ID RHG07_HUMAN Reviewed; 1528 AA. AC Q96QB1; B4DR10; B8PTI0; E9PDZ8; E9PF76; E9PGY9; O14868; O43199; Q7Z5R8; AC Q86UC6; Q9C0E0; Q9H7A2; DT 08-NOV-2002, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 4. DT 24-JAN-2024, entry version 194. DE RecName: Full=Rho GTPase-activating protein 7; DE AltName: Full=Deleted in liver cancer 1 protein; DE Short=DLC-1; DE AltName: Full=HP protein; DE AltName: Full=Rho-type GTPase-activating protein 7; DE AltName: Full=START domain-containing protein 12; DE Short=StARD12; DE AltName: Full=StAR-related lipid transfer protein 12; GN Name=DLC1; Synonyms=ARHGAP7, KIAA1723, STARD12; 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; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS SER-712; VAL-1199 AND RP CYS-1209. RX PubMed=9605766; RA Yuan B.Z., Miller M.J., Keck C.L., Zimonjic D.B., Thorgeirsson S.S., RA Popescu N.C.; RT "Cloning, characterization, and chromosomal localization of a gene RT frequently deleted in human liver cancer (DLC-1) homologous to rat RT RhoGAP."; RL Cancer Res. 58:2196-2199(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-791. RC TISSUE=Lung; RA Wei M.-H., Pack S., Ivanov S., Lerman M.I.; RT "Cloning and molecular characterization of the human ortholog of the rat RT dual regulator p122RhoGAP."; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND VARIANT MET-791. RA Jeong S.-J., Dimtchev A., Lerman M., Dritschilo A., Jung M.; RT "Identification of HP/DLC1 exon and introns."; RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANTS HIS-254; RP ASP-255 AND ILE-260 AND MET-791. 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND VARIANTS RP HIS-254; ASP-255; ILE-260 AND MET-791. RC TISSUE=Smooth muscle; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., RA Platzer M., Shimizu N., Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5), AND VARIANT RP ASP-255. RC TISSUE=Brain, and Lung; 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 [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-50 (ISOFORM 6), AND ALTERNATIVE PROMOTER RP USAGE. RC TISSUE=Liver; RX PubMed=21217778; DOI=10.1038/onc.2010.576; RA Low J.S., Tao Q., Ng K.M., Goh H.K., Shu X.S., Woo W.L., Ambinder R.F., RA Srivastava G., Shamay M., Chan A.T., Popescu N.C., Hsieh W.S.; RT "A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor RT growth and is frequently silenced in multiple common tumors."; RL Oncogene 30:1923-1935(2011). RN [9] RP INTERACTION WITH TNS4, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-877 AND RP TYR-879. RX PubMed=17190795; DOI=10.1083/jcb.200608015; RA Liao Y.C., Si L., deVere White R.W., Lo S.H.; RT "The phosphotyrosine-independent interaction of DLC-1 and the SH2 domain of RT cten regulates focal adhesion localization and growth suppression activity RT of DLC-1."; RL J. Cell Biol. 176:43-49(2007). RN [10] RP FUNCTION, DOMAIN SAM, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-879. RX PubMed=18786931; DOI=10.1074/jbc.m800617200; RA Kim T.Y., Healy K.D., Der C.J., Sciaky N., Bang Y.J., Juliano R.L.; RT "Effects of structure of Rho GTPase-activating protein DLC-1 on cell RT morphology and migration."; RL J. Biol. Chem. 283:32762-32770(2008). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND FOCAL ADHESION TARGETING. RX PubMed=19170769; DOI=10.1111/j.1365-2443.2008.01265.x; RA Kawai K., Iwamae Y., Yamaga M., Kiyota M., Ishii H., Hirata H., Homma Y., RA Yagisawa H.; RT "Focal adhesion-localization of START-GAP1/DLC1 is essential for cell RT motility and morphology."; RL Genes Cells 14:227-241(2009). RN [12] RP INTERACTION WITH TNS1. RX PubMed=19826001; DOI=10.1074/jbc.m109.059592; RA Hall E.H., Daugherty A.E., Choi C.K., Horwitz A.F., Brautigan D.L.; RT "Tensin1 requires protein phosphatase-1alpha in addition to RhoGAP DLC-1 to RT control cell polarization, migration, and invasion."; RL J. Biol. Chem. 284:34713-34722(2009). RN [13] RP FUNCTION, AND LIPID-BINDING REGION. RX PubMed=19710422; DOI=10.1091/mbc.e09-03-0247; RA Erlmann P., Schmid S., Horenkamp F.A., Geyer M., Pomorski T.G., RA Olayioye M.A.; RT "DLC1 activation requires lipid interaction through a polybasic region RT preceding the RhoGAP domain."; RL Mol. Biol. Cell 20:4400-4411(2009). RN [14] RP INTERACTION WITH TNS1. RX PubMed=20798394; DOI=10.1074/mcp.m110.003665; RA Hall E.H., Balsbaugh J.L., Rose K.L., Shabanowitz J., Hunt D.F., RA Brautigan D.L.; RT "Comprehensive analysis of phosphorylation sites in Tensin1 reveals RT regulation by p38MAPK."; RL Mol. Cell. Proteomics 9:2853-2863(2010). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-523; SER-526 AND SER-757, AND RP 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 [17] RP INTERACTION WITH TNS1. RX PubMed=26427649; DOI=10.1016/j.bbamcr.2015.09.028; RA Shih Y.P., Sun P., Wang A., Lo S.H.; RT "Tensin1 positively regulates RhoA activity through its interaction with RT DLC1."; RL Biochim. Biophys. Acta 1853:3258-3265(2015). RN [18] RP FUNCTION, AND INTERACTION WITH TNS3 AND PTEN. RX PubMed=26166433; DOI=10.1038/ncomms8721; RA Cao X., Kaneko T., Li J.S., Liu A.D., Voss C., Li S.S.; RT "A phosphorylation switch controls the spatiotemporal activation of Rho RT GTPases in directional cell migration."; RL Nat. Commun. 6:7721-7721(2015). RN [19] RP STRUCTURE BY NMR OF 438-518. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SAM-domain of rho-GTPase-activating protein 7."; RL Submitted (APR-2007) to the PDB data bank. RN [20] RP STRUCTURE BY NMR OF 454-513. RX PubMed=19317456; DOI=10.1021/bi9000936; RA Yang S., Noble C.G., Yang D.; RT "Characterization of DLC1-SAM equilibrium unfolding at the amino acid RT residue level."; RL Biochemistry 48:4040-4049(2009). RN [21] RP STRUCTURE BY NMR OF 451-513, MUTAGENESIS OF PHE-475; LEU-476 AND ARG-1114, RP INTERACTION WITH EF1A1, AND SUBCELLULAR LOCATION. RX PubMed=19158340; DOI=10.1242/jcs.027482; RA Zhong D., Zhang J., Yang S., Soh U.J., Buschdorf J.P., Zhou Y.T., Yang D., RA Low B.C.; RT "The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell RT migration."; RL J. Cell Sci. 122:414-424(2009). RN [22] RP VARIANTS SER-712; MET-791; ALA-959; GLN-998; ALA-1025; VAL-1199 AND RP CYS-1209. RX PubMed=10649492; RX DOI=10.1002/(sici)1098-1004(200002)15:2<156::aid-humu4>3.0.co;2-4; RA Wilson P.J., McGlinn E., Marsh A., Evans T., Arnold J., Wright K., RA Biden K., Young J., Wainwright B., Wicking C., Chenevix-Trench G.; RT "Sequence variants of DLC1 in colorectal and ovarian tumours."; RL Hum. Mutat. 15:156-165(2000). CC -!- FUNCTION: Functions as a GTPase-activating protein for the small CC GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream CC signaling. This induces morphological changes and detachment through CC cytoskeletal reorganization, playing a critical role in biological CC processes such as cell migration and proliferation. Also functions in CC vivo as an activator of the phospholipase PLCD1. Active DLC1 increases CC cell migration velocity but reduces directionality. Required for growth CC factor-induced epithelial cell migration; in resting cells, interacts CC with TNS3 while PTEN interacts with the p85 regulatory subunit of the CC PI3K kinase complex but growth factor stimulation induces CC phosphorylation of TNS3 and PTEN, causing them to change their binding CC preference so that PTEN interacts with DLC1 and TNS3 interacts with p85 CC (PubMed:26166433). The PTEN-DLC1 complex translocates to the posterior CC of migrating cells to activate RHOA while the TNS3-p85 complex CC translocates to the leading edge of migrating cells to promote RAC1 CC activation (PubMed:26166433). {ECO:0000269|PubMed:18786931, CC ECO:0000269|PubMed:19170769, ECO:0000269|PubMed:19710422, CC ECO:0000269|PubMed:26166433}. CC -!- SUBUNIT: Interacts with EF1A1, facilitates EF1A1 distribution to the CC membrane periphery and ruffles upon growth factor stimulation and CC suppresses cell migration (PubMed:19158340). Interacts with tensin TNS1 CC (via N-terminus); the interaction is decreased by phosphorylation of CC TNS1 (PubMed:19826001, PubMed:20798394, PubMed:26427649). Interacts CC with TNS3 and PTEN; in resting cells, interacts with TNS3 (via C2 CC tensin-type domain) but, following growth factor stimulation, TNS3 and CC PTEN are phosphorylated which leads to weakened interaction with TNS3 CC and enhanced interaction with PTEN (PubMed:26166433). Interacts (via C- CC terminus) with tensin TNS4 (via SH2 domain); the interaction is CC independent of tyrosine phosphorylation of DLC1 (PubMed:17190795). CC {ECO:0000269|PubMed:17190795, ECO:0000269|PubMed:19158340, CC ECO:0000269|PubMed:19826001, ECO:0000269|PubMed:20798394, CC ECO:0000269|PubMed:26166433, ECO:0000269|PubMed:26427649}. CC -!- INTERACTION: CC Q96QB1; P20936: RASA1; NbExp=7; IntAct=EBI-2608428, EBI-1026476; CC Q96QB1; Q923Q2: Stard13; Xeno; NbExp=2; IntAct=EBI-2608428, EBI-8393503; CC Q96QB1-1; Q04205: TNS1; Xeno; NbExp=7; IntAct=EBI-15638708, EBI-2607590; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell junction, focal adhesion CC {ECO:0000269|PubMed:17190795}. Membrane; Peripheral membrane protein. CC Note=Colocalizes with EF1A1 at actin-rich regions in the cell CC periphery. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6; CC Name=2; CC IsoId=Q96QB1-2; Sequence=Displayed; CC Name=1; CC IsoId=Q96QB1-1; Sequence=VSP_037871, VSP_037872; CC Name=3; CC IsoId=Q96QB1-3; Sequence=VSP_037873, VSP_037874; CC Name=4; CC IsoId=Q96QB1-4; Sequence=VSP_037871, VSP_044651; CC Name=5; CC IsoId=Q96QB1-5; Sequence=VSP_046331, VSP_046332; CC Name=6; Synonyms=i-4; CC IsoId=Q96QB1-6; Sequence=VSP_053836, VSP_053837; CC -!- TISSUE SPECIFICITY: Highest level of expression in the spleen, with CC rather lower levels in prostate, testis, ovary, small intestine and CC colon, but none in the thymus. CC -!- DOMAIN: The SAM domain mediates interaction with EF1A1, and functions CC as an autoinhibitory regulator of RhoGAP Activity. CC {ECO:0000269|PubMed:18786931}. CC -!