RHG35_HUMAN
ID RHG35_HUMAN Reviewed; 1499 AA.
AC Q9NRY4; A7E2A4; Q14452; Q9C0E1;
DT 04-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 3.
DT 03-AUG-2022, entry version 209.
DE RecName: Full=Rho GTPase-activating protein 35 {ECO:0000312|HGNC:HGNC:4591};
DE AltName: Full=Glucocorticoid receptor DNA-binding factor 1;
DE AltName: Full=Glucocorticoid receptor repression factor 1;
DE Short=GRF-1;
DE AltName: Full=Rho GAP p190A;
DE Short=p190-A {ECO:0000303|PubMed:11054565};
GN Name=ARHGAP35 {ECO:0000312|HGNC:HGNC:4591};
GN Synonyms=GRF1 {ECO:0000303|PubMed:1894621},
GN GRLF1 {ECO:0000303|PubMed:1894621}, KIAA1722,
GN P190A {ECO:0000303|PubMed:19673492},
GN p190ARHOGAP {ECO:0000303|PubMed:19673492};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:AAF80386.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11214970; DOI=10.1093/dnares/7.6.347;
RA Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIX. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:347-355(2000).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1491.
RC TISSUE=Mammary cancer;
RX PubMed=11054565; DOI=10.1016/s0378-1119(00)00387-5;
RA Tikoo A., Czekay S., Viars C., White S., Heath J.K., Arden K., Maruta H.;
RT "p190-A, a human tumor suppressor gene, maps to the chromosomal region
RT 19q13.3 that is reportedly deleted in some gliomas.";
RL Gene 257:23-31(2000).
RN [6] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 377-1453, AND FUNCTION.
RC TISSUE=Mammary cancer;
RX PubMed=1894621; DOI=10.1016/s0021-9258(19)47378-x;
RA LeClerc S., Palaniswami R., Xie B.X., Govindan M.V.;
RT "Molecular cloning and characterization of a factor that binds the human
RT glucocorticoid receptor gene and represses its expression.";
RL J. Biol. Chem. 266:17333-17340(1991).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [9]
RP PHOSPHORYLATION AT TYR-1105.
RX PubMed=18829532; DOI=10.1158/0008-5472.can-08-0997;
RA Shen C.H., Chen H.Y., Lin M.S., Li F.Y., Chang C.C., Kuo M.L.,
RA Settleman J., Chen R.H.;
RT "Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and
RT promote breast carcinoma growth, migration, and invasion.";
RL Cancer Res. 68:7779-7787(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-970 AND SER-1179, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1179, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-970; SER-975;
RP SER-1150 AND SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [14]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-1221; THR-1226 AND
RP SER-1236, MUTAGENESIS OF SER-1221; THR-1226 AND SER-1236, AND BINDING TO
RP PHOSPHOLIPIDS.
RX PubMed=19673492; DOI=10.1021/bi900667y;
RA Levay M., Settleman J., Ligeti E.;
RT "Regulation of the substrate preference of p190RhoGAP by protein kinase C-
RT mediated phosphorylation of a phospholipid binding site.";
RL Biochemistry 48:8615-8623(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-773; SER-975;
RP SER-1072; TYR-1087; TYR-1105; SER-1134 AND SER-1179, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP TISSUE SPECIFICITY.
RX PubMed=20675588; DOI=10.4049/jimmunol.0904163;
RA Nemeth T., Futosi K., Hably C., Brouns M.R., Jakob S.M., Kovacs M.,
RA Kertesz Z., Walzog B., Settleman J., Mocsai A.;
RT "Neutrophil functions and autoimmune arthritis in the absence of
RT p190RhoGAP: generation and analysis of a novel null mutation in mice.";
RL J. Immunol. 185:3064-3075(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589 AND SER-1179, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-1134; SER-1150 AND
RP SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-770; SER-773;
RP SER-1134; SER-1150; SER-1176 AND SER-1179, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589; SER-1001; SER-1150 AND
RP SER-1179, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP FUNCTION, AND DOMAIN.
RX PubMed=28894085; DOI=10.1038/s41467-017-00483-x;
RA Stiegler A.L., Boggon T.J.;
RT "p190RhoGAP proteins contain pseudoGTPase domains.";
RL Nat. Commun. 8:506-506(2017).
RN [23] {ECO:0007744|PDB:3C5H}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 13-249 IN COMPLEX WITH GTP
RP ANALOG.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the Ras homolog domain of human GRLF1 (p190RhoGAP).";
RL Submitted (JAN-2008) to the PDB data bank.
RN [24] {ECO:0007744|PDB:3FK2}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 1212-1439.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the RhoGAP domain of human glucocorticoid receptor
RT DNA-binding factor 1.";
RL Submitted (DEC-2008) to the PDB data bank.
RN [25]
RP STRUCTURE BY NMR OF 267-331, PHOSPHORYLATION AT TYR-308, AND INTERACTION
RP WITH GTF2I.
RX PubMed=19393245; DOI=10.1016/j.jmb.2009.04.035;
RA Bonet R., Ruiz L., Aragon E., Martin-Malpartida P., Macias M.J.;
RT "NMR structural studies on human p190-A RhoGAPFF1 revealed that domain
RT phosphorylation by the PDGF-receptor alpha requires its previous
RT unfolding.";
RL J. Mol. Biol. 389:230-237(2009).
CC -!- FUNCTION: Rho GTPase-activating protein (GAP) (PubMed:19673492,
CC PubMed:28894085). Binds several acidic phospholipids which inhibits the
CC Rho GAP activity to promote the Rac GAP activity (PubMed:19673492).
CC This binding is inhibited by phosphorylation by PRKCA
CC (PubMed:19673492). Involved in cell differentiation as well as cell
CC adhesion and migration, plays an important role in retinal tissue
CC morphogenesis, neural tube fusion, midline fusion of the cerebral
CC hemispheres and mammary gland branching morphogenesis (By similarity).
CC Transduces signals from p21-ras to the nucleus, acting via the ras
CC GTPase-activating protein (GAP) (By similarity). Transduces SRC-
CC dependent signals from cell-surface adhesion molecules, such as
CC laminin, to promote neurite outgrowth. Regulates axon outgrowth,
CC guidance and fasciculation (By similarity). Modulates Rho GTPase-
CC dependent F-actin polymerization, organization and assembly, is
CC involved in polarized cell migration and in the positive regulation of
CC ciliogenesis and cilia elongation (By similarity). During mammary gland
CC development, is required in both the epithelial and stromal
CC compartments for ductal outgrowth (By similarity). Represses
CC transcription of the glucocorticoid receptor by binding to the cis-
CC acting regulatory sequence 5'-GAGAAAAGAAACTGGAGAAACTC-3'; this function
CC is however unclear and would need additional experimental evidences
CC (PubMed:1894621). {ECO:0000250|UniProtKB:P81128,
CC ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:1894621,
CC ECO:0000269|PubMed:19673492, ECO:0000269|PubMed:28894085}.
CC -!- ACTIVITY REGULATION: Binding of acidic phospholipids inhibits the Rho
CC GAP activity and promotes the Rac GAP activity.
CC {ECO:0000269|PubMed:19673492}.
CC -!- SUBUNIT: Interacts with RASA1 (By similarity). Interacts with the
CC general transcription factor GTF2I, the interaction sequesters GTF2I in
CC the cytoplasm (PubMed:19393245). {ECO:0000250|UniProtKB:Q91YM2,
CC ECO:0000269|PubMed:19393245}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000250|UniProtKB:Q91YM2}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q91YM2}. Nucleus {ECO:0000305|PubMed:1894621}.
CC Cell membrane {ECO:0000250|UniProtKB:Q91YM2}. Note=In response to
CC integrins and SDC4 and upon phosphorylation by PKC, relocalizes from
CC the cytoplasm to regions of plasma membrane ruffling where it
CC colocalizes with polymerized actin. {ECO:0000250|UniProtKB:Q91YM2}.
CC -!- TISSUE SPECIFICITY: Detected in neutrophils (at protein level).
CC {ECO:0000269|PubMed:1894621}.
CC -!- DOMAIN: N-terminal part (1-266) has GTPase activity. Required for
CC proper cellular localization. {ECO:0000250|UniProtKB:Q91YM2}.
CC -!- DOMAIN: The pG1 pseudoGTPase domain does not bind GTP.
CC {ECO:0000269|PubMed:28894085}.
