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UniProtKB - Q99490 (AGAP2_HUMAN)

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Protein

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

Gene

AGAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

GTPase-activating protein (GAP) for ARF1 and ARF5, which also shows strong GTPase activity. Isoform 1 participates in the prevention of neuronal apoptosis by enhancing PI3 kinase activity. It 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. Isoform 2 does not stimulate PI3 kinase but may protect cells from apoptosis by stimulating Akt. It also regulates the adapter protein 1 (AP-1)-dependent trafficking of proteins in the endosomal system. It seems to be oncogenic. It is overexpressed in cancer cells, prevents apoptosis and promotes cancer cell invasion.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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi413 – 420GTPSequence analysis8
Nucleotide bindingi457 – 461GTPSequence analysis5
Nucleotide bindingi515 – 518GTPSequence analysis4
Zinc fingeri946 – 969C4-typePROSITE-ProRule annotationAdd BLAST24

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB-KW
  • GTPase activity Source: ARUK-UCL
  • GTP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • negative regulation of neuron apoptotic process Source: MGI
  • negative regulation of protein catabolic process Source: MGI
  • positive regulation of 1-phosphatidylinositol-3-kinase activity Source: ARUK-UCL
  • protein transport Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGTPase activation
Biological processProtein transport, Transport
LigandGTP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-373752 Netrin-1 signaling
SignaLinkiQ99490
SIGNORiQ99490

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
GTP-binding and GTPase-activating protein 2
Short name:
GGAP2
Phosphatidylinositol 3-kinase enhancer
Short name:
PIKE
Gene namesi
Name:AGAP2
Synonyms:CENTG1, KIAA0167
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000135439.11
HGNCiHGNC:16921 AGAP2
MIMi605476 gene
neXtProtiNX_Q99490

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi116986
OpenTargetsiENSG00000135439
PharmGKBiPA26411

Polymorphism and mutation databases

BioMutaiAGAP2
DMDMi97535883

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000742171 – 1192Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2Add BLAST1192

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei113PhosphoserineBy similarity1
Modified residuei128PhosphoserineBy similarity1
Modified residuei149PhosphoserineBy similarity1
Modified residuei638PhosphoserineCombined sources1
Modified residuei750PhosphoserineBy similarity1
Modified residuei752PhosphoserineBy similarity1
Modified residuei808PhosphoserineBy similarity1
Modified residuei927PhosphoserineBy similarity1
Modified residuei985PhosphoserineBy similarity1
Modified residuei1178PhosphoserineBy similarity1
Isoform 2 (identifier: Q99490-2)
Modified residuei682Phosphotyrosine1 Publication1
Modified residuei774Phosphotyrosine1 Publication1

Post-translational modificationi

Isoform PIKE-A is phosphorylated at Tyr-682 and Tyr-774 by FYN, preventing its apoptotic cleavage.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ99490
PaxDbiQ99490
PeptideAtlasiQ99490
PRIDEiQ99490
ProteomicsDBi78295
78296 [Q99490-2]

PTM databases

iPTMnetiQ99490
PhosphoSitePlusiQ99490

Expressioni

Tissue specificityi

Isoform 1 is brain-specific. Isoform 2 is ubiquitously expressed, with highest levels in brain and heart.5 Publications

Gene expression databases

BgeeiENSG00000135439
CleanExiHS_AGAP2
ExpressionAtlasiQ99490 baseline and differential
GenevisibleiQ99490 HS

Organism-specific databases

HPAiHPA023474

Interactioni

Subunit structurei

Isoform 1 interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2 (By similarity). Isoform 2 interacts with activated AKT1 in the presence of guanine nucleotides, and with the AP-1 complex.By similarity3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi125549, 17 interactors
IntActiQ99490, 8 interactors
MINTiQ99490
STRINGi9606.ENSP00000449241

Structurei

Secondary structure

11192
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi406 – 412Combined sources7
Helixi415 – 417Combined sources3
Helixi419 – 428Combined sources10
Beta strandi438 – 448Combined sources11
Beta strandi451 – 459Combined sources9
Beta strandi461 – 463Combined sources3
Helixi466 – 471Combined sources6
Beta strandi473 – 480Combined sources8
Helixi484 – 501Combined sources18
Beta strandi503 – 505Combined sources3
Beta strandi509 – 515Combined sources7
Beta strandi521 – 523Combined sources3
Helixi529 – 539Combined sources11
Beta strandi540 – 548Combined sources9
Turni549 – 552Combined sources4
Helixi555 – 574Combined sources20
Beta strandi677 – 686Combined sources10
Beta strandi695 – 703Combined sources9
Turni704 – 706Combined sources3
Beta strandi707 – 713Combined sources7
Helixi714 – 719Combined sources6
Beta strandi724 – 730Combined sources7
Beta strandi732 – 734Combined sources3
Beta strandi878 – 881Combined sources4
Beta strandi887 – 894Combined sources8
Helixi895 – 913Combined sources19

