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Protein

Rho GTPase-activating protein 35

Gene

Arhgap35

Organism
Rattus norvegicus (Rat)
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:9852136, PubMed:20439493). 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:9852136, PubMed:20439493). Transduces signals from p21-ras to the nucleus, acting via the ras GTPase-activating protein (GAP) (By similarity). Transduces SRC-dependent signal from cell-surface adhesion molecules, such as laminin, to promote neurite outgrowth. Regulates axon outgrowth, guidance and fasciculation (By similarity). 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 (By similarity). During mammary gland development, is required in both the epithelial and stromal compartments for ductal outgrowth (By similarity).By similarity2 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • GTPase activating protein binding Source: RGD
  • GTPase activator activity Source: UniProtKB
  • GTP binding Source: UniProtKB-KW
  • phospholipid binding Source: UniProtKB
  • protein complex binding Source: RGD

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Rho GTPase-activating protein 35Imported
Alternative name(s):
GAP-associated protein p190
Glucocorticoid receptor DNA-binding factor 1
Gene namesi
Name:Arhgap35Imported
Synonyms:Grlf1, P190A1 Publication, p190ARHOGAP1 Publication
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1308738. Arhgap35.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication
  • Cytoplasmcytoskeletoncilium basal body By similarity

  • 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.By similarity

GO - Cellular componenti

  • ciliary basal body Source: UniProtKB
  • cytosol Source: RGD
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi36S → N: Disrupts GTP-binding. No direct effect on GAP activity 'in vitro' but affects the activity regulation 'in vivo'. 1 Publication1
Mutagenesisi1284R → A: Abolishes GAP activity. 1 Publication1
Mutagenesisi1451S → A: Abolishes phosphorylation by MAPK, increases functional activity and enhances retention in peripheral membranes; when associated with 1476-A--A-1483. 1 Publication1
Mutagenesisi1476 – 1483SPPPTPQS → APPPAPQA: Abolishes phosphorylation by MAPK, increases functional activity and enhances retention in peripheral membranes; when associated with A-1451. 1 Publication8

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000567321 – 1499Rho GTPase-activating protein 35Add BLAST1499

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei308PhosphotyrosineBy similarity1
Modified residuei589PhosphoserineCombined sources1
Modified residuei770PhosphoserineBy similarity1
Modified residuei773PhosphoserineBy similarity1
Modified residuei970PhosphoserineBy similarity1
Modified residuei975PhosphoserineCombined sources1
Modified residuei985PhosphoserineCombined sources1
Modified residuei1072PhosphoserineBy similarity1
Modified residuei1087PhosphotyrosineBy similarity1
Modified residuei1105Phosphotyrosine; by ABL2 and PTK6By similarity1
Modified residuei1134PhosphoserineCombined sources1
Modified residuei1142PhosphoserineBy similarity1
Modified residuei1150PhosphoserineBy similarity1
Modified residuei1176PhosphoserineBy similarity1
Modified residuei1179PhosphoserineCombined sources1
Modified residuei1221PhosphoserineBy similarity1
Modified residuei1226PhosphothreonineBy similarity1
Modified residuei1236PhosphoserineBy similarity1
Modified residuei1472PhosphoserineBy similarity1
Modified residuei1476PhosphoserineBy similarity1
Modified residuei1480PhosphothreonineBy similarity1
Modified residuei1483PhosphoserineBy similarity1

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 (By similarity). In brain, phosphorylated by FYN and SRC (By similarity). 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 (PubMed:20439493). Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires priming by MAPK and inhibits RhoGAP activity and modulates polarized cell migration (By similarity).By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP81128.
PRIDEiP81128.

PTM databases

iPTMnetiP81128.
PhosphoSitePlusiP81128.

Expressioni

Tissue specificityi

Ubiquitously expressed.

Interactioni

Subunit structurei

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

GO - Molecular functioni

  • GTPase activating protein binding Source: RGD
  • protein complex binding Source: RGD

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021223.

Structurei

Secondary structure

11499
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1245 – 1249Combined sources5
Helixi1251 – 1254Combined sources4
Beta strandi1257 – 1259Combined sources3
Helixi1263 – 1275Combined sources13
Turni1280 – 1284Combined sources5
Helixi1289 – 1301Combined sources13
Turni1307 – 1309Combined sources3
Helixi1314 – 1327Combined sources14
Beta strandi1328 – 1330Combined sources3
Helixi1335 – 1345Combined sources11
Helixi1350 – 1361Combined sources12
Helixi1366 – 1383Combined sources18
Helixi1386 – 1389Combined sources4
Helixi1393 – 1398Combined sources6
Helixi1401 – 1405Combined sources5
Helixi1412 – 1416Combined sources5
Helixi1419 – 1430Combined sources12
Helixi1432 – 1436Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IRCX-ray1.72A/B1242-1439[»]
ProteinModelPortaliP81128.
SMRiP81128.
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 localizationBy similarityAdd BLAST266
Regioni1213 – 1236Required for phospholipid binding and regulation of the substrate preferenceBy similarityAdd BLAST24

Domaini

N-terminal part (1-266) has GTPase activity. Required for proper cellular localization.By similarity

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.
InParanoidiP81128.
PhylomeDBiP81128.

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.

P81128-1 [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 TKKPIVIVLT
210 220 230 240 250
KCDEGVERYI RDAHTFALSK KNLQVVETSA RSNVNVDLAF STLVQLIDKS
260 270 280 290 300
RGKTKIIPYF EALKQQSQQI ATAKDKYEWL VSRIVKSHNE NWLSVSRKMQ
310 320 330 340 350
ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA
360 370 380 390 400
LIPNLDEVDH LSCIKAKKLL ETKPEFLKWF VVLEETPWDE 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 SDPNIDRINL
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 GDPFSADDIL
810 820 830 840 850
SPVLQSQTCK SSHCGSSNSV LLELPIGVHK 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
EITKDLSYLD 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 RVSHNNKVNL 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):170,480
Last modified:November 2, 2016 - v3
Checksum:iB3AEBD920E98B310
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94721 Genomic RNA. No translation available.
PIRiA38218.
RefSeqiNP_001258061.1. NM_001271132.1.
XP_006228474.1. XM_006228412.3.
XP_008757141.1. XM_008758919.1.
UniGeneiRn.16508.

Genome annotation databases

EnsembliENSRNOT00000090519; ENSRNOP00000075649; ENSRNOG00000015852.
GeneIDi306400.
UCSCiRGD:1308738. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94721 Genomic RNA. No translation available.
PIRiA38218.
RefSeqiNP_001258061.1. NM_001271132.1.
XP_006228474.1. XM_006228412.3.
XP_008757141.1. XM_008758919.1.
UniGeneiRn.16508.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5IRCX-ray1.72A/B1242-1439[»]
ProteinModelPortaliP81128.
SMRiP81128.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021223.

PTM databases

iPTMnetiP81128.
PhosphoSitePlusiP81128.

Proteomic databases

PaxDbiP81128.
PRIDEiP81128.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000090519; ENSRNOP00000075649; ENSRNOG00000015852.
GeneIDi306400.
UCSCiRGD:1308738. rat.

Organism-specific databases

RGDi1308738. Arhgap35.

Phylogenomic databases

eggNOGiKOG4271. Eukaryota.
ENOG410XR4E. LUCA.
GeneTreeiENSGT00760000118863.
HOVERGENiHBG051844.
InParanoidiP81128.
PhylomeDBiP81128.

Miscellaneous databases

PROiP81128.

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_RAT
AccessioniPrimary (citable) accession number: P81128
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 4, 2003
Last sequence update: November 2, 2016
Last modified: November 30, 2016
This is version 125 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  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.