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O43295 (SRGP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1099 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HTTP428584EBI-368166,EBI-466029

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10991099SLIT-ROBO Rho GTPase-activating protein 3
PRO_0000056769

Regions

Domain22 – 8766FCH
Domain482 – 670189Rho-GAP
Domain720 – 77960SH3
Region1 – 492492F-BAR domain
Coiled coil352 – 39241 Potential
Coiled coil952 – 98736 Potential

Amino acid modifications

Modified residue8371Phosphoserine Ref.7

Natural variations

Alternative sequence480 – 51334PPCLP…EAFIK → GRRNARTRNQ in isoform 2.
VSP_010581
Alternative sequence480 – 48910PPCLPPKPQK → IQDKLYRL in isoform 3.
VSP_010582
Alternative sequence490 – 1099610Missing in isoform 3.
VSP_010583
Natural variant6231L → I in a breast cancer sample; somatic mutation. Ref.9
VAR_035550
Natural variant6281I → V.
Corresponds to variant rs2271207 [ dbSNP | Ensembl ].
VAR_049159

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (MEGAPa) (srGAP3a) [UniParc].

Last modified June 7, 2004. Version 3.
Checksum: 2D1BA2D338E1BF13

FASTA1,099124,504
        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) (srGAP3b) [UniParc].

Checksum: 442CA4D408B1F157
Show »

FASTA1,075121,780
Isoform 3 (MEGAPc) (srGAP3c) [UniParc].

Checksum: 1C99D701F9A3563B
Show »

FASTA48757,227

References

« Hide '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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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. expand/collapse author list , 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.
RefSeqNP_001028289.1. NM_001033117.2.
NP_055665.1. NM_014850.3.
UniGeneHs.654743.

3D structure databases

ProteinModelPortalO43295.
SMRO43295. Positions 26-337, 467-694, 749-800.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115230. 8 interactions.
IntActO43295. 8 interactions.
MINTMINT-2795945.
STRING9606.ENSP00000373347.

PTM databases

PhosphoSiteO43295.

Proteomic databases

PaxDbO43295.
PRIDEO43295.

Protocols and materials databases

DNASU9901.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360413; ENSP00000353587; ENSG00000196220. [O43295-2]
ENST00000383836; ENSP00000373347; ENSG00000196220. [O43295-1]
GeneID9901.
KEGGhsa:9901.
UCSCuc003brf.2. human. [O43295-1]
uc003brg.2. human. [O43295-2]
uc003brk.4. human. [O43295-3]

Organism-specific databases

CTD9901.
GeneCardsGC03M008998.
HGNCHGNC:19744. SRGAP3.
HPAHPA036959.
MIM606525. gene.
neXtProtNX_O43295.
Orphanet251612. Pilocytic astrocytoma.
PharmGKBPA134935463.
HUGESearch...
Search...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG264793.
HOGENOMHOG000039980.
HOVERGENHBG051637.
InParanoidO43295.
KOK07526.
OMAIQQILIT.
OrthoDBEOG7966FQ.
PhylomeDBO43295.
TreeFamTF315892.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_195021. Developmental Biology.

Gene expression databases

BgeeO43295.
CleanExHS_SRGAP2.
HS_SRGAP3.
GenevestigatorO43295.

Family and domain databases

Gene3D1.10.555.10. 1 hit.
InterProIPR001060. FCH_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR000198. RhoGAP_dom.
IPR001452. SH3_domain.
[Graphical view]
PfamPF00611. FCH. 1 hit.
PF00620. RhoGAP. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTSM00055. FCH. 1 hit.
SM00324. RhoGAP. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 1 hit.
SSF50044. SSF50044. 1 hit.
PROSITEPS50133. FCH. 1 hit.
PS50238. RHOGAP. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSRGAP3. human.
GeneWikiSRGAP3.
GenomeRNAi9901.
NextBio37331.
PROO43295.
SOURCESearch...

Entry information

Entry nameSRGP3_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 132 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM