P0DJJ0 · SRG2C_HUMAN
- ProteinSLIT-ROBO Rho GTPase-activating protein 2C
- GeneSRGAP2C
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids459 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Human-specific protein that acts as a key modifier of cortical connectivity in the human brain (PubMed:22559944, PubMed:27373832, PubMed:34707291).
Acts by inhibiting the functions of ancestral paralog SRGAP2/SRGAP2A, a postsynaptic protein that regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832).
SRGAP2C is unstable but is able to heterodimerize with SRGAP2/SRGAP2A, thereby reducing SRGAP2/SRGAP2A levels through proteasome-dependent degradation (PubMed:27373832, PubMed:28333212, PubMed:31822692).
Inhibition of SRGAP2/SRGAP2A by SRGAP2C leads to an increase in synaptic density and protracted synaptic maturation of both excitatory and inhibitory synapses (PubMed:27373832, PubMed:34707291).
Modifies cortical circuit connectivity by increasing the number of local and long-range cortical inputs received by layer 2/3 pyramidal neurons (PubMed:34707291).
Also able to increase the probability of sensory-evoked responses by layer 2/3 pyramidal neurons (PubMed:34707291).
Acts by inhibiting the functions of ancestral paralog SRGAP2/SRGAP2A, a postsynaptic protein that regulates excitatory and inhibitory synapse maturation and density in cortical pyramidal neurons (PubMed:22559944, PubMed:27373832).
SRGAP2C is unstable but is able to heterodimerize with SRGAP2/SRGAP2A, thereby reducing SRGAP2/SRGAP2A levels through proteasome-dependent degradation (PubMed:27373832, PubMed:28333212, PubMed:31822692).
Inhibition of SRGAP2/SRGAP2A by SRGAP2C leads to an increase in synaptic density and protracted synaptic maturation of both excitatory and inhibitory synapses (PubMed:27373832, PubMed:34707291).
Modifies cortical circuit connectivity by increasing the number of local and long-range cortical inputs received by layer 2/3 pyramidal neurons (PubMed:34707291).
Also able to increase the probability of sensory-evoked responses by layer 2/3 pyramidal neurons (PubMed:34707291).
Miscellaneous
This is one of the 3 duplications of the ancestral gene SRGAP2/SRGAP2A which has undergone human-specific segmental gene duplications (PubMed:22559943, PubMed:22559944).
The appearance of SRGAP2C in the human genome is estimated to 2,4 million years and corresponds to the beginning of neocortex expansion in human evolution (PubMed:22559943, PubMed:22559944, PubMed:34707291).
The emergence of SRGAP2C at the birth of the Homo lineage probably contributed to the evolution of specific structural and functional features of cortical circuits in the human cortex (PubMed:34707291).
The appearance of SRGAP2C in the human genome is estimated to 2,4 million years and corresponds to the beginning of neocortex expansion in human evolution (PubMed:22559943, PubMed:22559944, PubMed:34707291).
The emergence of SRGAP2C at the birth of the Homo lineage probably contributed to the evolution of specific structural and functional features of cortical circuits in the human cortex (PubMed:34707291).
Expression of SRGAP2C in mouse cortical pyramidal neurons leads to the emergence of human-specific traits of synaptic development, characterized by increases in the density of both excitatory and inhibitory synapses received by layer 2/3 pyramidal neurons and neotenic features of excitatory and inhibitory synaptic development (PubMed:22559944, PubMed:27373832, PubMed:34707291).
Mice humanized for SRGAP2C expression in all cortical pyramidal neurons show a shift in the fraction of layer 2/3 pyramidal neurons activated by sensory stimulation and an enhanced ability to learn a cortex-dependent sensory-discrimination task (PubMed:34707291).
Mice humanized for SRGAP2C expression in all cortical pyramidal neurons show a shift in the fraction of layer 2/3 pyramidal neurons activated by sensory stimulation and an enhanced ability to learn a cortex-dependent sensory-discrimination task (PubMed:34707291).
