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Protein

SLIT-ROBO Rho GTPase-activating protein 2

Gene

SRGAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • Rac GTPase binding Source: UniProtKB

GO - Biological processi

  • actin filament severing Source: UniProtKB
  • dendritic spine development Source: UniProtKB
  • extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration Source: UniProtKB
  • filopodium assembly Source: UniProtKB
  • lamellipodium assembly involved in ameboidal cell migration Source: UniProtKB
  • negative regulation of neuron migration Source: UniProtKB
  • neuron projection morphogenesis Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • regulation of small GTPase mediated signal transduction Source: Reactome
  • signal transduction Source: InterPro
  • substrate adhesion-dependent cell spreading Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Keywords - Biological processi

Neurogenesis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163486-MONOMER.
ReactomeiR-HSA-194840. Rho GTPase cycle.
R-HSA-428543. Inactivation of Cdc42 and Rac.
R-HSA-5663220. RHO GTPases Activate Formins.

Names & Taxonomyi

Protein namesi
Recommended name:
SLIT-ROBO Rho GTPase-activating protein 2
Short name:
srGAP2
Alternative name(s):
Formin-binding protein 2
Rho GTPase-activating protein 34
Gene namesi
Name:SRGAP2
Synonyms:ARHGAP34, FNBP2, KIAA0456, SRGAP2A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:19751. SRGAP2.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: GO_Central
  • cytosol Source: UniProtKB
  • dendritic spine head Source: UniProtKB
  • lamellipodium Source: UniProtKB
  • nucleus Source: UniProtKB-SubCell
  • phagocytic vesicle Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Involvement in diseasei

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).

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi927R → A: Loss of the ability to stimulate cell migration, to localize at the plasma membrane protrusions and to dimerize. 1 Publication1

Organism-specific databases

DisGeNETi23380.
PharmGKBiPA164742513.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000567671 – 1071SLIT-ROBO Rho GTPase-activating protein 2Add BLAST1071

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei206PhosphoserineBy similarity1
Modified residuei427PhosphoserineBy similarity1
Modified residuei500PhosphoserineBy similarity1
Modified residuei691PhosphoserineBy similarity1
Modified residuei695PhosphoserineBy similarity1
Modified residuei795PhosphoserineCombined sources1
Modified residuei916PhosphoserineCombined sources1
Modified residuei927Omega-N-methylated arginine; by PRMT51 Publication1
Modified residuei930PhosphoserineCombined sources1
Modified residuei990PhosphoserineBy similarity1
Modified residuei994PhosphoserineCombined sources1
Modified residuei1013PhosphoserineCombined sources1
Modified residuei1027PhosphoserineCombined sources1

Post-translational modificationi

Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiO75044.
MaxQBiO75044.
PaxDbiO75044.
PeptideAtlasiO75044.
PRIDEiO75044.

PTM databases

iPTMnetiO75044.
PhosphoSitePlusiO75044.

Expressioni

Gene expression databases

CleanExiHS_SRGAP2.

Organism-specific databases

HPAiHPA028191.
HPA028196.

Interactioni

Subunit structurei

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.By similarityCurated5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FASLGP480232EBI-1051034,EBI-495538
FMNL1O954663EBI-1051034,EBI-720020
HTTP428583EBI-1051034,EBI-466029
PRMT5O147444EBI-1051034,EBI-351098

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB
  • Rac GTPase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi116956. 23 interactors.
DIPiDIP-37618N.
IntActiO75044. 18 interactors.
MINTiMINT-1682591.
STRINGi9606.ENSP00000295713.

