Q3UHD9 (AGAP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Agap2
Synonyms:	Centg1, Kiaa0167

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1186 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 By similarity.
Enzyme regulation	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.
Subunit structure	Interacts with EPB41L1, PLCG1, NF2, HOMER1 and HOMER2 By similarity.
Subcellular location	Cytoplasm. Nucleus By similarity.
Domain	G domain binds GTP and has GTPase activity. Arf-GAP domain interacts with G domain and may regulate its GTPase activity. PH domain binds phospholipids and is required for nuclear targeting.
Sequence similarities	Belongs to the centaurin gamma-like family. Contains 2 ANK repeats. Contains 1 Arf-GAP domain. Contains 1 PH domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	ANK repeat Repeat Zinc-finger
Ligand	GTP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mammary gland alveolus development Inferred from mutant phenotype PubMed 20075866. Source: MGI negative regulation of apoptotic process Inferred from mutant phenotype PubMed 16841086PubMed 20075866. Source: MGI negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Inferred from electronic annotation. Source: Compara positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC positive regulation of JAK-STAT cascade Inferred from mutant phenotype PubMed 20075866. Source: MGI positive regulation of mammary gland epithelial cell proliferation Inferred from mutant phenotype PubMed 20075866. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype PubMed 20075866. Source: MGI regulation of ARF GTPase activity Inferred from electronic annotation. Source: InterPro small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	mitochondrion Inferred from electronic annotation. Source: Compara nucleolus Inferred from electronic annotation. Source: Compara
Molecular_function	ARF GTPase activator activity Inferred from electronic annotation. Source: InterPro GTP binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro protein kinase activator activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q3UHD9-1)

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.

