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O75044 (SRGP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SLIT-ROBO Rho GTPase-activating protein 2

Short name=srGAP2
Alternative name(s):
Formin-binding protein 2
Rho GTPase-activating protein 34
Gene names
Name:SRGAP2
Synonyms:ARHGAP34, FNBP2, KIAA0456, SRGAP2A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1071 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7 Ref.12 Ref.13

Subunit structure

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. Ref.2 Ref.6 Ref.7 Ref.12 Ref.13 Ref.14

Subcellular location

Cell membrane. Cell projectiondendritic spine. Cell junctionsynapsepostsynaptic cell membranepostsynaptic density By similarity. Cell junctionsynapsepostsynaptic cell membrane By similarity. Cell projectionlamellipodium. Cytoplasmic vesiclephagosome By similarity. Nucleus By similarity. Cytoplasm By similarity. Note: Recruited to actin-rich phagosomes during phagocytosis By similarity. Translocates from nucleus to cytoplasm during development By similarity. Ref.7 Ref.12 Ref.13

Domain

The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions. Ref.14

Post-translational modification

Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions. Ref.7

Involvement in disease

A chromosomal aberration disrupting SRGAP2 has been found in a patient with early infantile epileptic encephalopathy. Balanced translocation t(1;9)(q32;q13).

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 similarities

Contains 1 FCH domain.

Contains 1 Rho-GAP domain.

Contains 1 SH3 domain.

Sequence caution

The sequence BAA32301.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processNeurogenesis
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoplasmic vesicle
Membrane
Nucleus
Postsynaptic cell membrane
Synapse
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DomainCoiled coil
SH3 domain
   Molecular functionGTPase activation
   PTMMethylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament severing

Inferred from direct assay Ref.12. Source: UniProtKB

axon guidance

Traceable author statement. Source: Reactome

dendritic spine development

Inferred from direct assay Ref.13. Source: UniProtKB

extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration

Inferred from sequence or structural similarity. Source: UniProtKB

filopodium assembly

Inferred from direct assay Ref.13. Source: UniProtKB

lamellipodium assembly involved in ameboidal cell migration

Inferred from mutant phenotype Ref.7. Source: UniProtKB

negative regulation of neuron migration

Inferred from direct assay Ref.13. Source: UniProtKB

neuron projection morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Rac GTPase activity

Inferred from direct assay Ref.12. Source: UniProtKB

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

substrate adhesion-dependent cell spreading

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine head

Inferred from direct assay Ref.13. Source: UniProtKB

lamellipodium

Inferred from direct assay Ref.7. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

phagocytic vesicle

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.12. Source: UniProtKB

postsynaptic density

Inferred from sequence or structural similarity. Source: UniProtKB

postsynaptic membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRac GTPase activator activity

Inferred from direct assay Ref.12. Source: UniProtKB

Rac GTPase binding

Inferred from direct assay Ref.7Ref.12. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay Ref.7. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10711071SLIT-ROBO Rho GTPase-activating protein 2
PRO_0000056767

Regions

Domain22 – 8766FCH
Domain489 – 679191Rho-GAP
Domain728 – 78760SH3
Region1 – 501501F-BAR domain
Coiled coil362 – 40140 Potential
Coiled coil940 – 96728 Potential
Compositional bias843 – 90967Ser-rich

Amino acid modifications

Modified residue9271Omega-N-methylated arginine; by PRMT5 Ref.7
Modified residue9301Phosphoserine Ref.8

Natural variations

Natural variant8741R → G.
Corresponds to variant rs17018890 [ dbSNP | Ensembl ].
VAR_055834

Experimental info

Mutagenesis9271R → A: Loss of the ability to stimulate cell migration, to localize at the plasma membrane protrusions and to dimerize. Ref.7

Secondary structure

............. 1071
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O75044 [UniParc].

Last modified June 7, 2004. Version 2.
Checksum: D8BC1939D6776312

FASTA1,071120,881
        10         20         30         40         50         60 
MTSPAKFKKD KEIIAEYDTQ VKEIRAQLTE QMKCLDQQCE LRVQLLQDLQ DFFRKKAEIE 

        70         80         90        100        110        120 
MDYSRNLEKL AERFLAKTRS TKDQQFKKDQ NVLSPVNCWN LLLNQVKRES RDHTTLSDIY 

       130        140        150        160        170        180 
LNNIIPRFVQ VSEDSGRLFK KSKEVGQQLQ DDLMKVLNEL YSVMKTYHMY NADSISAQSK 

       190        200        210        220        230        240 
LKEAEKQEEK QIGKSVKQED RQTPRSPDST ANVRIEEKHV RRSSVKKIEK MKEKRQAKYT 

       250        260        270        280        290        300 
ENKLKAIKAR NEYLLALEAT NASVFKYYIH DLSDLIDQCC DLGYHASLNR ALRTFLSAEL 

       310        320        330        340        350        360 
NLEQSKHEGL DAIENAVENL DATSDKQRLM EMYNNVFCPP MKFEFQPHMG DMASQLCAQQ 

       370        380        390        400        410        420 
PVQSELVQRC QQLQSRLSTL KIENEEVKKT MEATLQTIQD IVTVEDFDVS DCFQYSNSME 

       430        440        450        460        470        480 
SVKSTVSETF MSKPSIAKRR ANQQETEQFY FTKMKEYLEG RNLITKLQAK HDLLQKTLGE 

       490        500        510        520        530        540 
SQRTDCSLAR RSSTVRKQDS SQAIPLVVES CIRFISRHGL QHEGIFRVSG SQVEVNDIKN 

       550        560        570        580        590        600 
AFERGEDPLA GDQNDHDMDS IAGVLKLYFR GLEHPLFPKD IFHDLMACVT MDNLQERALH 

       610        620        630        640        650        660 
IRKVLLVLPK TTLIIMRYLF AFLNHLSQFS EENMMDPYNL AICFGPSLMS VPEGHDQVSC 

       670        680        690        700        710        720 
QAHVNELIKT IIIQHENIFP SPRELEGPVY SRGGSMEDYC DSPHGETTPV EDSTQDVTAE 

       730        740        750        760        770        780 
HHTSDDECEP IEAIAKFDYV GRTARELSFK KGASLLLYQR ASDDWWEGRH NGIDGLIPHQ 

       790        800        810        820        830        840 
YIVVQDTEDG VVERSSPKSE IEVISEPPEE KVTARAGASC PSGGHVADIY LANINKQRKR 

       850        860        870        880        890        900 
PESGSIRKTF RSDSHGLSSS LTDSSSPGVG ASCRPSSQPI MSQSLPKEGP DKCSISGHGS 

       910        920        930        940        950        960 
LNSISRHSSL KNRLDSPQIR KTATAGRSKS FNNHRPMDPE VIAQDIEATM NSALNELREL 

       970        980        990       1000       1010       1020 
ERQSSVKHTP DVVLDTLEPL KTSPVVAPTS EPSSPLHTQL LKDPEPAFQR SASTAGDIAC 

      1030       1040       1050       1060       1070 
AFRPVKSVKM AAPVKPPATR PKPTVFPKTN ATSPGVNSST SPQSTDKSCT V 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain."
Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O.
DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[2]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ROBO1.
[3]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[4]"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] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[5]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FASLG.
[7]"srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization."
Guo S., Bao S.
J. Biol. Chem. 285:35133-35141(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, INTERACTION WITH PRMT5, METHYLATION AT ARG-927 BY PRMT5, MUTAGENESIS OF ARG-927.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-930, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2)."
Saitsu H., Osaka H., Sugiyama S., Kurosawa K., Mizuguchi T., Nishiyama K., Nishimura A., Tsurusaki Y., Doi H., Miyake N., Harada N., Kato M., Matsumoto N.
Am. J. Med. Genet. A 158A:199-205(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL REARRANGEMENT.
[12]"Bi-modal regulation of a formin by srGAP2."
Mason F.M., Heimsath E.G., Higgs H.N., Soderling S.H.
J. Biol. Chem. 286:6577-6586(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ACTIN FILAMENT SEVERING, RAC1 GAP ACTIVITY, INTERACTION WITH FMNL1; FMNL3 AND ROBO2, SUBCELLULAR LOCATION.
[13]"Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation."
Charrier C., Joshi K., Coutinho-Budd J., Kim J.E., Lambert N., de Marchena J., Jin W.L., Vanderhaeghen P., Ghosh A., Sassa T., Polleux F.
Cell 149:923-935(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SRGAP2C.
[14]"The F-BAR domains from srGAP1, srGAP2, and srGAP3 differentially regulate membrane deformation."
Coutinho-Budd J., Ghukasyan V., Zylka M.J., Polleux F.
J. Cell Sci. 125:3390-3401(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: HETEROOLIGOMERIZATION, DOMAIN F-BAR.
[15]"Solution structure of the SH3 domain of human SLIT-ROBO Rho GTPase-activating protein 2."
RIKEN structural genomics initiative (RSGI)
Submitted (OCT-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 729-787.
+Additional computationally mapped references.

Web resources

Protein Spotlight

Branching out - Issue 143 of October 2012

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB007925 mRNA. Translation: BAA32301.1. Different initiation.
PIRC59437.
RefSeqNP_001164108.1. NM_001170637.2.
NP_056141.2. NM_015326.3.
UniGeneHs.497575.
Hs.729527.
Hs.744555.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2DL8NMR-A729-787[»]
ProteinModelPortalO75044.
SMRO75044. Positions 444-679, 723-787.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116956. 17 interactions.
IntActO75044. 16 interactions.
MINTMINT-1682591.
STRING9606.ENSP00000408089.

PTM databases

PhosphoSiteO75044.

Proteomic databases

PaxDbO75044.
PRIDEO75044.

Protocols and materials databases

DNASU23380.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000414359; ENSP00000408089; ENSG00000163486.
GeneID23380.
KEGGhsa:23380.

Organism-specific databases

CTD23380.
GeneCardsGC01P206516.
H-InvDBHIX0001527.
HIX0029679.
HIX0116247.
HGNCHGNC:19751. SRGAP2.
HPAHPA028191.
HPA028196.
MIM606524. gene.
neXtProtNX_O75044.
PharmGKBPA164742513.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG264793.
HOGENOMHOG000039980.
HOVERGENHBG051637.
InParanoidO75044.
KOK07526.
PhylomeDBO75044.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_195021. Developmental Biology.

Gene expression databases

BgeeO75044.
CleanExHS_SRGAP2.
GenevestigatorO75044.

Family and domain databases

Gene3D1.10.555.10. 1 hit.
InterProIPR001060. FCH_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00611. FCH. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTSM00055. FCH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEPS50133. FCH. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSRGAP2. human.
EvolutionaryTraceO75044.
GeneWikiSRGAP2.
GenomeRNAi23380.
NextBio45477.
PROO75044.
SOURCESearch...

Entry information

Entry nameSRGP2_HUMAN
AccessionPrimary (citable) accession number: O75044
Entry history
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

Protein Spotlight

Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM