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O43295

- SRGP3_HUMAN

UniProt

O43295 - SRGP3_HUMAN

Protein

SLIT-ROBO Rho GTPase-activating protein 3

Gene

SRGAP3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 3 (07 Jun 2004)
      Previous versions | rss
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    Functioni

    GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons.2 Publications

    GO - Molecular functioni

    1. GTPase activator activity Source: UniProtKB-KW
    2. protein binding Source: IntAct

    GO - Biological processi

    1. regulation of small GTPase mediated signal transduction Source: Reactome
    2. small GTPase mediated signal transduction Source: Reactome

    Keywords - Molecular functioni

    GTPase activation

    Enzyme and pathway databases

    ReactomeiREACT_11051. Rho GTPase cycle.
    REACT_19342. Inactivation of Cdc42 and Rac.

    Names & Taxonomyi

    Protein namesi
    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 namesi
    Name:SRGAP3
    Synonyms:ARHGAP14, KIAA0411, KIAA1156, MEGAP, SRGAP2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 3

    Organism-specific databases

    HGNCiHGNC:19744. SRGAP3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome

    Pathology & Biotechi

    Involvement in diseasei

    A chromosomal aberration involving SRGAP3 is found in a patient with severe idiopathic mental retardation. Translocation t(X;3)(p11.2;p25).

    Organism-specific databases

    Orphaneti251612. Pilocytic astrocytoma.
    PharmGKBiPA134935463.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10991099SLIT-ROBO Rho GTPase-activating protein 3PRO_0000056769Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei837 – 8371Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO43295.
    PaxDbiO43295.
    PRIDEiO43295.

    PTM databases

    PhosphoSiteiO43295.

    Expressioni

    Tissue specificityi

    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.2 Publications

    Gene expression databases

    BgeeiO43295.
    CleanExiHS_SRGAP2.
    HS_SRGAP3.
    GenevestigatoriO43295.

    Organism-specific databases

    HPAiHPA036959.

    Interactioni

    Subunit structurei

    Homodimer Probable. Forms a heterooligomer with SRGAP1 and SRGAP2 through its F-BAR domain. Interacts with WASF1. Probably interacts with ROBO1. Interacts with FASLG.3 PublicationsCurated

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HTTP428584EBI-368166,EBI-466029

    Protein-protein interaction databases

    BioGridi115230. 8 interactions.
    IntActiO43295. 8 interactions.
    MINTiMINT-2795945.
    STRINGi9606.ENSP00000373347.

    Structurei

    3D structure databases

    ProteinModelPortaliO43295.
    SMRiO43295. Positions 26-337, 502-693, 749-800.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini22 – 8766FCHPROSITE-ProRule annotationAdd
    BLAST
    Domaini482 – 670189Rho-GAPPROSITE-ProRule annotationAdd
    BLAST
    Domaini720 – 77960SH3PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 492492F-BAR domainAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili352 – 39241Sequence AnalysisAdd
    BLAST
    Coiled coili952 – 98736Sequence AnalysisAdd
    BLAST

    Domaini

    The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.

    Sequence similaritiesi

    Contains 1 FCH domain.PROSITE-ProRule annotation
    Contains 1 Rho-GAP domain.PROSITE-ProRule annotation
    Contains 1 SH3 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil, SH3 domain

    Phylogenomic databases

    eggNOGiNOG264793.
    HOGENOMiHOG000039980.
    HOVERGENiHBG051637.
    InParanoidiO43295.
    KOiK07526.
    OMAiIQQILIT.
    OrthoDBiEOG7966FQ.
    PhylomeDBiO43295.
    TreeFamiTF315892.

