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Protein

Rho GTPase-activating protein 35

Gene

Arhgap35

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Rho GTPase-activating protein (GAP), binds several acidic phospholipids which inhibits the Rho GAP activity to promote the Rac GAP activity (PubMed:16971514). This binding is inhibited by phosphorylation by PRKCA (By similarity). Involved in cell differentiation as well as cell adhesion and migration, plays an important role in retinal tissue morphogenesis, neural tube fusion, midline fusion of the cerebral hemispheres and mammary gland branching morphogenesis (PubMed:11044403, PubMed:11283609, PubMed:18502760, PubMed:21945077). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (PubMed:16971514). Transduces SRC-dependent signal from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (PubMed:11283609). Modulates Rho GTPase-dependent F-actin polymerization, organization and assembly, is involved in polarized cell migration and in the positive regulation of ciliogenesis and cilia elongation (PubMed:11044403, PubMed:26859289, PubMed:18502760). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (PubMed:21945077).By similarity6 Publications

GO - Molecular functioni

GO - Biological processi

  • axonal fasciculation Source: UniProtKB
  • axon guidance Source: UniProtKB
  • camera-type eye development Source: MGI
  • cell migration Source: UniProtKB
  • cellular response to extracellular stimulus Source: UniProtKB
  • central nervous system neuron axonogenesis Source: UniProtKB
  • establishment or maintenance of actin cytoskeleton polarity Source: UniProtKB
  • forebrain development Source: MGI
  • integrin-mediated signaling pathway Source: MGI
  • mammary gland development Source: UniProtKB
  • negative regulation of Rho protein signal transduction Source: MGI
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • negative regulation of vascular permeability Source: MGI
  • neural tube closure Source: MGI
  • neuron projection guidance Source: UniProtKB
  • positive regulation of cilium assembly Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • positive regulation of neuron projection development Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • regulation of actin polymerization or depolymerization Source: UniProtKB
  • regulation of axonogenesis Source: UniProtKB
  • regulation of cell shape Source: MGI
  • small GTPase mediated signal transduction Source: InterPro
  • transcription, DNA-templated Source: UniProtKB-KW
  • wound healing, spreading of cells Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-194840. Rho GTPase cycle.
R-MMU-416550. Sema4D mediated inhibition of cell attachment and migration.
R-MMU-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho GTPase-activating protein 35Imported
Alternative name(s):
Glucocorticoid receptor DNA-binding factor 1
Gene namesi
Name:Arhgap35Imported
Synonyms:Grlf1, Kiaa1722, P190A1 Publication, p190ARHOGAP1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1929494. Arhgap35.

Subcellular locationi

GO - Cellular componenti

  • actin cytoskeleton Source: MGI
  • ciliary basal body Source: UniProtKB
  • cytoplasm Source: MGI
  • nucleus Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Deficiency leads to perinatal lethality and defective neural development. One third of the fetuses show exencephaly and spina bifida as well as defective kidney development.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1396L → Q in ENU mutant Arhgap35-D34; mutant animals show hypodysplastic kidneys and neural tube closure defects; the number of ciliated cells and cilia average length are drastically reduced in the proximal tubules. Results in loss of activation of GTP hydrolysis. 1 Publication1
Mutagenesisi1472S → A: Reduces phosphorylation by GSK3B by 50%. No effect on polarized cell migration. 1 Publication1
Mutagenesisi1476S → A: Abolishes phosphorylation by GSK3B. Reduces phosphorylation by MAPK. Affects polarized cell migration. Increases RhoGAP catalytic activity. 1 Publication1
Mutagenesisi1480T → A: Abolishes phosphorylation by GSK3B. Reduces phosphorylation by MAPK. Affects polarized cell migration. Increases RhoGAP catalytic activity. 1 Publication1
Mutagenesisi1483S → A: Abolishes phosphorylation by GSK3B. Reduces phosphorylation by MAPK. No effect on polarized cell migration. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000567311 – 1499Rho GTPase-activating protein 35Add BLAST1499