3D structure databases

ProteinModelPortaliQ99490
SMRiQ99490
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99490

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini676 – 910PHPROSITE-ProRule annotationAdd BLAST235
Domaini931 – 1051Arf-GAPPROSITE-ProRule annotationAdd BLAST121
Repeati1090 – 1119ANK 1Add BLAST30
Repeati1123 – 1152ANK 2Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 23Interaction with EPB41L1By similarityAdd BLAST23
Regioni180 – 225Interactions with HOMER1 and NF2By similarityAdd BLAST46
Regioni267 – 390Interaction with PLCG1By similarityAdd BLAST124
Regioni405 – 572G domainAdd BLAST168

Domaini

G domain binds GTP and has GTPase activity.
Arf-GAP domain interacts with G domain and may regulate its GTPase activity.
Although both PH domains of isoforms 1 and 2 bind phospholipids, they differently regulate subcellular location. PH domain of isoform 1 directs the protein to the nucleus, but PH domain of isoform 2 directs it to the cytosol. PH domain of isoform 2 is required for binding to AP-1.

Sequence similaritiesi

Belongs to the centaurin gamma-like family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri946 – 969C4-typePROSITE-ProRule annotationAdd BLAST24

Keywords - Domaini

ANK repeat, Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0705 Eukaryota
COG5347 LUCA
GeneTreeiENSGT00760000118874
HOGENOMiHOG000007233
HOVERGENiHBG054045
InParanoidiQ99490
KOiK17848
PhylomeDBiQ99490

Family and domain databases

CDDicd00204 ANK, 1 hit
Gene3Di1.25.40.20, 1 hit
2.30.29.30, 2 hits
3.30.40.160, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR037278 ARFGAP/RecO
IPR001164 ArfGAP_dom
IPR038508 ArfGAP_dom_sf
IPR027417 P-loop_NTPase
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR001806 Small_GTPase
PfamiView protein in Pfam
PF12796 Ank_2, 1 hit
PF01412 ArfGap, 1 hit
PF00071 Ras, 1 hit
PRINTSiPR00405 REVINTRACTNG
SMARTiView protein in SMART
SM00105 ArfGap, 1 hit
SM00233 PH, 1 hit
SUPFAMiSSF48403 SSF48403, 1 hit
SSF52540 SSF52540, 1 hit
SSF57863 SSF57863, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 1 hit
PS50115 ARFGAP, 1 hit
PS50003 PH_DOMAIN, 1 hit
PS51419 RAB, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q99490-1) [UniParc]FASTAAdd to basket
Also known as: PIKE-L

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 APPPPAPKPC KTVTTSGAKA 
       210        220        230        240        250
GGGKGAGSRL SWPESEGKPR VKGSKSSAGT GASVSAAATA AAAGGGGSTA 
       260        270        280        290        300
STSGGVGAGA GARGKLSPRK GKSKTLDNSD LHPGPPAGSP PPLTLPPTPS 
       310        320        330        340        350
PATAVTAASA QPPGPAPPIT LEPPAPGLKR GREGGRASTR DRKMLKFISG 
       360        370        380        390        400
IFTKSTGGPP GSGPLPGPPS LSSGSGSREL LGAELRASPK AVINSQEWTL 
       410        420        430        440        450
SRSIPELRLG VLGDARSGKS SLIHRFLTGS YQVLEKTESE QYKKEMLVDG 
       460        470        480        490        500
QTHLVLIREE AGAPDAKFSG WADAVIFVFS LEDENSFQAV SRLHGQLSSL 
       510        520        530        540        550
RGEGRGGLAL ALVGTQDRIS ASSPRVVGDA RARALCADMK RCSYYETCAT 
       560        570        580        590        600
YGLNVDRVFQ EVAQKVVTLR KQQQLLAACK SLPSSPSHSA ASTPVAGQAS 
       610        620        630        640        650
NGGHTSDYSS SLPSSPNVGH RELRAEAAAV AGLSTPGSLH RAAKRRTSLF 
       660        670        680        690        700
ANRRGSDSEK RSLDSRGETT GSGRAIPIKQ SFLLKRSGNS LNKEWKKKYV 
       710        720        730        740        750
TLSSNGFLLY HPSINDYIHS THGKEMDLLR TTVKVPGKRP PRAISAFGPS 
       760        770        780        790        800
ASINGLVKDM STVQMGEGLE ATTPMPSPSP SPSSLQPPPD QTSKHLLKPD 
       810        820        830        840        850
RNLARALSTD CTPSGDLSPL SREPPPSPMV KKQRRKKLTT PSKTEGSAGQ 
       860        870        880        890        900
AEAKRKMWKL KSFGSLRNIY KAEENFEFLI VSSTGQTWHF EAASFEERDA 
       910        920        930        940        950
WVQAIESQIL ASLQCCESSK VKLRTDSQSE AVAIQAIRNA KGNSICVDCG 
       960        970        980        990       1000
APNPTWASLN LGALICIECS GIHRNLGTHL SRVRSLDLDD WPRELTLVLT 
      1010       1020       1030       1040       1050
AIGNDTANRV WESDTRGRAK PSRDSSREER ESWIRAKYEQ LLFLAPLSTS 
      1060       1070       1080       1090       1100
EEPLGRQLWA AVQAQDVATV LLLLAHARHG PLDTSVEDPQ LRSPLHLAAE 
      1110       1120       1130       1140       1150
LAHVVITQLL LWYGADVAAR DAQGRTALFY ARQAGSQLCA DILLQHGCPG 
      1160       1170       1180       1190 
EGGSAATTPS AATTPSITAT PSPRRRSSAA SVGRADAPVA LV
Length:1,192
Mass (Da):124,674
Last modified:May 16, 2006 - v2
Checksum:i8DA53707C0127984
GO
Isoform 2 (identifier: Q99490-2) [UniParc]FASTAAdd to basket
Also known as: PIKE-A