    Family and domain databases

    Gene3Di1.10.555.10. 1 hit.
    InterProiIPR001060. FCH_dom.
    IPR008936. Rho_GTPase_activation_prot.
    IPR000198. RhoGAP_dom.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00611. FCH. 1 hit.
    PF00620. RhoGAP. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    SMARTiSM00055. FCH. 1 hit.
    SM00324. RhoGAP. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view]
    SUPFAMiSSF48350. SSF48350. 1 hit.
    SSF50044. SSF50044. 1 hit.
    PROSITEiPS50133. FCH. 1 hit.
    PS50238. RHOGAP. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O43295-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MSSQTKFKKD KEIIAEYEAQ IKEIRTQLVE QFKCLEQQSE SRLQLLQDLQ     50
    EFFRRKAEIE LEYSRSLEKL AERFSSKIRS SREHQFKKDQ YLLSPVNCWY 100
    LVLHQTRRES RDHATLNDIF MNNVIVRLSQ ISEDVIRLFK KSKEIGLQMH 150
    EELLKVTNEL YTVMKTYHMY HAESISAESK LKEAEKQEEK QFNKSGDLSM 200
    NLLRHEDRPQ RRSSVKKIEK MKEKRQAKYS ENKLKCTKAR NDYLLNLAAT 250
    NAAISKYYIH DVSDLIDCCD LGFHASLART FRTYLSAEYN LETSRHEGLD 300
    VIENAVDNLD SRSDKHTVMD MCNQVFCPPL KFEFQPHMGD EVCQVSAQQP 350
    VQTELLMRYH QLQSRLATLK IENEEVRKTL DATMQTLQDM LTVEDFDVSD 400
    AFQHSRSTES VKSAASETYM SKINIAKRRA NQQETEMFYF TKFKEYVNGS 450
    NLITKLQAKH DLLKQTLGEG ERAECGTTRP PCLPPKPQKM RRPRPLSVYS 500
    HKLFNGSMEA FIKDSGQAIP LVVESCIRYI NLYGLQQQGI FRVPGSQVEV 550
    NDIKNSFERG EDPLVDDQNE RDINSVAGVL KLYFRGLENP LFPKERFQDL 600
    ISTIKLENPA ERVHQIQQIL VTLPRVVIVV MRYLFAFLNH LSQYSDENMM 650
    DPYNLAICFG PTLMHIPDGQ DPVSCQAHIN EVIKTIIIHH EAIFPSPREL 700
    EGPVYEKCMA GGEEYCDSPH SEPGAIDEVD HDNGTEPHTS DEEVEQIEAI 750
    AKFDYMGRSP RELSFKKGAS LLLYHRASED WWEGRHNGVD GLIPHQYIVV 800
    QDMDDAFSDS LSQKADSEAS SGPLLDDKAS SKNDLQSPTE HISDYGFGGV 850
    MGRVRLRSDG AAIPRRRSGG DTHSPPRGLG PSIDTPPRAA ACPSSPHKIP 900
    LTRGRIESPE KRRMATFGSA GSINYPDKKA LSEGHSMRST CGSTRHSSLG 950
    DHKSLEAEAL AEDIEKTMST ALHELRELER QNTVKQAPDV VLDTLEPLKN 1000
    PPGPVSSEPA SPLHTIVIRD PDAAMRRSSS SSTEMMTTFK PALSARLAGA 1050
    QLRPPPMRPV RPVVQHRSSS SSSSGVGSPA VTPTEKMFPN SSADKSGTM 1099
    Length:1,099
    Mass (Da):124,504
    Last modified:June 7, 2004 - v3
    Checksum:i2D1BA2D338E1BF13
    GO
    Isoform 2 (identifier: O43295-2) [UniParc]FASTAAdd to Basket

    Also known as: MEGAPb, srGAP3b

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

    Show »
    Length:1,075
    Mass (Da):121,780
    Checksum:i442CA4D408B1F157
    GO
    Isoform 3 (identifier: O43295-3) [UniParc]FASTAAdd to Basket

    Also known as: MEGAPc, srGAP3c

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

    Show »
    Length:487
    Mass (Da):57,227
    Checksum:i1C99D701F9A3563B
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti623 – 6231L → I in a breast cancer sample; somatic mutation. 1 Publication
    VAR_035550
    Natural varianti628 – 6281I → V.
    Corresponds to variant rs2271207 [ dbSNP | Ensembl ].
    VAR_049159

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei480 – 51334PPCLP…EAFIK → GRRNARTRNQ in isoform 2. 2 PublicationsVSP_010581Add
    BLAST
    Alternative sequencei480 – 48910PPCLPPKPQK → IQDKLYRL in isoform 3. CuratedVSP_010582
    Alternative sequencei490 – 1099610Missing in isoform 3. CuratedVSP_010583Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF464189 mRNA. Translation: AAN57784.1.
    AF427144 mRNA. Translation: AAN07095.1.
    AB007871 mRNA. Translation: BAA24841.2.
    CCDSiCCDS2572.1. [O43295-1]
    CCDS33689.1. [O43295-2]
    RefSeqiNP_001028289.1. NM_001033117.2. [O43295-2]
    NP_055665.1. NM_014850.3. [O43295-1]
    UniGeneiHs.654743.

