: Loss of basal kinase activity and phorbol ester-stimulated kinase activity; when associated with A-748. Ref.4
	Mutagenesis	744	1	S → D: High basal kinase activity, loss of phorbol ester-stimulated kinase activity; when associated with D-748. Ref.4
	Mutagenesis	748	1	S → A: Loss of basal kinase activity and phorbol ester-stimulated kinase activity; when associated with A-744. Ref.4
	Mutagenesis	748	1	S → D: High basal kinase activity, loss of phorbol ester-stimulated kinase activity; when associated with D-744. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q62101-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 234486180521BDDA	FASTA	918	102,067
	10 20 30 40 50 60 MSVPPLLRPP SPLLPAAAAV AAAAAALVPG SGPAPFPAPG AAPAGGISFH LQIGLSREPV 70 80 90 100 110 120 LLLQDSSGDY SLAHVREMAC SIVDQKFPEC GFYGLYDKIL LFRHDPASDN ILQLVKIASD 130 140 150 160 170 180 IQEGDLIEVV LSASATFEDF QIRPHALFVH SYRAPAFCDH CGEMLWGLVR QGLKCEGCGL 190 200 210 220 230 240 NYHKRCAFKI PNNCSGVRRR RLSNVSLTGL GTVRTASAEF STSVPDEPLL SPVSPGFEQK 250 260 270 280 290 300 SPSESFIGRE KRSNSQSYIG RPIQLDKLLM SKVKVPHTFV IHSYTRPTVC QFCKKLLKGL 310 320 330 340 350 360 FRQGLQCKDC RFNCHKRCAP KVPNNCLGEV TINGELLSPG AESDVVMEEG SDDNDSERNS 370 380 390 400 410 420 GLMDDMDEAM VQDTEMALAE GQSGGAEMQD PDADQEDSNR TISPSTSNNI PLMRVVQSVK 430 440 450 460 470 480 HTKRRSSTVM KEGWMVHYTS KDTLRKRHYW RLDSKCITLF QNDTGSRYYK EIPLSEILCL 490 500 510 520 530 540 EPAKPSALTP VGATPHCFEI TTANVVYYVG ENVVNPSSSP PNNSVLPSGI GPDVARMWEV 550 560 570 580 590 600 AIQHALMPVI PKGSSVGSGS NSHKDISVSI SVSNCQIQEN VDISTVYQIF PDEVLGSGQF 610 620 630 640 650 660 GIVYGGKHRK TGRDVAIKII DKLRFPTKQE SQLRNEVAIL QNLHHPGVVN LECMFETPER 670 680 690 700 710 720 VFVVMEKLHG DMLEMILSSE KGWLPEHITK FLITQILVAL RHLHFKNIVH CDLKPENVLL 730 740 750 760 770 780 ASADPFPQVK LCDFGFARII GEKSFRRSVV GTPAYLAPEV LRNKGYNRSL DMWSVGVIIY 790 800 810 820 830 840 VSLSGTFPFN EDEDIHDQIQ NAAFMYPPNP WKEISHEAID LINNLLQVKM RKRYSVDKTL 850 860 870 880 890 900 SHPWLQDYQT WLDLRELECR IGERYITHES DDSRWEQYAG EQGLQYPAHL ISLSASHSDS 910 PEAEEREMKA LSERVSIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of protein kinase D: a target for diacylglycerol and phorbol esters with a distinctive catalytic domain." Valverde A.M., Sinnet-Smith J., Van Lint J., Rozengurt E. Proc. Natl. Acad. Sci. U.S.A. 91:8572-8576(1994) [PubMed: 8078925] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: BALB/c. Tissue: Lung.
[2]	"Characterization of serine 916 as an in vivo autophosphorylation site for protein kinase D/protein kinase Cmu." Matthews S.A., Rozengurt E., Cantrell D. J. Biol. Chem. 274:26543-26549(1999) [PubMed: 10473617] [Abstract] Cited for: PHOSPHORYLATION AT SER-916.
[3]	"Activation loop Ser744 and Ser748 in protein kinase D are transphosphorylated in vivo." Waldron R.T., Rey O., Iglesias T., Tugal T., Cantrell D., Rozengurt E. J. Biol. Chem. 276:32606-32615(2001) [PubMed: 11410586] [Abstract] Cited for: PHOSPHORYLATION AT SER-744 AND SER-748.
[4]	"Protein kinase C phosphorylates protein kinase D activation loop Ser744 and Ser748 and releases autoinhibition by the pleckstrin homology domain." Waldron R.T., Rozengurt E. J. Biol. Chem. 278:154-163(2003) [PubMed: 12407104] [Abstract] Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF SER-744 AND SER-748, PHOSPHORYLATION AT SER-744 AND SER-748.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed: 17242355] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed: 18973353] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-253, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z34524 mRNA. Translation: CAA84283.1.
IPI	IPI00122084.
PIR	I48719.
UniGene	Mm.133719
3D structure databases
HSSP	HSSP built from PDB template 1PTQ based on UniProtKB P28867.
ModBase	Search...
Protein-protein interaction databases
STRING	Q62101.
PTM databases
PhosphoSite	Q62101.
Proteomic databases
PRIDE	Q62101.
Genome annotation databases
Ensembl	ENSMUST00000002765; ENSMUSP00000002765; ENSMUSG00000002688; Mus musculus. [Genome view]
UCSC	uc007nmj.1. mouse.
Organism-specific databases
MGI	MGI:99879. Prkd1.
Phylogenomic databases
HOGENOM	Q62101.
HOVERGEN	Q62101.
Enzyme and pathway databases
BRENDA	2.7.11.1. 244. 2.7.11.13. 244.
Gene expression databases
ArrayExpress	Q62101.
Bgee	Q62101.
CleanEx	MM_PRKD1.
Genevestigator	Q62101.
GermOnline	ENSMUSG00000002688. Mus musculus.
Family and domain databases
InterPro	IPR020454. DAG/PE_bd. IPR011993. PH_type. IPR001849. Pleckstrin_homology. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR015727. Protein_Kinase_C_mu-related. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
PANTHER	PTHR22968. PKC_mu_like. 1 hit.
Pfam	PF00130. C1_1. 2 hits. PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PRINTS	PR00008. DAGPEDOMAIN.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. C1. 2 hits. SM00233. PH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
PROSITE	PS50003. PH_DOMAIN. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. 2 hits. PS50081. ZF_DAG_PE_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other Resources
SOURCE	Search...

Entry information

Entry name

KPCD1_MOUSE

Accession

Primary (citable) accession number: Q62101

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	November 1, 1996
Last modified:	October 13, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)