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Protein

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2

Gene

Agap2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. Aids the coupling of metabotropic glutamate receptor 1 (GRM1) to cytoplasmic PI3 kinase by interacting with Homer scaffolding proteins, and also seems to mediate anti-apoptotic effects of NGF by activating nuclear PI3 kinase.4 Publications

Enzyme regulationi

GAP activity is stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and, to a lesser extent, by phosphatidylinositol 3,4,5-trisphosphate (PIP3). Phosphatidic acid potentiates PIP2 stimulation (By similarity).By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi407 – 4148GTPSequence analysis
Nucleotide bindingi451 – 4555GTPSequence analysis
Nucleotide bindingi509 – 5124GTPSequence analysis
Zinc fingeri940 – 96324C4-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB-KW
  • GTP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activator activity Source: RGD
  • protein kinase binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Ligandi

GTP-binding, Metal-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2
Short name:
AGAP-2
Alternative name(s):
Centaurin-gamma-1
Short name:
Cnt-g1
Phosphatidylinositol 3-kinase enhancer
Short name:
PIKE
Gene namesi
Name:Agap2
Synonyms:Centg1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi628844. Agap2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • mitochondrion Source: Ensembl
  • nucleolus Source: Ensembl
  • nucleus Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi187 – 1871P → L: Abolishes interactions with HOMER1C and NF2. 2 Publications
Mutagenesisi414 – 4141S → N: Fails to activate PI3 kinase. 1 Publication
Mutagenesisi679 – 6791K → N: Abolishes phospholipid binding and nuclear localization; when associated to N-687. 1 Publication
Mutagenesisi687 – 6871K → N: Abolishes phospholipid binding and nuclear localization; when associated to N-679. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11861186Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2PRO_0000235914Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei113 – 1131PhosphoserineBy similarity
Modified residuei128 – 1281PhosphoserineBy similarity
Modified residuei149 – 1491PhosphoserineBy similarity
Modified residuei632 – 6321PhosphoserineBy similarity
Modified residuei744 – 7441PhosphoserineBy similarity
Modified residuei746 – 7461PhosphoserineBy similarity
Modified residuei802 – 8021PhosphoserineBy similarity
Modified residuei921 – 9211PhosphoserineBy similarity
Modified residuei979 – 9791PhosphoserineBy similarity
Modified residuei1172 – 11721PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8CGU4.
PRIDEiQ8CGU4.

PTM databases

iPTMnetiQ8CGU4.
PhosphoSiteiQ8CGU4.

Expressioni

Tissue specificityi

Present in cortex, hippocampus and olfactory bulb but absent in cerebellum (at protein level).2 Publications

Gene expression databases

ExpressionAtlasiQ8CGU4. baseline and differential.
GenevisibleiQ8CGU4. RN.

Interactioni

Subunit structurei

Interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DccQ631552EBI-4409108,EBI-1798965
Gria2P194914EBI-4409108,EBI-77718
Grip1P978794EBI-4409108,EBI-936113
Homer1Q9Z214-14EBI-4409108,EBI-4410552
UNC5BQ8IZJ19EBI-4409108,EBI-4409075From a different organism.
Unc5bO087226EBI-4409108,EBI-4404185

GO - Molecular functioni

  • protein kinase binding Source: RGD

Protein-protein interaction databases

BioGridi249323. 2 interactions.
IntActiQ8CGU4. 9 interactions.
MINTiMINT-231743.
STRINGi10116.ENSRNOP00000029533.

Structurei

3D structure databases

ProteinModelPortaliQ8CGU4.
SMRiQ8CGU4. Positions 396-570, 668-908.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini670 – 904235PHPROSITE-ProRule annotationAdd
BLAST
Domaini925 – 1045121Arf-GAPPROSITE-ProRule annotationAdd
BLAST
Repeati1084 – 111330ANK 1Add
BLAST
Repeati1117 – 114630ANK 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2323Interaction with EPB41L1Add
BLAST
Regioni180 – 22546Interactions with HOMER1 and NF2Add
BLAST
Regioni262 – 384123Interaction with PLCG1Add
BLAST
Regioni399 – 566168G domainBy similarityAdd
BLAST

Domaini

G domain binds GTP and has GTPase activity.By similarity
Arf-GAP domain interacts with G domain and may regulate its GTPase activity.By similarity
PH domain binds phospholipids and is required for nuclear targeting.By similarity

Sequence similaritiesi

Belongs to the centaurin gamma-like family.Curated
Contains 2 ANK repeats.PROSITE-ProRule annotation
Contains 1 Arf-GAP domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri940 – 96324C4-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

