O00750 (P3C2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta
Short name=PI3K-C2-beta
Short name=PtdIns-3-kinase C2 subunit beta
EC=2.7.1.154

Alternative name(s):
C2-PI3K
Phosphoinositide 3-kinase-C2-beta

Gene names

Name:

PIK3C2B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1634 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns. Does not phosphorylate PtdIns(4,5)P2. May be involved in EGF and PDGF signaling cascades. Ref.4
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate.
Cofactor	Calcium, magnesium, or manganese. Ref.4
Enzyme regulation	Activated by GRB2. Ref.5
Subunit structure	Part of a complex with ERBB2 and EGFR. Part of a complex with phosphorylated EGFR and GRB2. Interacts with phosphorylated EGFR and PDGFR, maybe indirectly. Interacts with GRB2 and SHC1. Ref.4 Ref.5
Subcellular location	Microsome. Cell membrane. Cytoplasm › cytosol. Nucleus. Endoplasmic reticulum. Note: Found mostly in the microsome, but also in the plasma membrane and cytosol. Nuclear in testis. Ref.6
Tissue specificity	Expressed in columnar and transitional epithelia, mononuclear cells, and ganglion cells (at protein level). Widely expressed, with highest levels in thymus and placenta and lowest in peripheral blood, skeletal muscle and kidney. Ref.1 Ref.6
Sequence similarities	Belongs to the PI3/PI4-kinase family. Contains 1 C2 domain. Contains 1 C2 PI3K-type domain. Contains 1 PI3K-RBD domain. Contains 1 PI3K/PI4K domain. Contains 1 PIK helical domain. Contains 1 PX (phox homology) domain.
Caution	It is uncertain whether Met-1 or Met-26 is the initiator.
Sequence caution	The sequence CAA74194.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Membrane Microsome Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: InterPro protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	endocytic vesicle Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell intracellular membrane-bounded organelle Non-traceable author statement. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell phosphatidylinositol 3-kinase complex Inferred from Biological aspect of Ancestor. Source: RefGenome plasma membrane Non-traceable author statement. Source: UniProtKB
Molecular_function	1-phosphatidylinositol-3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome 1-phosphatidylinositol-4-phosphate 3-kinase activity Non-traceable author statement Ref.2. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW lipid kinase activity Inferred from electronic annotation. Source: Compara phosphatidylinositol binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EGFR	P00533	7	EBI-641107,EBI-297353
ERBB2	P04626	2	EBI-641107,EBI-641062
GRB2	P62993	2	EBI-641107,EBI-401755
NCK1	P16333	3	EBI-641107,EBI-389883
TRIM27	P14373	5	EBI-641107,EBI-719493