- DOMAIN: The polybasic cluster is required for activation and mediates CC binding to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)) CC containing membranes. {ECO:0000269|PubMed:18786931}. CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative promoter usage. CC ubiquitously expressed, significantly down-regulated in multiple CC carcinoma cell lines. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB81637.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB21814.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40328/DLC1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF035119; AAB87700.1; -; mRNA. DR EMBL; AF026219; AAB81637.1; ALT_INIT; mRNA. DR EMBL; AF408781; AAK97501.1; -; Genomic_DNA. DR EMBL; AF408768; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408769; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408770; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408771; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408772; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408773; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408774; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408775; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408776; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408777; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408778; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408779; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AF408780; AAK97501.1; JOINED; Genomic_DNA. DR EMBL; AB051510; BAB21814.1; ALT_INIT; mRNA. DR EMBL; AK024774; BAB14996.1; -; mRNA. DR EMBL; AK299049; BAG61122.1; -; mRNA. DR EMBL; AC015641; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC019270; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC022844; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC106845; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC049842; AAH49842.1; -; mRNA. DR EMBL; BC054511; AAH54511.1; -; mRNA. DR EMBL; EU159199; ABX83661.1; -; mRNA. DR EMBL; EU159200; ABX83662.1; -; mRNA. DR CCDS; CCDS55201.1; -. [Q96QB1-4] DR CCDS; CCDS5989.1; -. [Q96QB1-2] DR CCDS; CCDS5990.1; -. [Q96QB1-1] DR CCDS; CCDS5991.2; -. [Q96QB1-5] DR CCDS; CCDS83253.1; -. [Q96QB1-6] DR RefSeq; NP_001157743.1; NM_001164271.1. [Q96QB1-4] DR RefSeq; NP_001303597.1; NM_001316668.1. [Q96QB1-6] DR RefSeq; NP_001335010.1; NM_001348081.1. [Q96QB1-2] DR RefSeq; NP_001335011.1; NM_001348082.1. [Q96QB1-4] DR RefSeq; NP_001335012.1; NM_001348083.1. [Q96QB1-4] DR RefSeq; NP_001335013.1; NM_001348084.1. [Q96QB1-4] DR RefSeq; NP_006085.2; NM_006094.4. [Q96QB1-1] DR RefSeq; NP_079043.3; NM_024767.3. [Q96QB1-5] DR RefSeq; NP_872584.2; NM_182643.2. [Q96QB1-2] DR RefSeq; XP_005273431.1; XM_005273374.1. DR PDB; 2DKY; NMR; -; A=451-515. DR PDB; 2GYT; NMR; -; A=451-513. DR PDB; 2KAP; NMR; -; A=454-513. DR PDB; 2LOZ; NMR; -; B=811-824. DR PDB; 3KUQ; X-ray; 2.30 A; A=1074-1283. DR PDB; 5FZT; X-ray; 2.10 A; B=904-926. DR PDBsum; 2DKY; -. DR PDBsum; 2GYT; -. DR PDBsum; 2KAP; -. DR PDBsum; 2LOZ; -. DR PDBsum; 3KUQ; -. DR PDBsum; 5FZT; -. DR AlphaFoldDB; Q96QB1; -. DR BMRB; Q96QB1; -. DR SMR; Q96QB1; -. DR BioGRID; 115667; 58. DR CORUM; Q96QB1; -. DR DIP; DIP-56928N; -. DR IntAct; Q96QB1; 41. DR MINT; Q96QB1; -. DR STRING; 9606.ENSP00000276297; -. DR