CC -!- PTM: Phosphorylation of Tyr-1105 by PTK6 promotes the association with
CC RASA1, inactivating RHOA while activating RAS. Phosphorylation at Tyr-
CC 308 by PDGFRA inhibits binding to GTF2I (PubMed:18829532,
CC PubMed:19393245). Phosphorylated by PRKCA at Ser-1221 and Thr-1226,
CC induces relocalization from the cytoplasm to regions of plasma membrane
CC ruffling and prevents the binding and substrate specificity regulation
CC by phospholipids (PubMed:19673492). In brain, phosphorylated by FYN and
CC SRC (By similarity). During focal adhesion formation, phosphorylated by
CC MAPK1 and MAPK3 at the C-terminal region, probably at Ser-1451, Ser-
CC 1476, Thr-1480 and Ser-1483. Phosphorylation by MAPK1 and MAPK3
CC inhibits GAP function and localizes ARGHAP35 away from newly forming
CC focal adhesions and stress fibers in cells spreading on fibronectin (By
CC similarity). Phosphorylation at Ser-1476 and Thr-1480 by GSK3B requires
CC priming by MAPK and inhibits RhoGAP activity and modulates polarized
CC cell migration (By similarity). {ECO:0000250|UniProtKB:P81128,
CC ECO:0000250|UniProtKB:Q91YM2, ECO:0000269|PubMed:18829532,
CC ECO:0000269|PubMed:19393245, ECO:0000269|PubMed:19673492}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA58618.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF80386.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAF80386.1; Type=Miscellaneous discrepancy; Note=Unlikely isoform. Aberrant splice sites.; Evidence={ECO:0000305};
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DR EMBL; AB051509; BAB21813.2; -; mRNA.
DR EMBL; CH471126; EAW57450.1; -; Genomic_DNA.
DR EMBL; BC150257; AAI50258.1; -; mRNA.
DR EMBL; AF159851; AAF80386.1; ALT_SEQ; mRNA.
DR EMBL; M73077; AAA58618.1; ALT_FRAME; mRNA.
DR CCDS; CCDS46127.1; -.
DR RefSeq; NP_004482.4; NM_004491.4.
DR RefSeq; XP_016882203.1; XM_017026714.1.
DR PDB; 2K85; NMR; -; A=267-331.
DR PDB; 3C5H; X-ray; 1.80 A; A=13-249.
DR PDB; 3FK2; X-ray; 2.80 A; A/B/C/D=1212-1439.
DR PDB; 6PXC; X-ray; 1.60 A; U=1100-1112.
DR PDB; 6WAY; X-ray; 1.50 A; V=1086-1093.
DR PDBsum; 2K85; -.
DR PDBsum; 3C5H; -.
DR PDBsum; 3FK2; -.
DR PDBsum; 6PXC; -.
DR PDBsum; 6WAY; -.
DR AlphaFoldDB; Q9NRY4; -.
DR BMRB; Q9NRY4; -.
DR SMR; Q9NRY4; -.
DR BioGRID; 109166; 94.
DR DIP; DIP-34578N; -.
DR IntAct; Q9NRY4; 21.
DR MINT; Q9NRY4; -.
DR STRING; 9606.ENSP00000385720; -.
DR BindingDB; Q9NRY4; -.
DR ChEMBL; CHEMBL4523646; -.
DR iPTMnet; Q9NRY4; -.
DR PhosphoSitePlus; Q9NRY4; -.
DR BioMuta; ARHGAP35; -.
DR DMDM; 408360250; -.
DR EPD; Q9NRY4; -.
DR jPOST; Q9NRY4; -.
DR MassIVE; Q9NRY4; -.
DR MaxQB; Q9NRY4; -.
DR PaxDb; Q9NRY4; -.
DR PeptideAtlas; Q9NRY4; -.
DR PRIDE; Q9NRY4; -.
DR ProteomicsDB; 82441; -.
DR Antibodypedia; 31509; 280 antibodies from 29 providers.
DR DNASU; 2909; -.
DR Ensembl; ENST00000404338.8; ENSP00000385720.2; ENSG00000160007.19.
DR Ensembl; ENST00000614079.1; ENSP00000483730.1; ENSG00000160007.19.
DR Ensembl; ENST00000672722.1; ENSP00000500409.1; ENSG00000160007.19.
DR GeneID; 2909; -.
DR KEGG; hsa:2909; -.
DR MANE-Select; ENST00000672722.1; ENSP00000500409.1; NM_004491.5; NP_004482.4.
DR UCSC; uc010ekv.4; human.
DR CTD; 2909; -.
DR DisGeNET; 2909; -.
DR GeneCards; ARHGAP35; -.
DR HGNC; HGNC:4591; ARHGAP35.
DR HPA; ENSG00000160007; Low tissue specificity.
DR MIM; 605277; gene.
DR neXtProt; NX_Q9NRY4; -.
DR OpenTargets; ENSG00000160007; -.
DR PharmGKB; PA28988; -.
DR VEuPathDB; HostDB:ENSG00000160007; -.
