Reactome | PIK3CA R38G [cytosol]

PIK3CA R38G [cytosol]

Stable Identifier

R-HSA-2395950

Type

Protein [EntityWithAccessionedSequence]

Species

Homo sapiens

Compartment

cytosol

Synonyms

PIK3CA Arg38Gly

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Disease (Homo sapiens)

- Diseases of signal transduction by growth factor receptors and second messengers (Homo sapiens)
  - PI3K/AKT Signaling in Cancer (Homo sapiens)
    - Constitutive Signaling by Aberrant PI3K in Cancer (Homo sapiens)
      - PI3K gain of function mutants phosphorylate PIP2 to PIP3 (Homo sapiens)
        
        PI3K mutants [plasma membrane] (Homo sapiens)
        
        PIK3R1:PIK3CA mutants [plasma membrane] (Homo sapiens)
        
        PIK3CA mutants [cytosol] (Homo sapiens)
        
        PIK3CA ABD domain mutants [cytosol] (Homo sapiens)
        
        PIK3CA R38G [cytosol] (Homo sapiens)
      - PI3K inhibitors block PI3K catalytic activity (Homo sapiens)
        
        PI3K Inhibitors:PI3K [cytosol] (Homo sapiens)
        
        PI3K mutants,Activator:PI3K [plasma membrane] (Homo sapiens)
        
        PI3K mutants [plasma membrane] (Homo sapiens)
        
        PIK3R1:PIK3CA mutants [plasma membrane] (Homo sapiens)
        
        PIK3CA mutants [cytosol] (Homo sapiens)
        
        PIK3CA ABD domain mutants [cytosol] (Homo sapiens)
        
        PIK3CA R38G [cytosol] (Homo sapiens)
        
        PI3K mutants,Activator:PI3K [plasma membrane] (Homo sapiens)
        
        PI3K mutants [plasma membrane] (Homo sapiens)
        
        PIK3R1:PIK3CA mutants [plasma membrane] (Homo sapiens)
        
        PIK3CA mutants [cytosol] (Homo sapiens)
        
        PIK3CA ABD domain mutants [cytosol] (Homo sapiens)
        
        PIK3CA R38G [cytosol] (Homo sapiens)

General

The arginine residue at position 38 of PIK3CA (R38) is located at a contact site between the ABD and kinase domains of PIK3CA. Substitution of this arginine residue with glycine in PIK3CA R38G mutant is likely to disrupt the interaction between the ABD domain and the kinase domain, causing a confomrational change of the kinase domain that leads to increased enzymatic activity (Huang et al. 2007).

Literature References

PubMed ID	Title	Journal	Year
18079394	The structure of a human p110alpha/p85alpha complex elucidates the effects of oncogenic PI3Kalpha mutations Huang, CH, Mandelker, D, Schmidt-Kittler, O, Samuels, Y, Velculescu, VE, Kinzler, KW, Vogelstein, B, Gabelli, SB, Amzel, LM	Science	2007

