AiPD: Autoinhibited Protein Database

O15530

Gene name	PDPK1 (PDK1)
Protein name	3-phosphoinositide-dependent protein kinase 1
Names	hPDK1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5170
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class	SERINE/THREONINE-PROTEIN KINASE (PTHR24356)

Descriptions

3-Phosphoinositide-dependent protein kinase-1 (PDPK1) plays a central role in activating the protein kinase A, G, and C subfamily. In particular, PDPK1 plays an important role in regulating the Akt survival pathway. PDPK1 forms a homodimer via its PH domain, which is an autoinhibited conformation. The ATP-binding site is buried in the structure and the PIF pocket in the kinase domain of one monomer is not accessible because of its occupancy by the αG helix of the other monomer. Thus, though the PH domain in PDPK1 does not mediate intramolecular interactions, it mediates the homodimerization by PH-PH interaction and results in autoinhibition. Deletion of the PH domain increases the interaction between PDPK1 and PKB.

Autoinhibitory domains (AIDs)

Target domain	82-342 (Protein kinase domain)
Relief mechanism	PTM, Ligand binding
Assay	Deletion assay, Mutagenesis experiment

AID

459-550 (PH domain)

Target domain

82-342 (Protein kinase domain)

Relief mechanism

PTM (Autophosphorylation of Ser241), Ligand binding (Binding of lipid second messengers)

Assay

Deletion assay, Mutagenesis experiment

Accessory elements

222-247 (Activation loop from InterPro)

Target domain	82-342 (Protein kinase domain)
Relief mechanism
Assay

References

Masters TA et al. (2010) "Regulation of 3-phosphoinositide-dependent protein kinase 1 activity by homodimerization in live cells", Science signaling, 3, ra78

Autoinhibited structure

Activated structure

71 structures for O15530

Entry ID	Method	Resolution	Chain	Position	Source
1H1W	X-ray	200 A	A	71-359	PDB
1OKY	X-ray	230 A	A	51-360	PDB
1OKZ	X-ray	251 A	A	51-360	PDB
1UU3	X-ray	170 A	A	51-360	PDB
1UU7	X-ray	190 A	A	51-360	PDB
1UU8	X-ray	250 A	A	51-360	PDB
1UU9	X-ray	195 A	A	72-357	PDB
1UVR	X-ray	281 A	A	71-359	PDB
1W1D	X-ray	150 A	A	409-556	PDB
1W1G	X-ray	145 A	A	409-556	PDB
1W1H	X-ray	145 A	A/B/C/D	409-556	PDB
1Z5M	X-ray	217 A	A	74-359	PDB
2BIY	X-ray	195 A	A	51-360	PDB
2PE0	X-ray	235 A	A	74-359	PDB
2PE1	X-ray	214 A	A	74-359	PDB
2PE2	X-ray	213 A	A	74-359	PDB
2R7B	X-ray	270 A	A	48-359	PDB
2VKI	X-ray	180 A	A	409-556	PDB
2XCH	X-ray	200 A	A	51-359	PDB
2XCK	X-ray	230 A	A	51-359	PDB
3H9O	X-ray	230 A	A	51-359	PDB
3HRC	X-ray	191 A	A	50-359	PDB
3HRF	X-ray	190 A	A	50-359	PDB
3ION	X-ray	240 A	A	48-359	PDB
3IOP	X-ray	220 A	A	48-359	PDB
3NAX	X-ray	175 A	A	66-362	PDB
3NAY	X-ray	260 A	A/B	66-362	PDB
3NUN	X-ray	220 A	A	67-358	PDB
3NUS	X-ray	275 A	A	73-358	PDB
3NUU	X-ray	198 A	A	73-358	PDB
3NUY	X-ray	210 A	A	73-358	PDB
3ORX	X-ray	220 A	A/B/C/D/E/F/G/H	51-359	PDB
3ORZ	X-ray	200 A	A/B/C/D	51-359	PDB
3OTU	X-ray	210 A	A	51-359	PDB
3PWY	X-ray	350 A	A	51-359	PDB
3QC4	X-ray	180 A	A/B	51-359	PDB
3QCQ	X-ray	250 A	A	48-359	PDB
3QCS	X-ray	249 A	A	48-359	PDB
3QCX	X-ray	230 A	A	48-359	PDB
3QCY	X-ray	220 A	A	48-359	PDB
3QD0	X-ray	199 A	A	48-359	PDB
3QD3	X-ray	200 A	A	48-359	PDB
3QD4	X-ray	230 A	A	48-359	PDB
3RCJ	X-ray	170 A	A	50-359	PDB
3RWP	X-ray	192 A	A	51-359	PDB
3RWQ	X-ray	255 A	A	51-359	PDB
3SC1	X-ray	270 A	A	50-359	PDB
4A06	X-ray	200 A	A	50-359	PDB
4A07	X-ray	185 A	A	50-359	PDB
4AW0	X-ray	143 A	A	51-359	PDB
4AW1	X-ray	168 A	A	51-359	PDB
4CT1	X-ray	185 A	A	50-359	PDB
4CT2	X-ray	125 A	A	50-359	PDB
4RQK	X-ray	155 A	A	50-359	PDB
4RQV	X-ray	150 A	A	50-359	PDB
4RRV	X-ray	141 A	A	50-359	PDB
4XX9	X-ray	140 A	A	50-359	PDB
5ACK	X-ray	124 A	A	50-359	PDB
5HKM	X-ray	210 A	A	51-359	PDB
5HNG	X-ray	301 A	A	51-359	PDB
5HO7	X-ray	300 A	A	51-359	PDB
5HO8	X-ray	270 A	A	51-359	PDB
5LVL	X-ray	140 A	A	50-359	PDB
5LVM	X-ray	126 A	A	50-359	PDB
5LVN	X-ray	138 A	A	50-359	PDB
5LVO	X-ray	109 A	A	50-359	PDB
5LVP	X-ray	250 A	A/B/C/D	50-359	PDB
5MRD	X-ray	141 A	A	50-359	PDB
6WJQ	X-ray	271 A	C/D	2-16	PDB
8DQT	X-ray	131 A	A	50-359	PDB
AF-O15530-F1	Predicted				AlphaFoldDB

