Reviewed,
UniProtKB/Swiss-Prot Q9UPQ3 (AGAP1_HUMAN)
Last modified
November 24, 2009.
Version 99.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 Short name=AGAP-1 Alternative name(s): Centaurin-gamma-2 GTP-binding and GTPase-activating protein 1 Short name=GGAP1 | ||||
| Gene names |
| ||||
| 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 | 857 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | GTPase-activating protein for ARF1 and, to a lesser extent, ARF5. Directly and specifically regulates the adapter protein 3 (AP-3)-dependent trafficking of proteins in the endosomal-lysosomal system. Ref.1 |
| Enzyme regulation | GAP activity stimulated by phosphatidylinositol 3,4,5-trisphosphate (PIP3) and, to a lesser extent, by phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphatidic acid potentiates PIP2 stimulation. |
| Subunit structure | Homodimer. Interacts with several subunits of the AP-3 protein complex: AP3M1, AP3S1 and AP3S2. Interacts with GUCY1A3 and GUCY1B3. Ref.8 Ref.9 |
| Subcellular location | Cytoplasm. Note: Associates with the endocytic compartment. Ref.1 Ref.7 |
| Tissue specificity | |
| Domain | The PH domain mediates AP-3 binding. |
| Post-translational modification | |
| Sequence similarities | Belongs to the centaurin gamma-like family. Contains 2 ANK repeats. Contains 1 Arf-GAP domain. Contains 1 PH domain. |
| Sequence caution | The sequence AAH60814.1 differs from that shown. Reason: Miscellaneous discrepancy. A 4-nucleotides insertion of unknown origin disrupts the reading frame. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Protein transport Transport |
| Cellular component | Cytoplasm |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | ANK repeat Repeat Zinc-finger |
| Ligand | GTP-binding Metal-binding Nucleotide-binding Zinc |
| Molecular function | GTPase activation |
| PTM | Phosphoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | protein transport Inferred from electronic annotation. Source: UniProtKB-KW regulation of ARF GTPase activityInferred from electronic annotation. Source: InterPro small GTPase mediated signal transductionInferred from electronic annotation. Source: InterPro |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | ARF GTPase activator activity Inferred from electronic annotation. Source: InterPro GTP bindingInferred from electronic annotation. Source: UniProtKB-KW zinc ion bindingInferred from electronic annotation. Source: UniProtKB-KW |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9UPQ3-1) 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: Q9UPQ3-2) The sequence of this isoform differs from the canonical sequence as follows: 442-494: Missing. | ||||||
| Isoform 3 (identifier: Q9UPQ3-3) The sequence of this isoform differs from the canonical sequence as follows: 352-405: MLLKRSGKSL...IDLLRTTVKV → LPFFVLALTA...SAQLSGAMMN 406-857: Missing. | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 857 | 857 | Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 | PRO_0000074218 | |||||
Regions | |||||||||
| Domain | 346 – 588 | 243 | PH | ||||||
| Domain | 609 – 729 | 121 | Arf-GAP | ||||||
| Repeat | 768 – 797 | 30 | ANK 1 | ||||||
| Repeat | 801 – 830 | 30 | ANK 2 | ||||||
| Nucleotide binding | 78 – 85 | 8 | GTP Potential | ||||||
| Nucleotide binding | 122 – 126 | 5 | GTP Potential | ||||||
| Nucleotide binding | 178 – 181 | 4 | GTP Potential | ||||||
| Zinc finger | 624 – 647 | 24 | C4-type | ||||||
| Region | 66 – 276 | 211 | Small GTPase-like | ||||||
Amino acid modifications | |||||||||
| Modified residue | 315 | 1 | Phosphoserine Ref.12 | ||||||
| Modified residue | 836 | 1 | Phosphothreonine Ref.11 | ||||||
Natural variations | |||||||||
| Alternative sequence | 352 – 405 | 54 | MLLKR…TTVKV → LPFFVLALTASTYLRPAGAR ARQSSPWPGPRGGQTSPHCA EGPQSAQLSGAMMN in isoform 3. | VSP_011181 | |||||
| Alternative sequence | 406 – 857 | 452 | Missing in isoform 3. | VSP_011182 | |||||
| Alternative sequence | 442 – 494 | 53 | Missing in isoform 2. | VSP_011183 | |||||
| Natural variant | 82 | 1 | S → G in an autistic patient. Ref.13 | VAR_026446 | |||||
| Natural variant | 148 | 1 | D → G: dbSNP rs17855721. Ref.5 | VAR_026447 | |||||
| Natural variant | 522 | 1 | P → L: dbSNP rs17840725. | VAR_048331 | |||||
| Natural variant | 671 | 1 | V → I: dbSNP rs2034648. Ref.1 Ref.13 Ref.2 Ref.3 Ref.6 | VAR_026448 | |||||
| Natural variant | 798 | 1 | R → G in an autistic patient. Ref.13 | VAR_026449 | |||||
| Natural variant | 829 | 1 | E → K: dbSNP rs15718. | VAR_019550 | |||||
| Natural variant | 854 | 1 | P → T in a family with an autistic patient. Ref.13 | VAR_026450 | |||||
Experimental info | |||||||||
| Mutagenesis | 647 | 1 | C → S: Loss of GAP activity. Ref.7 | ||||||
| Mutagenesis | 652 | 1 | R → K: Loss of GAP activity. No effect on AP-3-binding. Ref.7 | ||||||
| Sequence conflict | 288 | 1 | T → I Ref.1 | ||||||
| Sequence conflict | 288 | 1 | T → I Ref.2 | ||||||
