Q91Z67 (SRGP2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SLIT-ROBO Rho GTPase-activating protein 2
Short name=srGAP2

Alternative name(s):
Formin-binding protein 2
Formin-binding protein 27
Short name=FBP-27

Gene names

Name:	Srgap2
Synonyms:	Fbp27, Fnbp2

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1071 AA.
Sequence status	Complete.
Protein existence	Evidence 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. May play a role 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.10
Subunit structure	Homodimer. Interacts with FASLG By similarity. Interacts with PRMT5 By similarity. Probably interacts with ROBO1 and ROBO2. Interacts with RAC1; specifically stimulates RAC1 GTPase activity. Interacts (via SH3 domain) with FMNL1 (activated by RAC1); regulates the actin filament severing activity of FMNL1. Interacts (via SH3 domain) with FMNL3. Interacts (via SH3 domain) with GPHN. Ref.7 Ref.8 Ref.9
Subcellular location	Cell membrane By similarity. Cell projection › dendritic spine By similarity. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Cell junction › synapse › postsynaptic cell membrane. Cell projection › lamellipodium By similarity. Cytoplasmic vesicle › phagosome. Nucleus By similarity. Cytoplasm By similarity. Note: Recruited to actin-rich phagosomes during phagocytosis. Translocates from nucleus to cytoplasm during development By similarity. Ref.8 Ref.10
Developmental stage	Expressed throughout cortical development culminating at P1. Expression is reduced but still present in the adult cortex. Expressed in the cortical wall both in neuronal progenitors in the ventricular zone and post-mitotic neurons in the cortical plate (at protein level). Ref.7
Domain	The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.
Post-translational modification	Methylation at Arg-927 is required for the stimulation of cell migration, dimerization and localization at the plasma membrane protrusions By similarity.
Disruption phenotype	Mice are viable and show no abnormality of cortical lamination. However, a delay in dendritic spine maturation coupled to an increase in spine neck and spine density is observed. Ref.10
Sequence similarities	Contains 1 FCH domain. Contains 1 Rho-GAP domain. Contains 1 SH3 domain.

Ontologies

Keywords
Biological process	Neurogenesis
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoplasmic vesicle Membrane Nucleus Postsynaptic cell membrane Synapse
Domain	Coiled coil SH3 domain
Molecular function	GTPase activation
PTM	Methylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin filament severing Inferred from sequence or structural similarity. Source: UniProtKB dendritic spine development Inferred from mutant phenotype Ref.10. Source: UniProtKB extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration Inferred from mutant phenotype Ref.7. Source: UniProtKB filopodium assembly Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of neuron migration Inferred from sequence or structural similarity. Source: UniProtKB neuron projection morphogenesis Inferred from mutant phenotype Ref.7. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from direct assay Ref.8. Source: UniProtKB lamellipodium Inferred from electronic annotation. Source: UniProtKB-SubCell mitochondrial inner membrane Inferred from direct assay PubMed 12865426. Source: MGI nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell phagocytic vesicle Inferred from direct assay Ref.8. Source: UniProtKB plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB postsynaptic density Inferred from direct assay Ref.10. Source: UniProtKB postsynaptic membrane Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	Rac GTPase activator activity Inferred from direct assay Ref.7. Source: UniProtKB Rac GTPase binding Inferred from direct assay Ref.7. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1071	1071	SLIT-ROBO Rho GTPase-activating protein 2		PRO_0000056768
Regions
	Domain	22 – 87	66	FCH
	Domain	489 – 679	191	Rho-GAP
	Domain	728 – 787	60	SH3
	Region	1 – 502	502	F-BAR domain By similarity
	Coiled coil	363 – 401	39	Potential
	Coiled coil	940 – 968	29	Potential
Amino acid modifications
	Modified residue	799	1	Phosphoserine Ref.6
	Modified residue	927	1	Omega-N-methylated arginine; by PRMT5 By similarity
	Modified residue	930	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	527	1	R → L: Unable to stimulate RAC1 GTPase activity and to induce neurite branching. No effect on filopodia biogenesis and neurite outgrowth. Ref.7
	Mutagenesis	765	1	W → A: Loss of the ability to induce filopodia and to initiate neurite outgrowht. Ref.7
	Sequence conflict	598	1	A → V in AAL27032. Ref.3
	Sequence conflict	612	1	T → S in AAL27032. Ref.3
	Sequence conflict	662	1	A → S in AAL27032. Ref.3
	Sequence conflict	737	1	F → C in AAL27032. Ref.3
	Sequence conflict	765	1	W → L in AAL27032. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q91Z67 [UniParc]. Last modified January 9, 2007. Version 2. Checksum: 9093C63476BA605D	FASTA	1,071	120,798
	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 DLSDIIDQCC 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 IFHDLIACVT MDNLQERAVH 610 620 630 640 650 660 IRKVLLVLPK PTLIIMRYLF AFLNHLSQFS EENMMDPYNL AICFGPSLMS VPEGHDQVSC 670 680 690 700 710 720 QAHVNELIKT IIIQHENIFP NPRELEGPIY SRGGSMEDYC DSTHGETTSA EDSTQDVTAE 730 740 750 760 770 780 HHTSDDECEP IEAIAKFDYV GRTARELSFK KGASLLLYQR ASDDWWEGRH NGIDGLIPHQ 790 800 810 820 830 840 YIVVQDTEDG VVERSSPKSE IEVMSEPPEE KVTARTGASC PSGGHVADIY LANINKQRKR 850 860 870 880 890 900 PESGSIRKAF RSDSHGLGSS LTDSSSLGVG ASCRPSSQPI MSQNLPKEGP DKCSISGHGS 910 920 930 940 950 960 LNSISRHSSL KNRMDSPQIR KTATAGRSKS FNNHRPMDPE VIAQDIEATM NSALNELQEL 970 980 990 1000 1010 1020 ERQSSAKHTP DVVLDTLEPL KTSPVVAPTS EPSSPLHTQL LKDPEPAFQR SASTAGDIAC 1030 1040 1050 1060 1070 AFRPVKSVKM AAPVKPPATR PKPTVFPKTN ATSPGVNSSA SPQATDKSCT V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"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: NUCLEOTIDE SEQUENCE [MRNA] OF 432-836.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 538-1071. Strain: C57BL/6J. Tissue: Brain.
[5]	"Formin binding proteins bear WWP/WW domains that bind proline-rich peptides and functionally resemble SH3 domains." Chan D.C., Bedford M.T., Leder P. EMBO J. 15:1045-1054(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 732-782. Strain: FVB.
[6]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-799, MASS SPECTROMETRY. Tissue: Liver.
[7]	"The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis." Guerrier S., Coutinho-Budd J., Sassa T., Gresset A., Jordan N.V., Chen K., Jin W.L., Frost A., Polleux F. Cell 138:990-1004(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEURON MIGRATION AND MORPHOGENESIS, DEVELOPMENTAL STAGE, SUBUNIT, INTERACTION WITH RAC1, MUTAGENESIS OF ARG-527 AND TRP-765.
[8]	"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: INTERACTION WITH FMNL1; FMNL3 AND ROBO2, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[9]	"SH3 domain-based phototrapping in living cells reveals Rho family GAP signaling complexes." Okada H., Uezu A., Mason F.M., Soderblom E.J., Moseley M.A. III, Soderling S.H. Sci. Signal. 4:RS13-RS13(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GPHN.
[10]	"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 IN DENDRITIC SPINE MATURATION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Branching out - Issue 143 of October 2012

