O75747 (P3C2G_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Phosphoinositide 3-kinase-C2-gamma

Gene names

Name:

PIK3C2G

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	1445 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) that act as second messengers. May play a role in SDF1A-stimulated chemotaxis By similarity.
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 3,4-bisphosphate.
Subcellular location	Membrane; Peripheral membrane protein By similarity.
Tissue specificity	Highly expressed in liver, prostate and testis. Lower levels in small intestine, kidney and pancreas. Ref.1
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.
Sequence caution	The sequence CAA03853.1 differs from that shown. Reason: Erroneous termination at position 1446. Translated as stop.

Ontologies

Keywords
Biological process	Chemotaxis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemotaxis Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol-mediated signaling Inferred from electronic annotation. Source: InterPro small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	phosphatidylinositol 3-kinase complex Inferred from Biological aspect of Ancestor. Source: RefGenome plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	1-phosphatidylinositol-3-kinase activity Non-traceable author statement Ref.1. Source: UniProtKB 1-phosphatidylinositol-4-phosphate 3-kinase activity Inferred from Biological aspect of Ancestor. Source: RefGenome ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylinositol binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1445

1445

Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma

PRO_0000088799

Regions

Domain

285 – 371

87

PI3K-RBD

Domain

453 – 628

176

C2 PI3K-type

Domain

643 – 819

177

PIK helical

Domain

916 – 1180

265

PI3K/PI4K

Domain

1199 – 1311

113

PX

Domain

1328 – 1424

97

C2

Amino acid modifications

Modified residue

419

1

Phosphotyrosine Ref.5

Natural variations

Natural variant

146

1

P → L. Ref.3 Ref.4 Ref.6
Corresponds to variant rs11044004 [ dbSNP | Ensembl ].

VAR_056676

Natural variant

261

1

A → E.
Corresponds to variant rs7133666 [ dbSNP | Ensembl ].

VAR_056677

Natural variant

911

1

P → L. Ref.1 Ref.3 Ref.4
Corresponds to variant rs12312266 [ dbSNP | Ensembl ].

VAR_060323

Natural variant

1290

1

V → G.
Corresponds to variant rs12099555 [ dbSNP | Ensembl ].

VAR_060324

Natural variant

1442

1

N → T.
Corresponds to variant rs12816860 [ dbSNP | Ensembl ].

VAR_060325

Experimental info

Sequence conflict

129

1

Missing in EAW96387. Ref.3

Sequence conflict

129

1

Missing in AAI30278. Ref.4

Sequence conflict

965

1

G → R in CAA03853. Ref.1

Sequence conflict

1209

1

Missing in CAA03853. Ref.1

Sequence conflict

1314

1

Missing in CAA03853. Ref.1

Sequence conflict

1323

1

E → EK in CAA03853. Ref.1

Sequence conflict

1377

1

R → L in CAA03853. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1445

Helix Strand Turn

Details...

Beta strand

1204 – 1214

11

Beta strand

1217 – 1227

11

Beta strand

1232 – 1237

6

Helix

1239 – 1252

14

Turn

1253 – 1255

3

Helix

1267 – 1271

5

Helix

1273 – 1287

15

Helix

1292 – 1295

4

Helix

1298 – 1305

8

Sequences

	Sequence		Length	Mass (Da)
	O75747 [UniParc]. Last modified November 30, 2010. Version 3. Checksum: 8D02A3620AE4318D	FASTA	1,445	165,715
	10 20 30 40 50 60 MAYSWQTDPN PNESHEKQYE HQEFLFVNQP HSSSQVSLGF DQIVDEISGK IPHYESEIDE 70 80 90 100 110 120 NTFFVPTAPK WDSTGHSLNE AHQISLNEFT SKSRELSWHQ VSKAPAIGFS PSVLPKPQNT 130 140 150 160 170 180 NKECSWGSPI GKHHGADDSR FSILAPSFTS LDKINLEKEL ENENHNYHIG FESSIPPTNS 190 200 210 220 230 240 SFSSDFMPKE ENKRSGHVNI VEPSLMLLKG SLQPGMWEST WQKNIESIGC SIQLVEVPQS 250 260 270 280 290 300 SNTSLASFCN KVKKIRERYH AADVNFNSGK IWSTTTAFPY QLFSKTKFNI HIFIDNSTQP 310 320 330 340 350 360 LHFMPCANYL VKDLIAEILH FCTNDQLLPK DHILSVCGSE EFLQNDHCLG SHKMFQKDKS 370 380 390 400 410 420 VIQLHLQKSR EAPGKLSRKH EEDHSQFYLN QLLEFMHIWK VSRQCLLTLI RKYDFHLKYL 430 440 450 460 470 480 LKTQENVYNI IEEVKKICSV LGCVETKQIT DAVNELSLIL QRKGENFYQS SETSAKGLIE 490 500 510 520 530 540 KVTTELSTSI YQLINVYCNS FYADFQPVNV PRCTSYLNPG LPSHLSFTVY AAHNIPETWV 550 560 570 580 590 600 HRINFPLEIK SLPRESMLTV KLFGIACATN NANLLAWTCL PLFPKEKSIL GSMLFSMTLQ 610 620 630 640 650 660 SEPPVEMITP GVWDVSQPSP VTLQIDFPAT GWEYMKPDSE ENRSNLEEPL KECIKHIARL 670 680 690 700 710 720 SQKQTPLLLS EEKKRYLWFY RFYCNNENCS LPLVLGSAPG WDERTVSEMH TILRRWTFSQ 730 740 750 760 770 780 PLEALGLLTS SFPDQEIRKV AVQQLDNLLN DELLEYLPQL VQAVKFEWNL ESPLVQLLLH 790 800 810 820 830 840 RSLQSIQVAH RLYWLLKNAE NEAYFKSWYQ KLLAALQFCA GKALNDEFSK EQKLIKILGD 850 860 870 880 890 900 IGERVKSASD HQRQEVLKKE IGRLEEFFQD VNTCHLPLNP ALCIKGIDHD ACSYFTSNAL 910 920 930 940 950 960 PLKITFINAN PMGKNISIIF KAGDDLRQDM LVLQLIQVMD NIWLQEGLDM QMIIYRCLST 970 980 990 1000 1010 1020 GKDQGLVQMV PDAVTLAKIH RHSGLIGPLK ENTIKKWFSQ HNHLKADYEK ALRNFFYSCA 1030 1040 1050 1060 1070 1080 GWCVVTFILG VCDRHNDNIM LTKSGHMFHI DFGKFLGHAQ TFGGIKRDRA PFIFTSEMEY 1090 1100 1110 1120 1130 1140 FITEGGKNPQ HFQDFVELCC RAYNIIRKHS QLLLNLLEMM LYAGLPELSG IQDLKYVYNN 1150 1160 1170 1180 1190 1200 LRPQDTDLEA TSHFTKKIKE SLECFPVKLN NLIHTLAQMS AISPAKSTSQ TFPQESCLLS 1210 1220 1230 1240 1250 1260 TTRSIERATI LGFSKKSSNL YLIQVTHSNN ETSLTEKSFE QFSKLHSQLQ KQFASLTLPE 1270 1280 1290 1300 1310 1320 FPHWWHLPFT NSDHRRFRDL NHYMEQILNV SHEVTNSDCV LSFFLSEAVQ QTVEESSPVY 1330 1340 1350 1360 1370 1380 LGEKFPDKKP KVQLVISYED VKLTILVKHM KNIHLPDGSA PSAHVEFYLL PYPSEVRRRK 1390 1400 1410 1420 1430 1440 TKSVPKCTDP TYNEIVVYDE VTELQGHVLM LIVKSKTVFV GAINIRLCSV PLDKEKWYPL GNSII