External Reference Information

External Reference

UniProt:P42336 PIK3CA

Gene Names

PIK3CA

Chain

chain:1-1068

Reference Genes

BioGPS Gene:5290 PIK3CA

COSMIC (genes):PIK3CA PIK3CA

CTD Gene:5290 PIK3CA

dbSNP Gene:5290 PIK3CA

ENSEMBL:ENSG00000121879 PIK3CA

HGNC:8975 PIK3CA

KEGG:hsa:5290 PIK3CA

Monarch:5290 PIK3CA

NCBI Gene:5290 PIK3CA

OMIM:171834 PIK3CA

UCSC:P42336 PIK3CA

Reference Transcript

Other Identifiers

11745214_a_at

11763283_at

16948209

17122920

17122922

204369_PM_at

204369_at

231854_PM_at

231854_at

235980_PM_at

235980_at

2653839

2653841

2653852

2653853

2653854

2653855

2653856

2653857

2653858

2653860

2653861

2653862

2653864

2653865

2653866

2653867

2653868

2653869

2653871

2653872

2653873

2653874

2653875

2653876

2653877

2653879

2653880

2653881

2653882

2653883

2653884

2653885

2653890

3935882

3935885

3935887

3935889

3935891

3935893

3935895

3935897

40704_at

41969_at

5290

55954_at

8084016

81516_at

81657_at

83177_at

90039_at

A_14_P113684

A_14_P127878

A_14_P128410

A_21_P0012238

A_23_P92057

GE60386

GE88555

GO:0000166

GO:0001525

GO:0001889

GO:0001944

GO:0002376

GO:0003012

GO:0003824

GO:0004674

GO:0005515

GO:0005524

GO:0005737

GO:0005829

GO:0005886

GO:0005942

GO:0005943

GO:0005944

GO:0005975

GO:0006006

GO:0006325

GO:0006629

GO:0006909

GO:0007173

GO:0008286

GO:0010468

GO:0010592

GO:0010629

GO:0014704

GO:0014823

GO:0014870

GO:0016192

GO:0016242

GO:0016301

GO:0016303

GO:0016477

GO:0016740

GO:0030027

GO:0030036

GO:0030168

GO:0030295

GO:0030835

GO:0032008

GO:0032869

GO:0035005

GO:0035994

GO:0036092

GO:0038084

GO:0040014

GO:0043201

GO:0043276

GO:0043457

GO:0043491

GO:0043524

GO:0043542

GO:0043560

GO:0046854

GO:0046934

GO:0048009

GO:0048015

GO:0048471

GO:0048661

GO:0048856

GO:0048870

GO:0050852

GO:0051897

GO:0055119

GO:0060048

GO:0060612

GO:0071333

GO:0071464

GO:0071548

GO:0086003

GO:0097009

GO:0098772

GO:0106310

GO:0110053

GO:0140096

GO:0141068

GO:1903544

GO:1905477

GO:2000270

GO:2000811

HMNXSV003040760

Hs.120905.0.S1_3p_at

Hs.122419.0.S1_3p_at

ILMN_1705396

ILMN_1705468

PH_hs_0031379

TC03000951.hg

TC03002674.hg

TC22000929.hg

Z29090_at

g5453891_3p_at

p28442

Participates

as a candidate of

PIK3CA ABD domain mutants [cytosol] (Homo sapiens)

Other forms of this molecule

PIK3CA H1047L [cytosol]

PIK3CA H1047R [cytosol]

PIK3CA [cytosol]

PIK3CA R38C [cytosol]

PIK3CA R38S [cytosol]

PIK3CA R38H [cytosol]

PIK3CA E542Q [cytosol]

PIK3CA Q546P [cytosol]

PIK3CA Q546R [cytosol]

PIK3CA Q546H [cytosol]

PIK3CA E545G [cytosol]

PIK3CA Q546L [cytosol]

PIK3CA E542V [cytosol]

PIK3CA E545V [cytosol]

PIK3CA Q546E [cytosol]

PIK3CA E545Q [cytosol]

PIK3CA E545K [cytosol]

PIK3CA E545A [cytosol]

PIK3CA Q546K [cytosol]

PIK3CA E542K [cytosol]

PIK3CA H1047Y [cytosol]

PIK3CA M1043V [cytosol]

PIK3CA M1043T [cytosol]

PIK3CA M1043I [cytosol]

Modified Residues

Name

L-arginine 38 replaced with glycine

Coordinate

PsiMod

L-arginine removal [MOD:01632]

A protein modification that effectively removes or replaces an L-arginine.

glycine residue [MOD:00017]

A protein modification that effectively converts a source amino acid residue to a glycine.

Disease

Name	Identifier	Synonyms
cancer	DOID:162	malignant tumor, malignant neoplasm, primary cancer
glioblastoma	DOID:3068	GBM, adult glioblastoma multiforme, grade IV adult Astrocytic tumor, primary glioblastoma multiforme, spongioblastoma multiforme

Cross References

RefSeq

XP_054202821.1, XP_011511196.1, XP_054202819.1, XP_054202822.1, XP_006713721.1, NP_006209.2, XP_054202820.1, XP_054202818.1, XP_054202817.1, XP_054202823.1