DR eggNOG; KOG4271; Eukaryota.
DR GeneTree; ENSGT01030000234635; -.
DR HOGENOM; CLU_004268_0_0_1; -.
DR InParanoid; Q9NRY4; -.
DR OMA; YWGEVVR; -.
DR OrthoDB; 110157at2759; -.
DR PhylomeDB; Q9NRY4; -.
DR TreeFam; TF324451; -.
DR PathwayCommons; Q9NRY4; -.
DR Reactome; R-HSA-416550; Sema4D mediated inhibition of cell attachment and migration.
DR Reactome; R-HSA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013404; RAC2 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9013408; RHOG GTPase cycle.
DR Reactome; R-HSA-9013409; RHOJ GTPase cycle.
DR Reactome; R-HSA-9013423; RAC3 GTPase cycle.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696270; RND2 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q9NRY4; -.
DR SIGNOR; Q9NRY4; -.
DR BioGRID-ORCS; 2909; 31 hits in 1091 CRISPR screens.
DR ChiTaRS; ARHGAP35; human.
DR EvolutionaryTrace; Q9NRY4; -.
DR GeneWiki; GRLF1; -.
DR GenomeRNAi; 2909; -.
DR Pharos; Q9NRY4; Tbio.
DR PRO; PR:Q9NRY4; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9NRY4; protein.
DR Bgee; ENSG00000160007; Expressed in Brodmann (1909) area 23 and 196 other tissues.
DR Genevisible; Q9NRY4; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0032794; F:GTPase activating protein binding; IEA:Ensembl.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB.
DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB.
DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; ISS:UniProtKB.
DR GO; GO:0021955; P:central nervous system neuron axonogenesis; ISS:UniProtKB.
DR GO; GO:0030950; P:establishment or maintenance of actin cytoskeleton polarity; ISS:UniProtKB.
DR GO; GO:0030900; P:forebrain development; IEA:Ensembl.
DR GO; GO:0030879; P:mammary gland development; ISS:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISS:ARUK-UCL.
DR GO; GO:0043116; P:negative regulation of vascular permeability; IEA:Ensembl.
DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl.
DR GO; GO:0097485; P:neuron projection guidance; ISS:UniProtKB.
DR GO; GO:0045724; P:positive regulation of cilium assembly; ISS:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; ISS:UniProtKB.
DR GO; GO:0050770; P:regulation of axonogenesis; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl.
DR GO; GO:0008361; P:regulation of cell size; IBA:GO_Central.
DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0044319; P:wound healing, spreading of cells; ISS:UniProtKB.
DR Gene3D; 1.10.10.440; -; 2.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR002713; FF_domain.
DR InterPro; IPR036517; FF_domain_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR039007; pG1.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR032835; RhoGAP-FF1.
DR InterPro; IPR000198; RhoGAP_dom.
DR InterPro; IPR045786; RhoGAP_pG1_pG2.
DR InterPro; IPR039006; RhoGAP_pG2.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF01846; FF; 1.
DR Pfam; PF00071; Ras; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR Pfam; PF16512; RhoGAP-FF1; 1.
DR Pfam; PF19518; RhoGAP_pG1_pG2; 1.
DR SMART; SM00441; FF; 4.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF81698; SSF81698; 1.
DR PROSITE; PS51676; FF; 4.
DR PROSITE; PS51852; PG1; 1.
DR PROSITE; PS51853; PG2; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW DNA-binding; GTP-binding; GTPase activation; Lipid-binding; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Repressor; Transcription; Transcription regulation.
