RHG07_RAT
ID RHG07_RAT Reviewed; 1091 AA.
AC Q63744;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-NOV-2002, sequence version 3.
DT 25-MAY-2022, entry version 148.
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;
DE AltName: Full=p122-RhoGAP;
GN Name=Dlc1; Synonyms=Arhgap7, Rhogap, Stard12;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=7835339; DOI=10.1002/j.1460-2075.1995.tb07002.x;
RA Homma Y., Emori Y.;
RT "A dual functional signal mediator showing RhoGAP and phospholipase C-delta
RT stimulating activities.";
RL EMBO J. 14:286-291(1995).
RN [2]
RP FUNCTION, AND MUTAGENESIS OF ARG-677; LYS-714; ARG-718 AND ASN-787.
RX PubMed=10364218; DOI=10.1074/jbc.274.25.17757;
RA Sekimata M., Kabuyama Y., Emori Y., Homma Y.;
RT "Morphological changes and detachment of adherent cells induced by p122, a
RT GTPase-activating protein for Rho.";
RL J. Biol. Chem. 274:17757-17762(1999).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-129, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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 {ECO:0000250, ECO:0000269|PubMed:10364218}.
CC -!- SUBUNIT: Interacts with EF1A1, facilitates EF1A1 distribution to the
CC membrane periphery and ruffles upon growth factor stimulation and
CC suppresses cell migration. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell junction, focal
CC adhesion {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Note=Colocalizes with EF1A1 at actin-rich
CC 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA21675.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D31962; BAA21675.1; ALT_INIT; mRNA.
DR AlphaFoldDB; Q63744; -.
DR SMR; Q63744; -.
DR STRING; 10116.ENSRNOP00000014923; -.
DR iPTMnet; Q63744; -.
DR PhosphoSitePlus; Q63744; -.
DR PaxDb; Q63744; -.
DR PRIDE; Q63744; -.
DR RGD; 68416; Dlc1.
DR eggNOG; KOG2200; Eukaryota.
DR InParanoid; Q63744; -.
DR PhylomeDB; Q63744; -.
DR Reactome; R-RNO-8980692; RHOA GTPase cycle.
DR Reactome; R-RNO-9013026; RHOB GTPase cycle.
DR Reactome; R-RNO-9013106; RHOC GTPase cycle.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR Reactome; R-RNO-9013406; RHOQ GTPase cycle.
DR PRO; PR:Q63744; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005901; C:caveola; ISO:RGD.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005925; C:focal adhesion; ISO:RGD.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0032587; C:ruffle membrane; ISO:RGD.
DR GO; GO:0005096; F:GTPase activator activity; IDA:RGD.
DR GO; GO:0008289; F:lipid binding; IEA:InterPro.
DR GO; GO:0043274; F:phospholipase binding; IPI:RGD.
DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD.
DR GO; GO:0017166; F:vinculin binding; IPI:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0007202; P:activation of phospholipase C activity; IDA:RGD.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0007010; P:cytoskeleton organization; IDA:RGD.
DR GO; GO:0048041; P:focal adhesion assembly; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0021575; P:hindbrain morphogenesis; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISO:RGD.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; ISO:RGD.
DR GO; GO:0051497; P:negative regulation of stress fiber assembly; ISO:RGD.
DR GO; GO:0001843; P:neural tube closure; ISO:RGD.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISO:RGD.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISO:RGD.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 3.30.530.20; -; 1.
DR InterPro; IPR028854; DLC1.
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; PTHR12659:SF2; 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; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50238; RHOGAP; 1.
DR PROSITE; PS50848; START; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cytoplasm; GTPase activation; Membrane; Phosphoprotein;
KW Reference proteome; Tumor suppressor.
FT CHAIN 1..1091
FT /note="Rho GTPase-activating protein 7"
FT /id="PRO_0000056709"
FT DOMAIN 11..78
FT /note="SAM"
FT DOMAIN 641..847
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 877..1084
FT /note="START"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197"
FT REGION 119..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 274..447
FT /note="Focal adhesion-targeting (FAT)"
FT /evidence="ECO:0000250"
FT REGION 296..329
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 402..439
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 491..552
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 614..636
FT /note="Polybasic cluster (PBR)"
FT /evidence="ECO:0000250"
FT COMPBIAS 126..181
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QB1"
FT MOD_RES 89
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QB1"
FT MOD_RES 129
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96QB1"
FT MUTAGEN 677
FT /note="R->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10364218"
FT MUTAGEN 714
FT /note="K->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10364218"
FT MUTAGEN 718
FT /note="R->E: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10364218"
FT MUTAGEN 787
FT /note="N->V: No loss of activity."
FT /evidence="ECO:0000269|PubMed:10364218"
SQ SEQUENCE 1091 AA; 123414 MW; FB4A0924E0C36A15 CRC64;
MCRDEPDTMI LTQIEAKEAC DWLRVTGFPQ YAQLYEDLLF PIDIALVKRE HDFLDRDAIE
ALCRRLNTLN KCAVMKLEIS PHRKRSEDSD EEEPCAISGK WTFQRDSKRW SRLEEFDVFS
PKQDPIPGSP DNSRLQSATS RESMLTDLSE HQEVSSIRSL SSTSSSAPTH VPHSGEATTP
RTNSVISVCS SSHFVGNEDS FSSLPSPKEL SSFSFSMKGH EKNTKSKTRS LLKRMESLKL
KGSHHSKHKA PSKLGLIISA PILQEGMDEE KLKQLNCVEI SALNGNHINV PMVRKRSVSN
STQTSSSSSQ SETSSAVSTP SPVTRTRSLS TCNKRVGMYL EGFDPFSQSA FNNVTEQNYK
NRESYPEDTV FYIPEDHKPG TFPKALSNGS FCPSGNSSVN WRTGSFHGPG HLSLRRENSS
DSPKELKRRN SSSSVSSRMS IYDNVPGSIL YSSSGELADL ENEDIFPELD DILYHVKGMQ
RIVNQWSEKF SDEGDSDSAL DSVSPCPSSP KQIHLDVDHD RRTPSDLDST GNSLNEPEEP
TDIPERRDSG VGASLTRCNR HRLRWHSFQS SHRPSLNSVS LQINCQSVAQ MNLLQKYSLL
KLTALLEKYT PSNKHGFSWA VPKFMKRIKV PDYKDRSVFG VPLTVNVQRS GQPLPQSIQQ
AMRYLRNHCL DQVGLFRKSG VKSRIQALRQ MNESAEDYVN YEGQSAYDVA DMLKQYFRDL
PEPLMTNKLS ETFLQIYQYV PKDQRLQAIK AAIMLLPDEN REVLQTLLYF LSHVTAAVKE
NQMTPTNLAV CLAPSLFHLN TLKRENSSPR VMQRKQSLGK PDQKDLNENL AATQGLAHMI
AECKKLFQVP EEMSRCRNSY TEQELKPLTL EALGHLSNDQ PADYRHFLQD CVDGLFKEVK
EKFKGWVSYP TSEQAELSYK KVSEGPPLRL WRATIEVPAA PEEILKRLLK EQHLWDVDLL
DSKVIEILDS QTEIYQYVQN SMAPHPARDY VVLRTWRTNL PRGACALLFT SVDHDRAPVA
GVRVNVLLSR YLIEPCGSGK SKLTYMCRAD LRGHMPEWYT KSFGHLCAAE VVKIRDSFSN
QSTESKDTRS R