209 variants for O15530

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA394396354 rs1284780606	2	A>T		No	ClinGen gnomAD
CA276817485 rs1017287074	3	R>G		No	ClinGen TOPMed
rs965784029 CA276817490	4	T>I		No	ClinGen TOPMed
rs1597008688 CA394396372	5	T>A		No	ClinGen Ensembl
CA394396416 rs1276688995	9	Y>F		No	ClinGen TOPMed
CA394396431 rs1365784420	11	A>G		No	ClinGen TOPMed
CA394396427 rs1186877836	11	A>T		No	ClinGen TOPMed gnomAD
COSM42785 rs1455901588 CA394396433	12	V>M	central_nervous_system [Cosmic]	No	ClinGen cosmic curated TOPMed
rs1431051559 CA394396455	15	Q>P		No	ClinGen TOPMed gnomAD
CA394396456 rs1431051559	15	Q>R		No	ClinGen TOPMed gnomAD
CA276821040 rs76505791	17	S>C		No	ClinGen TOPMed gnomAD
rs1470591421 CA394396486	20	L>V		No	ClinGen gnomAD
CA394396494 rs1320549724	21	C>G		No	ClinGen TOPMed gnomAD
CA394396493 rs1320549724	21	C>R		No	ClinGen TOPMed gnomAD
CA394396495 rs1269819553	21	C>Y		No	ClinGen TOPMed
CA394396519 rs1209470249	24	P>L		No	ClinGen TOPMed
rs1387071207 CA394396529	26	P>L		No	ClinGen gnomAD
rs1205389248 CA394396546	28	M>I		No	ClinGen TOPMed
CA7845449 rs772871628	29	V>A		No	ClinGen ExAC gnomAD
CA394396555 rs1597035425	30	R>T		No	ClinGen Ensembl
rs1217640650 CA394396576	33	T>I		No	ClinGen TOPMed gnomAD
rs1324291270 CA394396596	36	S>N		No	ClinGen gnomAD
rs965288790 CA276821041	37	T>M		No	ClinGen TOPMed gnomAD
rs1466184317 CA394396609	38	P>H		No	ClinGen gnomAD
rs1300090215 CA394396608	38	P>S		No	ClinGen TOPMed
rs1245860798 CA394396613	39	P>A		No	ClinGen gnomAD
rs1292405645 CA394396616	39	P>R		No	ClinGen Ensembl
rs1476842625 CA394396618	40	G>S		No	ClinGen gnomAD
rs55824600 CA276821042	41	I>T		No	ClinGen Ensembl
CA394396662 rs1429547678	46	R>S		No	ClinGen gnomAD
CA394396683 rs1156285133	50	A>T		No	ClinGen TOPMed gnomAD
CA394396692 rs1319418139	51	M>T		No	ClinGen gnomAD
CA7845454 rs767328553	51	M>V		No	ClinGen ExAC TOPMed gnomAD
rs1305262606 CA394396705	53	G>S		No	ClinGen gnomAD
rs1470062791 CA394396716	54	T>I		No	ClinGen TOPMed
CA394396719 rs1376869859	55	A>S		No	ClinGen TOPMed
rs760555326 CA7845457	56	A>P		No	ClinGen ExAC TOPMed
rs1179308824 CA394396731	57	E>G		No	ClinGen TOPMed
rs753919385 CA7845459	57	E>K		No	ClinGen ExAC TOPMed gnomAD
rs753919385 CA394396728	57	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA394396736 rs1224211168	58	P>A		No	ClinGen gnomAD
CA394396740 rs1288879905	58	P>L		No	ClinGen TOPMed gnomAD
CA394396739 rs1288879905	58	P>R		No	ClinGen TOPMed gnomAD
rs779166111 CA7845461	59	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs757413961 CA7845460	59	R>W		No	ClinGen ExAC TOPMed gnomAD
rs750784265 CA7845462	60	P>S		No	ClinGen ExAC TOPMed gnomAD
CA394396752 rs1471450296	61	G>A		No	ClinGen TOPMed gnomAD
rs780402170 CA7845464	61	G>S		No	ClinGen ExAC TOPMed gnomAD
rs769074523 CA394396755	62	A>S		No	ClinGen ExAC gnomAD
CA7845466 rs769074523	62	A>T		No	ClinGen ExAC gnomAD
rs748817353 CA7845468	63	G>S		No	ClinGen ExAC TOPMed gnomAD
CA7845469 rs770692110	64	S>A		No	ClinGen ExAC gnomAD