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1634	1634	Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta		PRO_0000088798
Regions
	Domain	375 – 463	89	PI3K-RBD
	Domain	635 – 786	152	C2 PI3K-type
	Domain	805 – 981	177	PIK helical
	Domain	1079 – 1343	265	PI3K/PI4K
	Domain	1365 – 1481	117	PX
	Domain	1517 – 1608	92	C2
	Region	2 – 298	297	Interaction with GRB2
	Compositional bias	156 – 162	7	Pro-rich
	Compositional bias	169 – 174	6	Pro-rich
Experimental info
	Sequence conflict	6	1	G → D in CAA72168. Ref.1
	Sequence conflict	63	1	P → S in CAA74194. Ref.2
	Sequence conflict	75	1	R → W in CAA74194. Ref.2
	Sequence conflict	99	1	Q → L in CAA74194. Ref.2
	Sequence conflict	246	1	A → V in CAA72168. Ref.1
	Sequence conflict	278	1	K → E in CAA74194. Ref.2
	Sequence conflict	567	1	P → S in CAA74194. Ref.2
	Sequence conflict	664 – 665	2	EL → DM in CAA72168. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O00750 [UniParc]. Last modified August 30, 2005. Version 2. Checksum: CA817BA77C12E833	FASTA	1,634	184,768
	10 20 30 40 50 60 MSSTQGNGEH WKSLESVGIS RKELAMAEAL QMEYDALSRL RHDKEENRAK QNADPSLISW 70 80 90 100 110 120 DEPGVDFYSK PAGRRTDLKL LRGLSGSDPT LNYNSLSPQE GPPNHSTSQG PQPGSDPWPK 130 140 150 160 170 180 GSLSGDYLYI FDGSDGGVSS SPGPGDIEGS CKKLSPPPLP PRASIWDTPP LPPRKGSPSS 190 200 210 220 230 240 SKISQPSDIN TFSLVEQLPG KLLEHRILEE EEVLGGGGQG RLLGSVDYDG INDAITRLNL 250 260 270 280 290 300 KSTYDAEMLR DATRGWKEGR GPLDFSKDTS GKPVARSKTM PPQVPPRTYA SRYGNRKNAT 310 320 330 340 350 360 PGKNRRISAA PVGSRPHTVA NGHELFEVSE ERDEEVAAFC HMLDILRSGS DIQDYFLTGY 370 380 390 400 410 420 VWSAVTPSPE HLGDEVNLKV TVLCDRLQEA LTFTCNCSST VDLLIYQTLC YTHDDLRNVD 430 440 450 460 470 480 VGDFVLKPCG LEEFLQNKHA LGSHEYIQYC RKFDIDIRLQ LMEQKVVRSD LARTVNDDQS 490 500 510 520 530 540 PSTLNYLVHL QERPVKQTIS RQALSLLFDT YHNEVDAFLL ADGDFPLKAD RVVQSVKAIC 550 560 570 580 590 600 NALAAVETPE ITSALNQLPP CPSRMQPKIQ KDPSVLAVRE NREKVVEALT AAILDLVELY 610 620 630 640 650 660 CNTFNADFQT AVPGSRKHDL VQEACHFARS LAFTVYATHR IPIIWATSYE DFYLSCSLSH 670 680 690 700 710 720 GGKELCSPLQ TRRAHFSKYL FHLIVWDQQI CFPVQVNRLP RETLLCATLY ALPIPPPGSS 730 740 750 760 770 780 SEANKQRRVP EALGWVTTPL FNFRQVLTCG RKLLGLWPAT QENPSARWSA PNFHQPDSVI 790 800 810 820 830 840 LQIDFPTSAF DIKFTSPPGD KFSPRYEFGS LREEDQRKLK DIMQKESLYW LTDADKKRLW 850 860 870 880 890 900 EKRYYCHSEV SSLPLVLASA PSWEWACLPD IYVLLKQWTH MNHQDALGLL HATFPDQEVR 910 920 930 940 950 960 RMAVQWIGSL SDAELLDYLP QLVQALKYEC YLDSPLVRFL LKRAVSDLRV THYFFWLLKD 970 980 990 1000 1010 1020 GLKDSQFSIR YQYLLAALLC CCGKGLREEF NRQCWLVNAL AKLAQQVREA APSARQGILR 1030 1040 1050 1060 1070 1080 TGLEEVKQFF ALNGSCRLPL SPSLLVKGIV PRDCSYFNSN AVPLKLSFQN VDPLGENIRV 1090 1100 1110 1120 1130 1140 IFKCGDDLRQ DMLTLQMIRI MSKIWVQEGL DMRMVIFRCF STGRGRGMVE MIPNAETLRK 1150 1160 1170 1180 1190 1200 IQVEHGVTGS FKDRPLADWL QKHNPGEDEY EKAVENFIYS CAGCCVATYV LGICDRHNDN 1210 1220 1230 1240 1250 1260 IMLKTTGHMF HIDFGRFLGH AQMFGNIKRD RAPFVFTSDM AYVINGGDKP SSRFHDFVDL 1270 1280 1290 1300 1310 1320 CCQAYNLIRK HTHLFLNLLG LMLSCGIPEL SDLEDLKYVY DALRPQDTEA NATTYFTRLI 1330 1340 1350 1360 1370 1380 ESSLGSVATK LNFFIHNLAQ MKFTGSDDRL TLSFASRTHT LKSSGRISDV FLCRHEKIFH 1390 1400 1410 1420 1430 1440 PNKGYIYVVK VMRENTHEAT YIQRTFEEFQ ELHNKLRLLF PSSHLPSFPS RFVIGRSRGE 1450 1460 1470 1480 1490 1500 AVAERRREEL NGYIWHLIHA PPEVAECDLV YTFFHPLPRD EKAMGTSPAP KSSDGTWARP 1510 1520 1530 1540 1550 1560 VGKVGGEVKL SISYKNNKLF IMVMHIRGLQ LLQDGNDPDP YVKIYLLPDP QKTTKRKTKV 1570 1580 1590 1600 1610 1620 ARKTCNPTYN EMLVYDGIPK GDLQQRELQL SVLSEQGFWE NVLLGEVNIR LRELDLAQEK 1630 TGWFALGSRS HGTL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and cDNA cloning of a novel mammalian C2 domain-containing phosphoinositide 3-kinase, HsC2-PI3K." Brown R.A., Ho L.K.F., Weber-Hall S.J., Shipley J.M., Fry M.J. Biochem. Biophys. Res. Commun. 233:537-544(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY. Tissue: Mammary gland.