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei308PhosphotyrosineBy similarity1
Modified residuei589PhosphoserineCombined sources1
Modified residuei770PhosphoserineBy similarity1
Modified residuei773PhosphoserineCombined sources1
Modified residuei970PhosphoserineCombined sources1
Modified residuei975PhosphoserineCombined sources1
Modified residuei985PhosphoserineCombined sources1
Modified residuei1072PhosphoserineBy similarity1
Modified residuei1087PhosphotyrosineCombined sources1
Modified residuei1105Phosphotyrosine; by ABL2 and PTK6Combined sources1 Publication1
Modified residuei1134PhosphoserineCombined sources1
Modified residuei1142PhosphoserineCombined sources1
Modified residuei1150PhosphoserineBy similarity1
Modified residuei1176PhosphoserineBy similarity1
Modified residuei1179PhosphoserineCombined sources1
Modified residuei1221PhosphoserineBy similarity1
Modified residuei1226PhosphothreonineBy similarity1
Modified residuei1236PhosphoserineBy similarity1
Modified residuei1472Phosphoserine1 Publication1
Modified residuei1476Phosphoserine1 Publication1
Modified residuei1480Phosphothreonine1 Publication1
Modified residuei1483Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylation of Tyr-1105 by PTK6 promotes the association with RASA1, inactivating RHOA while activating RAS. Phosphorylation at Tyr-308 by PDGFRA inhibits binding to GTF2I (By similarity). Phosphorylated by PRKCA at Ser-1221 and Thr-1226, induces relocalization from the cytoplasm to regions of plasma membrane ruffling and prevents the binding and substrate specificity regulation by phospholipids (PubMed:11044403). In brain, phosphorylated by FYN and SRC (PubMed:11283609). During focal adhesion formation, phosphorylated by MAPK1 and MAPK3 at the C-terminal region, probably at Ser-1451, Ser-1476, Thr-1480 and Ser-1483. Phosphorylation by MAPK1 and MAPK3 inhibits GAP function and localizes ARGHAP35 away from newly forming focal adhesions and stress fibers in cells spreading on fibronectin (By similarity). Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires priming by MAPK and inhibits RhoGAP activity and modulates polarized cell migration (PubMed:18502760).By similarity3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ91YM2.
PaxDbiQ91YM2.
PRIDEiQ91YM2.

PTM databases

iPTMnetiQ91YM2.
PhosphoSitePlusiQ91YM2.

Expressioni

Tissue specificityi

Expressed in the developing kidneys (PubMed:26859289). Expressed in all regions of the mature nervous system (at protein level) (PubMed:11044403). Detected in neutrophils (at protein level) (PubMed:20675588).3 Publications

Developmental stagei

At E12.5, the highest level of expression is in the spinal cord and lower expression levels are seen in the developing brain. At E15.5, highly expressed in brain, spinal cord and eyes (PubMed:11044403). In developing kidney, at E17.5, low expression is observed in the glomerulus, while high expression levels are detected in the proximal tubule (PubMed:26859289). At E14.5, is expressed within the epithelial compartment of the embryonic mammary bud and at lower level in the surrounding stroma and skin. Also expressed at terminal end bunds (TEB) at comparable levels in body and cap cells as well as in fibroblasts and stroma surrounding the TEB (PubMed:21945077).3 Publications

Gene expression databases

BgeeiENSMUSG00000058230.
CleanExiMM_GRLF1.
ExpressionAtlasiQ91YM2. baseline and differential.
GenevisibleiQ91YM2. MM.

Interactioni

Subunit structurei

Interacts with the general transcription factor GTF2I, the interaction sequesters GTF2I in the cytoplasm (By similarity). Interacts with RASA1.By similarity1 Publication

Protein-protein interaction databases

BioGridi231317. 2 interactors.
IntActiQ91YM2. 1 interactor.
MINTiMINT-4096884.
STRINGi10090.ENSMUSP00000075242.

Structurei

3D structure databases

ProteinModelPortaliQ91YM2.
SMRiQ91YM2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini270 – 327FF 1Add BLAST58
Domaini368 – 422FF 2Add BLAST55
Domaini429 – 483FF 3Add BLAST55
Domaini485 – 550FF 4Add BLAST66
Domaini1249 – 1436Rho-GAPPROSITE-ProRule annotationAdd BLAST188

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 266Has GTPase activity, required for proper localization1 PublicationAdd BLAST266
Regioni1213 – 1236Required for phospholipid binding and regulation of the substrate preferenceBy similarityAdd BLAST24

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1440 – 1487Pro-richAdd BLAST48

Domaini

N-terminal part (1-266) has GTPase activity. Required for proper cellular localization. Mutation of this region is a severely defective loss of function. Mutants have defective morphogenesis of neural retinal tissue, agenesis of the corpus callosum due to defectuous midline fusion of the cerebral hemispheres (PubMed:11044403). Mutants show defects in axon guidance and fasciculation (PubMed:11283609).2 Publications

Sequence similaritiesi

Contains 4 FF domains.Curated
Contains 1 Rho-GAP domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG4271. Eukaryota.
ENOG410XR4E. LUCA.
GeneTreeiENSGT00760000118863.
HOVERGENiHBG051844.
InParanoidiQ91YM2.
KOiK05732.
OMAiPITEPPG.
OrthoDBiEOG091G00ZO.
PhylomeDBiQ91YM2.
TreeFamiTF324451.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR002713. FF_domain.
IPR027417. P-loop_NTPase.
IPR008936. Rho_GTPase_activation_prot.
IPR032835. RhoGAP-FF1.
IPR000198. RhoGAP_dom.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF01846. FF. 1 hit.
PF00071. Ras. 1 hit.
PF00620. RhoGAP. 1 hit.
PF16512. RhoGAP-FF1. 1 hit.
[Graphical view]
SMARTiSM00441. FF. 4 hits.
SM00324. RhoGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF81698. SSF81698. 1 hit.
PROSITEiPS51676. FF. 4 hits.
PS50238. RHOGAP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q91YM2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMMARKQDVR IPTYNISVVG LSGTEKEKGQ CGIGKSCLCN RFVRPSADEF
60 70 80 90 100
HLDHTSVLST SDFGGRVVNN DHFLYWGEVS RSLEDCVECK MHIVEQTEFI
110 120 130 140 150
DDQTFQPHRS TALQPYIKRA AATKLASAEK LMYFCTDQLG LEQDFEQKQM
160 170 180 190 200
PDGKLLVDGF LLGIDVSRGM NRNFDDQLKF VSNLYNQLAK TKKPIVVVLT
210 220 230 240 250
KCDEGVERYI RDAHTFALSK KNLQVVETSA RSNVNVDLAF STLVQLIDKS
260 270 280 290 300
RGKTKIIPYF EALKQQSQQI ATAKDKYEWL VSRIVKNHNE NWPSVSRKMQ
310 320 330 340 350
ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA
360 370 380 390 400
LIPNLDEVDH LSCIKAKKLL ETKPEFLKWF VVLEETPWDA TSHIDNMENE
410 420 430 440 450
RIPFDLMDTV PAEQLYETHL EKLRNERKRA EMRRAFKENL ETSPFITPGK
460 470 480 490 500
PWEEARSFIM NEDFYQWLEE SVYMDIYGKH QKQIIDRAKE EFQELLLEYS
510 520 530 540 550
ELFYELELDA KPSKEKMGVI QDVLGEEQRF KALQKLQAER DALILKHIHF
560 570 580 590 600
VYHPTKETCP SCPACVDAKI EHLISSRFIR PSDRNQKNSL SDLNIDRINL
610 620 630 640 650
VILGKDGLAR ELANEIRALC TNDDKYVIDG KMYELSLRPI EGNVRLPVNS
660 670 680 690 700
FQTPTFQPHG CLCLYNSKES LSYVVESIEK SRESTLGRRD NHLVHLPLTL
710 720 730 740 750
ILVNKRGDTS GETLHSLIQQ GQQIASKLQC VFLDPASAGI GYGRNINEKQ
760 770 780 790 800
ISQVLKGLLD SKRNLNLVSS TASIKDLADV DLRIVMCLMC GDPFSADDVL
810 820 830 840 850
SPVLQSQTCK SSHCGSSNSV LLELPIGLHK KRIELSVLSY HSSFSIRKSR
860 870 880 890 900
LVHGYIVFYS AKRKASLAML RAFLCEVQDI IPIQLVALTD GAIDVLDNDL
910 920 930 940 950
SREQLTEGEE IAQEIDGRFT SIPCSQPQHK LELFHPFFKD VVEKKNIIEA
960 970 980 990 1000
THMYDNVAEA CSTTEEVFNS PRAGSPLCNS NLQDSEEDVE PPSYHLFRED
1010 1020 1030 1040 1050
ATLPSLSKDH SKFSMELEGN DGLSFIMSNF ESKLNNKVPP PVKPKPPVHF
1060 1070 1080 1090 1100
DITKDLSYLD QGHREGQRKS MSSSPWMPQD GFDPSDYAEP MDAVVKPRNE
1110 1120 1130 1140 1150
EENIYSVPHD STQGKIITIR NINKAQSNGS GNGSDSEMDT SSLERGRKVS
1160 1170 1180 1190 1200
AVSKPVLYRT RCTRLGRFAS YRTSFSVGSD DELGPIRKKE EDQASQGYKG
1210 1220 1230 1240 1250
DNAVIPYETD EDPRRRNILR SLRRNTKKPK PKPRPSITKA TWESNYFGVP
1260 1270 1280 1290 1300
LTTVVTPEKP IPIFIERCIE YIEATGLSTE GIYRVSGNKS EMESLQRQFD
1310 1320 1330 1340 1350
QDHNLDLAEK DFTVNTVAGA MKSFFSELPD PLVPYSMQID LVEAHKINDR
1360 1370 1380 1390 1400
EQKLHALKEV LKKFPKENHE VFKYVISHLN KVSHNNKVNL MTSENLSICF
1410 1420 1430 1440 1450
WPTLMRPDFS SMDALTATRS YQTIIELFIQ QCPFFFYNRP ISEPPGAAPG
1460 1470 1480 1490
SPSAMAPTVP FLTSTPATSQ PSPPQSPPPT PQSPMQPLLS SQLQAEHTL
Length:1,499
Mass (Da):170,393
Last modified:January 9, 2007 - v3
Checksum:i7E13EC38257CE950
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK147326 mRNA. Translation: BAE27848.1.
AK147688 mRNA. Translation: BAE28076.1.
AK173242 Transcribed RNA. Translation: BAD32520.1.
CCDSiCCDS20851.1.
RefSeqiNP_766327.3. NM_172739.4.
XP_006539872.1. XM_006539809.3.
XP_011248814.1. XM_011250512.2.
UniGeneiMm.28646.
Mm.400358.