rs1409386034 CA394396768	64	S>C		No	ClinGen TOPMed gnomAD
CA7845470 rs774190389	65	L>Q		No	ClinGen ExAC gnomAD
CA7845472 rs771854875	68	A>V		No	ClinGen ExAC gnomAD
rs1597035808 CA394396795	69	Q>E		No	ClinGen Ensembl
CA394396798 rs1365702484	69	Q>R		No	ClinGen TOPMed
rs775183994 CA7845473	71	P>A		No	ClinGen ExAC gnomAD
CA7845475 rs535696352	71	P>L		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA7845474 rs775183994	71	P>S		No	ClinGen ExAC gnomAD
rs761949625 CA7845477	72	P>L		No	ClinGen ExAC gnomAD
CA394396816 rs1253349049	73	Q>K		No	ClinGen gnomAD
rs750705121 CA7845479	75	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1437977244 CA394396831	75	R>W		No	ClinGen gnomAD
rs751870190 CA7845482	78	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs766725088 CA7845481	78	R>W		No	ClinGen ExAC gnomAD
CA7845484 rs755452051	79	P>A		No	ClinGen ExAC TOPMed gnomAD
rs1199074561 CA394396855	79	P>R		No	ClinGen TOPMed
CA394396853 rs755452051	79	P>S		No	ClinGen ExAC TOPMed gnomAD
rs755452051 CA7845483	79	P>T		No	ClinGen ExAC TOPMed gnomAD
CA7845485 rs748800896	80	E>Q		No	ClinGen ExAC gnomAD
rs1487067767 CA394396867	81	D>G		No	ClinGen TOPMed
rs756879724 CA7845486	81	D>N		No	ClinGen ExAC gnomAD
rs1410652176 CA394396879	83	K>Q		No	ClinGen gnomAD
rs745496613 CA7845488	83	K>R		No	ClinGen ExAC gnomAD
CA394396893 rs1454464844	84	F>L		No	ClinGen gnomAD
rs1338659610 CA394396891	84	F>S		No	ClinGen gnomAD
rs1343052697 CA394396921	89	G>R		No	ClinGen gnomAD
rs1567152732 CA394396939	91	G>A		No	ClinGen Ensembl
rs746838429 CA7845493	92	S>A		No	ClinGen ExAC gnomAD
CA394396945 rs1275850722	92	S>C		No	ClinGen gnomAD
CA394396965 rs1244284890	95	T>M		No	ClinGen gnomAD
rs1366281463 CA394397026	104	T>A		No	ClinGen Ensembl
rs1490894241 CA394397095	112	I>V		No	ClinGen TOPMed gnomAD
rs1251113391 CA394397157	121	E>Q		No	ClinGen gnomAD
rs1471570158 CA394397168	122	N>S		No	ClinGen gnomAD
CA394397172 rs1266981351	123	K>Q		No	ClinGen TOPMed
rs551607067 CA276821241	126	Y>C		No	ClinGen 1000Genomes TOPMed gnomAD
CA394397227 rs1275491881	131	R>W		No	ClinGen TOPMed
rs1228305905 CA394397258	135	S>L		No	ClinGen TOPMed
CA394397262 rs1276912178	136	R>C		No	ClinGen TOPMed
CA394397275 rs1234422517	138	D>G		No	ClinGen TOPMed
CA394397309 rs1457257651	143	V>I		No	ClinGen TOPMed gnomAD
CA394397316 rs1321154067	144	K>E		No	ClinGen TOPMed
rs1392815536 CA394397333	146	Y>S		No	ClinGen TOPMed
rs1370635114 CA394397339	147	F>V		No	ClinGen TOPMed
rs924372495 CA276821242	152	D>N		No	ClinGen TOPMed
rs748035328 CA7845517	152	D>V		No	ClinGen ExAC TOPMed gnomAD
rs956039573 CA276821243	153	E>K		No	ClinGen TOPMed
CA394397603 rs1555446124	182	T>I		No	ClinGen Ensembl
rs764571812 CA7845527	240	N>K		No	ClinGen ExAC gnomAD
CA394398084 rs1443259994	240	N>S		No	ClinGen TOPMed
CA394398105 rs1167649518	243	V>M		No	ClinGen TOPMed gnomAD
CA394398132 rs1463114174	246	A>P		No	ClinGen gnomAD
CA7845529 rs757889593	246	A>V		No	ClinGen ExAC gnomAD
rs1356651659 CA394398141	247	Q>R		No	ClinGen TOPMed