Isoform 2 (identifier: Q3UHD9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     847-866: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1186	1186	Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 2		PRO_0000235913
Regions
	Domain	670 – 904	235	PH
	Domain	925 – 1045	121	Arf-GAP
	Repeat	1084 – 1113	30	ANK 1
	Repeat	1117 – 1146	30	ANK 2
	Nucleotide binding	407 – 414	8	GTP Potential
	Nucleotide binding	451 – 455	5	GTP Potential
	Nucleotide binding	509 – 512	4	GTP Potential
	Zinc finger	940 – 963	24	C4-type
	Region	1 – 23	23	Interaction with EPB41L1 By similarity
	Region	180 – 225	46	Interactions with HOMER1 and NF2 By similarity
	Region	262 – 384	123	Interaction with PLCG1 By similarity
	Region	399 – 566	168	G domain
Amino acid modifications
	Modified residue	149	1	Phosphoserine Ref.3
	Modified residue	262	1	Phosphoserine Ref.3
	Modified residue	632	1	Phosphoserine Ref.4
	Modified residue	802	1	Phosphoserine Ref.4
	Modified residue	859	1	Phosphoserine Ref.4
	Modified residue	921	1	Phosphoserine Ref.4
Natural variations
	Alternative sequence	847 – 866	20	Missing in isoform 2.		VSP_018542
Experimental info
	Sequence conflict	381	1	T → A in BAD90236. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 11, 2005. Version 1. Checksum: E9B4F3EDB66CBEC8	FASTA	1,186	124,511
	10 20 30 40 50 60 MSRGAGALQR RTTTYLISLT LVKLESVPPP PPSPSAAAAG APGARGSEPR DPGSPRGSEE 70 80 90 100 110 120 PGKKRHERLF HRQDALWIST SSAGTGGAEP PALSPAPASP ARPVSPAPGR RLSLWAAPPG 130 140 150 160 170 180 PPLSGGLSPD SKPGGAPSSS RRPLLSSPSW GGPEPEGRTG GGVPGSSSPH PGTGSRRLKV 190 200 210 220 230 240 APPPPAPKPF KTVTTSGAKA GGGKGAGSRL SWPESEGKPR VKGSKSTAGT GASAAAAGGG 250 260 270 280 290 300 GSAAVTTSGG VGAGAGTRGK LSPRKGKSKT LDNSDLHPGP SAGSPPLTVP AIPVPATSVT 310 320 330 340 350 360 ATSTQPLGPA PPITLEPPAP GLKRGREGGR ASTRDRKMLK FISGIFTKST GGPPGPGPLP 370 380 390 400 410 420 GPQGLSSSSG SRELLGAELR TSPKAVVNSQ EWTLSRSIPE LRLGVLGDVR SGKSSLIHRF 430 440 450 460 470 480 LTGSYQVLEK IESEQYKKEM LVDGQTHLVL IREEAGAPDA KFSGWADAVI FVFSLEDESS 490 500 510 520 530 540 FQAVSRLHGQ LSSLRGEGRG GLALALVGTQ DRISASSPRV VGDARARALC TDMKRCSYYE 550 560 570 580 590 600 TCATYGLNVD RVFQEVAQKV VTLRKQQQLL AACKSLPSSP SHSAASTPVA GQASNGGHTS 610 620 630 640 650 660 DYSSSLPSSP NVGHRELRAE AAAVAGLSTP GSLHRAAKRR TSLFANRRGS DAEKRSLDSR 670 680 690 700 710 720 GETTGSGRAI PIKQSFLLKR SGNSLNKEWK KKYVTLSSNG FLLYHPSIND YIHSTHGKEM 730 740 750 760 770 780 DLLRTTVKVP GKRPPRAISA FGPSASINGL VKDMSTVQMG EGPEASTPMP SPSPSPSSLQ 790 800 810 820 830 840 LPTDQTSKHL LKPDRNLARA LSTDCTPSGD LSPLSREPPP SPMVKKQRRK KLSTPSKTEG 850 860 870 880 890 900 SAVQAEAKRK MWKLKSFGSL RNIYKAEENF EFLIVSSTGQ TWHFEAASFE ERDAWVQAIE 910 920 930 940 950 960 SQILASLQCC ESSKVKLRTD SQSEAVAIQA IRNAKGNSTC VDCGAPNPTW ASLNLGALIC 970 980 990 1000 1010 1020 IECSGIHRNL GTHLSRVRSL DLDDWPRELT LVLTAIGNDT ANRVWESDTR GRAKPTRDSS 1030 1040 1050 1060 1070 1080 REERESWIRA KYEQLLFLAP LGTTEEPLGR QLWAAVEAQD VAAVLLLLAH ARHGPLDTSV 1090 1100 1110 1120 1130 1140 EDPQLRSPLH LAAELAHVVI TQLLLWYGAD VAARDAQGRT ALFYARQAGS QLCADILLQH 1150 1160 1170 1180 GCPGEGGSTA TTPSAATTPS ITATPSPRRR SSAASLGRVD TTIALV
	Isoform 2 [UniParc]. Checksum: 6148D768484401DA	FASTA	1,166	122,103
	10 20 30 40 50 60 MSRGAGALQR RTTTYLISLT LVKLESVPPP PPSPSAAAAG APGARGSEPR DPGSPRGSEE 70 80 90 100 110 120 PGKKRHERLF HRQDALWIST SSAGTGGAEP PALSPAPASP ARPVSPAPGR RLSLWAAPPG 130 140 150 160 170 180 PPLSGGLSPD SKPGGAPSSS RRPLLSSPSW GGPEPEGRTG GGVPGSSSPH PGTGSRRLKV 190 200 210 220 230 240 APPPPAPKPF KTVTTSGAKA GGGKGAGSRL SWPESEGKPR VKGSKSTAGT GASAAAAGGG 250 260 270 280 290 300 GSAAVTTSGG VGAGAGTRGK LSPRKGKSKT LDNSDLHPGP SAGSPPLTVP AIPVPATSVT 310 320 330 340 350 360 ATSTQPLGPA PPITLEPPAP GLKRGREGGR ASTRDRKMLK FISGIFTKST GGPPGPGPLP 370 380 390 400 410 420 GPQGLSSSSG SRELLGAELR TSPKAVVNSQ EWTLSRSIPE LRLGVLGDVR SGKSSLIHRF 430 440 450 460 470 480 LTGSYQVLEK IESEQYKKEM LVDGQTHLVL IREEAGAPDA KFSGWADAVI FVFSLEDESS 490 500 510 520 530 540 FQAVSRLHGQ LSSLRGEGRG GLALALVGTQ DRISASSPRV VGDARARALC TDMKRCSYYE 550 560 570 580 590 600 TCATYGLNVD RVFQEVAQKV VTLRKQQQLL AACKSLPSSP SHSAASTPVA GQASNGGHTS 610 620 630 640 650 660 DYSSSLPSSP NVGHRELRAE AAAVAGLSTP GSLHRAAKRR TSLFANRRGS DAEKRSLDSR 670 680 690 700 710 720 GETTGSGRAI PIKQSFLLKR SGNSLNKEWK KKYVTLSSNG FLLYHPSIND YIHSTHGKEM 730 740 750 760 770 780 DLLRTTVKVP GKRPPRAISA FGPSASINGL VKDMSTVQMG EGPEASTPMP SPSPSPSSLQ 790 800 810 820 830 840 LPTDQTSKHL LKPDRNLARA LSTDCTPSGD LSPLSREPPP SPMVKKQRRK KLSTPSKTEG 850 860 870 880 890 900 SAVQAEEENF EFLIVSSTGQ TWHFEAASFE ERDAWVQAIE SQILASLQCC ESSKVKLRTD 910 920 930 940 950 960 SQSEAVAIQA IRNAKGNSTC VDCGAPNPTW ASLNLGALIC IECSGIHRNL GTHLSRVRSL 970 980 990 1000 1010 1020 DLDDWPRELT LVLTAIGNDT ANRVWESDTR GRAKPTRDSS REERESWIRA KYEQLLFLAP 1030 1040 1050 1060 1070 1080 LGTTEEPLGR QLWAAVEAQD VAAVLLLLAH ARHGPLDTSV EDPQLRSPLH LAAELAHVVI 1090 1100 1110 1120 1130 1140 TQLLLWYGAD VAARDAQGRT ALFYARQAGS QLCADILLQH GCPGEGGSTA TTPSAATTPS 1150 1160 ITATPSPRRR SSAASLGRVD TTIALV