[2]	"Human phosphoinositide 3-kinase C2beta, the role of calcium and the C2 domain in enzyme activity." Arcaro A., Volinia S., Zvelebil M.J., Stein R.C., Watton S.J., Layton M.J., Gout I., Ahmadi K., Downward J., Waterfield M.D. J. Biol. Chem. 273:33082-33090(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Monocyte.
[3]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Class II phosphoinositide 3-kinases are downstream targets of activated polypeptide growth factor receptors." Arcaro A., Zvelebil M.J., Wallasch C., Ullrich A., Waterfield M.D., Domin J. Mol. Cell. Biol. 20:3817-3830(2000) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH ERBB2 AND EGFR, INTERACTION WITH EGFR AND PDGFR, COFACTOR, FUNCTION.
[5]	"Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2." Wheeler M., Domin J. Mol. Cell. Biol. 21:6660-6667(2001) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH GRB2 AND EGFR, INTERACTION WITH SHC1 AND GRB2, ENZYME REGULATION.
[6]	"Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation." El Sheikh S.S., Domin J., Tomtitchong P., Abel P., Stamp G., Lalani E.-N. BMC Clin. Pathol. 3:4-4(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Y11312 mRNA. Translation: CAA72168.1. Y13892 mRNA. Translation: CAA74194.1. Different initiation. AL606489 Genomic DNA. Translation: CAI16572.1.
IPI	IPI00292056.
PIR	JC5500. PC4346.
RefSeq	NP_002637.3. NM_002646.3.
UniGene	Hs.497487.
3D structure databases
ProteinModelPortal	O00750.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00750. 7 interactions.
MINT	MINT-2794980.
STRING	9606.ENSP00000356155.
PTM databases
PhosphoSite	O00750.
Proteomic databases
PaxDb	O00750.
PeptideAtlas	O00750.
PRIDE	O00750.
Protocols and materials databases
DNASU	5287.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367187; ENSP00000356155; ENSG00000133056.
GeneID	5287.
KEGG	hsa:5287.
UCSC	uc001haw.3. human.
Organism-specific databases
CTD	5287.
GeneCards	GC01M204391.
HGNC	HGNC:8972. PIK3C2B.
HPA	HPA030515.
MIM	602838. gene.
neXtProt	NX_O00750.
PharmGKB	PA33305.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5032.
HOVERGEN	HBG082099.
InParanoid	O00750.
KO	K00923.
OMA	GTWARPV.
OrthoDB	EOG4BK52X.
PhylomeDB	O00750.
Enzyme and pathway databases
BRENDA	2.7.1.137. 2681.
Reactome	REACT_111217. Metabolism.
SignaLink	O00750.
Gene expression databases
ArrayExpress	O00750.
Bgee	O00750.
CleanEx	HS_PIK3C2B.
Genevestigator	O00750.
GermOnline	ENSG00000133056. Homo sapiens.
Family and domain databases
Gene3D	1.10.1070.11. 1 hit. 1.25.40.70. 1 hit. 3.30.1520.10. 1 hit.
InterPro	IPR016024. ARM-type_fold. IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR018029. C2_membr_targeting. IPR011009. Kinase-like_dom. IPR001683. Phox. IPR000403. PI3/4_kinase_cat_dom. IPR018936. PI3/4_kinase_CS. IPR002420. PI3K_C2_dom. IPR000341. PI3K_Ras-bd_dom. IPR015433. PI_Kinase. IPR001263. PInositide-3_kin_accessory_dom. [Graphical view]
PANTHER	PTHR10048. PTHR10048. 1 hit.
Pfam	PF00168. C2. 1 hit. PF00454. PI3_PI4_kinase. 1 hit. PF00792. PI3K_C2. 1 hit. PF00794. PI3K_rbd. 1 hit. PF00613. PI3Ka. 1 hit. PF00787. PX. 1 hit. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00142. PI3K_C2. 1 hit. SM00144. PI3K_rbd. 1 hit. SM00145. PI3Ka. 1 hit. SM00146. PI3Kc. 1 hit. SM00312. PX. 1 hit. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit. SSF49562. C2_CaLB. 2 hits. SSF56112. Kinase_like. 1 hit. SSF64268. PX. 1 hit.
PROSITE	PS50004. C2. 1 hit. PS00915. PI3_4_KINASE_1. 1 hit. PS00916. PI3_4_KINASE_2. 1 hit. PS50290. PI3_4_KINASE_3. 1 hit. PS51547. PI3K_C2. 1 hit. PS51546. PI3K_RBD. 1 hit. PS51545. PIK_HELICAL. 1 hit. PS50195. PX. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O00750.
ChEMBL	CHEMBL5554.
ChiTaRS	PIK3C2B. human.
GenomeRNAi	5287.
NextBio	20430.
SOURCE	Search...

Entry information

Entry name

P3C2B_HUMAN

Accession

Primary (citable) accession number: O00750
Secondary accession number(s): O95666, Q5SW99

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	August 30, 2005
Last modified:	May 29, 2013
This is version 137 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.