CA7845531 rs370069297	249	V>I		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs373278831 CA276821610	252	E>K		No	ClinGen ESP TOPMed gnomAD
CA7845534 rs144186731	255	T>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs769705993 CA7845535	258	S>F		No	ClinGen ExAC TOPMed gnomAD
rs749355083 CA7845537	259	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1445078205 CA394398248	260	C>Y		No	ClinGen gnomAD
CA7845573 rs755812280	378	N>S		No	ClinGen ExAC TOPMed gnomAD
CA394399152 rs1479922882	379	L>V		No	ClinGen Ensembl
CA7845574 rs763731140	380	L>V		No	ClinGen ExAC gnomAD
rs561462097 CA276822450	382	Q>H		No	ClinGen 1000Genomes
rs753681549 CA394399192	385	C>F		No	ClinGen ExAC TOPMed gnomAD
rs1318577768 CA394399190	385	C>R		No	ClinGen gnomAD
rs753681549 CA7845575	385	C>Y		No	ClinGen ExAC TOPMed gnomAD
rs1167163560 CA394399206	387	Q>E		No	ClinGen TOPMed
rs370279457 CA7845576	387	Q>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA394399214 rs1567164251	388	V>L		No	ClinGen Ensembl
rs779064858 CA7845577	390	S>L		No	ClinGen ExAC TOPMed gnomAD
CA394399234 rs1270753328	391	S>F		No	ClinGen TOPMed gnomAD
CA394399238 rs1361007557	392	S>Y		No	ClinGen gnomAD
CA276822452 rs200076126	393	S>C		No	ClinGen Ensembl
CA394399247 rs1272187031	394	S>P		No	ClinGen TOPMed
rs945402056 CA276822453	395	H>R		No	ClinGen TOPMed
CA7845580 rs780305703	396	S>C		No	ClinGen ExAC gnomAD
CA394399260 rs1597061858	396	S>P		No	ClinGen Ensembl
CA7845583 rs776800040	397	L>R		No	ClinGen ExAC TOPMed gnomAD
rs768924605 CA7845582	397	L>V		No	ClinGen ExAC TOPMed gnomAD
CA7845585 rs370494924	398	S>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs1441563937 CA394399277	399	A>V		No	ClinGen gnomAD
rs1043839627 CA276822457	401	D>N		No	ClinGen TOPMed
CA7845588 rs76887737	402	T>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA7845589 rs75824263	402	T>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs75824263 CA394399294	402	T>R		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs994360991 CA276822459	403	G>C		No	ClinGen TOPMed
CA7845593 rs139732994	403	G>D		No	ClinGen ESP ExAC TOPMed gnomAD
rs994360991 CA394399295	403	G>S		No	ClinGen TOPMed
rs535986266 CA276822462	405	P>H		No	ClinGen Ensembl
CA394399326 rs1597062071	408	S>A		No	ClinGen Ensembl
rs758443705 CA7845596	408	S>L		No	ClinGen ExAC gnomAD
CA7845597 rs780213417	410	S>G		No	ClinGen ExAC gnomAD
CA7845599 rs755138312	411	N>H		No	ClinGen ExAC gnomAD
CA7845600 rs149931764	411	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs1040058248 CA276822464	412	I>V		No	ClinGen TOPMed
CA394399367 rs1209673323	414	Q>R		No	ClinGen TOPMed
rs770192179 CA7845602	415	Y>C		No	ClinGen ExAC gnomAD
rs771442872 CA7845605	418	D>G		No	ClinGen ExAC gnomAD
CA394399404 rs1286398704	420	D>N		No	ClinGen TOPMed
CA276822469 rs547797391	421	S>L		No	ClinGen gnomAD
rs547797391 CA394399415	421	S>W		No	ClinGen gnomAD
CA7845611 rs765088097	423	S>C		No	ClinGen ExAC TOPMed gnomAD
CA394399453 rs1417169484	427	D>H		No	ClinGen TOPMed
CA7845612 rs552355299	427	D>V		No	ClinGen 1000Genomes ExAC gnomAD