The sequence of this isoform differs from the canonical sequence as follows:
     1-336: Missing.
     337-390: ASTRDRKMLK...LGAELRASPK → MHAQRQFVVA...IQASLDSIRE
     853-872: Missing.

Show »
Length:836
Mass (Da):90,537
Checksum:iB8E42631BC06D5DC
GO

Sequence cautioni

The sequence BAA11484 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1137Q → H in AAC39522 (PubMed:9192850).Curated1
Sequence conflicti1147G → A in AAC39522 (PubMed:9192850).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036183339T → A in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_026438455V → A in a glioblastoma cell line. 1 Publication1
Natural variantiVAR_022046507G → S. Corresponds to variant dbSNP:rs2301553Ensembl.1
Natural variantiVAR_026439518R → G in a sarcoma cell line. 1 Publication1
Natural variantiVAR_026440568T → I in a neuroblastoma cell line. 1 Publication1
Natural variantiVAR_026441651A → V in a glioblastoma cell line. 1 Publication1
Natural variantiVAR_026442767E → V in a glioblastoma cell line. 1 Publication1
Natural variantiVAR_036184816D → Y in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_026443939N → D in a glioblastoma cell line. 1 Publication1
Natural variantiVAR_026444947V → M in a sarcoma cell line. 1 Publication1
Natural variantiVAR_0264451022S → P in a glioblastoma cell line. 1 Publication1
Natural variantiVAR_0555321124G → V1 PublicationCorresponds to variant dbSNP:rs238521Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0185311 – 336Missing in isoform 2. 5 PublicationsAdd BLAST336
Alternative sequenceiVSP_018532337 – 390ASTRD…RASPK → MHAQRQFVVAAVRAEVRRHE VAKQALNRLRKLAERVDDPE LQDSIQASLDSIRE in isoform 2. 5 PublicationsAdd BLAST54
Alternative sequenceiVSP_018533853 – 872Missing in isoform 2. 5 PublicationsAdd BLAST20

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U81031 Genomic DNA Translation: AAC39522.2
AF384128 mRNA Translation: AAO39848.1
AY128689 mRNA Translation: AAM97540.1
D79989 mRNA Translation: BAA11484.2 Different initiation.
AF413077 mRNA Translation: AAL04171.1
AK292672 mRNA Translation: BAF85361.1
CH471054 Genomic DNA Translation: EAW97049.1
BC028020 mRNA Translation: AAH28020.1
CCDSiCCDS44932.1 [Q99490-1]
CCDS8951.1 [Q99490-2]
RefSeqiNP_001116244.1, NM_001122772.2
NP_055585.1, NM_014770.3 [Q99490-2]
UniGeneiHs.302435

Genome annotation databases

EnsembliENST00000257897; ENSP00000257897; ENSG00000135439 [Q99490-2]
GeneIDi116986
KEGGihsa:116986
UCSCiuc001spr.4 human [Q99490-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiAGAP2_HUMAN
AccessioniPrimary (citable) accession number: Q99490
Secondary accession number(s): A8K9F7
, O00578, Q548E0, Q8IWU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 16, 2006
Last modified: June 20, 2018
This is version 192 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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