GlyGen; Q96QB1; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q96QB1; -. DR PhosphoSitePlus; Q96QB1; -. DR BioMuta; DLC1; -. DR DMDM; 313104315; -. DR EPD; Q96QB1; -. DR jPOST; Q96QB1; -. DR MassIVE; Q96QB1; -. DR MaxQB; Q96QB1; -. DR PaxDb; 9606-ENSP00000276297; -. DR PeptideAtlas; Q96QB1; -. DR ProteomicsDB; 19782; -. DR ProteomicsDB; 20045; -. DR ProteomicsDB; 20421; -. DR ProteomicsDB; 77848; -. [Q96QB1-2] DR ProteomicsDB; 77849; -. [Q96QB1-1] DR ProteomicsDB; 77850; -. [Q96QB1-3] DR Antibodypedia; 22182; 270 antibodies from 36 providers. DR CPTC; Q96QB1; 3 antibodies. DR DNASU; 10395; -. DR Ensembl; ENST00000276297.9; ENSP00000276297.4; ENSG00000164741.15. [Q96QB1-2] DR Ensembl; ENST00000316609.9; ENSP00000321034.5; ENSG00000164741.15. [Q96QB1-3] DR Ensembl; ENST00000358919.6; ENSP00000351797.2; ENSG00000164741.15. [Q96QB1-1] DR Ensembl; ENST00000511869.1; ENSP00000425878.1; ENSG00000164741.15. [Q96QB1-5] DR Ensembl; ENST00000512044.6; ENSP00000422595.2; ENSG00000164741.15. [Q96QB1-6] DR Ensembl; ENST00000520226.5; ENSP00000428028.1; ENSG00000164741.15. [Q96QB1-4] DR GeneID; 10395; -. DR KEGG; hsa:10395; -. DR MANE-Select; ENST00000276297.9; ENSP00000276297.4; NM_182643.3; NP_872584.2. DR UCSC; uc003wwk.2; human. [Q96QB1-2] DR AGR; HGNC:2897; -. DR CTD; 10395; -. DR DisGeNET; 10395; -. DR GeneCards; DLC1; -. DR HGNC; HGNC:2897; DLC1. DR HPA; ENSG00000164741; Low tissue specificity. DR MalaCards; DLC1; -. DR MIM; 604258; gene. DR neXtProt; NX_Q96QB1; -. DR OpenTargets; ENSG00000164741; -. DR PharmGKB; PA27351; -. DR VEuPathDB; HostDB:ENSG00000164741; -. DR eggNOG; KOG2200; Eukaryota. DR GeneTree; ENSGT00950000183061; -. DR HOGENOM; CLU_004367_1_0_1; -. DR InParanoid; Q96QB1; -. DR OMA; AMSHESM; -. DR OrthoDB; 2883046at2759; -. DR PhylomeDB; Q96QB1; -. DR TreeFam; TF314044; -. DR PathwayCommons; Q96QB1; -. 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-9013406; RHOQ GTPase cycle. DR SignaLink; Q96QB1; -. DR SIGNOR; Q96QB1; -. DR BioGRID-ORCS; 10395; 12 hits in 1151 CRISPR screens. DR ChiTaRS; DLC1; human. DR EvolutionaryTrace; Q96QB1; -. DR GeneWiki; DLC1; -. DR GenomeRNAi; 10395; -. DR Pharos; Q96QB1; Tbio. DR PRO; PR:Q96QB1; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q96QB1; Protein. DR Bgee; ENSG00000164741; Expressed in adrenal tissue and 182 other cell types or tissues. DR ExpressionAtlas; Q96QB1; baseline and differential. DR GO; GO:0005901; C:caveola; IDA:UniProtKB. DR GO; GO:0030864; C:cortical actin cytoskeleton; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0045121; C:membrane raft; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032587; C:ruffle membrane; IDA:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IMP:UniProtKB. DR GO; GO:0008289; F:lipid binding; IEA:InterPro. DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; ISS:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB. DR GO; GO:0048041; P:focal adhesion assembly; ISS:UniProtKB. DR GO; GO:0030900; P:forebrain development; ISS:UniProtKB. DR GO; GO:0003007; P:heart morphogenesis; ISS:UniProtKB. DR GO; GO:0021575; P:hindbrain morphogenesis; ISS:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; IDA:UniProtKB. DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IMP:UniProtKB. DR GO; GO:0051497; P:negative regulation of stress fiber assembly; IDA:UniProtKB. DR GO; GO:0001843; P:neural tube closure; ISS:UniProtKB. DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IDA:UniProtKB. DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IDA:UniProtKB. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB. DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR CDD; cd04375; RhoGAP_DLC1; 1. DR CDD; cd09591; SAM_DLC1; 1. DR CDD; cd08908; START_STARD12-like; 1. DR Gene3D; 1.10.287.2070; -; 1. DR Gene3D; 3.30.530.20; -; 1. DR Gene3D; 1.10.555.10; Rho GTPase activation protein; 1. DR IDEAL; IID00677; -. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR000198; RhoGAP_dom. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR023393; START-like_dom_sf. DR InterPro; IPR002913; START_lipid-bd_dom. DR PANTHER; PTHR12659:SF2; RHO GTPASE-ACTIVATING PROTEIN 7; 1. DR PANTHER; PTHR12659; RHO-TYPE GTPASE ACTIVATING PROTEIN; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF07647; SAM_2; 1. DR Pfam; PF01852; START; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00234; START; 1. DR SUPFAM; SSF55961; Bet v1-like; 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS50848; START; 1. DR Genevisible; Q96QB1; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative promoter usage; Alternative splicing; KW Cell junction; Cytoplasm; GTPase activation; Membrane; Phosphoprotein; KW Reference proteome; Tumor suppressor. FT CHAIN 1..1528 FT /note="Rho GTPase-activating protein 7" FT /id="PRO_0000056707" FT DOMAIN 448..515 FT /note="SAM" FT DOMAIN 1078..1284 FT /note="Rho-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT DOMAIN 1314..1521 FT /note="START" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197" FT REGION 72..94 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 288..310 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 372..436 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 558..617 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 710..884 FT /note="Focal adhesion-targeting (FAT)" FT REGION 732..764 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 829..876 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 928..990 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1051..1073 FT /note="Polybasic cluster (PBR)" FT COMPBIAS 76..94 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 398..436 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 586..617 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 523 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 526 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 566 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q63744" FT MOD_RES 757 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..437 FT /note="Missing (in isoform 1 and isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:9605766, ECO:0000303|Ref.2" FT /id="VSP_037871" FT VAR_SEQ 1..45 FT /note="MSVAIRKRSWEEHVTHWMGQPFNSDDRNTACHHGLVADSLQASME -> MGD FT PKAHVMARPLRAPLRRSFSDHIRDSTARALDVIWKNTRDRRL (in isoform 6)" FT /evidence="ECO:0000303|PubMed:21217778" FT /id="VSP_053836" FT VAR_SEQ 46..448 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:21217778" FT /id="VSP_053837" FT VAR_SEQ 438..511 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_044651" FT VAR_SEQ 438..450 FT /note="TAIQGISEKEKAE -> MCRKKPDTMILTQ (in isoform 