ANK repeat, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0705. Eukaryota.
COG5347. LUCA.
GeneTreeiENSGT00760000118874.
HOGENOMiHOG000007233.
HOVERGENiHBG054045.
InParanoidiQ8CGU4.
KOiK17848.
OMAiDTANRVW.
OrthoDBiEOG72VH5V.
PhylomeDBiQ8CGU4.
TreeFamiTF317762.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
2.30.29.30. 2 hits.
3.40.50.300. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001164. ArfGAP.
IPR027417. P-loop_NTPase.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
PF01412. ArfGap. 1 hit.
PF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00405. REVINTRACTNG.
SMARTiSM00105. ArfGap. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF50729. SSF50729. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS51419. RAB. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8CGU4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSRGAGALQR RTTTYLISLT LVKLESVPPP PPSPSAAAVG APGARGSEPR
60 70 80 90 100
DPGSPRGAEE PGKKRHERLF HRQDALWIST SSAGAGGAEP PALSPAPASP
110 120 130 140 150
ARPVSPAPGR RLSLWAAPPG PPLSGGLSPD SKPGGAPSSS RRPLLSSPSW
160 170 180 190 200
GGPEPEGRTG GGVPGSSSPH PGTGSRRLKV APPPPAPKPF KTVTTSGAKA
210 220 230 240 250
GGGKGAGSRL SWPESEGKPR VKGSKSTAGT GASAVAAGGG GSAAVTTSGG
260 270 280 290 300
VGAGAGARGK LSPRKGKSKT LDNSDLHPGP SAGSPPLTVP AIPVPATSVT
310 320 330 340 350
AASTQPLGPA PPITLEPPAP GLKRGREGGR ASTRDRKMLK FISGIFTKST
360 370 380 390 400
GGPPGPGPLP GPQGLSSSSG SRELLGAELR ASPKAVVNSQ EWTLSRSIPE
410 420 430 440 450
LRLGVLGDVR SGKSSLIHRF LTGSYQVLEK PESEQYKKEM LVDGQTHLVL
460 470 480 490 500
IREEAGAPDA KFSGWADAVI FVFSLEDESS FQAVSHLHGQ LISLRGEGRG
510 520 530 540 550
GLALALVGTQ DRISASSPRV VGDARARALC TDMKRCSYYE TCATYGLNVD
560 570 580 590 600
RVFQEVAQKV VTLRKQQQLL AACKSLPSSP SHSAASTPVA GQASNGGHTS
610 620 630 640 650
DYSSSLPSSP NVGHRELRAE AAAVAGLSTP GSLHRAAKRR TSLFANRRGS
660 670 680 690 700
DSEKRSLDSR GETTGSGRAI PIKQSFLLKR SGNSLNKEWK KKYVTLSSNG
710 720 730 740 750
FLLYHPSIND YIHSTHGKEM DLLRTTVKVP GKRPPRAISA FGPSASINGL
760 770 780 790 800
VKDMSTVQMG EGPEASTPMP SPSPSPSSLQ LPTDQTSKHL LKPDRNLARA
810 820 830 840 850
LSTDCTPSGD LSPLSREPPP SPMVKKQRRK KLSTPSKTEG SAVQAEAKRK
860 870 880 890 900
MWKLKSFGSL RNIYKAEENF EFLIVSSTGQ TWHFEAASFE ERDAWVQAIE
910 920 930 940 950
SQILASLQCC ESSKVKLRTD SQSEAVAIQA IRNAKGNSTC VDCGAPNPTW
960 970 980 990 1000
ASLNLGALIC IECSGIHRNL GTHLSRVRSL DLDDWPRELT LVLTAIGNDT
1010 1020 1030 1040 1050
ANRVWESDTR GRAKPTRDSS REERESWIRA KYEQLLFLAP LGTTEEPLGR
1060 1070 1080 1090 1100
QLWAAVEAQD VAAVLLLLAH ARHGPLDTSV EDPQLRSPLH LAAELAHVVI
1110 1120 1130 1140 1150
TQLLLWYGAD VAARDAQGRT ALFYARQAGS QLCADILLQH GCPGEGGSTA
1160 1170 1180
TTPSAATTPS ITATPSPRRR SSAASLGRVD TTIALV
Length:1,186
Mass (Da):124,438
Last modified:March 1, 2003 - v1
Checksum:iB9C8E987D2989378
GO

Sequence cautioni

The sequence AAF97595.1 differs from that shown. Reason: Frameshift at several positions. This sequence would represent a shorter strictly nuclear isoform named PIKE-S. It may be an artifactual frameshifted form whose existence in vivo is dubious.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY128688 mRNA. Translation: AAM97539.1.
AF280816 mRNA. Translation: AAF97595.1. Frameshift.
RefSeqiNP_075415.2. NM_023026.2.
UniGeneiRn.91094.