CA7845613 rs145034828	429	Q>E		No	ClinGen ESP ExAC
rs1205759672 CA394399468	429	Q>R		No	ClinGen gnomAD
rs751583488 CA7845615	432	E>K		No	ClinGen ExAC gnomAD
CA276822475 rs1022721779	434	E>D		No	ClinGen Ensembl
CA394399515 rs1364009602	435	K>N		No	ClinGen gnomAD
rs374111988 CA7845617	436	R>K		No	ClinGen ESP ExAC
rs142153837 CA7845620	440	E>*		No	ClinGen ESP ExAC TOPMed gnomAD
rs749712375 CA7845621	440	E>V		No	ClinGen ExAC TOPMed gnomAD
CA7845623 rs533780852	445	G>V		No	ClinGen 1000Genomes ExAC gnomAD
CA394383516 rs1464654956	450	Q>P		No	ClinGen TOPMed
CA276823794 rs374649760	454	N>D		No	ClinGen gnomAD
CA394383671 rs1441301361	463	V>M		No	ClinGen gnomAD
CA394383714 rs1378928701	466	R>Q		No	ClinGen gnomAD
COSM3420901 CA7845685 rs753410336	466	R>W	large_intestine [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs773372279 CA7845715	477	L>F		No	ClinGen ExAC gnomAD
rs1423615874 CA394383969	489	P>L		No	ClinGen gnomAD
rs768116696 CA7845720	491	N>D		No	ClinGen ExAC gnomAD
CA7845721 rs775814028	491	N>I		No	ClinGen ExAC gnomAD
rs966963577 CA276823965	492	K>R		No	ClinGen TOPMed
CA276823966 rs1001507233	494	L>M		No	ClinGen TOPMed
rs761277571 CA7845722	497	E>K		No	ClinGen ExAC gnomAD
rs1279605766 CA394384085	499	P>H		No	ClinGen TOPMed
CA394384079 rs1263044277	499	P>S		No	ClinGen gnomAD
CA7845723 rs764588339	502	Q>R		No	ClinGen ExAC TOPMed gnomAD
rs749966481 CA7845724	503	E>D		No	ClinGen ExAC gnomAD
CA394384183 rs1276042216	504	L>I		No	ClinGen TOPMed
rs1446601314 CA394384207	505	R>L		No	ClinGen gnomAD
rs758036081 CA7845725	508	A>T		No	ClinGen ExAC gnomAD
rs1291358013 CA394384436	514	F>L		No	ClinGen gnomAD
CA7845726 rs766091042	514	F>Y		No	ClinGen ExAC
rs974348443 CA276823970	515	F>L		No	ClinGen Ensembl
rs549158095 CA276823971	518	T>M		No	ClinGen 1000Genomes gnomAD
rs1423482494 CA394384637	519	P>L		No	ClinGen gnomAD
rs1389216086 CA394384727 COSM1376975	522	T>M	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA7845752 rs749357936	526	M>I		No	ClinGen ExAC gnomAD
rs1354621651 CA394384925	533	H>P		No	ClinGen gnomAD
CA394384941 rs1192895734	534	K>R		No	ClinGen TOPMed
rs1263687601 CA394385002	537	R>S		No	ClinGen gnomAD
CA7845755 rs551293304	541	E>D		No	ClinGen 1000Genomes ExAC gnomAD
rs1488966394 CA394385062	541	E>K		No	ClinGen TOPMed
rs772355571 CA7845756	542	V>I		No	ClinGen ExAC gnomAD
rs1272589968 CA394385111	544	R>K		No	ClinGen TOPMed
rs1456303446 CA394385130	546	R>*		No	ClinGen gnomAD
rs148008907 CA276824018	546	R>Q		No	ClinGen 1000Genomes ESP TOPMed gnomAD
CA394385149 rs1320127013	547	Y>C		No	ClinGen TOPMed
rs1007127163 CA276824019	551	P>L		No	ClinGen TOPMed gnomAD
rs1007127163 CA394385217	551	P>R		No	ClinGen TOPMed gnomAD
rs901482387 CA276824020	553	A>T		No	ClinGen TOPMed
rs201983709 CA394385252	554	A>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs201983709 CA7845761	554	A>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1448297439 CA394385259	554	A>V		No	ClinGen TOPMed
rs1597079648 CA394385264	555	V>L		No	ClinGen Ensembl

