O43295 (SRGP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SLIT-ROBO Rho GTPase-activating protein 3
Short name=srGAP3

Alternative name(s):
Mental disorder-associated GAP
Rho GTPase-activating protein 14
WAVE-associated Rac GTPase-activating protein
Short name=WRP

Gene names

Name:	SRGAP3
Synonyms:	ARHGAP14, KIAA0411, KIAA1156, MEGAP, SRGAP2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1099 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons. Ref.1 Ref.2
Subunit structure	Homodimer Probable. Forms a heterooligomer with SRGAP1 and SRGAP2 through its F-BAR domain. Interacts with WASF1. Probably interacts with ROBO1. Interacts with FASLG. Ref.1 Ref.5 Ref.8
Tissue specificity	Highly expressed in adult and fetal brain. Expressed at low levels in kidney. Isoform 3 is expressed in the kidney but is absent in the brain. Ref.1 Ref.2
Domain	The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.
Involvement in disease	A chromosomal aberration involving SRGAP3 is found in a patient with severe idiopathic mental retardation. Translocation t(X;3)(p11.2;p25).
Sequence similarities	Contains 1 FCH domain. Contains 1 Rho-GAP domain. Contains 1 SH3 domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Domain	Coiled coil SH3 domain
Molecular function	GTPase activation
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of GTPase activity Inferred from electronic annotation. Source: GOC regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O43295-1)

Also known as: MEGAPa; srGAP3a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O43295-2)

Also known as: MEGAPb; srGAP3b;

The sequence of this isoform differs from the canonical sequence as follows:
     480-513: PPCLPPKPQKMRRPRPLSVYSHKLFNGSMEAFIK → GRRNARTRNQ

Isoform 3 (identifier: O43295-3)

Also known as: MEGAPc; srGAP3c;

The sequence of this isoform differs from the canonical sequence as follows:
     480-489: PPCLPPKPQK → IQDKLYRL
     490-1099: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1099	1099	SLIT-ROBO Rho GTPase-activating protein 3		PRO_0000056769
Regions
	Domain	22 – 87	66	FCH
	Domain	482 – 670	189	Rho-GAP
	Domain	720 – 779	60	SH3
	Region	1 – 492	492	F-BAR domain
	Coiled coil	352 – 392	41	Potential
	Coiled coil	952 – 987	36	Potential
Amino acid modifications
	Modified residue	837	1	Phosphoserine Ref.7
	Modified residue	1070	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	480 – 513	34	PPCLP…EAFIK → GRRNARTRNQ in isoform 2.		VSP_010581
	Alternative sequence	480 – 489	10	PPCLPPKPQK → IQDKLYRL in isoform 3.		VSP_010582
	Alternative sequence	490 – 1099	610	Missing in isoform 3.		VSP_010583
	Natural variant	623	1	L → I in a breast cancer sample; somatic mutation. Ref.9		VAR_035550
	Natural variant	628	1	I → V. Corresponds to variant rs2271207 [ dbSNP | Ensembl ].		VAR_049159