Structurei

Secondary structure

11071
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi731 – 737Combined sources7
Beta strandi742 – 746Combined sources5
Beta strandi754 – 762Combined sources9
Beta strandi765 – 770Combined sources6
Beta strandi773 – 778Combined sources6
Helixi779 – 781Combined sources3
Beta strandi782 – 784Combined sources3
Helixi791 – 795Combined sources5
Helixi800 – 804Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DL8NMR-A729-787[»]
4RTTX-ray1.87A/B729-815[»]
4RUGX-ray1.73A/B729-815[»]
ProteinModelPortaliO75044.
SMRiO75044.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75044.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 325F-BARPROSITE-ProRule annotationAdd BLAST304
Domaini489 – 679Rho-GAPPROSITE-ProRule annotationAdd BLAST191
Domaini728 – 787SH3PROSITE-ProRule annotationAdd BLAST60

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili362 – 401Sequence analysisAdd BLAST40
Coiled coili940 – 967Sequence analysisAdd BLAST28

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi843 – 909Ser-richAdd BLAST67

Domaini

The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.1 Publication

Sequence similaritiesi

Contains 1 F-BAR domain.PROSITE-ProRule annotation
Contains 1 Rho-GAP domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, SH3 domain

Phylogenomic databases

eggNOGiKOG3565. Eukaryota.
ENOG410XS44. LUCA.
HOGENOMiHOG000039980.
HOVERGENiHBG051637.
InParanoidiO75044.
KOiK07526.
PhylomeDBiO75044.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
InterProiIPR031160. F_BAR.
IPR001060. FCH_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001452. SH3_domain.
IPR030252. srGAP2.
[Graphical view]
PANTHERiPTHR14166:SF6. PTHR14166:SF6. 1 hit.
PfamiPF00611. FCH. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00055. FCH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEiPS51741. F_BAR. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O75044-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTSPAKFKKD KEIIAEYDTQ VKEIRAQLTE QMKCLDQQCE LRVQLLQDLQ
60 70 80 90 100
DFFRKKAEIE MDYSRNLEKL AERFLAKTRS TKDQQFKKDQ NVLSPVNCWN
110 120 130 140 150
LLLNQVKRES RDHTTLSDIY LNNIIPRFVQ VSEDSGRLFK KSKEVGQQLQ
160 170 180 190 200
DDLMKVLNEL YSVMKTYHMY NADSISAQSK LKEAEKQEEK QIGKSVKQED
210 220 230 240 250
RQTPRSPDST ANVRIEEKHV RRSSVKKIEK MKEKRQAKYT ENKLKAIKAR
260 270 280 290 300
NEYLLALEAT NASVFKYYIH DLSDLIDQCC DLGYHASLNR ALRTFLSAEL
310 320 330 340 350
NLEQSKHEGL DAIENAVENL DATSDKQRLM EMYNNVFCPP MKFEFQPHMG
360 370 380 390 400
DMASQLCAQQ PVQSELVQRC QQLQSRLSTL KIENEEVKKT MEATLQTIQD
410 420 430 440 450
IVTVEDFDVS DCFQYSNSME SVKSTVSETF MSKPSIAKRR ANQQETEQFY
460 470 480 490 500
FTKMKEYLEG RNLITKLQAK HDLLQKTLGE SQRTDCSLAR RSSTVRKQDS
510 520 530 540 550
SQAIPLVVES CIRFISRHGL QHEGIFRVSG SQVEVNDIKN AFERGEDPLA
560 570 580 590 600
GDQNDHDMDS IAGVLKLYFR GLEHPLFPKD IFHDLMACVT MDNLQERALH
610 620 630 640 650
IRKVLLVLPK TTLIIMRYLF AFLNHLSQFS EENMMDPYNL AICFGPSLMS
660 670 680 690 700
VPEGHDQVSC QAHVNELIKT IIIQHENIFP SPRELEGPVY SRGGSMEDYC
710 720 730 740 750
DSPHGETTPV EDSTQDVTAE HHTSDDECEP IEAIAKFDYV GRTARELSFK
760 770 780 790 800
KGASLLLYQR ASDDWWEGRH NGIDGLIPHQ YIVVQDTEDG VVERSSPKSE
810 820 830 840 850
IEVISEPPEE KVTARAGASC PSGGHVADIY LANINKQRKR PESGSIRKTF
860 870 880 890 900
RSDSHGLSSS LTDSSSPGVG ASCRPSSQPI MSQSLPKEGP DKCSISGHGS
910 920 930 940 950
LNSISRHSSL KNRLDSPQIR KTATAGRSKS FNNHRPMDPE VIAQDIEATM
960 970 980 990 1000
NSALNELREL ERQSSVKHTP DVVLDTLEPL KTSPVVAPTS EPSSPLHTQL
1010 1020 1030 1040 1050
LKDPEPAFQR SASTAGDIAC AFRPVKSVKM AAPVKPPATR PKPTVFPKTN
1060 1070
ATSPGVNSST SPQSTDKSCT V
Length:1,071
Mass (Da):120,881
Last modified:June 7, 2004 - v2
Checksum:iD8BC1939D6776312
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055834874R → G.Corresponds to variant rs17018890dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007925 mRNA. Translation: BAA32301.1. Different initiation.
CCDSiCCDS73017.1.
PIRiC59437.
RefSeqiNP_001164108.1. NM_001170637.3.
NP_056141.2. NM_015326.4.
UniGeneiHs.497575.
Hs.729527.
Hs.744555.

