dbPTM

KPCI_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCI_HUMAN
UniProt AC	P41743
Protein Name	Protein kinase C iota type
Gene Name	PRKCI
Organism	Homo sapiens (Human).
Sequence Length	596
Subcellular Localization	Cytoplasm . Membrane . Endosome . Nucleus . Transported into the endosome through interaction with SQSTM1/p62. After phosphorylation by SRC, transported into the nucleus through interaction with KPNB1. Colocalizes with CDK7 in the cytoplasm and nucle
Protein Description	Calcium- and diacylglycerol-independent serine/ threonine-protein kinase that plays a general protective role against apoptotic stimuli, is involved in NF-kappa-B activation, cell survival, differentiation and polarity, and contributes to the regulation of microtubule dynamics in the early secretory pathway. Is necessary for BCR-ABL oncogene-mediated resistance to apoptotic drug in leukemia cells, protecting leukemia cells against drug-induced apoptosis. In cultured neurons, prevents amyloid beta protein-induced apoptosis by interrupting cell death process at a very early step. In glioblastoma cells, may function downstream of phosphatidylinositol 3-kinase (PI(3)K) and PDPK1 in the promotion of cell survival by phosphorylating and inhibiting the pro-apoptotic factor BAD. Can form a protein complex in non-small cell lung cancer (NSCLC) cells with PARD6A and ECT2 and regulate ECT2 oncogenic activity by phosphorylation, which in turn promotes transformed growth and invasion. In response to nerve growth factor (NGF), acts downstream of SRC to phosphorylate and activate IRAK1, allowing the subsequent activation of NF-kappa-B and neuronal cell survival. Functions in the organization of the apical domain in epithelial cells by phosphorylating EZR. This step is crucial for activation and normal distribution of EZR at the early stages of intestinal epithelial cell differentiation. Forms a protein complex with LLGL1 and PARD6B independently of PARD3 to regulate epithelial cell polarity. Plays a role in microtubule dynamics in the early secretory pathway through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). In human coronary artery endothelial cells (HCAEC), is activated by saturated fatty acids and mediates lipid-induced apoptosis..