ZINC - World Drugs

PK3CA_HUMAN

Guide to Pharmacology - Targets

2153

OpenTargets

ENSG00000121879

ENSEMBL

ENSP00000263967, ENST00000263967, ENSG00000121879

Mondo

0018177

ZINC - FDA approved

PK3CA_HUMAN

ZINC - Substances

PK3CA_HUMAN

ZINC - Biogenic

PK3CA_HUMAN

ZINC target

P42336

PRO

P42336

PDB

8TU6, 8TS8, 4JPS, 8BFU, 8EXO, 9ASG, 4WAF, 5DXH, 7K71, 5SX8, 8TWY, 4L23, 4L1B, 8TSC, 8DCP, 7R9V, 8ILR, 6GVH, 7L1B, 7MYN, 8W9A, 8V8I, 5XGH, 5SXE, 5SXK, 8DD8, 8V8U, 8SBC, 4L2Y, 8TSB, 5SWR, 8EXU, 8TS7, 7K6N, 9B4S, 7JIU, 8VCL, 5UKJ, 7TZ7, 5SWO, 4YKN, 7MLK, 8OW2, 8V8H, 6OAC, 6GVG, 6PYS, 7PG5, 5SXI, 7MYO, 7L1C, 3HHM, 5SXB, 5XGI, 5ITD, 7K6O, 8TS9, 5SW8, 8TSA, 5SWG, 7K6M, 4OVV, 8DD4, 5UBR, 5SWP, 5SX9, 8V8J, 4TV3, 9E8M, 8ILS, 5DXT, 8SBJ, 4TUU, 8GUB, 8AM0, 5XGJ, 7L1D, 8W9B, 5SXF, 6VO7, 9ASF, 7RRG, 5SXC, 9C15, 4ZOP, 5UK8, 8GUA, 3HIZ, 8EXV, 4OVU, 8TGD, 5FI4, 8EXL, 6GVI, 8TSD, 2ENQ, 5SWT, 2RD0, 7R9Y, 8TDU, 8ILV, 3ZIM, 6NCT, 6GVF, 5SXA, 7PG6, 9B4T, 8GUD, 5SXD, 5UL1, 8DCX, 8V8V, 5SXJ

ZINC - Investigational

PK3CA_HUMAN

ZINC - Metabolites

PK3CA_HUMAN

COSMIC

COSV55892918

IntEnz

2.7.1.137

GeneCards

PIK3CA

HPA

ENSG00000121879-PIK3CA

Pharos - Targets

P42336

Orphanet

PIK3CA

ZINC - Predictions - Purchasable

PK3CA_HUMAN

HMDB Protein

HMDBP01236

Interactors (24)