FT CHAIN 1..1499
FT /note="Rho GTPase-activating protein 35"
FT /id="PRO_0000056730"
FT DOMAIN 270..327
FT /note="FF 1"
FT DOMAIN 368..422
FT /note="FF 2"
FT DOMAIN 429..483
FT /note="FF 3"
FT DOMAIN 485..550
FT /note="FF 4"
FT DOMAIN 592..767
FT /note="pG1 pseudoGTPase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01199"
FT DOMAIN 783..947
FT /note="pG2 pseudoGTPase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01200"
FT DOMAIN 1249..1436
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 1..266
FT /note="Has GTPase activity, required for proper
FT localization"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT REGION 1058..1089
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1124..1146
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1177..1207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1213..1236
FT /note="Required for phospholipid binding and regulation of
FT the substrate preference"
FT /evidence="ECO:0000269|PubMed:19673492"
FT REGION 1446..1499
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1124..1139
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1182..1196
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1451..1469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1470..1486
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 28
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT BINDING 33..37
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT BINDING 52
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT BINDING 56
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT BINDING 95..97
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT BINDING 201..203
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT BINDING 229..231
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|Ref.23, ECO:0007744|PDB:3C5H"
FT MOD_RES 308
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:19393245"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 970
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 975
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1001
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1072
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1087
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 1105
FT /note="Phosphotyrosine; by ABL2 and PTK6"
FT /evidence="ECO:0000269|PubMed:18829532,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 1134
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 1142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1176
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1179
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1221
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000269|PubMed:19673492"
FT MOD_RES 1226
FT /note="Phosphothreonine; by PKC/PRKCA"
FT /evidence="ECO:0000269|PubMed:19673492"
FT MOD_RES 1236
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000269|PubMed:19673492"
FT MOD_RES 1472
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1476
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1480
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MOD_RES 1483
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91YM2"
FT MUTAGEN 1221
FT /note="S->A: No effect on total phosphorylation levels.
FT Abolishes inhibition of phospholipid binding by PRKCA
FT phosphorylation. Decreases phosphorylation by PRKCA; when
FT associated with A-1226. Abolishes phosphorylation by PRKCA;
FT when associated with A-1126 and A-1236."
FT /evidence="ECO:0000269|PubMed:19673492"
FT MUTAGEN 1221
FT /note="S->D: Enhances Rac GAP activity."
FT /evidence="ECO:0000269|PubMed:19673492"
FT MUTAGEN 1226
FT /note="T->A: No effect on total phosphorylation levels.
FT Abolishes inhibition of phospholipid binding by PRKCA
FT phosphorylation. Decreases phosphorylation by PRKCA; when
FT associated with A-1221. Abolishes phosphorylation by PRKCA;
FT when associated with A-1121 and A-1236."
FT /evidence="ECO:0000269|PubMed:19673492"
FT MUTAGEN 1226
FT /note="T->D: Enhances Rac GAP activity."
FT /evidence="ECO:0000269|PubMed:19673492"
FT MUTAGEN 1236
FT /note="S->A: No effect on total phosphorylation levels. No
FT effect on inhibition of phospholipid binding by PRKCA
FT phosphorylation. Abolishes phosphorylation by PRKCA; when
FT associated with A-1121 and A-1226."
FT /evidence="ECO:0000269|PubMed:19673492"
FT CONFLICT 251
FT /note="R -> P (in Ref. 5; AAF80386)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="V -> D (in Ref. 5; AAF80386)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="S -> G (in Ref. 5; AAF80386)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="Q -> A (in Ref. 5; AAF80386 and 6; AAA58618)"
FT /evidence="ECO:0000305"
FT CONFLICT 474
FT /note="M -> T (in Ref. 5; AAF80386 and 6; AAA58618)"
FT /evidence="ECO:0000305"
FT CONFLICT 978
FT /note="C -> S (in Ref. 5; AAF80386)"
FT /evidence="ECO:0000305"
FT CONFLICT 1292
FT /note="M -> I (in Ref. 5; AAF80386)"
FT /evidence="ECO:0000305"
FT CONFLICT 1452..1453
FT /note="PS -> RN (in Ref. 6; AAA58618)"
FT /evidence="ECO:0000305"
FT STRAND 14..21
FT /evidence="ECO:0007829|PDB:3C5H"
FT TURN 25..30
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 35..43
FT /evidence="ECO:0007829|PDB:3C5H"
FT TURN 47..49
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 60..63
FT /evidence="ECO:0007829|PDB:3C5H"
FT TURN 66..70
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 72..79
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 91..96
FT /evidence="ECO:0007829|PDB:3C5H"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 116..120
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 123..126
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 136..138
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 154..156
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 174..190
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 195..200
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 207..218
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:3C5H"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:3C5H"
FT TURN 230..233
FT /evidence="ECO:0007829|PDB:3C5H"
FT HELIX 236..248
FT /evidence="ECO:0007829|PDB:3C5H"
FT TURN 268..271
FT /evidence="ECO:0007829|PDB:2K85"
FT HELIX 272..284
FT /evidence="ECO:0007829|PDB:2K85"
FT STRAND 286..288
FT /evidence="ECO:0007829|PDB:2K85"
FT HELIX 292..299
FT /evidence="ECO:0007829|PDB:2K85"
FT HELIX 303..311
FT /evidence="ECO:0007829|PDB:2K85"
FT HELIX 314..330
FT /evidence="ECO:0007829|PDB:2K85"
FT HELIX 1251..1254
FT /evidence="ECO:0007829|PDB:3FK2"
FT STRAND 1257..1259
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1263..1275
FT /evidence="ECO:0007829|PDB:3FK2"
FT TURN 1280..1284
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1289..1301
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1308..1310
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1314..1327
FT /evidence="ECO:0007829|PDB:3FK2"
FT STRAND 1328..1330
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1335..1344
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1350..1362
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1366..1383
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1386..1389
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1393..1405
FT /evidence="ECO:0007829|PDB:3FK2"
FT STRAND 1409..1412
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1414..1430
FT /evidence="ECO:0007829|PDB:3FK2"
FT HELIX 1432..1436
FT /evidence="ECO:0007829|PDB:3FK2"
SQ SEQUENCE 1499 AA; 170514 MW; 8CCB493414A7E3E6 CRC64;
MMMARKQDVR IPTYNISVVG LSGTEKEKGQ CGIGKSCLCN RFVRPSADEF HLDHTSVLST
SDFGGRVVNN DHFLYWGEVS RSLEDCVECK MHIVEQTEFI DDQTFQPHRS TALQPYIKRA
AATKLASAEK LMYFCTDQLG LEQDFEQKQM PDGKLLVDGF LLGIDVSRGM NRNFDDQLKF
VSNLYNQLAK TKKPIVVVLT KCDEGVERYI RDAHTFALSK KNLQVVETSA RSNVNVDLAF
STLVQLIDKS RGKTKIIPYF EALKQQSQQI ATAKDKYEWL VSRIVKNHNE NWLSVSRKMQ
ASPEYQDYVY LEGTQKAKKL FLQHIHRLKH EHIERRRKLY LAALPLAFEA LIPNLDEIDH
LSCIKAKKLL ETKPEFLKWF VVLEETPWDA TSHIDNMENE RIPFDLMDTV PAEQLYEAHL
EKLRNERKRV EMRRAFKENL ETSPFITPGK PWEEARSFIM NEDFYQWLEE SVYMDIYGKH
QKQIIDKAKE EFQELLLEYS ELFYELELDA KPSKEKMGVI QDVLGEEQRF KALQKLQAER
DALILKHIHF VYHPTKETCP SCPACVDAKI EHLISSRFIR PSDRNQKNSL SDPNIDRINL
VILGKDGLAR ELANEIRALC TNDDKYVIDG KMYELSLRPI EGNVRLPVNS FQTPTFQPHG
CLCLYNSKES LSYVVESIEK SRESTLGRRD NHLVHLPLTL ILVNKRGDTS GETLHSLIQQ
GQQIASKLQC VFLDPASAGI GYGRNINEKQ ISQVLKGLLD SKRNLNLVSS TASIKDLADV
DLRIVMCLMC GDPFSADDIL FPVLQSQTCK SSHCGSNNSV LLELPIGLHK KRIELSVLSY
HSSFSIRKSR LVHGYIVFYS AKRKASLAML RAFLCEVQDI IPIQLVALTD GAVDVLDNDL
SREQLTEGEE IAQEIDGRFT SIPCSQPQHK LEIFHPFFKD VVEKKNIIEA THMYDNAAEA
CSTTEEVFNS PRAGSPLCNS NLQDSEEDIE PSYSLFREDT SLPSLSKDHS KLSMELEGND
GLSFIMSNFE SKLNNKVPPP VKPKPPVHFE ITKGDLSYLD QGHRDGQRKS VSSSPWLPQD
GFDPSDYAEP MDAVVKPRNE EENIYSVPHD STQGKIITIR NINKAQSNGS GNGSDSEMDT
SSLERGRKVS IVSKPVLYRT RCTRLGRFAS YRTSFSVGSD DELGPIRKKE EDQASQGYKG
DNAVIPYETD EDPRRRNILR SLRRNTKKPK PKPRPSITKA TWESNYFGVP LTTVVTPEKP
IPIFIERCIE YIEATGLSTE GIYRVSGNKS EMESLQRQFD QDHNLDLAEK DFTVNTVAGA
MKSFFSELPD PLVPYNMQID LVEAHKINDR EQKLHALKEV LKKFPKENHE VFKYVISHLN
KVSHNNKVNL MTSENLSICF WPTLMRPDFS TMDALTATRT YQTIIELFIQ QCPFFFYNRP
ITEPPGARPS SPSAVASTVP FLTSTPVTSQ PSPPQSPPPT PQSPMQPLLP SQLQAEHTL
