O43295 (SRGP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
November 16, 2011.
Version 110.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: SLIT-ROBO Rho GTPase-activating protein 3 Short name=srGAP3 Alternative name(s): Mental disorder-associated GAP Rho GTPase-activating protein 14 WAVE-associated Rac GTPase-activating protein Short name=WRP srGAP2 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1099 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons. Ref.1 Ref.2 |
| Subunit structure | Interacts with WASF1. Probably interacts with ROBO1. Interacts with FASLG. Ref.1 Ref.5 Ref.8 |
| Tissue specificity | Highly expressed in adult and fetal brain. Expressed at low levels in kidney. Isoform 3 is expressed in the kidney but is absent in the brain. Ref.1 Ref.2 |
| Involvement in disease | Note=A chromosomal aberration involving SRGAP3 is found in a patient with severe idiopathic mental retardation. Translocation t(X;3)(p11.2;p25). |
| Sequence similarities | Contains 1 FCH domain. Contains 1 Rho-GAP domain. Contains 1 SH3 domain. |
Ontologies
| Keywords | |
|---|---|
| Coding sequence diversity | Alternative splicing Chromosomal rearrangement Polymorphism |
| Domain | Coiled coil SH3 domain |
| Molecular function | GTPase activation |
| PTM | Acetylation Phosphoprotein |
| Technical term | Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological process | regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transductionTraceable author statement. Source: Reactome |
| Cellular component | cytosol Traceable author statement. Source: Reactome |
| Molecular function | GTPase activator activity Inferred 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: O43295-1) Also known as: MEGAPa; srGAP3a; 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: O43295-2) Also known as: MEGAPb; srGAP3b; The sequence of this isoform differs from the canonical sequence as follows: 480-513: PPCLPPKPQKMRRPRPLSVYSHKLFNGSMEAFIK → GRRNARTRNQ | ||||||
| Isoform 3 (identifier: O43295-3) Also known as: MEGAPc; srGAP3c; The sequence of this isoform differs from the canonical sequence as follows: 480-489: PPCLPPKPQK → IQDKLYRL 490-1099: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1099 | 1099 | SLIT-ROBO Rho GTPase-activating protein 3 | PRO_0000056769 | |||||
Regions | |||||||||
| Domain | 22 – 87 | 66 | FCH | ||||||
| Domain | 482 – 670 | 189 | Rho-GAP | ||||||
| Domain | 720 – 779 | 60 | SH3 | ||||||
| Coiled coil | 352 – 392 | 41 | Potential | ||||||
| Coiled coil | 952 – 987 | 36 | Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 220 | 1 | N6-acetyllysine Ref.9 | ||||||
| Modified residue | 222 | 1 | N6-acetyllysine Ref.9 | ||||||
| Modified residue | 224 | 1 | N6-acetyllysine Ref.9 | ||||||
| Modified residue | 602 | 1 | Phosphoserine Ref.6 | ||||||
| Modified residue | 837 | 1 | Phosphoserine Ref.7 | ||||||
| Modified residue | 858 | 1 | Phosphoserine Ref.7 | ||||||
| Modified residue | 1070 | 1 | Phosphoserine By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 480 – 513 | 34 | PPCLP…EAFIK → GRRNARTRNQ in isoform 2. | VSP_010581 | |||||
| Alternative sequence | 480 – 489 | 10 | PPCLPPKPQK → IQDKLYRL in isoform 3. | VSP_010582 | |||||
| Alternative sequence | 490 – 1099 | 610 | Missing in isoform 3. | VSP_010583 | |||||
| Natural variant | 623 | 1 | L → I in a breast cancer sample; somatic mutation. Ref.10 | VAR_035550 | |||||
| Natural variant | 628 | 1 | I → V. Corresponds to variant rs2271207 [ dbSNP | Ensembl ]. | VAR_049159 | |||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling." Soderling S.H., Binns K.L., Wayman G.A., Davee S.M., Ong S.H., Pawson T., Scott J.D. Nat. Cell Biol. 4:970-975(2002) [PubMed: 12447388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH WASF1. |
| [2] | "The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative role in severe mental retardation." Endris V., Wogatzky B., Leimer U., Bartsch D., Zatyka M., Latif F., Maher E.R., Tariverdian G., Kirsch S., Karch D., Rappold G.A. Proc. Natl. Acad. Sci. U.S.A. 99:11754-11759(2002) [PubMed: 12195014] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 2 AND 3), FUNCTION, TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION. |
| [3] | "Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed: 9455477] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-1099 (ISOFORM 2). Tissue: Brain. |
| [4] | "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION. |
| [5] | "Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway." Wong K., Ren X.R., Huang Y.Z., Xie Y., Liu G., Saito H., Tang H., Wen L., Brady-Kalnay S.M., Mei L., Wu J.Y., Xiong W.C., Rao Y. Cell 107:209-221(2001) [PubMed: 11672528] [Abstract] Cited for: INTERACTION WITH ROBO1. |
| [6] | "Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602, MASS SPECTROMETRY. Tissue: Platelet. |
| [7] | "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-837 AND SER-858, MASS SPECTROMETRY. Tissue: Cervix carcinoma. |
| [8] | "Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening." Voss M., Lettau M., Janssen O. BMC Immunol. 10:53-53(2009) [PubMed: 19807924] [Abstract] Cited for: INTERACTION WITH FASLG. |
| [9] | "Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220; LYS-222 AND LYS-224, MASS SPECTROMETRY. |
| [10] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-623. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF464189 mRNA. Translation: AAN57784.1. AF427144 mRNA. Translation: AAN07095.1. AB007871 mRNA. Translation: BAA24841.2. |
| IPI | IPI00218087. IPI00412209. IPI00412210. |
| RefSeq | NP_001028289.1. NM_001033117.1. NP_055665.1. NM_014850.2. |
| UniGene | Hs.654743. |
3D structure databases | |
| ProteinModelPortal | O43295. |
| SMR | O43295. Positions 493-696, 749-800. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | O43295. 3 interactions. |
| STRING | O43295. |
PTM databases | |
| PhosphoSite | O43295. |
Proteomic databases | |
| PRIDE | O43295. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000383836; ENSP00000373347; ENSG00000196220. |
| GeneID | 9901. |
| KEGG | hsa:9901. |
| UCSC | uc003brf.1. human. uc003brg.1. human. |
Organism-specific databases | |
| CTD | 9901. |
| GeneCards | GC03M008998. |
| HGNC | HGNC:19744. SRGAP3. |
| HPA | HPA036959. |
| MIM | 606525. gene. |
| neXtProt | NX_O43295. |
| PharmGKB | PA134935463. |
| HUGE | Search... Search... |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG18680. |
| HOGENOM | HBG356471. |
| HOVERGEN | HBG051637. |
| InParanoid | O43295. |
| OMA | RVRLRSD. |
| OrthoDB | EOG4JT04N. |
| PhylomeDB | O43295. |
Enzyme and pathway databases | |
| Reactome | REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_112697. Developmental Biology. |
Gene expression databases | |
| ArrayExpress | O43295. |
| Bgee | O43295. |
| CleanEx | HS_SRGAP2. HS_SRGAP3. |
| Genevestigator | O43295. |
| GermOnline | ENSG00000196220. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001060. FCH. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. IPR001452. SH3_domain. [Graphical view] |
| Gene3D | G3DSA:1.10.555.10. RhoGAP. 1 hit. |
| KO | K07526. |
| Pfam | PF00611. FCH. 1 hit. PF00620. RhoGAP. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view] |
| SMART | SM00055. FCH. 1 hit. SM00324. RhoGAP. 1 hit. SM00326. SH3. 1 hit. [Graphical view] |
| SUPFAM | SSF48350. Rho_GAP. 1 hit. SSF50044. SH3. 1 hit. |
| PROSITE | PS50133. FCH. 1 hit. PS50238. RHOGAP. 1 hit. PS50002. SH3. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 37331. |
| SOURCE | Search... |
Entry information
| Entry name | SRGP2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O43295 Secondary accession number(s): Q8IX13, Q8IZV8 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: 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