Q91Z67 · SRGP2_MOUSE
- ProteinSLIT-ROBO Rho GTPase-activating protein 2
- GeneSrgap2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1071 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Postsynaptic RAC1 GTPase activating protein (GAP) that plays a key role in neuronal morphogenesis and migration mainly during development of the cerebral cortex (PubMed:19737524, PubMed:22559944, PubMed:27373832).
Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:19737524, PubMed:22559944, PubMed:27373832).
SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (PubMed:27373832).
Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:19737524, PubMed:22559944, PubMed:26439400).
Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (PubMed:26439400).
In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:22559944).
Regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:19737524, PubMed:22559944, PubMed:27373832).
SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through its RAC1-specific GTPase activating activity, while it promotes maturation of both excitatory and inhibitory synapses through its ability to bind to the postsynaptic scaffolding protein HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at inhibitory synapses (PubMed:27373832).
Mechanistically, acts by binding and deforming membranes, thereby regulating actin dynamics to regulate cell migration and differentiation (PubMed:19737524, PubMed:22559944, PubMed:26439400).
Promotes cell repulsion and contact inhibition of locomotion: localizes to protrusions with curved edges and controls the duration of RAC1 activity in contact protrusions (PubMed:26439400).
In non-neuronal cells, may also play a role in cell migration by regulating the formation of lamellipodia and filopodia (PubMed:22559944).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSLIT-ROBO Rho GTPase-activating protein 2
- Short namessrGAP2
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ91Z67
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Recruited to actin-rich phagosomes during phagocytosis (PubMed:21148482).
Translocates from nucleus to cytoplasm during development (By similarity).
Translocates from nucleus to cytoplasm during development (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are viable and show no abnormality of cortical lamination. However, a delay in dendritic spine maturation coupled to an increase in spine neck and spine density is observed.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 340-343 | Abolished interaction with HOMER1. | ||||
Sequence: PMKF → LMKC | ||||||
Mutagenesis | 527 | Abolished RAC1 GTPase activity. Abolished ability to induce neurite branching. No effect on filopodia biogenesis and neurite outgrowth. | ||||
Sequence: R → L | ||||||
Mutagenesis | 765 | Loss of the ability to induce filopodia and to initiate neurite outgrowth. Abolished interaction with GPHN. | ||||
Sequence: W → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 34 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000056768 | 1-1071 | SLIT-ROBO Rho GTPase-activating protein 2 | |||
Sequence: MTSPAKFKKDKEIIAEYDTQVKEIRAQLTEQMKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAERFLAKTRSTKDQQFKKDQNVLSPVNCWNLLLNQVKRESRDHTTLSDIYLNNIIPRFVQVSEDSGRLFKKSKEVGQQLQDDLMKVLNELYSVMKTYHMYNADSISAQSKLKEAEKQEEKQIGKSVKQEDRQTPRSPDSTANVRIEEKHVRRSSVKKIEKMKEKRQAKYTENKLKAIKARNEYLLALEATNASVFKYYIHDLSDIIDQCCDLGYHASLNRALRTFLSAELNLEQSKHEGLDAIENAVENLDATSDKQRLMEMYNNVFCPPMKFEFQPHMGDMASQLCAQQPVQSELVQRCQQLQSRLSTLKIENEEVKKTMEATLQTIQDIVTVEDFDVSDCFQYSNSMESVKSTVSETFMSKPSIAKRRANQQETEQFYFTKMKEYLEGRNLITKLQAKHDLLQKTLGESQRTDCSLARRSSTVRKQDSSQAIPLVVESCIRFISRHGLQHEGIFRVSGSQVEVNDIKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTIIIQHENIFPNPRELEGPIYSRGGSMEDYCDSTHGETTSAEDSTQDVTAEHHTSDDECEPIEAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYIVVQDTEDGVVERSSPKSEIEVMSEPPEEKVTARTGASCPSGGHVADIYLANINKQRKRPESGSIRKAFRSDSHGLGSSLTDSSSLGVGASCRPSSQPIMSQNLPKEGPDKCSISGHGSLNSISRHSSLKNRMDSPQIRKTATAGRSKSFNNHRPMDPEVIAQDIEATMNSALNELQELERQSSAKHTPDVVLDTLEPLKTSPVVAPTSEPSSPLHTQLLKDPEPAFQRSASTAGDIACAFRPVKSVKMAAPVKPPATRPKPTVFPKTNATSPGVNSSASPQATDKSCTV | ||||||
Modified residue | 206 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 427 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 500 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 691 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 695 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 724 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 795 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 916 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 927 | Symmetric dimethylarginine; by PRMT5 | ||||
Sequence: R | ||||||
Modified residue | 930 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 990 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 994 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1013 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 1027 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Developmental stage
Expressed throughout cortical development culminating at P1. Expression is reduced but still present in the adult cortex. Expressed in the cortical wall both in neuronal progenitors in the ventricular zone and post-mitotic neurons in the cortical plate (at protein level).