Genome annotation databases

EnsembliENSRNOT00000031230; ENSRNOP00000029533; ENSRNOG00000025584.
GeneIDi65218.
KEGGirno:65218.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY128688 mRNA. Translation: AAM97539.1.
AF280816 mRNA. Translation: AAF97595.1. Frameshift.
RefSeqiNP_075415.2. NM_023026.2.
UniGeneiRn.91094.

3D structure databases

ProteinModelPortaliQ8CGU4.
SMRiQ8CGU4. Positions 396-570, 668-908.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249323. 2 interactions.
IntActiQ8CGU4. 9 interactions.
MINTiMINT-231743.
STRINGi10116.ENSRNOP00000029533.

PTM databases

iPTMnetiQ8CGU4.
PhosphoSiteiQ8CGU4.

Proteomic databases

PaxDbiQ8CGU4.
PRIDEiQ8CGU4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000031230; ENSRNOP00000029533; ENSRNOG00000025584.
GeneIDi65218.
KEGGirno:65218.

Organism-specific databases

CTDi116986.
RGDi628844. Agap2.

Phylogenomic databases

eggNOGiKOG0705. Eukaryota.
COG5347. LUCA.
GeneTreeiENSGT00760000118874.
HOGENOMiHOG000007233.
HOVERGENiHBG054045.
InParanoidiQ8CGU4.
KOiK17848.
OMAiDTANRVW.
OrthoDBiEOG72VH5V.
PhylomeDBiQ8CGU4.
TreeFamiTF317762.

Miscellaneous databases

NextBioi614193.
PROiQ8CGU4.

Gene expression databases

ExpressionAtlasiQ8CGU4. baseline and differential.
GenevisibleiQ8CGU4. RN.

Family and domain databases

Gene3Di1.25.40.20. 1 hit.
2.30.29.30. 2 hits.
3.40.50.300. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001164. ArfGAP.
IPR027417. P-loop_NTPase.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF12796. Ank_2. 1 hit.
PF01412. ArfGap. 1 hit.
PF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00405. REVINTRACTNG.
SMARTiSM00105. ArfGap. 1 hit.
SM00233. PH. 1 hit.
[Graphical view]
SUPFAMiSSF48403. SSF48403. 1 hit.
SSF50729. SSF50729. 2 hits.
SSF52540. SSF52540. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 1 hit.
PS50115. ARFGAP. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS51419. RAB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis."
    Rong R., Ahn J.-Y., Huang H., Nagata E., Kalman D., Kapp J.A., Tu J., Worley P.F., Snyder S.H., Ye K.
    Nat. Neurosci. 6:1153-1161(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH HOMER1 AND HOMER2, MUTAGENESIS OF PRO-187.
    Strain: Brown Norway.
    Tissue: Brain.
  2. "PIKE: a nuclear GTPase that enhances PI3kinase activity and is regulated by protein 4.1N."
    Ye K., Hurt K.J., Wu F.Y., Fang M., Luo H.R., Hong J.J., Blackshaw S., Ferris C.D., Snyder S.H.
    Cell 103:919-930(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-754, GTP-BINDING, TISSUE SPECIFICITY, INTERACTION WITH EPB41L1, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF SER-414.
  3. "Phospholipase C gamma 1 is a physiological guanine nucleotide exchange factor for the nuclear GTPase PIKE."
    Ye K., Aghdasi B., Luo H.R., Moriarity J.L., Wu F.Y., Hong J.J., Hurt K.J., Bae S.S., Suh P.-G., Snyder S.H.
    Nature 415:541-544(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PLCG1.
  4. "PIKE/nuclear PI 3-kinase signaling mediates the antiapoptotic actions of NGF in the nucleus."
    Ahn J.-Y., Rong R., Liu X., Ye K.
    EMBO J. 23:3995-4006(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L."
    Rong R., Tang X., Gutmann D.H., Ye K.
    Proc. Natl. Acad. Sci. U.S.A. 101:18200-18205(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NF2, MUTAGENESIS OF PRO-187.
  6. "Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt signalings."
    Hu Y., Liu Z., Ye K.
    Proc. Natl. Acad. Sci. U.S.A. 102:16853-16858(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-679 AND LYS-687.
  7. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1172, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiAGAP2_RAT
AccessioniPrimary (citable) accession number: Q8CGU4
Secondary accession number(s): Q9JHW8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: March 1, 2003
Last modified: May 11, 2016
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.