SLIT-ROBO Rho GTPase-activating protein 3

Names and origin

Protein names

Recommended name:
    SLIT-ROBO Rho GTPase-activating protein 3
      Short name=srGAP3
Alternative name(s):
    srGAP2
    WAVE-associated Rac GTPase-activating protein
      Short name=WRP
    Mental disorder-associated GAP
    Rho GTPase-activating protein 14

Gene names

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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	1099 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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	Interacts with WASF1. Probably interacts with ROBO1. Ref.1 Ref.5
Tissue specificity	Highly expressed in adult and fetal brain. Expressed at low levels in kidney. Ref.1 Ref.2
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.

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Ontologies

Keywords
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Domain	Coiled coil SH3 domain
Molecular function	GTPase activation
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	intracellular Inferred from electronic annotation. Source: InterPro
Molecular function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

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Alternative products

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

Isoform 1 (identifier: O43295-1) Also known as: MEGAPa; 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; 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; The sequence of this isoform differs from the canonical sequence as follows: 480-489: PPCLPPKPQK → IQDKLYRL 490-1099: Missing.

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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

Coiled coil

352 – 392

41

Potential

Coiled coil

952 – 987

36

Potential

Amino acid modifications

Modified residue

220

1

N6-acetyllysine Ref.8

Modified residue

222

1

N6-acetyllysine Ref.8

Modified residue

224

1

N6-acetyllysine Ref.8

Modified residue

602

1

Phosphoserine Ref.6

Modified residue

837

1

Phosphoserine Ref.7

Modified residue

858

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: dbSNP rs2271207.

VAR_049159

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Sequences

Sequence		Length	Mass (Da)
Isoform 1 (MEGAPa) [UniParc]. Last modified June 7, 2004. Version 3. Checksum: 2D1BA2D338E1BF13 Show »	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 « Hide
Isoform 2 (MEGAPb). Checksum: 442CA4D408B1F157 Show »	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 « Hide
Isoform 3 (MEGAPc). Checksum: 1C99D701F9A3563B Show »	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 « Hide

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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: 12447388] [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: 12195014] [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: 9455477] [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: 12168954] [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: 11672528] [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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-602, MASS SPECTROMETRY. 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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-837 AND SER-858, MASS SPECTROMETRY.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-220; LYS-222 AND LYS-224, MASS SPECTROMETRY.
[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. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-623.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	AF464189 mRNA. Translation: AAN57784.1. AF427144 mRNA. Translation: AAN07095.1. AB007871 mRNA. Translation: BAA24841.2.
IPI	IPI00218087. IPI00412209. IPI00412210.
RefSeq	NP_001028289.1. NP_055665.1.
UniGene	Hs.654743
3D structure databases
HSSP	HSSP built from PDB template 1AZE based on UniProtKB P29354.
SMR	O43295. Positions 749-800.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43295. 2 interactions.
STRING	O43295.
PTM databases
PhosphoSite	O43295.
Proteomic databases
PRIDE	O43295.
Genome annotation databases
Ensembl	ENST00000360413; ENSP00000353587; ENSG00000196220; Homo sapiens. [Genome view] ENST00000383836; ENSP00000373347; ENSG00000196220; Homo sapiens. [Genome view] ENST00000433332; ENSP00000406259; ENSG00000196220; Homo sapiens. [Genome view]
GeneID	9901.
KEGG	hsa:9901.
UCSC	uc003brf.1. human. uc003brg.1. human.
Organism-specific databases
CTD	9901.
GeneCards	GC03M008998.
H-InvDB	HIX0003024. HIX0077832.
HGNC	HGNC:19744. SRGAP3.
MIM	606525. gene.
PharmGKB	PA134935463.
HUGE	Search... Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O43295.
HOVERGEN	O43295.
OMA	CPSSPHK.
Enzyme and pathway databases
Reactome	REACT_11044. Signaling by Rho GTPases. REACT_18266. Axon guidance.
Gene expression databases
ArrayExpress	O43295.
Bgee	O43295.
CleanEx	HS_SRGAP2. HS_SRGAP3.
Genevestigator	O43295.
GermOnline	ENSG00000196220. Homo sapiens.
Family and domain databases
InterPro	IPR001060. FCH. IPR000198. RhoGAP. IPR001452. SH3_domain. [Graphical view]
Gene3D	G3DSA:1.10.555.10. RhoGAP. 1 hit.
Pfam	PF00611. FCH. 1 hit. PF00620. RhoGAP. 1 hit. PF00018. SH3_1. 1 hit. [Graphical view]
ProDom	PD000066. SH3. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00055. FCH. 1 hit. SM00324. RhoGAP. 1 hit. SM00326. SH3. 1 hit. [Graphical view]
PROSITE	PS50133. FCH. 1 hit. PS50238. RHOGAP. 1 hit. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	37331.
SOURCE	Search...

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Entry information

Entry name

SRGP2_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:	November 3, 2009
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Alternative products

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents