ID RHG07_BOVIN Reviewed; 1112 AA.
AC A7E300;
DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 24-JAN-2024, entry version 86.
DE RecName: Full=Rho GTPase-activating protein 7;
DE AltName: Full=Deleted in liver cancer 1 protein homolog;
DE Short=DLC-1;
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, STARD12;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2007) to the EMBL/GenBank/DDBJ databases.
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 (By similarity).
CC Required for growth factor-induced epithelial cell migration; in
CC resting cells, interacts with TNS3 while PTEN interacts with the p85
CC regulatory subunit of the PI3K kinase complex but growth factor
CC stimulation induces phosphorylation of TNS3 and PTEN, causing them to
CC change their binding preference so that PTEN interacts with DLC1 and
CC TNS3 interacts with p85 (By similarity). The PTEN-DLC1 complex
CC translocates to the posterior of migrating cells to activate RHOA while
CC the TNS3-p85 complex translocates to the leading edge of migrating
CC cells to promote RAC1 activation (By similarity).
CC {ECO:0000250|UniProtKB:Q96QB1}.
CC -!- SUBUNIT: Interacts with EF1A1, facilitates EF1A1 distribution to the
CC membrane periphery and ruffles upon growth factor stimulation and
CC suppresses cell migration. Interacts with tensin TNS1 (via N-terminus);
CC the interaction is decreased by phosphorylation of TNS1. Interacts with
CC TNS3 and PTEN; in resting cells, interacts with TNS3 (via C2 tensin-
CC type domain) but, following growth factor stimulation, TNS3 and PTEN
CC are phosphorylated which leads to weakened interaction with TNS3 and
CC enhanced interaction with PTEN. Interacts (via C-terminus) with tensin
CC TNS4 (via SH2 domain); the interaction is independent of tyrosine
CC phosphorylation of DLC1. {ECO:0000250|UniProtKB:Q96QB1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell junction, focal
CC adhesion {ECO:0000250|UniProtKB:Q96QB1}. Membrane {ECO:0000250};
CC Peripheral membrane protein {ECO:0000250}. Note=Colocalizes with EF1A1
CC at actin-rich regions in the cell periphery. {ECO:0000250}.
CC -!- DOMAIN: The SAM domain mediates interaction with EF1A1, and functions
CC as an autoinhibitory regulator of RhoGAP Activity. {ECO:0000250}.
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:0000250}.
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DR EMBL; BC151638; AAI51639.1; -; mRNA.
DR RefSeq; NP_001095963.1; NM_001102493.1.
DR AlphaFoldDB; A7E300; -.
DR SMR; A7E300; -.
DR STRING; 9913.ENSBTAP00000020668; -.
DR PaxDb; 9913-ENSBTAP00000020664; -.
DR GeneID; 511433; -.
DR KEGG; bta:511433; -.
DR CTD; 10395; -.
DR eggNOG; KOG2200; Eukaryota.
DR InParanoid; A7E300; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005925; C:focal adhesion; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IBA:GO_Central.
DR GO; GO:0005096; F:GTPase activator activity; IBA:GO_Central.
DR GO; GO:0008289; F:lipid binding; IEA:InterPro.
DR GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd04375; RhoGAP_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 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.
PE 2: Evidence at transcript level;
KW Cell junction; Cytoplasm; GTPase activation; Membrane; Phosphoprotein;
KW Reference proteome; Tumor suppressor.
FT CHAIN 1..1112
FT /note="Rho GTPase-activating protein 7"
FT /id="PRO_0000382027"
FT DOMAIN 37..104
FT /note="SAM"
FT DOMAIN 662..868
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 898..1105
FT /note="START"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197"
FT REGION 146..203
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 296..468
FT /note="Focal adhesion-targeting (FAT)"
FT /evidence="ECO:0000250"
FT REGION 318..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 405..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 512..574
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 635..657
FT /note="Polybasic cluster (PBR)"
FT /evidence="ECO:0000250"
FT COMPBIAS 165..193
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 407..427
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 112
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QB1"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QB1"
FT MOD_RES 155
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63744"
FT MOD_RES 343
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QB1"
SQ SEQUENCE 1112 AA; 125468 MW; 3AE63CBAA1295112 CRC64;
MARPLRAPLR RSFSDHIRDS TARALDVIWK NTRDRRLAEI EAKEACDWLR AAGFPQYAQL
YEDLLFPIDI SSVKREHDFL DRDAIEALCR RLNTLNKCAV MKLEISPHRK RSEDSDEDEP
CAISGKWTFQ RDSKRWSRLE EFDVFSPKQD PIPGSPDAVH LKSAPSHENM QTDLSDRQEV
ASVHSTGSLT THAPQRGEAA PARTNSVLSV CSSGTFVGND DSFCSLPSPK ELSSFSFSMK
GHEKAAKSKT HSLLKRMESL KLKGSHHSKH KAPSKLGLII SGPILQEGVD EEKLKQLNCV
EISALNGNHI NVPMVRKRSI SSSTQTSSSS SQSETSSNVS TPSPVTRTRS LSACNKRGGM
YLEGFDPFNQ STFNNVMEQN CKNRESYPED TVFYIPEDHK PGTFPKALSN GSFSPSGNNS
SVNWRTGSFH GPGHISLRRE NSSPKELKRR NSSSSVSSRL SIYDNVPGSI LYSSSGDLAD
LENEDIFPEL DDILYHVKGM QRIVNQWSEK FSDEGDSDSA LDSVSPCPSS PKQIHLDVDN
DRATPSDLDS TGNSLNEPEE PSDIPERRDS GVGASLTRSN RHRLRWHSFQ SSHRPSLNSV
SLQINCQSVA QMNLLQKYSL LKLTALLEKY TPSNKHGFSW AVPKFMKRIK VPDYKDRNVF
GVPLTVNVQR TGQPLPQSIQ QAMRYLRNHC LDQVGLFRKS GVKSRIQALR QMNESTIDCV
NYEGQSAYDV ADMLKQYFRD LPEPLMTNKL SETFLQIYQY VPKDQRLQAI KAAIMLLPDE
NREVLQTLLY FLSDVTAAVK ENQMTPTNLA VCLAPSLFHL NTLKRENSSP RVMQRKQSLG
KPDQKDLNEN LAATQGLAHM IAECKKLFQV PEEMSRCRNS YTEQELKPLT LEALGRLCND
DSADYQHFLQ DCVDSLFKEV KEKFKGWVSY STSEQAELSY KKVSEGPPLR LWRATIEVPA
TPEEILKRLL KEQHLWDVDL LDSKVIEILD SQTEIYQYVQ NSMAPHPARD YVVLRTWRTN
LPKGACALLL TSVDHDRAPV VGVRVNVLLA RYLIEPCGSG KSKLTYMCRA DLRGHMPEWY
TKSFGHLCAA EVVKIRDSFS HQNTETKDTK SR
//