| Sequence conflict | 288 | 1 | T → I Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "GGAPs, a new family of bifunctional GTP-binding and GTPase-activating proteins." Xia C., Ma W., Stafford L.J., Liu C., Gong L., Martin J.F., Liu M. Mol. Cell. Biol. 23:2476-2488(2003) [PubMed: 12640130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ILE-671, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, FUNCTION. Tissue: Heart. |
| [2] | "Kiaa1099 as a member (centaurin gamma2) of the centaurin ArfGAP protein family." Hong W. Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT ILE-671. |
| [3] | "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed: 10470851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ILE-671. Tissue: Brain. |
| [4] | "Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. Wilson R.K.Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), VARIANT GLY-148. Tissue: Placenta. |
| [6] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 429-857 (ISOFORM 1), VARIANT ILE-671. Tissue: Teratocarcinoma. |
| [7] | "AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton." Nie Z., Stanley K.T., Stauffer S., Jacques K.M., Hirsch D.S., Takei J., Randazzo P.A. J. Biol. Chem. 277:48965-48975(2002) [PubMed: 12388557] [Abstract] Cited for: CHARACTERIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-647 AND ARG-652. |
| [8] | "Specific regulation of the adaptor protein complex AP-3 by the Arf GAP AGAP1." Nie Z., Boehm M., Boja E.S., Vass W.C., Bonifacino J.S., Fales H.M., Randazzo P.A. Dev. Cell 5:513-521(2003) [PubMed: 12967569] [Abstract] Cited for: INTERACTION WITH THE AP-3 COMPLEX. |
| [9] | "AGAP1, a novel binding partner of nitric oxide-sensitive guanylyl cyclase." Meurer S., Pioch S., Wagner K., Mueller-Esterl W., Gross S. J. Biol. Chem. 279:49346-49354(2004) [PubMed: 15381706] [Abstract] Cited for: SUBUNIT, TISSUE SPECIFICITY, PHOSPHORYLATION, INTERACTION WITH GUCY1A3 AND GUCY1B3. |
| [10] | "The Arf GAPs AGAP1 and AGAP2 distinguish between the adaptor protein complexes AP-1 and AP-3." Nie Z., Fei J., Premont R.T., Randazzo P.A. J. Cell Sci. 118:3555-3566(2005) [PubMed: 16079295] [Abstract] Cited for: TISSUE SPECIFICITY. |
| [11] | "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-836, MASS SPECTROMETRY. |
| [12] | "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-315, MASS SPECTROMETRY. |
| [13] | "Evaluation of the chromosome 2q37.3 gene CENTG2 as an autism susceptibility gene." Wassink T.H., Piven J., Vieland V.J., Jenkins L., Frantz R., Bartlett C.W., Goedken R., Childress D., Spence M.A., Smith M., Sheffield V.C. Am. J. Med. Genet. B Neuropsychiatr. Genet. 136:36-44(2005) [PubMed: 15892143] [Abstract] Cited for: VARIANTS GLY-82; ILE-671; GLY-798 AND THR-854. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AY033765 mRNA. Translation: AAK56506.1. AF413078 mRNA. Translation: AAL04172.1. AB029022 mRNA. Translation: BAA83051.2. Different initiation. AC012305 Genomic DNA. No translation available. AC019047 Genomic DNA. No translation available. AC064874 Genomic DNA. No translation available. AC073989 Genomic DNA. No translation available. AC079400 Genomic DNA. No translation available. BC060814 mRNA. Translation: AAH60814.1. Sequence problems. BC140856 mRNA. Translation: AAI40857.1. AK001722 mRNA. Translation: BAA91862.1. Different initiation. | |
| IPI | IPI00456242. IPI00456244. IPI00456246. |
| RefSeq | NP_001032208.1. NP_055729.2. |
| UniGene | Hs.435039 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q9UPQ3. |
PTM databases | |
| PhosphoSite | Q9UPQ3. |
Genome annotation databases | |
| Ensembl | ENST00000304032; ENSP00000307634; ENSG00000157985; Homo sapiens. [Genome view] |
| GeneID | 116987. |
| KEGG | hsa:116987. |
| UCSC | uc002vvs.1. human. uc002vvt.1. human. |
Organism-specific databases | |
| CTD | 116987. |
| GeneCards | GC02P236068. |
| H-InvDB | HIX0007225. HIX0008821. HIX0020594. |
| HGNC | HGNC:16922. AGAP1. |
| MIM | 608651. gene. |
| PharmGKB | PA26412. |
| HUGE | Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q9UPQ3. |
| HOVERGEN | Q9UPQ3. |
| OrthoDB | EOG94F8VM |
Gene expression databases | |
| ArrayExpress | Q9UPQ3. |
| Bgee | Q9UPQ3. |
| CleanEx | HS_AGAP1. |
| Genevestigator | Q9UPQ3. |
| GermOnline | ENSG00000157985. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR001164. ArfGAP. IPR013684. MIRO-like. IPR001849. Pleckstrin_homology. IPR005225. Small_GTP_bd. IPR020851. Small_GTPase. [Graphical view] |
| Gene3D | G3DSA:1.25.40.20. ANK. 1 hit. |
| Pfam | PF00023. Ank. 2 hits. 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] |
| TIGRFAMs | TIGR00231. small_GTP. 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 Resources | |
| NextBio | 80074. |
| SOURCE | Search... |
Entry information
| Entry name | AGAP1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9UPQ3 Secondary accession number(s): B2RTX7 Q9NV93 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