Accession	#Entities	Entities	Confidence Score	Evidence (IntAct)
UniProt:P27986 PIK3R1	16	PIK3R1 [plasma membrane] (R-HSA-198365) PIK3R1 [cytosol] (R-HSA-74789) K63polyUb-PIK3R1 [cytosol] (R-HSA-3080572) PIK3R1 R574T [plasma membrane] (R-HSA-2399540) PIK3R1 R574I [plasma membrane] (R-HSA-2399536) PIK3R1 D560H [plasma membrane] (R-HSA-2399432) PIK3R1 N564K [plasma membrane] (R-HSA-2399431) PIK3R1 K459del [plasma membrane] (R-HSA-2399554) PIK3R1 N564D [plasma membrane] (R-HSA-2399427) PIK3R1 D560Y [plasma membrane] (R-HSA-2399421) PIK3R1 R574_T576del [plasma membrane] (R-HSA-2399544) PIK3R1 H450_E451del [plasma membrane] (R-HSA-2399545) PIK3R1 Y463_L466del [plasma membrane] (R-HSA-2399546) PIK3R1 K379E [plasma membrane] (R-HSA-8944148) PIK3R1 G376R [plasma membrane] (R-HSA-2399717) p-Y-PIK3R1 [cytosol] (R-HSA-9680647)	0.964	63
UniProt:O00459 PIK3R2	3	PIK3R2 [cytosol] (R-HSA-74791) K63polyUb-PIK3R2 [cytosol] (R-HSA-3080554) p-Y464-PIK3R2 [cytosol] (R-HSA-9860512)	0.899	49
UniProt:Q92569 PIK3R3	2	PIK3R3 [cytosol] (R-HSA-205223) K63polyUb-PIK3R3 [cytosol] (R-HSA-3080574)	0.897	48
UniProt:P35568 IRS1	5	p-Y-IRS1 [plasma membrane] (R-HSA-198366) p-Y-IRS1 [cytosol] (R-HSA-74772) IRS1 [cytosol] (R-HSA-74769) IRS1 [plasma membrane] (R-HSA-2425392) p-6Y-IRS1 [plasma membrane] (R-HSA-2445090)	0.853	42
UniProt:P62993 GRB2	1	GRB2 [cytosol] (R-HSA-8983328)	0.8	6
UniProt:P21860 ERBB3			0.723	18
UniProt:P27986-2 PIK3R1			0.556	3
UniProt:P54253 ATX1			0.556	3
UniProt:P54252 ATXN3	2	ATXN3 [nucleoplasm] (R-HSA-6783285) ATXN3 [cytosol] (R-HSA-5625607)	0.556	3
UniProt:P42858 HTT	1	HTT [nucleoplasm] (R-HSA-9023590)	0.556	3
UniProt:P01100 FOS	2	FOS [nucleoplasm] (R-HSA-450216) p-T325,T331,S362,S374-FOS [nucleoplasm] (R-HSA-450283)	0.556	3
UniProt:Q6ZMZ0 RNF19B	1	RNF19B [cytosol] (R-HSA-975969)	0.527	2
UniProt:Q8WTX9 ZDHC1			0.527	2
UniProt:Q9NZU1 FLRT1	1	FLRT1 [plasma membrane] (R-HSA-5656050)	0.527	2
UniProt:Q01523 DEFA5	5	DEFA5(1-94) [Golgi lumen] (R-HSA-1467267) DEFA5(20-94) [Golgi lumen] (R-HSA-1467208) DEFA5(20-94) [secretory granule lumen] (R-HSA-1471358) DEFA5(20-94) [extracellular region] (R-HSA-1471344) DEFA5(?-94) [extracellular region] (R-HSA-1462017)	0.527	2
UniProt:Q9H8J5 MANS1			0.527	2
UniProt:Q8TDQ0 HAVCR2	1	HAVCR2 [plasma membrane] (R-HSA-5340408)	0.527	2
UniProt:Q15365 PCBP1	1	PCBP1 [nucleoplasm] (R-HSA-71919)	0.527	2
UniProt:Q9UHF4 IL20RA	1	IL20RA [plasma membrane] (R-HSA-448713)	0.527	2
UniProt:Q9UH99 SUN2	1	SUN2 [nuclear envelope] (R-HSA-912382)	0.527	2
UniProt:P03496 NS	2	NS1 [nucleoplasm] (R-FLU-169113) NS1 [cytosol] (R-FLU-169118)	0.527	7
UniProt:P04637 TP53	20	Unfolded TP53 [cytosol] (R-HSA-6813797) TP53 [cytosol] (R-HSA-8869337) PolyUb-TP53 [nucleoplasm] (R-HSA-6782509) polySUMO2,3-K386-TP53 [nucleoplasm] (R-HSA-2997661) TP53 F341C [nucleoplasm] (R-HSA-9726318) TP53 G334V [nucleoplasm] (R-HSA-9726126) TP53 L330H [nucleoplasm] (R-HSA-9726124) TP53 A347T [nucleoplasm] (R-HSA-9726339) TP53 R337C [nucleoplasm] (R-HSA-9726118) TP53 L344P [nucleoplasm] (R-HSA-9726075) TP53 L344R [nucleoplasm] (R-HSA-9726073) TP53 R337H [nucleoplasm] (R-HSA-9726169) TP53 R337P [nucleoplasm] (R-HSA-9726168) TP53 L330P [nucleoplasm] (R-HSA-9726136) TP53 L348S [nucleoplasm] (R-HSA-9726366) TP53 R337L [nucleoplasm] (R-HSA-9726163) TP53 K351E [nucleoplasm] (R-HSA-9726258) TP53 F338I [nucleoplasm] (R-HSA-9726358) TP53 R342P [nucleoplasm] (R-HSA-9726101) TP53 L330R [nucleoplasm] (R-HSA-9726133)	0.483	2
UniProt:O43791 SPOP	3	SPOP [cytosol] (R-HSA-9929375) p-S6-SPOP [cytosol] (R-HSA-9929374) SPOP [nucleoplasm] (R-HSA-5635035)	0.471	4
UniProt:P42336 PIK3CA	20	PIK3CA H1047L [cytosol] (R-HSA-1500714) PIK3CA H1047R [cytosol] (R-HSA-1500716) PIK3CA [cytosol] (R-HSA-74787) PIK3CA R38C [cytosol] (R-HSA-1500691) PIK3CA R38G [cytosol] (R-HSA-2395950) PIK3CA R38S [cytosol] (R-HSA-2395947) PIK3CA R38H [cytosol] (R-HSA-1500718) PIK3CA E542Q [cytosol] (R-HSA-2328003) PIK3CA Q546P [cytosol] (R-HSA-1500695) PIK3CA Q546R [cytosol] (R-HSA-2362373) PIK3CA Q546H [cytosol] (R-HSA-2362374) PIK3CA E545G [cytosol] (R-HSA-1500709) PIK3CA Q546L [cytosol] (R-HSA-2362375) PIK3CA E542V [cytosol] (R-HSA-2328074) PIK3CA E545V [cytosol] (R-HSA-2362365) PIK3CA Q546E [cytosol] (R-HSA-2362383) PIK3CA E545Q [cytosol] (R-HSA-2362362) PIK3CA E545K [cytosol] (R-HSA-1500706) PIK3CA E545A [cytosol] (R-HSA-2362355) PIK3CA Q546K [cytosol] (R-HSA-1500705)	0.462	3

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