RBP1_RAT
ID RBP1_RAT Reviewed; 647 AA.
AC Q62796; O55195;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=RalA-binding protein 1 {ECO:0000303|PubMed:7623849};
DE Short=RalBP1 {ECO:0000303|PubMed:7623849};
DE AltName: Full=Cytocentrin {ECO:0000303|PubMed:9973605};
DE AltName: Full=Dinitrophenyl S-glutathione ATPase {ECO:0000250|UniProtKB:Q15311};
DE Short=DNP-SG ATPase {ECO:0000250|UniProtKB:Q15311};
DE EC=7.6.2.2 {ECO:0000250|UniProtKB:Q15311};
DE EC=7.6.2.3 {ECO:0000250|UniProtKB:Q15311};
DE AltName: Full=Ral-interacting protein 1;
GN Name=Ralbp1 {ECO:0000312|RGD:621134};
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], FUNCTION, INTERACTION WITH RALA, TISSUE
RP SPECIFICITY, AND DOMAIN.
RC TISSUE=Brain;
RX PubMed=7623849; DOI=10.1128/mcb.15.8.4578;
RA Cantor S.B., Urano T., Feig L.A.;
RT "Identification and characterization of Ral-binding protein 1, a potential
RT downstream target of Ral GTPases.";
RL Mol. Cell. Biol. 15:4578-4584(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=9973605; DOI=10.1242/jcs.112.5.707;
RA Quaroni A., Paul E.C.A.;
RT "Cytocentrin is a Ral-binding protein involved in the assembly and function
RT of the mitotic apparatus.";
RL J. Cell Sci. 112:707-718(1999).
RN [3]
RP INTERACTION WITH REPS1, AND REGION.
RC TISSUE=Muscle;
RX PubMed=9395447; DOI=10.1074/jbc.272.50.31230;
RA Yamaguchi A., Urano T., Goi T., Feig L.A.;
RT "An eps homology (EH) domain protein that binds to the ral-GTPase target,
RT RalBP1.";
RL J. Biol. Chem. 272:31230-31234(1997).
RN [4]
RP FUNCTION, INTERACTION WITH REPS2, AND REGION.
RC TISSUE=Brain;
RX PubMed=9422736; DOI=10.1074/jbc.273.2.814;
RA Ikeda M., Ishida O., Hinoi T., Kishida S., Kikuchi A.;
RT "Identification and characterization of a novel protein interacting with
RT Ral-binding protein 1, a putative effector protein of Ral.";
RL J. Biol. Chem. 273:814-821(1998).
RN [5]
RP FUNCTION.
RX PubMed=10393179; DOI=10.1093/emboj/18.13.3629;
RA Nakashima S., Morinaka K., Koyama S., Ikeda M., Kishida M., Okawa K.,
RA Iwamatsu A., Kishida S., Kikuchi A.;
RT "Small G protein Ral and its downstream molecules regulate endocytosis of
RT EGF and insulin receptors.";
RL EMBO J. 18:3629-3642(1999).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-48; SER-62 AND SER-463, AND
RP IDENTIFICATION BY 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: Multifunctional protein that functions as a downstream
CC effector of RALA and RALB. As a GTPase-activating protein/GAP can
CC inactivate CDC42 and RAC1 by stimulating their GTPase activity
CC (PubMed:7623849, PubMed:9422736). As part of the Ral signaling pathway,
CC may also regulate ligand-dependent EGF and insulin receptors-mediated
CC endocytosis (PubMed:10393179). During mitosis, may act as a scaffold
CC protein in the phosphorylation of EPSIN/EPN1 by the mitotic kinase
CC cyclin B-CDK1, preventing endocytosis during that phase of the cell
CC cycle. During mitosis, also controls mitochondrial fission as an
CC effector of RALA. Recruited to mitochondrion by RALA, acts as a
CC scaffold to foster the mitotic kinase cyclin B-CDK1-mediated
CC phosphorylation and activation of DNM1L (By similarity).
CC {ECO:0000250|UniProtKB:Q15311, ECO:0000269|PubMed:10393179,
CC ECO:0000269|PubMed:7623849, ECO:0000269|PubMed:9422736}.
