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Protein

SLIT-ROBO Rho GTPase-activating protein 2

Gene

SRGAP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionGTPase activation
Biological processNeurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-194840 Rho GTPase cycle
R-HSA-428543 Inactivation of CDC42 and RAC1
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: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000266028.7
HGNCiHGNC:19751 SRGAP2
MIMi606524 gene
neXtProtiNX_O75044

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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).1 Publication

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
OpenTargetsiENSG00000266028
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 residuei724PhosphoserineCombined sources1
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
PaxDbiO75044
PeptideAtlasiO75044
PRIDEiO75044
ProteomicsDBi49722

PTM databases

iPTMnetiO75044
PhosphoSitePlusiO75044

Expressioni

Gene expression databases

BgeeiENSG00000266028 Expressed in 200 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_SRGAP2
ExpressionAtlasiO75044 baseline and differential

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116956, 96 interactors
DIPiDIP-37618N
IntActiO75044, 24 interactors
MINTiO75044
STRINGi9606.ENSP00000295713

Structurei

Secondary structure

11071
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Coiled coil, SH3 domain

Phylogenomic databases

eggNOGiKOG3565 Eukaryota
ENOG410XS44 LUCA
GeneTreeiENSGT00760000118863
HOGENOMiHOG000039980
HOVERGENiHBG051637
InParanoidiO75044
KOiK07526
OMAiGSTEDYC
OrthoDBiEOG091G0113
PhylomeDBiO75044

Family and domain databases

CDDicd11955 SH3_srGAP1-3, 1 hit
Gene3Di1.10.555.10, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR031160 F_BAR
IPR001060 FCH_dom
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR035648 srGAP1/2/3_SH3
IPR030252 srGAP2
PANTHERiPTHR14166:SF6 PTHR14166:SF6, 1 hit
PfamiView protein in Pfam
PF00611 FCH, 1 hit
PF00620 RhoGAP, 1 hit
PF00018 SH3_1, 1 hit
SMARTiView protein in SMART
SM00055 FCH, 1 hit
SM00324 RhoGAP, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS51741 F_BAR, 1 hit
PS50238 RHOGAP, 1 hit
PS50002 SH3, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All

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
DSPHGETTSV 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):120,871
Last modified:December 20, 2017 - v3
Checksum:i5693E6AF33A03E97
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7ZM87B7ZM87_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
1,070Annotation score:
A0A075B7E9A0A075B7E9_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
294Annotation score:
Q5VZB4Q5VZB4_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2 RP11-421E17.2-002
450Annotation score:
A0A075B7E6A0A075B7E6_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
224Annotation score:
A0A075B7B5A0A075B7B5_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
789Annotation score:
E9PDX4E9PDX4_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
305Annotation score:
A0A075B743A0A075B743_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
118Annotation score:
A0A075B7C8A0A075B7C8_HUMAN
SLIT-ROBO Rho GTPase-activating pro...
SRGAP2
86Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti709S → P in BAA32301 (PubMed:16710414).1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055834874R → G. Corresponds to variant dbSNP:rs17018890Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC244023 Genomic DNA No translation available.
AC244034 Genomic DNA No translation available.
AC244035 Genomic DNA No translation available.
AC244158 Genomic DNA No translation available.
AB007925 mRNA Translation: BAA32301.1 Different initiation.
BC132872 mRNA Translation: AAI32873.1
BC132874 mRNA Translation: AAI32875.1
CCDSiCCDS73017.1
PIRiC59437
RefSeqiNP_001164108.1, NM_001170637.3
NP_056141.2, NM_015326.4
XP_005277567.1, XM_005277510.2
UniGeneiHs.497575
Hs.729527
Hs.744555

Genome annotation databases

EnsembliENST00000573034; ENSP00000459615; ENSG00000266028
GeneIDi23380
KEGGihsa:23380
UCSCiuc031vli.2 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Protein Spotlight

Branching out - Issue 143 of October 2012

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC244023 Genomic DNA No translation available.
AC244034 Genomic DNA No translation available.
AC244035 Genomic DNA No translation available.
AC244158 Genomic DNA No translation available.
AB007925 mRNA Translation: BAA32301.1 Different initiation.
BC132872 mRNA Translation: AAI32873.1
BC132874 mRNA Translation: AAI32875.1
CCDSiCCDS73017.1
PIRiC59437
RefSeqiNP_001164108.1, NM_001170637.3
NP_056141.2, NM_015326.4
XP_005277567.1, XM_005277510.2
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[»]
5I6JX-ray2.70A1-484[»]
5I6RX-ray2.15A1-484[»]
5I7DX-ray3.95A/B1-484[»]
ProteinModelPortaliO75044
SMRiO75044
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116956, 96 interactors
DIPiDIP-37618N
IntActiO75044, 24 interactors
MINTiO75044
STRINGi9606.ENSP00000295713

PTM databases

iPTMnetiO75044
PhosphoSitePlusiO75044

Proteomic databases

EPDiO75044
PaxDbiO75044
PeptideAtlasiO75044
PRIDEiO75044
ProteomicsDBi49722

Protocols and materials databases

DNASUi23380
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000573034; ENSP00000459615; ENSG00000266028
GeneIDi23380
KEGGihsa:23380
UCSCiuc031vli.2 human

Organism-specific databases

CTDi23380
DisGeNETi23380
EuPathDBiHostDB:ENSG00000266028.7
GeneCardsiSRGAP2
H-InvDBiHIX0001527
HIX0029679
HIX0116247
HGNCiHGNC:19751 SRGAP2
HPAiHPA028191
HPA028196
MIMi606524 gene
neXtProtiNX_O75044
OpenTargetsiENSG00000266028
PharmGKBiPA164742513
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3565 Eukaryota
ENOG410XS44 LUCA
GeneTreeiENSGT00760000118863
HOGENOMiHOG000039980
HOVERGENiHBG051637
InParanoidiO75044
KOiK07526
OMAiGSTEDYC
OrthoDBiEOG091G0113
PhylomeDBiO75044

Enzyme and pathway databases

ReactomeiR-HSA-194840 Rho GTPase cycle
R-HSA-428543 Inactivation of CDC42 and RAC1
R-HSA-5663220 RHO GTPases Activate Formins

Miscellaneous databases

ChiTaRSiSRGAP2 human
EvolutionaryTraceiO75044
GeneWikiiSRGAP2
GenomeRNAii23380
PROiPR:O75044
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000266028 Expressed in 200 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_SRGAP2
ExpressionAtlasiO75044 baseline and differential

Family and domain databases

CDDicd11955 SH3_srGAP1-3, 1 hit
Gene3Di1.10.555.10, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR031160 F_BAR
IPR001060 FCH_dom
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR035648 srGAP1/2/3_SH3
IPR030252 srGAP2
PANTHERiPTHR14166:SF6 PTHR14166:SF6, 1 hit
PfamiView protein in Pfam
PF00611 FCH, 1 hit
PF00620 RhoGAP, 1 hit
PF00018 SH3_1, 1 hit
SMARTiView protein in SMART
SM00055 FCH, 1 hit
SM00324 RhoGAP, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF48350 SSF48350, 1 hit
SSF50044 SSF50044, 1 hit
PROSITEiView protein in PROSITE
PS51741 F_BAR, 1 hit
PS50238 RHOGAP, 1 hit
PS50002 SH3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSRGP2_HUMAN
AccessioniPrimary (citable) accession number: O75044
Secondary accession number(s): A2RUF3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2004
Last sequence update: December 20, 2017
Last modified: November 7, 2018
This is version 165 of the entry and version 3 of the sequence. See 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

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
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