Genome annotation databases

GeneIDi23380.
KEGGihsa:23380.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

Branching out - Issue 143 of October 2012

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007925 mRNA. Translation: BAA32301.1. Different initiation.
CCDSiCCDS73017.1.
PIRiC59437.
RefSeqiNP_001164108.1. NM_001170637.3.
NP_056141.2. NM_015326.4.
UniGeneiHs.497575.
Hs.729527.
Hs.744555.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2DL8NMR-A729-787[»]
4RTTX-ray1.87A/B729-815[»]
4RUGX-ray1.73A/B729-815[»]
ProteinModelPortaliO75044.
SMRiO75044.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116956. 23 interactors.
DIPiDIP-37618N.
IntActiO75044. 18 interactors.
MINTiMINT-1682591.
STRINGi9606.ENSP00000295713.

PTM databases

iPTMnetiO75044.
PhosphoSitePlusiO75044.

Proteomic databases

EPDiO75044.
MaxQBiO75044.
PaxDbiO75044.
PeptideAtlasiO75044.
PRIDEiO75044.

Protocols and materials databases

DNASUi23380.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi23380.
KEGGihsa:23380.

Organism-specific databases

CTDi23380.
DisGeNETi23380.
GeneCardsiSRGAP2.
H-InvDBHIX0001527.
HIX0029679.
HIX0116247.
HGNCiHGNC:19751. SRGAP2.
HPAiHPA028191.
HPA028196.
MIMi606524. gene.
neXtProtiNX_O75044.
PharmGKBiPA164742513.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3565. Eukaryota.
ENOG410XS44. LUCA.
HOGENOMiHOG000039980.
HOVERGENiHBG051637.
InParanoidiO75044.
KOiK07526.
PhylomeDBiO75044.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000163486-MONOMER.
ReactomeiR-HSA-194840. Rho GTPase cycle.
R-HSA-428543. Inactivation of Cdc42 and Rac.
R-HSA-5663220. RHO GTPases Activate Formins.

Miscellaneous databases

ChiTaRSiSRGAP2. human.
EvolutionaryTraceiO75044.
GeneWikiiSRGAP2.
GenomeRNAii23380.
PROiO75044.
SOURCEiSearch...

Gene expression databases

CleanExiHS_SRGAP2.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
InterProiIPR031160. F_BAR.
IPR001060. FCH_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001452. SH3_domain.
IPR030252. srGAP2.
[Graphical view]
PANTHERiPTHR14166:SF6. PTHR14166:SF6. 1 hit.
PfamiPF00611. FCH. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTiSM00055. FCH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEiPS51741. F_BAR. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSRGP2_HUMAN
AccessioniPrimary (citable) accession number: O75044
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: June 7, 2004
Last modified: November 2, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.