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O43295

- SRGP3_HUMAN

UniProt

O43295 - SRGP3_HUMAN

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Protein
SLIT-ROBO Rho GTPase-activating protein 3
Gene
SRGAP3, ARHGAP14, KIAA0411, KIAA1156, MEGAP, SRGAP2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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
Complete GO annotation...

GO - Biological processi

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

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
Complete GO annotation...

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 3
PRO_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 Inferred. Forms a heterooligomer with SRGAP1 and SRGAP2 through its F-BAR domain. Interacts with WASF1. Probably interacts with ROBO1. Interacts with FASLG.3 Publications

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 8766FCH
Add
BLAST
Domaini482 – 670189Rho-GAP
Add
BLAST
Domaini720 – 77960SH3
Add
BLAST

Region

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

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili352 – 39241 Reviewed prediction
Add
BLAST
Coiled coili952 – 98736 Reviewed prediction
Add
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 FCH domain.
Contains 1 Rho-GAP domain.
Contains 1 SH3 domain.

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.
VSP_010581Add
BLAST
Alternative sequencei480 – 48910PPCLPPKPQK → IQDKLYRL in isoform 3.
VSP_010582
Alternative sequencei490 – 1099610Missing in isoform 3.
VSP_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...

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 136 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

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