Gene expression databases
Interaction
Subunit
Homodimer (PubMed:19737524).
Forms a heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain (By similarity).
Interacts (via SH3 domain) with GPHN (PubMed:22126966, PubMed:27373832).
Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1 and actin dynamics (PubMed:21148482).
Interacts (via SH3 domain) with FMNL3 (PubMed:21148482).
Interacts with RAC1; specifically stimulates RAC1 GTPase activity (PubMed:19737524).
Interacts (via F-BAR domain) with HOMER1 (PubMed:27373832).
Interacts with ROBO1 and ROBO2 (PubMed:21148482).
Interacts with FASLG (By similarity).
Interacts with PRMT5 (By similarity).
Forms a heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain (By similarity).
Interacts (via SH3 domain) with GPHN (PubMed:22126966, PubMed:27373832).
Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1 and actin dynamics (PubMed:21148482).
Interacts (via SH3 domain) with FMNL3 (PubMed:21148482).
Interacts with RAC1; specifically stimulates RAC1 GTPase activity (PubMed:19737524).
Interacts (via F-BAR domain) with HOMER1 (PubMed:27373832).
Interacts with ROBO1 and ROBO2 (PubMed:21148482).
Interacts with FASLG (By similarity).
Interacts with PRMT5 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 22-325 | F-BAR | ||||
Sequence: KEIRAQLTEQMKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAERFLAKTRSTKDQQFKKDQNVLSPVNCWNLLLNQVKRESRDHTTLSDIYLNNIIPRFVQVSEDSGRLFKKSKEVGQQLQDDLMKVLNELYSVMKTYHMYNADSISAQSKLKEAEKQEEKQIGKSVKQEDRQTPRSPDSTANVRIEEKHVRRSSVKKIEKMKEKRQAKYTENKLKAIKARNEYLLALEATNASVFKYYIHDLSDIIDQCCDLGYHASLNRALRTFLSAELNLEQSKHEGLDAIENAVENLDATSD | ||||||
Compositional bias | 181-204 | Basic and acidic residues | ||||
Sequence: LKEAEKQEEKQIGKSVKQEDRQTP | ||||||
Region | 181-211 | Disordered | ||||
Sequence: LKEAEKQEEKQIGKSVKQEDRQTPRSPDSTA | ||||||
Coiled coil | 363-401 | |||||
Sequence: QSELVQRCQQLQSRLSTLKIENEEVKKTMEATLQTIQDI | ||||||
Domain | 489-679 | Rho-GAP | ||||
Sequence: ARRSSTVRKQDSSQAIPLVVESCIRFISRHGLQHEGIFRVSGSQVEVNDIKNAFERGEDPLAGDQNDHDMDSIAGVLKLYFRGLEHPLFPKDIFHDLIACVTMDNLQERAVHIRKVLLVLPKPTLIIMRYLFAFLNHLSQFSEENMMDPYNLAICFGPSLMSVPEGHDQVSCQAHVNELIKTIIIQHENIF | ||||||
Region | 700-726 | Disordered | ||||
Sequence: CDSTHGETTSAEDSTQDVTAEHHTSDD | ||||||
Domain | 728-787 | SH3 | ||||
Sequence: CEPIEAIAKFDYVGRTARELSFKKGASLLLYQRASDDWWEGRHNGIDGLIPHQYIVVQDT | ||||||
Compositional bias | 795-809 | Basic and acidic residues | ||||
Sequence: SSPKSEIEVMSEPPE | ||||||
Region | 795-819 | Disordered | ||||
Sequence: SSPKSEIEVMSEPPEEKVTARTGAS | ||||||
Region | 838-918 | Disordered | ||||
Sequence: RKRPESGSIRKAFRSDSHGLGSSLTDSSSLGVGASCRPSSQPIMSQNLPKEGPDKCSISGHGSLNSISRHSSLKNRMDSPQ | ||||||
Compositional bias | 855-884 | Polar residues | ||||
Sequence: HGLGSSLTDSSSLGVGASCRPSSQPIMSQN | ||||||
Compositional bias | 896-918 | Polar residues | ||||
Sequence: SGHGSLNSISRHSSLKNRMDSPQ | ||||||
Coiled coil | 940-968 | |||||
Sequence: EVIAQDIEATMNSALNELQELERQSSAKH | ||||||
Region | 984-1012 | Disordered | ||||
Sequence: PVVAPTSEPSSPLHTQLLKDPEPAFQRSA | ||||||
Region | 1029-1071 | Disordered | ||||
Sequence: KMAAPVKPPATRPKPTVFPKTNATSPGVNSSASPQATDKSCTV | ||||||
Compositional bias | 1045-1071 | Polar residues | ||||
Sequence: VFPKTNATSPGVNSSASPQATDKSCTV |
Domain
The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,071
- Mass (Da)120,798
- Last updated2007-01-09 v2
- Checksum9093C63476BA605D
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A087WNM1 | A0A087WNM1_MOUSE | Srgap2 | 858 | ||
A0A087WNR5 | A0A087WNR5_MOUSE | Srgap2 | 55 | ||
A0A087WS59 | A0A087WS59_MOUSE | Srgap2 | 451 | ||
A0A087WRV4 | A0A087WRV4_MOUSE | Srgap2 | 110 | ||
A0A087WS73 | A0A087WS73_MOUSE | Srgap2 | 267 | ||
A0A087WSQ1 | A0A087WSQ1_MOUSE | Srgap2 | 649 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 181-204 | Basic and acidic residues | ||||
Sequence: LKEAEKQEEKQIGKSVKQEDRQTP | ||||||
Sequence conflict | 598 | in Ref. 3; AAL27032 | ||||
Sequence: A → V | ||||||
Sequence conflict | 612 | in Ref. 3; AAL27032 | ||||
Sequence: T → S | ||||||
Sequence conflict | 662 | in Ref. 3; AAL27032 | ||||
Sequence: A → S | ||||||
Sequence conflict | 737 | in Ref. 3; AAL27032 | ||||
Sequence: F → C | ||||||
Sequence conflict | 765 | in Ref. 3; AAL27032 | ||||
Sequence: W → L | ||||||
Compositional bias | 795-809 | Basic and acidic residues | ||||
Sequence: SSPKSEIEVMSEPPE | ||||||
Compositional bias | 855-884 | Polar residues | ||||
Sequence: HGLGSSLTDSSSLGVGASCRPSSQPIMSQN | ||||||
Compositional bias | 896-918 | Polar residues | ||||
Sequence: SGHGSLNSISRHSSLKNRMDSPQ | ||||||
Compositional bias | 1045-1071 | Polar residues | ||||
Sequence: VFPKTNATSPGVNSSASPQATDKSCTV |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC109299 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC120217 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC165436 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC151081 EMBL· GenBank· DDBJ | AAI51082.1 EMBL· GenBank· DDBJ | mRNA | ||
BC151082 EMBL· GenBank· DDBJ | AAI51083.1 EMBL· GenBank· DDBJ | mRNA | ||
BC158055 EMBL· GenBank· DDBJ | AAI58056.1 EMBL· GenBank· DDBJ | mRNA | ||
BC172152 EMBL· GenBank· DDBJ | AAI72152.1 EMBL· GenBank· DDBJ | mRNA | ||
AY057900 EMBL· GenBank· DDBJ | AAL27032.1 EMBL· GenBank· DDBJ | mRNA | ||
AK132220 EMBL· GenBank· DDBJ | BAE21041.1 EMBL· GenBank· DDBJ | mRNA | ||
U40752 EMBL· GenBank· DDBJ | AAC52480.1 EMBL· GenBank· DDBJ | mRNA |