No associated diseases with O15530

4 regional properties for O15530

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	82 - 342	IPR000719
active_site	Serine/threonine-protein kinase, active site	201 - 213	IPR008271
binding_site	Protein kinase, ATP binding site	88 - 111	IPR017441
domain	PDK1-type, PH domain	441 - 547	IPR033931

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Cytoplasm Nucleus Cell membrane; Peripheral membrane protein Cell junction, focal adhesion	Tyrosine phosphorylation seems to occur only at the cell membrane Translocates to the cell membrane following insulin stimulation by a mechanism that involves binding to GRB14 and INSR SRC and HSP90 promote its localization to the cell membrane Its nuclear localization is dependent on its association with PTPN6 and its phosphorylation at Ser-396 Restricted to the nucleus in neuronal cells while in non-neuronal cells it is found in the cytoplasm The Ser-241 phosphorylated form is distributed along the perinuclear region in neuronal cells while in non-neuronal cells it is found in both the nucleus and the cytoplasm IGF1 transiently increases phosphorylation at Ser-241 of neuronal PDPK1, resulting in its translocation to other cellular compartments The tyrosine-phosphorylated form colocalizes with PTK2B in focal adhesions after angiotensin II stimulation
PANTHER Family	PTHR24356	SERINE/THREONINE-PROTEIN KINASE
PANTHER Subfamily	PTHR24356:SF163	3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1-RELATED
PANTHER Protein Class	non-receptor serine/threonine protein kinase protein modifying enzyme
PANTHER Pathway Category	Inflammation mediated by chemokine and cytokine signaling pathway PDK1 Ras Pathway PDK CCKR signaling map PDPK1 PI3 kinase pathway PDK1 ACT PI3 kinase pathway PDK1 p53 pathway feedback loops 2 PDK1/2 p53 pathway PDK1/2 Interleukin signaling pathway PDK1/2 Insulin/IGF pathway-protein kinase B signaling cascade PDK1/2 PDGF signaling pathway PDK1/2 PI3 kinase pathway P110ACT

8 GO annotations of cellular component

Name	Definition
cell projection	A prolongation or process extending from a cell, e.g. a flagellum or axon.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic vesicle	A vesicle found in the cytoplasm of a cell.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
focal adhesion	A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ).
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynaptic density	An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.