1)" FT /evidence="ECO:0000303|PubMed:9605766, ECO:0000303|Ref.2" FT /id="VSP_037872" FT VAR_SEQ 450..498 FT /note="EIEAKEACDWLRATGFPQYAQLYEDFLFPIDISLVKREHDFLDRDAIEA -> FT AVKSVKLEVDEDKSTKGSNFSNSEVAIGLSPYTFPQKRLFHVAGEENIT (in FT isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037873" FT VAR_SEQ 450..463 FT /note="EIEAKEACDWLRAT -> GKLTFWFCFLANLF (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_046331" FT VAR_SEQ 464..1528 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_046332" FT VAR_SEQ 499..1528 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_037874" FT VARIANT 27 FT /note="R -> C (in dbSNP:rs34575560)" FT /id="VAR_059293" FT VARIANT 81 FT /note="L -> V (in dbSNP:rs3816748)" FT /id="VAR_059294" FT VARIANT 254 FT /note="Q -> H (in dbSNP:rs11203495)" FT /evidence="ECO:0000269|PubMed:11214970, FT ECO:0000269|PubMed:14702039" FT /id="VAR_059295" FT VARIANT 255 FT /note="N -> D (in dbSNP:rs11203494)" FT /evidence="ECO:0000269|PubMed:11214970, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334" FT /id="VAR_059296" FT VARIANT 260 FT /note="T -> I (in dbSNP:rs3816747)" FT /evidence="ECO:0000269|PubMed:11214970, FT ECO:0000269|PubMed:14702039" FT /id="VAR_059297" FT VARIANT 320 FT /note="Q -> H (in dbSNP:rs34591797)" FT /id="VAR_059298" FT VARIANT 712 FT /note="N -> S (in dbSNP:rs1044092)" FT /evidence="ECO:0000269|PubMed:10649492, FT ECO:0000269|PubMed:9605766" FT /id="VAR_014229" FT VARIANT 791 FT /note="V -> M (in dbSNP:rs532841)" FT /evidence="ECO:0000269|PubMed:10649492, FT ECO:0000269|PubMed:11214970, ECO:0000269|PubMed:14702039, FT ECO:0000269|Ref.2, ECO:0000269|Ref.3" FT /id="VAR_014230" FT VARIANT 959 FT /note="T -> A (in dbSNP:rs121908500)" FT /evidence="ECO:0000269|PubMed:10649492" FT /id="VAR_014231" FT VARIANT 998 FT /note="H -> Q (in dbSNP:rs149295187)" FT /evidence="ECO:0000269|PubMed:10649492" FT /id="VAR_014232" FT VARIANT 1025 FT /note="V -> A" FT /evidence="ECO:0000269|PubMed:10649492" FT /id="VAR_014233" FT VARIANT 1199 FT /note="E -> V (in dbSNP:rs1044093)" FT /evidence="ECO:0000269|PubMed:10649492, FT ECO:0000269|PubMed:9605766" FT /id="VAR_014234" FT VARIANT 1209 FT /note="S -> C (in dbSNP:rs1044094)" FT /evidence="ECO:0000269|PubMed:10649492, FT ECO:0000269|PubMed:9605766" FT /id="VAR_014235" FT MUTAGEN 475 FT /note="F->G: Abolishes interaction with EF1A1." FT /evidence="ECO:0000269|PubMed:19158340" FT MUTAGEN 476 FT /note="L->G: Abolishes interaction with EF1A1." FT /evidence="ECO:0000269|PubMed:19158340" FT MUTAGEN 877 FT /note="S->A: Abolishes interaction with TNS4 and results in FT diffuse cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:17190795" FT MUTAGEN 879 FT /note="Y->F: Unable to displace endogenous DLC1 from focal FT adhesions. Abolishes interaction with TNS4 and results in FT diffuse cytoplasmic localization." FT /evidence="ECO:0000269|PubMed:17190795, FT ECO:0000269|PubMed:18786931" FT MUTAGEN 1114 FT /note="R->E: No catalytic activity." FT /evidence="ECO:0000269|PubMed:19158340" FT CONFLICT 43 FT /note="S -> C (in Ref. 5; BAB14996)" FT /evidence="ECO:0000305" FT CONFLICT 130 FT /note="T -> I (in Ref. 5; BAB14996)" FT /evidence="ECO:0000305" FT CONFLICT 571 FT /note="H -> L (in Ref. 4; BAB21814)" FT /evidence="ECO:0000305" FT CONFLICT 1114 FT /note="R -> K (in Ref. 1; AAB87700)" FT /evidence="ECO:0000305" FT CONFLICT 1364 FT /note="P -> R (in Ref. 1; AAB87700)" FT /evidence="ECO:0000305" FT HELIX 449..463 FT /evidence="ECO:0007829|PDB:2DKY" FT HELIX 468..473 FT /evidence="ECO:0007829|PDB:2DKY" FT TURN 474..476 FT /evidence="ECO:0007829|PDB:2KAP" FT HELIX 481..487 FT /evidence="ECO:0007829|PDB:2DKY" FT TURN 488..490 FT /evidence="ECO:0007829|PDB:2DKY" FT HELIX 493..509 FT /evidence="ECO:0007829|PDB:2DKY" FT TURN 510..514 FT /evidence="ECO:0007829|PDB:2DKY" FT HELIX 906..920 FT /evidence="ECO:0007829|PDB:5FZT" FT HELIX 1080..1087 FT /evidence="ECO:0007829|PDB:3KUQ" FT STRAND 1088..1091 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1093..1105 FT /evidence="ECO:0007829|PDB:3KUQ" FT TURN 1110..1114 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1119..1129 FT /evidence="ECO:0007829|PDB:3KUQ" FT STRAND 1131..1134 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1143..1156 FT /evidence="ECO:0007829|PDB:3KUQ" FT STRAND 1157..1159 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1166..1176 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1179..1181 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1182..1191 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1195..1213 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1215..1218 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1222..1234 FT /evidence="ECO:0007829|PDB:3KUQ" FT HELIX 1260..1278 FT /evidence="ECO:0007829|PDB:3KUQ" FT CONFLICT Q96QB1-6:49..50 FT /note="EA -> KP (in Ref. 8; ABX83661/ABX83662)" FT /evidence="ECO:0000305" SQ SEQUENCE 1528 AA; 170591 MW; 5D20F29CC606302E CRC64; MSVAIRKRSW EEHVTHWMGQ PFNSDDRNTA CHHGLVADSL QASMEKDATL NVDRKEKCVS LPDCCHGSEL RDFPGRPMGH LSKDVDENDS HEGEDQFLSL EASTETLVHV SDEDNNADLC LTDDKQVLNT QGQKTSGQHM IQGAGSLEKA LPIIQSNQVS SNSWGIAGET ELALVKESGE RKVTDSISKS LELCNEISLS EIKDAPKVNA VDTLNVKDIA PEKQLLNSAV IAQQRRKPDP PKDENERSTC NVVQNEFLDT PCTNRGLPLL KTDFGSCLLQ PPSCPNGMSA ENGLEKSGFS QHQNKSPPKV KAEDGMQCLQ LKETLATQEP TDNQVRLRKR KEIREDRDRA RLDSMVLLIM KLDQLDQDIE NALSTSSSPS GTPTNLRRHV PDLESGSESG ADTISVNQTR VNLSSDTEST DLPSSTPVAN SGTKPKTTAI QGISEKEKAE IEAKEACDWL RATGFPQYAQ LYEDFLFPID ISLVKREHDF LDRDAIEALC RRLNTLNKCA VMKLEISPHR KRSDDSDEDE PCAISGKWTF QRDSKRWSRL EEFDVFSPKQ DLVPGSPDDS HPKDGPSPGG TLMDLSERQE VSSVRSLSST GSLPSHAPPS EDAATPRTNS VISVCSSSNL AGNDDSFGSL PSPKELSSFS FSMKGHEKTA KSKTRSLLKR MESLKLKSSH HSKHKAPSKL GLIISGPILQ EGMDEEKLKQ LNCVEISALN GNRINVPMVR KRSVSNSTQT SSSSSQSETS SAVSTPSPVT RTRSLSACNK RVGMYLEGFD PFNQSTFNNV VEQNFKNRES YPEDTVFYIP EDHKPGTFPK ALTNGSFSPS GNNGSVNWRT GSFHGPGHIS LRRENSSDSP KELKRRNSSS SMSSRLSIYD NVPGSILYSS SGDLADLENE DIFPELDDIL YHVKGMQRIV NQWSEKFSDE GDSDSALDSV SPCPSSPKQI HLDVDNDRTT PSDLDSTGNS LNEPEEPSEI PERRDSGVGA SLTRSNRHRL RWHSFQSSHR PSLNSVSLQI NCQSVAQMNL LQKYSLLKLT ALLEKYTPSN KHGFSWAVPK FMKRIKVPDY KDRSVFGVPL TVNVQRTGQP LPQSIQQAMR YLRNHCLDQV GLFRKSGVKS RIQALRQMNE GAIDCVNYEG QSAYDVADML KQYFRDLPEP LMTNKLSETF LQIYQYVPKD QRLQAIKAAI MLLPDENREV LQTLLYFLSD VTAAVKENQM TPTNLAVCLA PSLFHLNTLK RENSSPRVMQ RKQSLGKPDQ KDLNENLAAT QGLAHMIAEC KKLFQVPEEM SRCRNSYTEQ ELKPLTLEAL GHLGNDDSAD YQHFLQDCVD GLFKEVKEKF KGWVSYSTSE QAELSYKKVS EGPPLRLWRS VIEVPAVPEE ILKRLLKEQH LWDVDLLDSK VIEILDSQTE IYQYVQNSMA PHPARDYVVL RTWRTNLPKG ACALLLTSVD HDRAPVVGVR VNVLLSRYLI EPCGPGKSKL TYMCRVDLRG HMPEWYTKSF GHLCAAEVVK IRDSFSNQNT ETKDTKSR //