SRGP2_RAT
ID SRGP2_RAT Reviewed; 1071 AA.
AC D4A208;
DT 05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=SLIT-ROBO Rho GTPase-activating protein 2 {ECO:0000303|PubMed:17710530};
DE Short=srGAP2 {ECO:0000303|PubMed:17710530};
GN Name=Srgap2 {ECO:0000303|PubMed:17710530, ECO:0000312|RGD:1566016};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=17710530; DOI=10.1007/s10571-007-9187-4;
RA Yao Q., Jin W.L., Wang Y., Ju G.;
RT "Regulated shuttling of Slit-Robo-GTPase activating proteins between
RT nucleus and cytoplasm during brain development.";
RL Cell. Mol. Neurobiol. 28:205-221(2008).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206; SER-427 AND SER-691, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=27748913; DOI=10.3892/mmr.2016.5795;
RA Jiao Q., Wang L., Zhang Z., Wang Y., Yan H., Ma W., Jin W., Lu H., Liu Y.;
RT "Dynamic expression of srGAP2 in cell nuclei and cytoplasm during the
RT differentiation of rat neural stem cells in vitro.";
RL Mol. Med. Report. 14:4599-4605(2016).
CC -!- FUNCTION: Postsynaptic RAC1 GTPase activating protein (GAP) that plays
CC a key role in neuronal morphogenesis and migration mainly during
CC development of the cerebral cortex. Regulates excitatory and inhibitory
CC synapse maturation and density in cortical pyramidal neurons.
CC SRGAP2/SRGAP2A limits excitatory and inhibitory synapse density through
CC its RAC1-specific GTPase activating activity, while it promotes
CC maturation of both excitatory and inhibitory synapses through its
CC ability to bind to the postsynaptic scaffolding protein HOMER1 at
CC excitatory synapses, and the postsynaptic protein GPHN at inhibitory
CC synapses. Mechanistically, acts by binding and deforming membranes,
CC thereby regulating actin dynamics to regulate cell migration and
CC differentiation. Promotes cell repulsion and contact inhibition of
CC locomotion: localizes to protrusions with curved edges and controls the
CC duration of RAC1 activity in contact protrusions. In non-neuronal
CC cells, may also play a role in cell migration by regulating the
CC formation of lamellipodia and filopodia.
CC {ECO:0000250|UniProtKB:Q91Z67}.
CC -!- SUBUNIT: Homodimer. Forms a heterooligomer with SRGAP1 and SRGAP3
CC through its F-BAR domain. Interacts (via SH3 domain) with GPHN.
CC Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates
CC the actin filament severing activity of FMNL1 and actin dynamics.
CC Interacts (via SH3 domain) with FMNL3. Interacts with RAC1;
CC specifically stimulates RAC1 GTPase activity. Interacts (via F-BAR
CC domain) with HOMER1. Interacts with ROBO1 and ROBO2 (By similarity).
CC Interacts with FASLG. Interacts with PRMT5 (By similarity).
CC {ECO:0000250|UniProtKB:O75044, ECO:0000250|UniProtKB:Q91Z67}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O75044}.
CC Cell projection, dendritic spine {ECO:0000250|UniProtKB:O75044}.
CC Postsynaptic density {ECO:0000250|UniProtKB:Q91Z67}. Postsynaptic cell
CC membrane {ECO:0000250|UniProtKB:Q91Z67}. Cell projection, lamellipodium
CC {ECO:0000250|UniProtKB:O75044}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:Q91Z67}. Nucleus {ECO:0000269|PubMed:17710530,
CC ECO:0000269|PubMed:27748913}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:17710530, ECO:0000269|PubMed:27748913}.
CC Note=Recruited to actin-rich phagosomes during phagocytosis (By
CC similarity). Translocates from nucleus to cytoplasm during development
CC (PubMed:17710530). {ECO:0000250|UniProtKB:Q91Z67,
CC ECO:0000269|PubMed:17710530}.
CC -!- DEVELOPMENTAL STAGE: Expressed in brain during neonatal period. Not
CC detected in adult brain (at protein level).
CC {ECO:0000269|PubMed:17710530}.
CC -!- DOMAIN: The F-BAR domain mediates oligomerization, binds membranes, and
CC induces plasma membrane protrusions. {ECO:0000250|UniProtKB:O75044}.
CC -!- PTM: Methylation at Arg-927 is required for the stimulation of cell
CC migration, dimerization and localization at the plasma membrane
CC protrusions. {ECO:0000250|UniProtKB:O75044}.
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DR EMBL; AABR06074665; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_006249844.1; XM_006249782.3.
DR RefSeq; XP_006249845.1; XM_006249783.3.
DR AlphaFoldDB; D4A208; -.
DR SMR; D4A208; -.
DR BioGRID; 262246; 1.
DR IntAct; D4A208; 1.
DR MINT; D4A208; -.
DR STRING; 10116.ENSRNOP00000008976; -.
DR iPTMnet; D4A208; -.
DR PhosphoSitePlus; D4A208; -.
DR jPOST; D4A208; -.
DR PaxDb; D4A208; -.
DR PeptideAtlas; D4A208; -.
DR PRIDE; D4A208; -.
DR Ensembl; ENSRNOT00000085967; ENSRNOP00000068925; ENSRNOG00000006733.
DR GeneID; 360840; -.
DR UCSC; RGD:1566016; rat.
DR CTD; 23380; -.
DR RGD; 1566016; Srgap2.
DR eggNOG; KOG3565; Eukaryota.
DR GeneTree; ENSGT00950000182824; -.
DR InParanoid; D4A208; -.
DR OMA; EDFCDSP; -.
DR OrthoDB; 1245523at2759; -.