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | glutamatergic synapse | |
Molecular Function | protein heterodimerization activity | |
Molecular Function | protein homodimerization activity | |
Biological Process | cerebral cortex development | |
Biological Process | excitatory synapse assembly | |
Biological Process | extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration | |
Biological Process | inhibitory synapse assembly | |
Biological Process | negative regulation of dendritic spine development | |
Biological Process | negative regulation of filopodium assembly | |
Biological Process | positive regulation of neuron migration | |
Biological Process | regulation of synapse assembly |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSLIT-ROBO Rho GTPase-activating protein 2C
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP0DJJ0
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 73 | Does not improve solubility; when associated with R-108, R-205, R-235 and R-250. | ||||
Sequence: H → R | ||||||
Mutagenesis | 108 | Does not improve solubility; when associated with R-73, R-205, R-235 and R-250. | ||||
Sequence: W → R | ||||||
Mutagenesis | 205 | Does not improve solubility; when associated with R-73, R-108, R-235 and R-250. | ||||
Sequence: C → R | ||||||
Mutagenesis | 235 | Does not improve solubility; when associated with R-73, R-108, R-205 and R-250. | ||||
Sequence: H → R | ||||||
Mutagenesis | 250 | Does not improve solubility; when associated with R-73, R-108, R-205 and R-235. | ||||
Sequence: Q → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 521 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000418193 | 1-459 | UniProt | SLIT-ROBO Rho GTPase-activating protein 2C | |||
Sequence: MTSPAKFKKDKEIIAEYDTQVKEIRAQLTEQMKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAEHFLAKTRSTKDQQFKKDQNVLSPVNCWNLLLNQVKWESRDHTTLSDIYLNNIIPRFVQVSEDSGRLFKKSKEVGQQLQDDLMKVLNELYSVMKTYHMYNADSISAQSKLKEAEKQEEKQIGKSVKQEDRQTPCSPDSTANVRIEEKHVRRSSVKKIEKMKEKHQAKYTENKLKAIKAQNEYLLALEATNASVFKYYIHDLSDLIDQCCDLGYHASLNRALRTFLSAELNLEQSKHEGLDAIENAVENLDATSDKQRLMEMYNNVFCPPMKFEFQPHMGDMASQLCAQQPVQSELVQRCQQLQSRLSTLKIENEEVKKTMEATLQTIQDIVTVEDFDVSDCFQYSNSMESVKSTVSETFMSKPSIAKRRANQQETEQFYFTVRECYGF | |||||||
Modified residue (large scale data) | 424 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 427 | PRIDE | Phosphoserine | ||||
Sequence: S |
Proteomic databases
PTM databases
Interaction
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region, coiled coil.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 22-325 | F-BAR | ||||
Sequence: KEIRAQLTEQMKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAEHFLAKTRSTKDQQFKKDQNVLSPVNCWNLLLNQVKWESRDHTTLSDIYLNNIIPRFVQVSEDSGRLFKKSKEVGQQLQDDLMKVLNELYSVMKTYHMYNADSISAQSKLKEAEKQEEKQIGKSVKQEDRQTPCSPDSTANVRIEEKHVRRSSVKKIEKMKEKHQAKYTENKLKAIKAQNEYLLALEATNASVFKYYIHDLSDLIDQCCDLGYHASLNRALRTFLSAELNLEQSKHEGLDAIENAVENLDATSD | ||||||
Compositional bias | 181-197 | Basic and acidic residues | ||||
Sequence: LKEAEKQEEKQIGKSVK | ||||||
Region | 181-211 | Disordered | ||||
Sequence: LKEAEKQEEKQIGKSVKQEDRQTPCSPDSTA | ||||||
Coiled coil | 363-401 | |||||
Sequence: QSELVQRCQQLQSRLSTLKIENEEVKKTMEATLQTIQDI |
Domain
SRGAP2C is truncated at its C-terminus compared to SRGAP2/SRGAP2A (PubMed:28333212).
It only contains an extended F-BAR domain that lacks the last C-terminal 49 amino acids of SRGAP2/SRGAP2A, which are replaced with seven unique C-terminal amino acids (PubMed:28333212).
In addition, SRGAP2C acquired a series of unique nonsynonymous base pair mutations selectively targeting five arginine residues compared to SRGAP2B (PubMed:28333212).
This truncation and these specific arginine mutations reduce solubility of SRGAP2C and increase its ability to heterodimerize with SRGAP2/SRGAP2A to form an insoluble complex (PubMed:28333212).
It only contains an extended F-BAR domain that lacks the last C-terminal 49 amino acids of SRGAP2/SRGAP2A, which are replaced with seven unique C-terminal amino acids (PubMed:28333212).
In addition, SRGAP2C acquired a series of unique nonsynonymous base pair mutations selectively targeting five arginine residues compared to SRGAP2B (PubMed:28333212).
This truncation and these specific arginine mutations reduce solubility of SRGAP2C and increase its ability to heterodimerize with SRGAP2/SRGAP2A to form an insoluble complex (PubMed:28333212).
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length459
- Mass (Da)53,484
- Last updated2012-07-11 v1
- Checksum3FBAC28FE3C43297
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A087X0L1 | A0A087X0L1_HUMAN | SRGAP2C | 305 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 181-197 | Basic and acidic residues | ||||
Sequence: LKEAEKQEEKQIGKSVK | ||||||
Sequence conflict | 278 | in Ref. 3; BC112927 | ||||
Sequence: Missing |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AC243994 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC244021 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC244453 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC112927 EMBL· GenBank· DDBJ | - | mRNA | No translation available. |