Protein Sequence	MPTQRDSSTMSHTVAGGGSGDHSHQVRVKAYYRGDIMITHFEPSISFEGLCNEVRDMCSFDNEQLFTMKWIDEEGDPCTVSSQLELEEAFRLYELNKDSELLIHVFPCVPERPGMPCPGEDKSIYRRGARRWRKLYCANGHTFQAKRFNRRAHCAICTDRIWGLGRQGYKCINCKLLVHKKCHKLVTIECGRHSLPQEPVMPMDQSSMHSDHAQTVIPYNPSSHESLDQVGEEKEAMNTRESGKASSSLGLQDFDLLRVIGRGSYAKVLLVRLKKTDRIYAMKVVKKELVNDDEDIDWVQTEKHVFEQASNHPFLVGLHSCFQTESRLFFVIEYVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTSTFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPFDIVGSSDNPDQNTEDYLFQVILEKQIRIPRSLSVKAASVLKSFLNKDPKERLGCHPQTGFADIQGHPFFRNVDWDMMEQKQVVPPFKPNISGEFGLDNFDSQFTNEPVQLTPDDDDIVRKIDQSEFEGFEYINPLLMSAEECV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MPTQRDSST ------CCCCCCCCC	36.92	20068231
3	Phosphorylation	-----MPTQRDSSTM -----CCCCCCCCCC	34.63	29496963
7	Phosphorylation	-MPTQRDSSTMSHTV -CCCCCCCCCCCCEE	29.87	23927012
8	Phosphorylation	MPTQRDSSTMSHTVA CCCCCCCCCCCCEEC	32.21	23927012
9	Phosphorylation	PTQRDSSTMSHTVAG CCCCCCCCCCCEECC	27.01	23927012
11	Phosphorylation	QRDSSTMSHTVAGGG CCCCCCCCCEECCCC	18.98	25159151
13	Phosphorylation	DSSTMSHTVAGGGSG CCCCCCCEECCCCCC	12.54	25159151
19	Phosphorylation	HTVAGGGSGDHSHQV CEECCCCCCCCCCEE	44.30	25159151
23	Phosphorylation	GGGSGDHSHQVRVKA CCCCCCCCCEEEEEE	21.98	20068231
44	Phosphorylation	MITHFEPSISFEGLC EEEEECCCCCCHHHH	24.54	18489133
46	Phosphorylation	THFEPSISFEGLCNE EEECCCCCCHHHHHH	22.91	18489133
59	Phosphorylation	NEVRDMCSFDNEQLF HHHHHHHCCCCCCCE	29.06	27134283
123	Phosphorylation	PCPGEDKSIYRRGAR CCCCCCCCHHHHHHH	36.85	20873877
125	Phosphorylation	PGEDKSIYRRGARRW CCCCCCHHHHHHHHH	11.01	20873877
136	Phosphorylation	ARRWRKLYCANGHTF HHHHEEEEECCCCCE	7.80	25159151
142	Phosphorylation	LYCANGHTFQAKRFN EEECCCCCEEEEECC	20.88	28857561
175	Acetylation	GYKCINCKLLVHKKC CCEECCCEEEEECCC	40.13	25953088
184	Ubiquitination	LVHKKCHKLVTIECG EEECCCCEEEEEECC	54.87	29967540
187	Phosphorylation	KKCHKLVTIECGRHS CCCCEEEEEECCCCC	22.84	28857561
194	Phosphorylation	TIECGRHSLPQEPVM EEECCCCCCCCCCCC	40.14	21406692
206	Phosphorylation	PVMPMDQSSMHSDHA CCCCCCCHHCCCCCC	25.93	23663014
207	Phosphorylation	VMPMDQSSMHSDHAQ CCCCCCHHCCCCCCC	18.19	23663014
210	Phosphorylation	MDQSSMHSDHAQTVI CCCHHCCCCCCCEEC	23.58	23663014
215	Phosphorylation	MHSDHAQTVIPYNPS CCCCCCCEECCCCCC	22.61	23663014
219	Phosphorylation	HAQTVIPYNPSSHES CCCEECCCCCCCCCC	28.69	23663014
222	Phosphorylation	TVIPYNPSSHESLDQ EECCCCCCCCCCHHH	40.46	23663014
223	Phosphorylation	VIPYNPSSHESLDQV ECCCCCCCCCCHHHH	32.31	28348404
226	Phosphorylation	YNPSSHESLDQVGEE CCCCCCCCHHHHHHH	31.64	23663014
234	Sumoylation	LDQVGEEKEAMNTRE HHHHHHHHHHHHHHH	46.61	-
239	Phosphorylation	EEKEAMNTRESGKAS HHHHHHHHHHCCCCC	23.80	28102081
242	Phosphorylation	EAMNTRESGKASSSL HHHHHHHCCCCCHHC	42.16	28102081
244	Ubiquitination	MNTRESGKASSSLGL HHHHHCCCCCHHCCC	55.14	29967540
246	Phosphorylation	TRESGKASSSLGLQD HHHCCCCCHHCCCCC	24.76	30278072
247	Phosphorylation	RESGKASSSLGLQDF HHCCCCCHHCCCCCH	34.15	30278072