    Genome annotation databases

    EnsembliENST00000360413; ENSP00000353587; ENSG00000196220. [O43295-2]
    ENST00000383836; ENSP00000373347; ENSG00000196220. [O43295-1]
    GeneIDi9901.
    KEGGihsa:9901.
    UCSCiuc003brf.2. human. [O43295-1]
    uc003brg.2. human. [O43295-2]
    uc003brk.4. human. [O43295-3]

    Keywords - Coding sequence diversityi

    Alternative splicing, Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF464189 mRNA. Translation: AAN57784.1 .
    AF427144 mRNA. Translation: AAN07095.1 .
    AB007871 mRNA. Translation: BAA24841.2 .
    CCDSi CCDS2572.1. [O43295-1 ]
    CCDS33689.1. [O43295-2 ]
    RefSeqi NP_001028289.1. NM_001033117.2. [O43295-2 ]
    NP_055665.1. NM_014850.3. [O43295-1 ]
    UniGenei Hs.654743.

    3D structure databases

    ProteinModelPortali O43295.
    SMRi O43295. Positions 26-337, 502-693, 749-800.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115230. 8 interactions.
    IntActi O43295. 8 interactions.
    MINTi MINT-2795945.
    STRINGi 9606.ENSP00000373347.

    PTM databases

    PhosphoSitei O43295.

    Proteomic databases

    MaxQBi O43295.
    PaxDbi O43295.
    PRIDEi O43295.

    Protocols and materials databases

    DNASUi 9901.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000360413 ; ENSP00000353587 ; ENSG00000196220 . [O43295-2 ]
    ENST00000383836 ; ENSP00000373347 ; ENSG00000196220 . [O43295-1 ]
    GeneIDi 9901.
    KEGGi hsa:9901.
    UCSCi uc003brf.2. human. [O43295-1 ]
    uc003brg.2. human. [O43295-2 ]
    uc003brk.4. human. [O43295-3 ]

    Organism-specific databases

    CTDi 9901.
    GeneCardsi GC03M008998.
    HGNCi HGNC:19744. SRGAP3.
    HPAi HPA036959.
    MIMi 606525. gene.
    neXtProti NX_O43295.
    Orphaneti 251612. Pilocytic astrocytoma.
    PharmGKBi PA134935463.
    HUGEi Search...
    Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG264793.
    HOGENOMi HOG000039980.
    HOVERGENi HBG051637.
    InParanoidi O43295.
    KOi K07526.
    OMAi IQQILIT.
    OrthoDBi EOG7966FQ.
    PhylomeDBi O43295.
    TreeFami TF315892.

    Enzyme and pathway databases

    Reactomei REACT_11051. Rho GTPase cycle.
    REACT_19342. Inactivation of Cdc42 and Rac.

    Miscellaneous databases

    ChiTaRSi SRGAP3. human.
    GeneWikii SRGAP3.
    GenomeRNAii 9901.
    NextBioi 37331.
    PROi O43295.
    SOURCEi Search...

    Gene expression databases

    Bgeei O43295.
    CleanExi HS_SRGAP2.
    HS_SRGAP3.
    Genevestigatori O43295.

    Family and domain databases

    Gene3Di 1.10.555.10. 1 hit.
    InterProi IPR001060. FCH_dom.
    IPR008936. Rho_GTPase_activation_prot.
    IPR000198. RhoGAP_dom.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF00611. FCH. 1 hit.
    PF00620. RhoGAP. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    SMARTi SM00055. FCH. 1 hit.
    SM00324. RhoGAP. 1 hit.
    SM00326. SH3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48350. SSF48350. 1 hit.
    SSF50044. SSF50044. 1 hit.
    PROSITEi PS50133. FCH. 1 hit.
    PS50238. RHOGAP. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    7. 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. Cited for: VARIANT [LARGE SCALE ANALYSIS] ILE-623.

    Entry informationi

    Entry nameiSRGP3_HUMAN
    AccessioniPrimary (citable) accession number: O43295
    Secondary accession number(s): Q8IX13, Q8IZV8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: June 7, 2004
    Last modified: October 1, 2014
    This is version 137 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 3
      Human chromosome 3: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3