UniProt functional annotation for O75044



	UniProt functional annotation for O75044

UniProt code: O75044.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: RAC1 GTPase activating protein (GAP) that binds and deforms membranes, and regulates actin dynamics to regulate cell migration and differentiation. Plays an important role in different aspects of neuronal morphogenesis and migration mainly during development of the cerebral cortex. This includes the biogenesis of neurites, where it is required for both axons and dendrites outgrowth, and the maturation of the dendritic spines. Also stimulates the branching of the leading process and negatively regulates neuron radial migration in the cerebral cortex. Its interaction and inhibition by SRGAP2C reduces the rate of spine maturation, alters dendritic spine morphology and density and indirectly increases neuronal migration. It may have implications for cognition, learning and memory. In non-neuronal cells, it may also play a role in cell migration by regulating the formation of lamellipodia and filopodia. {ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944}.

Subunit: Homodimer (Probable). Forms a heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain. Interacts (via SH3 domain) with GPHN (By similarity). Interacts with SRGAP2C; formation of the heterodimer alters SRGAP2 function. Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1 and actin dynamics. Interacts (via SH3 domain) with FMNL3. Interacts with RAC1; specifically stimulates RAC1 GTPase activity. Probably interacts with ROBO1 and ROBO2. Interacts with FASLG. Interacts with PRMT5. {ECO:0000250, ECO:0000269|PubMed:11672528, ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20810653, ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944, ECO:0000305}.

Subcellular location: Cell membrane. Cell projection, dendritic spine. Cell junction, synapse, postsynaptic density {ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250}. Cell projection, lamellipodium. Cytoplasmic vesicle, phagosome {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Recruited to actin-rich phagosomes during phagocytosis. Translocates from nucleus to cytoplasm during development. {ECO:0000250}.

Domain: The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions. {ECO:0000269|PubMed:22467852}.

Ptm: Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions. {ECO:0000269|PubMed:20810653}.

Disease: Note=A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13) (PubMed:22106086). {ECO:0000269|PubMed:22106086}.

Miscellaneous: There are 3 duplications of SRGAP2 in the human genome as a result of segmental gene duplications. SRGAP2C is the only one to be fixed at a diploid state in the human genome. Moreover, SRGAP2C is functional, interacts with and inhibits SRGAP2 and is human-specific. The appearance of SRGAP2C in the human genome is estimated to 2,4 million years ago, which corresponds to the beginning of neocortex expansion in human evolution and it may have played an important role in this process through its interaction with SRGAP2 function.

Sequence caution: Sequence=BAA32301.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		RAC1 GTPase activating protein (GAP) that binds and deforms membranes, and regulates actin dynamics to regulate cell migration and differentiation. Plays an important role in different aspects of neuronal morphogenesis and migration mainly during development of the cerebral cortex. This includes the biogenesis of neurites, where it is required for both axons and dendrites outgrowth, and the maturation of the dendritic spines. Also stimulates the branching of the leading process and negatively regulates neuron radial migration in the cerebral cortex. Its interaction and inhibition by SRGAP2C reduces the rate of spine maturation, alters dendritic spine morphology and density and indirectly increases neuronal migration. It may have implications for cognition, learning and memory. In non-neuronal cells, it may also play a role in cell migration by regulating the formation of lamellipodia and filopodia. {ECO:0000269\|PubMed:20810653, ECO:0000269\|PubMed:21148482, ECO:0000269\|PubMed:22559944}.


Subunit:		Homodimer (Probable). Forms a heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain. Interacts (via SH3 domain) with GPHN (By similarity). Interacts with SRGAP2C; formation of the heterodimer alters SRGAP2 function. Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1 and actin dynamics. Interacts (via SH3 domain) with FMNL3. Interacts with RAC1; specifically stimulates RAC1 GTPase activity. Probably interacts with ROBO1 and ROBO2. Interacts with FASLG. Interacts with PRMT5. {ECO:0000250, ECO:0000269\|PubMed:11672528, ECO:0000269\|PubMed:19807924, ECO:0000269\|PubMed:20810653, ECO:0000269\|PubMed:21148482, ECO:0000269\|PubMed:22559944, ECO:0000305}.
Subcellular location:		Cell membrane. Cell projection, dendritic spine. Cell junction, synapse, postsynaptic density {ECO:0000250}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250}. Cell projection, lamellipodium. Cytoplasmic vesicle, phagosome {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Note=Recruited to actin-rich phagosomes during phagocytosis. Translocates from nucleus to cytoplasm during development. {ECO:0000250}.
Domain:		The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions. {ECO:0000269\|PubMed:22467852}.
Ptm:		Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions. {ECO:0000269\|PubMed:20810653}.
Disease:		Note=A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13) (PubMed:22106086). {ECO:0000269\|PubMed:22106086}.
Miscellaneous:		There are 3 duplications of SRGAP2 in the human genome as a result of segmental gene duplications. SRGAP2C is the only one to be fixed at a diploid state in the human genome. Moreover, SRGAP2C is functional, interacts with and inhibits SRGAP2 and is human-specific. The appearance of SRGAP2C in the human genome is estimated to 2,4 million years ago, which corresponds to the beginning of neocortex expansion in human evolution and it may have played an important role in this process through its interaction with SRGAP2 function.
Sequence caution:		Sequence=BAA32301.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};