UniProtKB - Q91YM2 (RHG35_MOUSE)
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Protein
Rho GTPase-activating protein 35
Gene
Arhgap35
Organism
Mus musculus (Mouse)
Status
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
- GTPase activator activity Source: UniProtKB
- GTPase activity Source: InterPro
- GTP binding Source: InterPro
- phospholipid binding Source: UniProtKB
- RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
- transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: MGI
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
- transcription, DNA-templated Source: UniProtKB-KW
- wound healing, spreading of cells Source: UniProtKB
Keywordsi
| Molecular function | DNA-binding, GTPase activation, Repressor |
| Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
| Reactomei | R-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 35ImportedAlternative name(s): Glucocorticoid receptor DNA-binding factor 1 |
| Gene namesi | |
| Organismi | Mus musculus (Mouse) |
| Taxonomic identifieri | 10090 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
| Proteomesi |
|
Organism-specific databases
| MGIi | MGI:1929494. Arhgap35. |
Subcellular locationi
- Cytoplasm › cytoskeleton › cilium basal body 1 Publication
- Cytoplasm 1 Publication
- Nucleus Curated
- Cell membrane 1 Publication
Note: In response to integrins and SDC4 and upon phosphorylation by PKC, relocalizes from the cytoplasm to regions of plasma membrane ruffling where it colocalizes with polymerized actin.1 Publication
GO - Cellular componenti
- actin cytoskeleton Source: MGI
- ciliary basal body Source: UniProtKB
- cytoplasm Source: MGI
- nucleus Source: UniProtKB-SubCell
- plasma membrane Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, NucleusPathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 1396 | L → 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 Publication | 1 | |
| Mutagenesisi | 1472 | S → A: Reduces phosphorylation by GSK3B by 50%. No effect on polarized cell migration. 1 Publication | 1 | |
| Mutagenesisi | 1476 | S → A: Abolishes phosphorylation by GSK3B. Reduces phosphorylation by MAPK. Affects polarized cell migration. Increases RhoGAP catalytic activity. 1 Publication | 1 | |
| Mutagenesisi | 1480 | T → A: Abolishes phosphorylation by GSK3B. Reduces phosphorylation by MAPK. Affects polarized cell migration. Increases RhoGAP catalytic activity. 1 Publication | 1 | |
| Mutagenesisi | 1483 | S → A: Abolishes phosphorylation by GSK3B. Reduces phosphorylation by MAPK. No effect on polarized cell migration. 1 Publication | 1 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000056731 | 1 – 1499 | Rho GTPase-activating protein 35Add BLAST | 1499 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 308 | PhosphotyrosineBy similarity | 1 | |
| Modified residuei | 589 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 770 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 773 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 970 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 975 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 985 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1072 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1087 | PhosphotyrosineCombined sources | 1 | |
| Modified residuei | 1105 | Phosphotyrosine; by ABL2 and PTK6Combined sources1 Publication | 1 | |
| Modified residuei | 1134 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1142 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1150 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1176 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1179 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1221 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1226 | PhosphothreonineBy similarity | 1 | |
| Modified residuei | 1236 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 1472 | Phosphoserine1 Publication | 1 | |
| Modified residuei | 1476 | Phosphoserine1 Publication | 1 | |
| Modified residuei | 1480 | Phosphothreonine1 Publication | 1 | |
| Modified residuei | 1483 | Phosphoserine1 Publication | 1 |
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
PhosphoproteinProteomic databases
| MaxQBi | Q91YM2. |
| PaxDbi | Q91YM2. |
| PRIDEi | Q91YM2. |
PTM databases
| iPTMneti | Q91YM2. |
| PhosphoSitePlusi | Q91YM2. |
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
| Bgeei | ENSMUSG00000058230. |
| CleanExi | MM_GRLF1. |
| ExpressionAtlasi | Q91YM2. baseline and differential. |
| Genevisiblei | Q91YM2. 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
| BioGridi | 231317. 2 interactors. |
| IntActi | Q91YM2. 1 interactor. |
| MINTi | MINT-4096884. |
| STRINGi | 10090.ENSMUSP00000075242. |
Structurei
3D structure databases
| ProteinModelPortali | Q91YM2. |
| SMRi | Q91YM2. |
| ModBasei | Search... |
| MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Domaini | 270 – 327 | FF 1Add BLAST | 58 | |
| Domaini | 368 – 422 | FF 2Add BLAST | 55 | |
| Domaini | 429 – 483 | FF 3Add BLAST | 55 | |
| Domaini | 485 – 550 | FF 4Add BLAST | 66 | |
| Domaini | 1249 – 1436 | Rho-GAPPROSITE-ProRule annotationAdd BLAST | 188 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 1 – 266 | Has GTPase activity, required for proper localization1 PublicationAdd BLAST | 266 | |
| Regioni | 1213 – 1236 | Required for phospholipid binding and regulation of the substrate preferenceBy similarityAdd BLAST | 24 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 1440 – 1487 | Pro-richAdd BLAST | 48 |
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
Keywords - Domaini
RepeatPhylogenomic databases
| eggNOGi | KOG4271. Eukaryota. ENOG410XR4E. LUCA. |
| GeneTreei | ENSGT00760000118863. |
| HOVERGENi | HBG051844. |
| InParanoidi | Q91YM2. |
| KOi | K05732. |
| OMAi | MLRAFLC. |
| OrthoDBi | EOG091G00ZO. |
| PhylomeDBi | Q91YM2. |
| TreeFami | TF324451. |
Family and domain databases
| InterProi | View protein in InterPro IPR002713. FF_domain. IPR027417. P-loop_NTPase. IPR008936. Rho_GTPase_activation_prot. IPR032835. RhoGAP-FF1. IPR000198. RhoGAP_dom. IPR001806. Small_GTPase. |
| Pfami | View protein in Pfam PF01846. FF. 1 hit. PF00071. Ras. 1 hit. PF00620. RhoGAP. 1 hit. PF16512. RhoGAP-FF1. 1 hit. |
| SMARTi | View protein in SMART SM00441. FF. 4 hits. SM00324. RhoGAP. 1 hit. |
| SUPFAMi | SSF48350. SSF48350. 1 hit. SSF52540. SSF52540. 2 hits. SSF81698. SSF81698. 1 hit. |
| PROSITEi | View protein in PROSITE PS51676. FF. 4 hits. PS50238. RHOGAP. 1 hit. |
Sequencei
Sequence statusi: Complete.
Q91YM2-1 [UniParc]FASTAAdd to basket
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
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. |
| CCDSi | CCDS20851.1. |
| RefSeqi | NP_766327.3. NM_172739.4. XP_006539872.1. XM_006539809.3. XP_011248814.1. XM_011250512.2. |
| UniGenei | Mm.28646. Mm.400358. |
Genome annotation databases
| Ensembli | ENSMUST00000075845; ENSMUSP00000075242; ENSMUSG00000058230. ENSMUST00000171937; ENSMUSP00000127379; ENSMUSG00000058230. |
| GeneIDi | 232906. |
| KEGGi | mmu:232906. |
| UCSCi | uc009fhw.1. mouse. |
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. |
Entry informationi
| Entry namei | RHG35_MOUSE | |
| Accessioni | Q91YM2Primary (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: | June 7, 2017 | |
| This is version 147 of the entry and version 3 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
Complete proteome, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