7 GO annotations of molecular function

Name	Definition
3-phosphoinositide-dependent protein kinase activity	Phosphatidylinositol-3-phosphate-dependent catalysis of the reaction: ATP + a protein = ADP + a phosphoprotein.
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
phospholipase activator activity	Increases the activity of a phospholipase, an enzyme that catalyzes of the hydrolysis of a glycerophospholipid.
phospholipase binding	Binding to a phospholipase.
protein serine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity	Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity	Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.

29 GO annotations of biological process

Name	Definition
actin cytoskeleton organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
activation of protein kinase B activity	Any process that initiates the activity of the inactive enzyme protein kinase B.
calcium-mediated signaling	Any intracellular signal transduction in which the signal is passed on within the cell via calcium ions.
cell migration	The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
cellular response to epidermal growth factor stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an epidermal growth factor stimulus.
cellular response to insulin stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an insulin stimulus. Insulin is a polypeptide hormone produced by the islets of Langerhans of the pancreas in mammals, and by the homologous organs of other organisms.
epidermal growth factor receptor signaling pathway	The series of molecular signals initiated by binding of a ligand to the tyrosine kinase receptor EGFR (ERBB1) on the surface of a cell. The pathway ends with regulation of a downstream cellular process, e.g. transcription.
extrinsic apoptotic signaling pathway	The series of molecular signals in which a signal is conveyed from the cell surface to trigger the apoptotic death of a cell. The pathway starts with either a ligand binding to a cell surface receptor, or a ligand being withdrawn from a cell surface receptor (e.g. in the case of signaling by dependence receptors), and ends when the execution phase of apoptosis is triggered.
hyperosmotic response	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of detection of, or exposure to, a hyperosmotic environment, i.e. an environment with a higher concentration of solutes than the organism or cell.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of cardiac muscle cell apoptotic process	Any process that decreases the rate or extent of cardiac cell apoptotic process, a form of programmed cell death induced by external or internal signals that trigger the activity of proteolytic caspases whose actions dismantle a cardiac muscle cell and result in its death.
negative regulation of endothelial cell apoptotic process	Any process that stops, prevents or reduces the frequency, rate or extent of endothelial cell apoptotic process.
negative regulation of protein kinase activity	Any process that stops, prevents, or reduces the frequency, rate or extent of protein kinase activity.
negative regulation of toll-like receptor signaling pathway	Any process that stops, prevents, or reduces the frequency, rate, or extent of toll-like receptor signaling pathway.
negative regulation of transforming growth factor beta receptor signaling pathway	Any process that stops, prevents, or reduces the frequency, rate or extent of any TGF-beta receptor signaling pathway.
peptidyl-serine phosphorylation	The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
peptidyl-threonine phosphorylation	The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
positive regulation of angiogenesis	Any process that activates or increases angiogenesis.
positive regulation of blood vessel endothelial cell migration	Any process that activates or increases the frequency, rate or extent of the migration of the endothelial cells of blood vessels.
positive regulation of phospholipase activity	Any process that increases the frequency, rate or extent of phospholipase activity, the hydrolysis of a phospholipid.
positive regulation of protein localization to plasma membrane	Any process that activates or increases the frequency, rate or extent of protein localization to plasma membrane.
positive regulation of release of sequestered calcium ion into cytosol	Any process that activates or increases the frequency, rate or extent of the release into the cytosolic compartment of calcium ions sequestered in the endoplasmic reticulum or mitochondria.
positive regulation of sprouting angiogenesis	Any process that activates or increases the frequency, rate or extent of sprouting angiogenesis.
positive regulation of vascular endothelial cell proliferation	Any process that activates or increases the frequency, rate or extent of vascular endothelial cell proliferation.
protein autophosphorylation	The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation).
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of I-kappaB kinase/NF-kappaB signaling	Any process that modulates I-kappaB kinase/NF-kappaB signaling.
regulation of mast cell degranulation	Any process that modulates the frequency, rate, or extent of mast cell degranulation.
type B pancreatic cell development	The process whose specific outcome is the progression of a type B pancreatic cell over time, from its formation to the mature structure. A type B pancreatic cell is a cell located towards center of the islets of Langerhans that secretes insulin.