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (MEGAPa) (srGAP3a) [UniParc]. Last modified June 7, 2004. Version 3. Checksum: 2D1BA2D338E1BF13	FASTA	1,099	124,504
	10 20 30 40 50 60 MSSQTKFKKD KEIIAEYEAQ IKEIRTQLVE QFKCLEQQSE SRLQLLQDLQ EFFRRKAEIE 70 80 90 100 110 120 LEYSRSLEKL AERFSSKIRS SREHQFKKDQ YLLSPVNCWY LVLHQTRRES RDHATLNDIF 130 140 150 160 170 180 MNNVIVRLSQ ISEDVIRLFK KSKEIGLQMH EELLKVTNEL YTVMKTYHMY HAESISAESK 190 200 210 220 230 240 LKEAEKQEEK QFNKSGDLSM NLLRHEDRPQ RRSSVKKIEK MKEKRQAKYS ENKLKCTKAR 250 260 270 280 290 300 NDYLLNLAAT NAAISKYYIH DVSDLIDCCD LGFHASLART FRTYLSAEYN LETSRHEGLD 310 320 330 340 350 360 VIENAVDNLD SRSDKHTVMD MCNQVFCPPL KFEFQPHMGD EVCQVSAQQP VQTELLMRYH 370 380 390 400 410 420 QLQSRLATLK IENEEVRKTL DATMQTLQDM LTVEDFDVSD AFQHSRSTES VKSAASETYM 430 440 450 460 470 480 SKINIAKRRA NQQETEMFYF TKFKEYVNGS NLITKLQAKH DLLKQTLGEG ERAECGTTRP 490 500 510 520 530 540 PCLPPKPQKM RRPRPLSVYS HKLFNGSMEA FIKDSGQAIP LVVESCIRYI NLYGLQQQGI 550 560 570 580 590 600 FRVPGSQVEV NDIKNSFERG EDPLVDDQNE RDINSVAGVL KLYFRGLENP LFPKERFQDL 610 620 630 640 650 660 ISTIKLENPA ERVHQIQQIL VTLPRVVIVV MRYLFAFLNH LSQYSDENMM DPYNLAICFG 670 680 690 700 710 720 PTLMHIPDGQ DPVSCQAHIN EVIKTIIIHH EAIFPSPREL EGPVYEKCMA GGEEYCDSPH 730 740 750 760 770 780 SEPGAIDEVD HDNGTEPHTS DEEVEQIEAI AKFDYMGRSP RELSFKKGAS LLLYHRASED 790 800 810 820 830 840 WWEGRHNGVD GLIPHQYIVV QDMDDAFSDS LSQKADSEAS SGPLLDDKAS SKNDLQSPTE 850 860 870 880 890 900 HISDYGFGGV MGRVRLRSDG AAIPRRRSGG DTHSPPRGLG PSIDTPPRAA ACPSSPHKIP 910 920 930 940 950 960 LTRGRIESPE KRRMATFGSA GSINYPDKKA LSEGHSMRST CGSTRHSSLG DHKSLEAEAL 970 980 990 1000 1010 1020 AEDIEKTMST ALHELRELER QNTVKQAPDV VLDTLEPLKN PPGPVSSEPA SPLHTIVIRD 1030 1040 1050 1060 1070 1080 PDAAMRRSSS SSTEMMTTFK PALSARLAGA QLRPPPMRPV RPVVQHRSSS SSSSGVGSPA 1090 VTPTEKMFPN SSADKSGTM
	Isoform 2 (MEGAPb) (srGAP3b) [UniParc]. Checksum: 442CA4D408B1F157	FASTA	1,075	121,780
	10 20 30 40 50 60 MSSQTKFKKD KEIIAEYEAQ IKEIRTQLVE QFKCLEQQSE SRLQLLQDLQ EFFRRKAEIE 70 80 90 100 110 120 LEYSRSLEKL AERFSSKIRS SREHQFKKDQ YLLSPVNCWY LVLHQTRRES RDHATLNDIF 130 140 150 160 170 180 MNNVIVRLSQ ISEDVIRLFK KSKEIGLQMH EELLKVTNEL YTVMKTYHMY HAESISAESK 190 200 210 220 230 240 LKEAEKQEEK QFNKSGDLSM NLLRHEDRPQ RRSSVKKIEK MKEKRQAKYS ENKLKCTKAR 250 260 270 280 290 300 NDYLLNLAAT NAAISKYYIH DVSDLIDCCD LGFHASLART FRTYLSAEYN LETSRHEGLD 310 320 330 340 350 360 VIENAVDNLD SRSDKHTVMD MCNQVFCPPL KFEFQPHMGD EVCQVSAQQP VQTELLMRYH 370 380 390 400 410 420 QLQSRLATLK IENEEVRKTL DATMQTLQDM LTVEDFDVSD AFQHSRSTES VKSAASETYM 430 440 450 460 470 480 SKINIAKRRA NQQETEMFYF TKFKEYVNGS NLITKLQAKH DLLKQTLGEG ERAECGTTRG 490 500 510 520 530 540 RRNARTRNQD SGQAIPLVVE SCIRYINLYG LQQQGIFRVP GSQVEVNDIK NSFERGEDPL 550 560 570 580 590 600 VDDQNERDIN SVAGVLKLYF RGLENPLFPK ERFQDLISTI KLENPAERVH QIQQILVTLP 610 620 630 640 650 660 RVVIVVMRYL FAFLNHLSQY SDENMMDPYN LAICFGPTLM HIPDGQDPVS CQAHINEVIK 670 680 690 700 710 720 TIIIHHEAIF PSPRELEGPV YEKCMAGGEE YCDSPHSEPG AIDEVDHDNG TEPHTSDEEV 730 740 750 760 770 780 EQIEAIAKFD YMGRSPRELS FKKGASLLLY HRASEDWWEG RHNGVDGLIP HQYIVVQDMD 790 800 810 820 830 840 DAFSDSLSQK ADSEASSGPL LDDKASSKND LQSPTEHISD YGFGGVMGRV RLRSDGAAIP 850 860 870 880 890 900 RRRSGGDTHS PPRGLGPSID TPPRAAACPS SPHKIPLTRG RIESPEKRRM ATFGSAGSIN 910 920 930 940 950 960 YPDKKALSEG HSMRSTCGST RHSSLGDHKS LEAEALAEDI EKTMSTALHE LRELERQNTV 970 980 990 1000 1010 1020 KQAPDVVLDT LEPLKNPPGP VSSEPASPLH TIVIRDPDAA MRRSSSSSTE MMTTFKPALS 1030 1040 1050 1060 1070 ARLAGAQLRP PPMRPVRPVV QHRSSSSSSS GVGSPAVTPT EKMFPNSSAD KSGTM
	Isoform 3 (MEGAPc) (srGAP3c) [UniParc]. Checksum: 1C99D701F9A3563B	FASTA	487	57,227
	10 20 30 40 50 60 MSSQTKFKKD KEIIAEYEAQ IKEIRTQLVE QFKCLEQQSE SRLQLLQDLQ EFFRRKAEIE 70 80 90 100 110 120 LEYSRSLEKL AERFSSKIRS SREHQFKKDQ YLLSPVNCWY LVLHQTRRES RDHATLNDIF 130 140 150 160 170 180 MNNVIVRLSQ ISEDVIRLFK KSKEIGLQMH EELLKVTNEL YTVMKTYHMY HAESISAESK 190 200 210 220 230 240 LKEAEKQEEK QFNKSGDLSM NLLRHEDRPQ RRSSVKKIEK MKEKRQAKYS ENKLKCTKAR 250 260 270 280 290 300 NDYLLNLAAT NAAISKYYIH DVSDLIDCCD LGFHASLART FRTYLSAEYN LETSRHEGLD 310 320 330 340 350 360 VIENAVDNLD SRSDKHTVMD MCNQVFCPPL KFEFQPHMGD EVCQVSAQQP VQTELLMRYH 370 380 390 400 410 420 QLQSRLATLK IENEEVRKTL DATMQTLQDM LTVEDFDVSD AFQHSRSTES VKSAASETYM 430 440 450 460 470 480 SKINIAKRRA NQQETEMFYF TKFKEYVNGS NLITKLQAKH DLLKQTLGEG ERAECGTTRI QDKLYRL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling." Soderling S.H., Binns K.L., Wayman G.A., Davee S.M., Ong S.H., Pawson T., Scott J.D. Nat. Cell Biol. 4:970-975(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH WASF1.
[2]	"The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative role in severe mental retardation." Endris V., Wogatzky B., Leimer U., Bartsch D., Zatyka M., Latif F., Maher E.R., Tariverdian G., Kirsch S., Karch D., Rappold G.A. Proc. Natl. Acad. Sci. U.S.A. 99:11754-11759(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 2 AND 3), FUNCTION, TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION.
[3]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-1099 (ISOFORM 2). Tissue: Brain.
[4]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[5]	"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.
[6]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Platelet.
[7]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-837, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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.
[9]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-623.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF464189 mRNA. Translation: AAN57784.1. AF427144 mRNA. Translation: AAN07095.1. AB007871 mRNA. Translation: BAA24841.2.
IPI	IPI00218087. IPI00412209. IPI00412210.
RefSeq	NP_001028289.1. NM_001033117.2. NP_055665.1. NM_014850.3.
UniGene	Hs.654743.
3D structure databases
ProteinModelPortal	O43295.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43295. 3 interactions.
STRING	9606.ENSP00000373347.
PTM databases
PhosphoSite	O43295.
Proteomic databases
PaxDb	O43295.
PRIDE	O43295.
Protocols and materials databases
DNASU	9901.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360413; ENSP00000353587; ENSG00000196220. ENST00000383836; ENSP00000373347; ENSG00000196220.
GeneID	9901.
KEGG	hsa:9901.
UCSC	uc003brf.1. human. uc003brg.1. human. uc003brk.3. human.
Organism-specific databases
CTD	9901.
GeneCards	GC03M008998.
HGNC	HGNC:19744. SRGAP3.
HPA	HPA036959.
MIM	606525. gene.
neXtProt	NX_O43295.
PharmGKB	PA134935463.
HUGE	Search... Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG264793.
HOGENOM	HOG000039980.
HOVERGEN	HBG051637.
InParanoid	O43295.
KO	K07526.
OMA	IQQILIT.
OrthoDB	EOG4JT04N.
PhylomeDB	O43295.
Enzyme and pathway databases
Reactome	REACT_111045. Developmental Biology. REACT_111102. Signal Transduction. REACT_96538. Developmental Biology.
Gene expression databases
Bgee	O43295.
CleanEx	HS_SRGAP2. HS_SRGAP3.
Genevestigator	O43295.
GermOnline	ENSG00000196220. Homo sapiens.
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	SRGAP3. human.
GenomeRNAi	9901.
NextBio	37331.
SOURCE	Search...

Entry information

Entry name

SRGP3_HUMAN

Accession

Primary (citable) accession number: O43295
Secondary accession number(s): Q8IX13, Q8IZV8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	June 7, 2004
Last modified:	May 1, 2013
This is version 123 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.