CC -!- FUNCTION: Could also function as a primary ATP-dependent active
CC transporter for glutathione conjugates of electrophiles. May also
CC actively catalyze the efflux of a wide range of substrates including
CC xenobiotics like doxorubicin (DOX) contributing to cell multidrug
CC resistance. {ECO:0000250|UniProtKB:Q15311}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an S-substituted glutathione(in) + ATP + H2O = ADP + an S-
CC substituted glutathione(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:19121, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:90779,
CC ChEBI:CHEBI:456216; EC=7.6.2.3;
CC Evidence={ECO:0000250|UniProtKB:Q15311};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19122;
CC Evidence={ECO:0000250|UniProtKB:Q15311};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + xenobioticSide 1 = ADP + phosphate +
CC xenobioticSide 2.; EC=7.6.2.2;
CC Evidence={ECO:0000250|UniProtKB:Q15311};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + leukotriene C4(in) = ADP + H(+) + leukotriene
CC C4(out) + phosphate; Xref=Rhea:RHEA:38963, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57973, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000250|UniProtKB:Q15311};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38964;
CC Evidence={ECO:0000250|UniProtKB:Q15311};
CC -!- SUBUNIT: Interacts with the GTP-bound form of RALA (via effector
CC domain); during mitosis, recruits RALBP1 to the mitochondrion where it
CC promotes DNM1L phosphorylation and mitochondrial fission
CC (PubMed:7623849). Interacts with DNM1L; mediates its mitotic kinase
CC cyclin B-CDK1-mediated phosphorylation during mitosis to promote
CC mitochondrial fission. Interacts with the mitotic kinase cyclin B-CDK1
CC during mitosis. Interacts with the GTP-bound form of RALB (via effector
CC domain) (By similarity). Interacts with REPS1; the interaction is
CC direct and does not affect RALA-binding nor GTPase activator activity
CC of RALBP1 (PubMed:9395447). Interacts with REPS2; the interaction is
CC direct and does not affect RALA-binding nor GTPase activator activity
CC of RALBP1 (PubMed:9422736). Interacts with EPN1, NUMB and TFAP2A during
CC interphase and mitosis. Interacts with AP2M1; as part of the AP2
CC complex. Interacts with CDC42. Interacts with RAC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q15311, ECO:0000269|PubMed:7623849,
CC ECO:0000269|PubMed:9395447, ECO:0000269|PubMed:9422736}.
CC -!- INTERACTION:
CC Q62796; P24385: CCND1; Xeno; NbExp=2; IntAct=EBI-3956409, EBI-375001;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q15311};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q15311}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:9973605}. Cytoplasm, cytoskeleton, spindle
CC pole {ECO:0000269|PubMed:9973605}. Nucleus
CC {ECO:0000250|UniProtKB:Q15311}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q15311}. Note=Cytosolic protein that transiently
CC associates with the mitotic spindle poles in early prophase, and
CC dissociates from them after completion of mitosis (PubMed:9973605).
CC Targeted to the plasma membrane through its interaction with RALB,
CC directed by FGF signaling. Docking on the membrane is required to
CC transduce the Ral signal (By similarity). Recruited by RALA to the
CC mitochondrion during mitosis where it regulates mitochondrial fission.
CC Nuclear localization is cell cycle dependent while membrane
CC localization is seen in adherent cells. The region involved in membrane
CC association could form transmembrane domains and expose a part of the
CC protein extracellularly (By similarity). {ECO:0000250|UniProtKB:Q15311,
CC ECO:0000250|UniProtKB:Q9PT60, ECO:0000269|PubMed:9973605}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:7623849}.
CC -!- DOMAIN: The Rho-GAP domain mediates the GTPase activator activity
CC toward CDC42. {ECO:0000305|PubMed:7623849}.
CC -!- PTM: Tyrosine-phosphorylated upon stimulation of cells with EGF.
CC {ECO:0000250|UniProtKB:Q62172}.
CC -!- PTM: May undergo proteolytic cleavage to give peptides which reassemble
CC to form a transporter complex. {ECO:0000250|UniProtKB:Q15311}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB91537.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U28830; AAA80654.1; -; mRNA.
DR EMBL; U82623; AAB91537.1; ALT_FRAME; mRNA.
DR PIR; A57467; A57467.
DR RefSeq; NP_114456.1; NM_032067.1.
DR AlphaFoldDB; Q62796; -.
DR SMR; Q62796; -.
DR BioGRID; 249880; 2.
DR IntAct; Q62796; 3.
DR MINT; Q62796; -.
DR STRING; 10116.ENSRNOP00000033120; -.
DR iPTMnet; Q62796; -.
DR PhosphoSitePlus; Q62796; -.
DR PaxDb; Q62796; -.
DR GeneID; 84014; -.
DR KEGG; rno:84014; -.
DR UCSC; RGD:621134; rat.
DR CTD; 10928; -.
DR RGD; 621134; Ralbp1.
DR eggNOG; KOG4370; Eukaryota.