27 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q03407	PKH1	Serine/threonine-protein kinase PKH1	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)	PR
Q9W0V1	Pdk1	3-phosphoinositide-dependent protein kinase 1	Drosophila melanogaster (Fruit fly)	SS
Q05513	PRKCZ	Protein kinase C zeta type	Homo sapiens (Human)	SS
P41743	PRKCI	Protein kinase C iota type	Homo sapiens (Human)	EV
Q16512	PKN1	Serine/threonine-protein kinase N1	Homo sapiens (Human)	EV
Q6P5Z2	PKN3	Serine/threonine-protein kinase N3	Homo sapiens (Human)	SS
Q16513	PKN2	Serine/threonine-protein kinase N2	Homo sapiens (Human)	EV
P24723	PRKCH	Protein kinase C eta type	Homo sapiens (Human)	SS
Q02156	PRKCE	Protein kinase C epsilon type	Homo sapiens (Human)	SS
Q04759	PRKCQ	Protein kinase C theta type	Homo sapiens (Human)	PR
Q05655	PRKCD	Protein kinase C delta type	Homo sapiens (Human)	SS
P17252	PRKCA	Protein kinase C alpha type	Homo sapiens (Human)	EV
P05129	PRKCG	Protein kinase C gamma type	Homo sapiens (Human)	SS
P05771	PRKCB	Protein kinase C beta type	Homo sapiens (Human)	SS
P31751	AKT2	RAC-beta serine/threonine-protein kinase	Homo sapiens (Human)	EV SS
P31749	AKT1	RAC-alpha serine/threonine-protein kinase	Homo sapiens (Human)	EV
Q9Y243	AKT3	RAC-gamma serine/threonine-protein kinase	Homo sapiens (Human)	SS
Q96BR1	SGK3	Serine/threonine-protein kinase Sgk3	Homo sapiens (Human)	SS
Q9HBY8	SGK2	Serine/threonine-protein kinase Sgk2	Homo sapiens (Human)	SS
O00141	SGK1	Serine/threonine-protein kinase Sgk1	Homo sapiens (Human)	PR
Q15208	STK38	Serine/threonine-protein kinase 38	Homo sapiens (Human)	EV
Q9Y2H1	STK38L	Serine/threonine-protein kinase 38-like	Homo sapiens (Human)	EV
Q6A1A2	PDPK2P	Putative 3-phosphoinositide-dependent protein kinase 2	Homo sapiens (Human)	PR
Q9Z2A0	Pdpk1	3-phosphoinositide-dependent protein kinase 1	Mus musculus (Mouse)	SS
O55173	Pdpk1	3-phosphoinositide-dependent protein kinase 1	Rattus norvegicus (Rat)	SS
Q9Y1J3	pdk-1	3-phosphoinositide-dependent protein kinase 1	Caenorhabditis elegans	SS
Q4V3C8	PDPK2	3-phosphoinositide-dependent protein kinase 2	Arabidopsis thaliana (Mouse-ear cress)	PR

10	20	30	40	50	60
MARTTSQLYD	AVPIQSSVVL	CSCPSPSMVR	TQTESSTPPG	IPGGSRQGPA	MDGTAAEPRP
70	80	90	100	110	120
GAGSLQHAQP	PPQPRKKRPE	DFKFGKILGE	GSFSTVVLAR	ELATSREYAI	KILEKRHIIK
130	140	150	160	170	180
ENKVPYVTRE	RDVMSRLDHP	FFVKLYFTFQ	DDEKLYFGLS	YAKNGELLKY	IRKIGSFDET
190	200	210	220	230	240
CTRFYTAEIV	SALEYLHGKG	IIHRDLKPEN	ILLNEDMHIQ	ITDFGTAKVL	SPESKQARAN
250	260	270	280	290	300
SFVGTAQYVS	PELLTEKSAC	KSSDLWALGC	IIYQLVAGLP	PFRAGNEYLI	FQKIIKLEYD
310	320	330	340	350	360
FPEKFFPKAR	DLVEKLLVLD	ATKRLGCEEM	EGYGPLKAHP	FFESVTWENL	HQQTPPKLTA
370	380	390	400	410	420
YLPAMSEDDE	DCYGNYDNLL	SQFGCMQVSS	SSSSHSLSAS	DTGLPQRSGS	NIEQYIHDLD
430	440	450	460	470	480
SNSFELDLQF	SEDEKRLLLE	KQAGGNPWHQ	FVENNLILKM	GPVDKRKGLF	ARRRQLLLTE
490	500	510	520	530	540
GPHLYYVDPV	NKVLKGEIPW	SQELRPEAKN	FKTFFVHTPN	RTYYLMDPSG	NAHKWCRKIQ
550
EVWRQRYQSH	PDAAVQ