248	Phosphorylation	ESGKASSSLGLQDFD HCCCCCHHCCCCCHH	24.78	30278072
256	Phosphorylation	LGLQDFDLLRVIGRG CCCCCHHHEEEECCC	3.12	11713277
264	Phosphorylation	LRVIGRGSYAKVLLV EEEECCCCCEEEEEE	22.13	28102081
265	Phosphorylation	RVIGRGSYAKVLLVR EEECCCCCEEEEEEE	17.17	11713277
271	Phosphorylation	SYAKVLLVRLKKTDR CCEEEEEEECCCCCC	6.19	11713277
280	Phosphorylation	LKKTDRIYAMKVVKK CCCCCCEEEEEEEEH	11.09	11713277
287	Ubiquitination	YAMKVVKKELVNDDE EEEEEEEHHHCCCCC	44.67	29967540
325	Phosphorylation	LHSCFQTESRLFFVI HHHCEECCCEEEEEE	24.07	11713277
334	Phosphorylation	RLFFVIEYVNGGDLM EEEEEEEEECCCCHH	6.52	11713277
380	Ubiquitination	GIIYRDLKLDNVLLD CCEEEEECCCCEEEC	59.07	33845483
397	Phosphorylation	GHIKLTDYGMCKEGL CCEEECCCCCCCCCC	11.09	-
400	Phosphorylation	KLTDYGMCKEGLRPG EECCCCCCCCCCCCC	2.93	18669648
401	Phosphorylation	LTDYGMCKEGLRPGD ECCCCCCCCCCCCCC	46.02	18669648
402	Phosphorylation	TDYGMCKEGLRPGDT CCCCCCCCCCCCCCC	59.54	18669648
403	Phosphorylation	DYGMCKEGLRPGDTT CCCCCCCCCCCCCCC	16.69	18669648
409	Phosphorylation	EGLRPGDTTSTFCGT CCCCCCCCCCCCCCC	28.67	30266825
410	Phosphorylation	GLRPGDTTSTFCGTP CCCCCCCCCCCCCCC	30.43	30266825
411	Phosphorylation	LRPGDTTSTFCGTPN CCCCCCCCCCCCCCC	22.91	30266825
412	Phosphorylation	RPGDTTSTFCGTPNY CCCCCCCCCCCCCCC	22.35	22322096
416	Phosphorylation	TTSTFCGTPNYIAPE CCCCCCCCCCCCCHH	15.00	23927012
419	Phosphorylation	TFCGTPNYIAPEILR CCCCCCCCCCHHHHC	10.32	23927012
430	Phosphorylation	EILRGEDYGFSVDWW HHHCCCCCCCCHHHH	18.77	17335005
451	Phosphorylation	FEMMAGRSPFDIVGS HHHHHCCCCCCEECC	29.06	20873877
458	Phosphorylation	SPFDIVGSSDNPDQN CCCCEECCCCCCCCC	24.51	20873877
459	Phosphorylation	PFDIVGSSDNPDQNT CCCEECCCCCCCCCC	35.16	26657352
466	Phosphorylation	SDNPDQNTEDYLFQV CCCCCCCCHHHHHHH	25.30	20873877
469	Phosphorylation	PDQNTEDYLFQVILE CCCCCHHHHHHHHHH	11.81	27642862
477	Ubiquitination	LFQVILEKQIRIPRS HHHHHHHCCCCCCCC	47.80	-
484	Phosphorylation	KQIRIPRSLSVKAAS CCCCCCCCHHHHHHH	21.46	24719451
488	Ubiquitination	IPRSLSVKAASVLKS CCCCHHHHHHHHHHH	34.55	33845483
488	Acetylation	IPRSLSVKAASVLKS CCCCHHHHHHHHHHH	34.55	25953088
494	Acetylation	VKAASVLKSFLNKDP HHHHHHHHHHHCCCH	36.69	25953088
499	Ubiquitination	VLKSFLNKDPKERLG HHHHHHCCCHHHHCC	77.03	29967540
544	Phosphorylation	PPFKPNISGEFGLDN CCCCCCCCCCCCCCC	38.62	22199227
554	Phosphorylation	FGLDNFDSQFTNEPV CCCCCCCCCCCCCCC	24.05	22199227
557	Phosphorylation	DNFDSQFTNEPVQLT CCCCCCCCCCCCCCC	30.91	29116813
564	Phosphorylation	TNEPVQLTPDDDDIV CCCCCCCCCCCCHHH	13.95	15143057
584	Phosphorylation	SEFEGFEYINPLLMS HHCCCCCCCHHHHHC	12.07	27642862
591	Phosphorylation	YINPLLMSAEECV-- CCHHHHHCHHHCC--	32.28	26074081