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC109299 Genomic DNA. No translation available. AC120217 Genomic DNA. No translation available. AC165436 Genomic DNA. No translation available. BC151081 mRNA. Translation: AAI51082.1. BC151082 mRNA. Translation: AAI51083.1. BC158055 mRNA. Translation: AAI58056.1. BC172152 mRNA. Translation: AAI72152.1. AY057900 mRNA. Translation: AAL27032.1. AK132220 mRNA. Translation: BAE21041.1. U40752 mRNA. Translation: AAC52480.1.
IPI	IPI00676293.
PIR	S64712.
RefSeq	NP_001074480.2. NM_001081011.2.
UniGene	Mm.276259.
3D structure databases
ProteinModelPortal	Q91Z67.
SMR	Q91Z67. Positions 505-679, 723-787.
ModBase	Search...
PTM databases
PhosphoSite	Q91Z67.
Proteomic databases
PaxDb	Q91Z67.
PRIDE	Q91Z67.
Protocols and materials databases
DNASU	14270.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000097588; ENSMUSP00000095195; ENSMUSG00000026425.
GeneID	14270.
KEGG	mmu:14270.
UCSC	uc007cng.2. mouse.
Organism-specific databases
CTD	23380.
MGI	MGI:109605. Srgap2.
Phylogenomic databases
eggNOG	NOG264793.
GeneTree	ENSGT00690000101648.
HOGENOM	HOG000039980.
HOVERGEN	HBG051637.
KO	K07526.
OMA	ANVRIEE.
OrthoDB	EOG4MSCXF.
Gene expression databases
Bgee	Q91Z67.
CleanEx	MM_SRGAP2.
Genevestigator	Q91Z67.
GermOnline	ENSMUSG00000026425. Mus musculus.
Family and domain databases
Gene3D	1.10.555.10. 1 hit.
InterPro	IPR001060. FCH_dom. IPR008936. Rho_GTPase_activation_prot. IPR000198. RhoGAP_dom. IPR001452. SH3_domain. [Graphical view]
Pfam	PF00611. FCH. 1 hit. PF00620. RhoGAP. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
SMART	SM00055. FCH. 1 hit. SM00324. RhoGAP. 1 hit. SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF48350. Rho_GAP. 1 hit. SSF50044. SH3. 1 hit.
PROSITE	PS50133. FCH. 1 hit. PS50238. RHOGAP. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	SRGAP2. mouse.
NextBio	285639.
SOURCE	Search...

Entry information

Entry name

SRGP2_MOUSE

Accession

Primary (citable) accession number: Q91Z67
Secondary accession number(s): B2RY13, Q3V1V8, Q61054

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 7, 2004
Last sequence update:	January 9, 2007
Last modified:	May 1, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program