References

[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[2]	"Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., Koga H. Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 138-1186 (ISOFORM 2). Tissue: Fetal brain.
[3]	"Comprehensive identification of phosphorylation sites in postsynaptic density preparations." Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L. Mol. Cell. Proteomics 5:914-922(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149 AND SER-262, MASS SPECTROMETRY. Tissue: Brain.
[4]	"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations." Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M. Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632; SER-802; SER-859 AND SER-921, MASS SPECTROMETRY. Tissue: Brain cortex.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK147446 mRNA. Translation: BAE27918.1. AK220325 mRNA. Translation: BAD90236.1.
IPI	IPI00349020. IPI00754509.
RefSeq	NP_001028435.1. NM_001033263.4.
UniGene	Mm.336761.
3D structure databases
ProteinModelPortal	Q3UHD9.
SMR	Q3UHD9. Positions 396-570, 668-746, 867-908, 928-1150.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q3UHD9. 4 interactions.
STRING	10090.ENSMUSP00000043466.
PTM databases
PhosphoSite	Q3UHD9.
Proteomic databases
PaxDb	Q3UHD9.
PRIDE	Q3UHD9.
Protocols and materials databases
DNASU	216439.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000039259; ENSMUSP00000043466; ENSMUSG00000025422.
GeneID	216439.
KEGG	mmu:216439.
UCSC	uc007hhx.1. mouse. uc007hhy.1. mouse.
Organism-specific databases
CTD	116986.
MGI	MGI:3580016. Agap2.
Rouge	Search...
Phylogenomic databases
eggNOG	COG5347.
GeneTree	ENSGT00690000102002.
HOGENOM	HOG000007233.
HOVERGEN	HBG054045.
InParanoid	Q3UHD9.
KO	K12491.
OMA	DTANRVW.
OrthoDB	EOG45QHCN.
Gene expression databases
Bgee	Q3UHD9.
Genevestigator	Q3UHD9.
Family and domain databases
Gene3D	1.25.40.20. 1 hit. 2.30.29.30. 2 hits.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR001164. ArfGAP. IPR013684. MIRO-like. IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. [Graphical view]
Pfam	PF12796. Ank_2. 1 hit. PF01412. ArfGap. 1 hit. PF08477. Miro. 1 hit. PF00169. PH. 1 hit. [Graphical view]
PRINTS	PR00405. REVINTRACTNG.
SMART	SM00248. ANK. 2 hits. SM00105. ArfGap. 1 hit. SM00233. PH. 1 hit. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
NextBio	375150.
SOURCE	Search...

Entry information

Entry name

AGAP2_MOUSE

Accession

Primary (citable) accession number: Q3UHD9
Secondary accession number(s): Q5DU45

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2006
Last sequence update:	October 11, 2005
Last modified:	May 1, 2013
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program