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of a third human C2-domain-containing class II phosphoinositide 3-kinase, PI3K-C2gamma, and chromosomal assignment of this gene (PIK3C2G) to 12p12." Rozycka M., Lu Y.-J., Brown R.A., Lau M.R., Shipley J.M., Fry M.J. Genomics 54:569-574(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT LEU-911. Tissue: Liver, Mammary gland and Prostate.
[2]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS LEU-146 AND LEU-911.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS LEU-146 AND LEU-911.
[5]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-419, MASS SPECTROMETRY. Tissue: Prostate cancer.
[6]	"Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population." Daimon M., Sato H., Oizumi T., Toriyama S., Saito T., Karasawa S., Jimbu Y., Wada K., Kameda W., Susa S., Yamaguchi H., Emi M., Muramatsu M., Kubota I., Kawata S., Kato T. Biochem. Biophys. Res. Commun. 365:466-471(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LEU-146.
[7]	"Crystal structure of the phox homology domain of human phosphoinositide-3-kinase-C2-gamma." Structural genomics consortium (SGC) Submitted (NOV-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 1204-1307.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AJ000008 mRNA. Translation: CAA03853.1. Different termination.
AC087236 Genomic DNA. No translation available.
AC087240 Genomic DNA. No translation available.
AC091815 Genomic DNA. No translation available.
AC092851 Genomic DNA. No translation available.
CH471094 Genomic DNA. Translation: EAW96387.1.
BC130277 mRNA. Translation: AAI30278.1.

IPI

IPI00922656.

PIR

PC4347.

RefSeq

NP_004561.3. NM_004570.4.

UniGene

Hs.22500.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WWE	X-ray	1.25	A	1204-1307	[»]

ProteinModelPortal

O75747.

SMR

O75747. Positions 228-1165, 1204-1307, 1332-1440.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000404845.

PTM databases

PhosphoSite

O75747.

Proteomic databases

PaxDb

O75747.

PRIDE

O75747.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266497; ENSP00000266497; ENSG00000139144.
ENST00000433979; ENSP00000404845; ENSG00000139144.

GeneID

5288.

KEGG

hsa:5288.

UCSC

uc001rdt.3. human.

Organism-specific databases

CTD

5288.

GeneCards

GC12P018414.

H-InvDB

HIX0036732.

HGNC

HGNC:8973. PIK3C2G.

MIM

609001. gene.

neXtProt

NX_O75747.

PharmGKB

PA33306.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5032.

HOGENOM

HOG000168239.

HOVERGEN

HBG053398.

InParanoid

O75747.

KO

K00923.

PhylomeDB

O75747.

Enzyme and pathway databases

BioCyc

MetaCyc:HS06583-MONOMER.

BRENDA

2.7.1.137. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O75747.

Bgee

O75747.

CleanEx

HS_PIK3C2G.

Genevestigator

O75747.

GermOnline

ENSG00000139144. 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.
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

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. False negative.
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

O75747.

ChEMBL

CHEMBL1163120.

EvolutionaryTrace

O75747.

GenomeRNAi

5288.

NextBio

20434.

SOURCE

Search...

Entry information

Entry name

P3C2G_HUMAN

Accession

Primary (citable) accession number: O75747
Secondary accession number(s): A1L3U0

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 126 of the entry and version 3 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.