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
256	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
265	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
271	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
280	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
325	Y	Phosphorylation	Kinase	SRC64	-	PhosphoELM
334	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
412	T	Phosphorylation	Kinase	PDPK1	O15530	Uniprot
564	T	Phosphorylation	Kinase	PIK3C2A	O00443	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	VHL	P40337	PMID:11574546
-	K	Ubiquitination	E3 ubiquitin ligase	SMURF1	Q9HCE7	PMID:20804422

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
412	T	Phosphorylation	16125198
Phosphorylation at Thr-412 in the activation loop is not mandatory for activation (By similarity).
564	T	Phosphorylation	21406692
Phosphorylated at Thr-564 during the initial phase of long term potentiation (By similarity).

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of KPCI_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PAR6A_HUMAN	PARD6A	physical	16189514
BAD_HUMAN	BAD	physical	15705582
RAB4A_HUMAN	RAB4A	physical	12832475
SQSTM_HUMAN	SQSTM1	physical	9566925
SMG1_HUMAN	SMG1	physical	8524286
G3P_HUMAN	GAPDH	physical	11724794
PDPK1_HUMAN	PDPK1	physical	10764742
FRS2_HUMAN	FRS2	physical	10383403
IKKB_HUMAN	IKBKB	physical	10022904
IKKA_HUMAN	CHUK	physical	10022904
PARD3_HUMAN	PARD3	physical	14676191
MARK4_HUMAN	MARK4	physical	14676191
SQSTM_HUMAN	SQSTM1	physical	14676191
PAR6B_HUMAN	PARD6B	physical	14676191
NIPS2_HUMAN	GBAS	physical	14676191
L2GL1_HUMAN	LLGL1	physical	14676191
HS90A_HUMAN	HSP90AA1	physical	14676191
L2GL2_HUMAN	LLGL2	physical	14676191
CDC37_HUMAN	CDC37	physical	14676191
NIPS1_HUMAN	NIPSNAP1	physical	14676191
PAR6G_HUMAN	PARD6G	physical	14676191
RPGF2_HUMAN	RAPGEF2	physical	14676191
MYO10_HUMAN	MYO10	physical	14676191
MBP_HUMAN	MBP	physical	21315177
CDK7_HUMAN	CDK7	physical	21315177
PAR6A_HUMAN	PARD6A	physical	11257119
ZO1_HUMAN	TJP1	physical	11257119
MP2K5_HUMAN	MAP2K5	physical	12813044
SQSTM_HUMAN	SQSTM1	physical	12813044
PAR6A_HUMAN	PARD6A	physical	12813044
A4_HUMAN	APP	physical	21832049
SQSTM_HUMAN	SQSTM1	physical	20808283
GAB1_HUMAN	GAB1	physical	22883624
PAR6B_HUMAN	PARD6B	physical	23718855
PAR6A_HUMAN	PARD6A	physical	16861740
PAR6B_HUMAN	PARD6B	physical	23439680
PAR6A_HUMAN	PARD6A	physical	25416956
PAR6B_HUMAN	PARD6B	physical	25416956
KIF23_HUMAN	KIF23	physical	26344197
PPM1A_HUMAN	PPM1A	physical	26344197
PPM1B_HUMAN	PPM1B	physical	26344197
LA_HUMAN	SSB	physical	26496610
MAGD2_HUMAN	MAGED2	physical	26496610
ZN609_HUMAN	ZNF609	physical	26496610
TM208_HUMAN	TMEM208	physical	26496610
4ET_HUMAN	EIF4ENIF1	physical	26496610
TPC13_HUMAN	TRAPPC13	physical	26496610
PAR6B_HUMAN	PARD6B	physical	26496610
GWL_HUMAN	MASTL	physical	26496610
SQSTM_HUMAN	SQSTM1	physical	26187466
MARK4_HUMAN	MARK4	physical	26346160

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00675	Tamoxifen

Regulatory Network of KPCI_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Crystal structure of the catalytic domain of human atypical proteinkinase C-iota reveals interaction mode of phosphorylation site in turnmotif."; Messerschmidt A., Macieira S., Velarde M., Baedeker M., Benda C.,Jestel A., Brandstetter H., Neuefeind T., Blaesse M.; J. Mol. Biol. 352:918-931(2005). Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-596, IDENTIFICATION BYMASS SPECTROMETRY, AND PHOSPHORYLATION AT THR-412 AND THR-564.	16125198 [Abstract]
"Phosphorylation of tyrosine 256 facilitates nuclear import ofatypical protein kinase C."; White W.O., Seibenhener M.L., Wooten M.W.; J. Cell. Biochem. 85:42-53(2002). Cited for: INTERACTION WITH KPNB1, SUBCELLULAR LOCATION, PHOSPHORYLATION ATTYR-265, AND MUTAGENESIS OF TYR-265.	11891849 [Abstract]
"Nerve growth factor stimulates multisite tyrosine phosphorylation andactivation of the atypical protein kinase C's via a src kinasepathway."; Wooten M.W., Vandenplas M.L., Seibenhener M.L., Geetha T.,Diaz-Meco M.T.; Mol. Cell. Biol. 21:8414-8427(2001). Cited for: PHOSPHORYLATION AT TYR-265; TYR-280 AND TYR-334, AND MUTAGENESIS OFTYR-265; TYR-280 AND TYR-334.	11713277 [Abstract]

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