DR InParanoid; Q62796; -.
DR OrthoDB; 514124at2759; -.
DR PhylomeDB; Q62796; -.
DR Reactome; R-RNO-9013148; CDC42 GTPase cycle.
DR Reactome; R-RNO-9013149; RAC1 GTPase cycle.
DR PRO; PR:Q62796; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0015431; F:ABC-type glutathione S-conjugate transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0008559; F:ABC-type xenobiotic transporter activity; IEA:UniProtKB-EC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; ISO:RGD.
DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0022857; F:transmembrane transporter activity; ISO:RGD.
DR GO; GO:0042910; F:xenobiotic transmembrane transporter activity; ISO:RGD.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:1900753; P:doxorubicin transport; ISO:RGD.
DR GO; GO:0006897; P:endocytosis; IMP:RGD.
DR GO; GO:0007052; P:mitotic spindle organization; IDA:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISS:UniProtKB.
DR GO; GO:1903378; P:positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway; IMP:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032489; P:regulation of Cdc42 protein signal transduction; IDA:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISO:RGD.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IPI:RGD.
DR GO; GO:0055085; P:transmembrane transport; ISO:RGD.
DR GO; GO:1990961; P:xenobiotic detoxification by transmembrane export across the plasma membrane; ISO:RGD.
DR Gene3D; 1.10.555.10; -; 1.
DR InterPro; IPR039767; RALBP1.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR000198; RhoGAP_dom.
DR PANTHER; PTHR12783; PTHR12783; 1.
DR Pfam; PF00620; RhoGAP; 1.
DR SMART; SM00324; RhoGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR PROSITE; PS50238; RHOGAP; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell cycle; Cell division; Cell membrane;
KW Cytoplasm; Cytoskeleton; GTPase activation; Membrane; Mitochondrion;
KW Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Translocase; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT CHAIN 2..647
FT /note="RalA-binding protein 1"
FT /id="PRO_0000056735"
FT DOMAIN 192..380
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT REGION 1..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 102..119
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9PT60"
FT REGION 154..219
FT /note="Mediates association with membranes and could form
FT transmembrane domains"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT REGION 163..186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..499
FT /note="Mediates interaction with RALA and RALB"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT REGION 500..647
FT /note="Mediates interaction with REPS1 and REPS2"
FT /evidence="ECO:0000269|PubMed:9395447,
FT ECO:0000269|PubMed:9422736"
FT REGION 525..550
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 601..647
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..70
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 115..151
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 601..615
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..647
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 69..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT BINDING 418..425
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 30
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 44
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 48
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 92
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 93
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 461
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15311"
FT CONFLICT 40
FT /note="E -> G (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
FT CONFLICT 86
FT /note="V -> A (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="F -> L (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="F -> L (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
FT CONFLICT 372
FT /note="L -> V (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
FT CONFLICT 423
FT /note="F -> L (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
FT CONFLICT 516
FT /note="R -> P (in Ref. 2; AAB91537)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 647 AA; 75252 MW; 7E6301E037B7F737 CRC64;
MTECFLPPTS SPSEHRRAEH GSGLTRTPSS EEISPTKFPE LYRTGEPSPP HDILHEPPDI
VSDDEKDHGK KKGKFKKKEK RTEGYVAFQE DSSGDEAESP SKMKRSKGIH VFKKPSFSKK
KEKDFKIKEK PKEEKHKEEK HKEEKHKEKK CKDFTAADVV KQWKEKKKKK KPTQEPEVPQ
TDAPSLRPIF GAPFADAVER TMMYDGIRLP AVFRECVDYM EKHGMKCEGI YRVSGIKSKV
DELKAAYDRE ESPNLEEYEP NTVASLLKQY LRDLPENLLT KELMPRFEEA CGRTTEVEKV
QEFQRLLREL PEYNHLLLSW LIVHMDHVIA KELETKMNIQ NISIVLSPTV QISNRVLYVL
FTHVQELFGT VLLKQVTRPL RWSNMATMPT LPETQAGIKE EIRRQEFLLN CLHRDLQGGI
KDFSKEERLW EVQRILTALK RKLREAKRQE CETKIAQEIA SLSKEDVSKE ETNENEEVIN
ILLAQENEIL TEQEELLAME QFLRRQIASE KEEIDRLRAE IAEIQSRQHG RSETEEYSSD
SESESEDEEE LQIILEDLQR QNEELEIKNN HLNQAVHEER EAIVELRVQL RLLQMLRAKS
EQQLQEEEEP ERRGGTGPLP CEGVLEVRAA KEQAKPSPSK DRKETPI
