P0DJJ0 · SRG2C_HUMAN

  • Protein
    SLIT-ROBO Rho GTPase-activating protein 2C
  • Gene
    SRGAP2C
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

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).
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).

GO annotations

AspectTerm
Cellular Componentglutamatergic synapse
Molecular Functionprotein heterodimerization activity
Molecular Functionprotein homodimerization activity
Biological Processcerebral cortex development
Biological Processexcitatory synapse assembly
Biological Processextension of a leading process involved in cell motility in cerebral cortex radial glia guided migration
Biological Processinhibitory synapse assembly
Biological Processnegative regulation of dendritic spine development
Biological Processnegative regulation of filopodium assembly
Biological Processpositive regulation of neuron migration
Biological Processregulation of synapse assembly

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    SLIT-ROBO Rho GTPase-activating protein 2C
  • Alternative names
    • SLIT-ROBO Rho GTPase activating protein 2 pseudogene 1

Gene names

    • Name
      SRGAP2C
    • Synonyms
      SRGAP2P1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P0DJJ0

Proteomes

Organism-specific databases

Subcellular Location

Disease & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis73Does not improve solubility; when associated with R-108, R-205, R-235 and R-250.
Mutagenesis108Does not improve solubility; when associated with R-73, R-205, R-235 and R-250.
Mutagenesis205Does not improve solubility; when associated with R-73, R-108, R-235 and R-250.
Mutagenesis235Does not improve solubility; when associated with R-73, R-108, R-205 and R-250.
Mutagenesis250Does not improve solubility; when associated with R-73, R-108, R-205 and R-235.

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.

Go to variant viewer

Organism-specific databases

Miscellaneous

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
ChainPRO_00004181931-459UniProtSLIT-ROBO Rho GTPase-activating protein 2C
Modified residue (large scale data)424PRIDEPhosphoserine
Modified residue (large scale data)427PRIDEPhosphoserine

Proteomic databases

PTM databases

Expression

Tissue specificity

Ubiquitously expressed with higher expression in cerebellum (PubMed:22559943, PubMed:22559944).
Probably expressed in fetal and adult neurons (at protein level) (PubMed:22559943).

Gene expression databases

Organism-specific databases

Interaction

Subunit

Homodimer (PubMed:22559944).
Interacts (via F-BAR domain) with SRGAP2/SRGAP2A (via F-BAR domain); formation of the heterodimer inhibits SRGAP2/SRGAP2A function (PubMed:22559944, PubMed:28333212, PubMed:34707291).

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, compositional bias, region, coiled coil.

TypeIDPosition(s)Description
Domain22-325F-BAR
Compositional bias181-197Basic and acidic residues
Region181-211Disordered
Coiled coil363-401

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).

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    459
  • Mass (Da)
    53,484
  • Last updated
    2012-07-11 v1
  • Checksum
    3FBAC28FE3C43297
MTSPAKFKKDKEIIAEYDTQVKEIRAQLTEQMKCLDQQCELRVQLLQDLQDFFRKKAEIEMDYSRNLEKLAEHFLAKTRSTKDQQFKKDQNVLSPVNCWNLLLNQVKWESRDHTTLSDIYLNNIIPRFVQVSEDSGRLFKKSKEVGQQLQDDLMKVLNELYSVMKTYHMYNADSISAQSKLKEAEKQEEKQIGKSVKQEDRQTPCSPDSTANVRIEEKHVRRSSVKKIEKMKEKHQAKYTENKLKAIKAQNEYLLALEATNASVFKYYIHDLSDLIDQCCDLGYHASLNRALRTFLSAELNLEQSKHEGLDAIENAVENLDATSDKQRLMEMYNNVFCPPMKFEFQPHMGDMASQLCAQQPVQSELVQRCQQLQSRLSTLKIENEEVKKTMEATLQTIQDIVTVEDFDVSDCFQYSNSMESVKSTVSETFMSKPSIAKRRANQQETEQFYFTVRECYGF

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A087X0L1A0A087X0L1_HUMANSRGAP2C305

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias181-197Basic and acidic residues
Sequence conflict278in Ref. 3; BC112927

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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.

Genome annotation databases

Similar Proteins

Disclaimer

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