Reviewed, UniProtKB/Swiss-Prot O00750 (P3C2B_HUMAN)

Names and origin

Protein names

Recommended name:
    Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide
    EC=2.7.1.154
Alternative name(s):
    Phosphoinositide 3-Kinase-C2-beta
    PtdIns-3-kinase C2 beta
      Short name=PI3K-C2beta
    C2-PI3K

Gene names

Name:

PIK3C2B

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1634 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.6 Ref.1
Sequence similarities	Belongs to the PI3/PI4-kinase family. Contains 1 C2 domain. Contains 1 PI3K/PI4K domain. Contains 1 PX (phox homology) domain.
Caution	It is uncertain whether Met-1 or Met-26 is the initiator.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Membrane Microsome Nucleus
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	phosphoinositide phosphorylation Inferred from electronic annotation. Source: InterPro phosphoinositide-mediated signaling Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Non-traceable author statement. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell phosphoinositide 3-kinase complex Inferred from electronic annotation. Source: InterPro plasma membrane Non-traceable author statement. Source: UniProtKB
Molecular function	1-phosphatidylinositol-3-kinase activity Inferred from electronic annotation. Source: InterPro ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol-4-phosphate 3-kinase activity Ref.2 Non-traceable author statement. Source: UniProtKB phosphoinositide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.4 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EGFR	P00533	4	EBI-641107,EBI-297353
GRB2	P62993	1	EBI-641107,EBI-401755
NCK1	P16333	1	EBI-641107,EBI-389883
PDGFRB	P09619	1	EBI-641107,EBI-641237
PIK3R1	P27986	1	EBI-641107,EBI-79464

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 beta polypeptide		PRO_0000088798
Regions
	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
Amino acid modifications
	Modified residue	155	1	Phosphoserine Ref.7
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)
	O00750-1 [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: 9144573] [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: 9830063] [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: 16710414] [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: 10805725] [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: 11533253] [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: 14563213] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-155, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Hs.497487
3D structure databases
HSSP	HSSP built from PDB template 1E8Y based on UniProtKB P48736.
ModBase	Search...
Protein-protein interaction databases
IntAct	O00750. 6 interactions.
PTM databases
PhosphoSite	O00750.
Proteomic databases
PeptideAtlas	O00750.
PRIDE	O00750.
Genome annotation databases
Ensembl	ENSG00000133056. Homo sapiens. [Contig view]
GeneID	5287.
KEGG	hsa:5287.
Organism-specific databases
GeneCards	GC01M202658.
H-InvDB	HIX0028835.
HGNC	HGNC:8972. PIK3C2B.
MIM	602838. gene.
PharmGKB	PA33305.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	O00750.
OMA	O00750. KESLYWL.
Enzyme and pathway databases
BRENDA	2.7.1.137. 247. 2.7.1.154. 247.
Gene expression databases
ArrayExpress	O00750.
Bgee	O00750.
CleanEx	HS_PIK3C2B.
GermOnline	ENSG00000133056. Homo sapiens.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR018029. C2_membr_targeting. IPR000403. PI3/4_kinase_cat. IPR018936. PI3/4_kinase_CS. IPR002420. PI3K_C2. IPR000341. PI3K_ras_bd. IPR001263. PI3Ka. IPR015433. PI_Kinase. IPR001683. PX. [Graphical view]
Gene3D	G3DSA:1.10.1070.11. PI3/4_kinase_cat. 1 hit. G3DSA:1.25.40.70. PI3Ka. 1 hit. G3DSA:3.30.1520.10. PX. 1 hit.
PANTHER	PTHR10048. PI_Kinase. 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]
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. PS50195. PX. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	July 7, 2009
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)