DR PhylomeDB; D4A208; -.
DR TreeFam; TF315892; -.
DR Reactome; R-RNO-5663220; RHO GTPases Activate Formins.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR Reactome; R-RNO-9013420; RHOU GTPase cycle.
DR Reactome; R-RNO-9013423; RAC3 GTPase cycle.
DR Reactome; R-RNO-9035034; RHOF GTPase cycle.
DR PRO; PR:D4A208; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000006733; Expressed in lung and 18 other tissues.
DR ExpressionAtlas; D4A208; baseline and differential.
DR Genevisible; D4A208; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; ISO:RGD.
DR GO; GO:0044327; C:dendritic spine head; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0051014; P:actin filament severing; ISS:UniProtKB.
DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB.
DR GO; GO:1904861; P:excitatory synapse assembly; ISO:RGD.
DR GO; GO:0021816; P:extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration; ISS:UniProtKB.
DR GO; GO:0046847; P:filopodium assembly; ISS:UniProtKB.
DR GO; GO:1904862; P:inhibitory synapse assembly; ISO:RGD.
DR GO; GO:0003363; P:lamellipodium assembly involved in ameboidal cell migration; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; IBA:GO_Central.
DR GO; GO:2001223; P:negative regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0030334; P:regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; ISO:RGD.
DR CDD; cd11955; SH3_srGAP1-3; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.20.1270.60; -; 1.
DR InterPro; IPR027267; AH/BAR_dom_sf.
DR InterPro; IPR031160; F_BAR.
DR InterPro; IPR001060; FCH_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR035648; srGAP1/2/3_SH3.
DR InterPro; IPR030252; srGAP2.
DR PANTHER; PTHR14166:SF6; PTHR14166:SF6; 1.
DR Pfam; PF00611; FCH; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF00018; SH3_1; 1.
DR SMART; SM00055; FCH; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF103657; SSF103657; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51741; F_BAR; 1.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Coiled coil; Cytoplasm;
KW Cytoplasmic vesicle; GTPase activation; Membrane; Methylation;
KW Neurogenesis; Nucleus; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; SH3 domain; Synapse.
FT CHAIN 1..1071
FT /note="SLIT-ROBO Rho GTPase-activating protein 2"
FT /id="PRO_0000418882"
FT DOMAIN 22..325
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 489..679
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 728..787
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 181..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 703..726
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 794..820
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 835..936
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 983..1012
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1029..1071
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 363..401
FT /evidence="ECO:0000255"
FT COILED 940..968
FT /evidence="ECO:0000255"
FT COMPBIAS 181..204
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 794..809
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 855..884
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 896..931
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1045..1071
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 206
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 427
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 500
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Z67"
FT MOD_RES 691
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 695
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Z67"
FT MOD_RES 724
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 795
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 916
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 927
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 930
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 990
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91Z67"
FT MOD_RES 994
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 1013
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
FT MOD_RES 1027
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75044"
SQ SEQUENCE 1071 AA; 120878 MW; 8713C1B08C9FC9C6 CRC64;
MTSPAKFKKD KEIIAEYDTQ VKEIRAQLTE QMKCLDQQCE LRVQLLQDLQ DFFRKKAEIE
MDYSRNLEKL AERFLAKTRS TKDQQFKKDQ NVLSPVNCWN LLLNQVKRES RDHTTLSDIY
LNNIIPRFVQ VSEDSGRLFK KSKEVGQQLQ DDLMKVLNEL YSVMKTYHMY NADSISAQSK
LKEAEKQEEK QIGKSVKQED RQTPRSPDST ANVRIEEKHV RRSSVKKIEK MKEKRQAKYT
ENKLKAIKAR NEYLLALEAT NASVFKYYIH DLSDIIDQCC DLGYHASLNR ALRTFLSAEL
NLEQSKHEGL DAIENAVENL DATSDKQRLM EMYNNVFCPP MKFEFQPHMG DMASQLCAQQ
PVQSELVQRR QQLQSRLSTL KIENEEVKKT MEATLQTIQD IVTVEDFDVS DCFQYSNSME
SVKSTVSETF MSKPSIAKRR ANQQETEQFY FTKMKEYLEG RNLITKLQAK HDLLQKTLGE
SQRTDCSLAR RSSTVRKQDS SQAIPLVVES CIRFISRHGL RHEGVFRVSG SQVEVNDIKN
AFERGEDPLA GDQNDHDMDS IAGVLKLYFR GLEHPLFPKD IFHDLIACVT MDNLQERAVH
IRKVLLVLPK PTLIIMRYLF AFLNHLSQFS EENMMDPYNL AICFGPSLMS VPEGHDQVSC
QAHVNELIKT IIIQHENIFP NPRELEGPIY SRGGSMEDYC DSTHGETISA EDSTQDVTAE
HHTSDDECEP IEAIAKFDYV GRTARELSFK KGASLLLYQR ASDDWWEGRH NGIDGLIPHQ
YIVVQDTEDG VVERSSPKSE IEVMSEPPEE KVTARTGASC PSGGHVADIY LANINKQRKR
PESGSIRKAF RSDSHGLGSS LTDSSSPGVG ASCRPSSQPI MSQNLPKEGP DKCSISGHGS
LNSISRHSSL KNRMDSPQIR KTATAGRSKS FNNHRPMDPE VIAQDIEATM NSALNELQEL
ERQSSAKHTP DVVLDTLEPL KTSPVVAPTS EPSSPLHTQL LKDPEPAFQR SASTAGDIAC
AFRPVKSVKM AAPVKPPATR PKPTVFPKTN ATSPGVNSSA SPQSTDKSCT V