Genome annotation databases

EnsembliENSMUST00000075845; ENSMUSP00000075242; ENSMUSG00000058230.
ENSMUST00000171937; ENSMUSP00000127379; ENSMUSG00000058230.
GeneIDi232906.
KEGGimmu:232906.
UCSCiuc009fhw.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK147326 mRNA. Translation: BAE27848.1.
AK147688 mRNA. Translation: BAE28076.1.
AK173242 Transcribed RNA. Translation: BAD32520.1.
CCDSiCCDS20851.1.
RefSeqiNP_766327.3. NM_172739.4.
XP_006539872.1. XM_006539809.3.
XP_011248814.1. XM_011250512.2.
UniGeneiMm.28646.
Mm.400358.

3D structure databases

ProteinModelPortaliQ91YM2.
SMRiQ91YM2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi231317. 2 interactors.
IntActiQ91YM2. 1 interactor.
MINTiMINT-4096884.
STRINGi10090.ENSMUSP00000075242.

PTM databases

iPTMnetiQ91YM2.
PhosphoSitePlusiQ91YM2.

Proteomic databases

MaxQBiQ91YM2.
PaxDbiQ91YM2.
PRIDEiQ91YM2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000075845; ENSMUSP00000075242; ENSMUSG00000058230.
ENSMUST00000171937; ENSMUSP00000127379; ENSMUSG00000058230.
GeneIDi232906.
KEGGimmu:232906.
UCSCiuc009fhw.1. mouse.

Organism-specific databases

CTDi2909.
MGIiMGI:1929494. Arhgap35.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG4271. Eukaryota.
ENOG410XR4E. LUCA.
GeneTreeiENSGT00760000118863.
HOVERGENiHBG051844.
InParanoidiQ91YM2.
KOiK05732.
OMAiPITEPPG.
OrthoDBiEOG091G00ZO.
PhylomeDBiQ91YM2.
TreeFamiTF324451.

Enzyme and pathway databases

ReactomeiR-MMU-194840. Rho GTPase cycle.
R-MMU-416550. Sema4D mediated inhibition of cell attachment and migration.
R-MMU-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.

Miscellaneous databases

PROiQ91YM2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000058230.
CleanExiMM_GRLF1.
ExpressionAtlasiQ91YM2. baseline and differential.
GenevisibleiQ91YM2. MM.

Family and domain databases

Gene3Di1.10.555.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR002713. FF_domain.
IPR027417. P-loop_NTPase.
IPR008936. Rho_GTPase_activation_prot.
IPR032835. RhoGAP-FF1.
IPR000198. RhoGAP_dom.
IPR001806. Small_GTPase.
[Graphical view]
PfamiPF01846. FF. 1 hit.
PF00071. Ras. 1 hit.
PF00620. RhoGAP. 1 hit.
PF16512. RhoGAP-FF1. 1 hit.
[Graphical view]
SMARTiSM00441. FF. 4 hits.
SM00324. RhoGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF81698. SSF81698. 1 hit.
PROSITEiPS51676. FF. 4 hits.
PS50238. RHOGAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRHG35_MOUSE
AccessioniPrimary (citable) accession number: Q91YM2
Secondary accession number(s): Q3UGY1, Q69ZC4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2003
Last sequence update: January 9, 2007
Last modified: November 30, 2016
This is version 142 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.