ID GDS1_BOVIN Reviewed; 608 AA.
AC Q04173; A0A3Q1M477; Q9TS36;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 24-JAN-2024, entry version 110.
DE RecName: Full=Rap1 GTPase-GDP dissociation stimulator 1;
DE AltName: Full=Exchange factor smgGDS;
DE AltName: Full=SMG GDS protein;
DE AltName: Full=SMG P21 stimulatory GDP/GTP exchange protein;
GN Name=RAP1GDS1;
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 [MRNA] (ISOFORM 2), AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Brain;
RX PubMed=1901951; DOI=10.1128/mcb.11.5.2873-2880.1991;
RA Kaibuchi K., Mizuno T., Fujioka H., Yamamoto T., Kishi K., Fukumoto Y.,
RA Hori Y., Takai Y.;
RT "Molecular cloning of the cDNA for stimulatory GDP/GTP exchange protein for
RT smg p21s (ras p21-like small GTP-binding proteins) and characterization of
RT stimulatory GDP/GTP exchange protein.";
RL Mol. Cell. Biol. 11:2873-2880(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=1495270;
RA Yamamoto T.;
RT "The stimulatory GDP/GTP exchange protein for ras p21-related small GTP-
RT binding proteins.";
RL Kobe J. Med. Sci. 38:37-56(1992).
RN [3] {ECO:0000312|Proteomes:UP000009136}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS ASN-196 AND
RP ALA-385.
RC STRAIN=Hereford {ECO:0000312|Proteomes:UP000009136};
RA Rosen B.D., Bickhart D.M., Koren S., Schnabel R.D., Hall R., Zimin A.,
RA Dreischer C., Schultheiss S., Schroeder S.G., Elsik C.G., Couldrey C.,
RA Liu G.E., Van Tassell C.P., Phillippy A.M., Smith T.P.L., Medrano J.F.;
RT "ARS-UCD1.2.";
RL Submitted (MAR-2018) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 400-406.
RC TISSUE=Brain;
RX PubMed=2118909; DOI=10.1016/s0021-9258(17)46268-5;
RA Yamamoto T., Kaibuchi K., Mizuno T., Hiroyoshi M., Shirataki H., Takai Y.;
RT "Purification and characterization from bovine brain cytosol of proteins
RT that regulate the GDP/GTP exchange reaction of smg p21s, ras p21-like GTP-
RT binding proteins.";
RL J. Biol. Chem. 265:16626-16634(1990).
CC -!- FUNCTION: Acts as a GEF (guanine nucleotide exchange factor) for the
CC Rho family of small GTP-binding proteins (G proteins) that stimulates
CC the dissociation of GDP to enable subsequent binding of GTP.
CC Additionally, appears to chaperone the processing and/or trafficking of
CC small GTPases containing a C-terminal polybasic region independently of
CC GEF activity. Targets include RAP1A/RAP1B, RHOA, RHOB, RHOC, RAC1 and
CC KRAS. Regulates mitochondrial dynamics by controlling RHOT function to
CC promote mitochondrial fission during high calcium conditions. Able to
CC promote the Ca(2+) release from the endoplasmic reticulum via both
CC inositol trisphosphate (Ins3P) and ryanodine sensitive receptors
CC leading to a enhanced mitochondrial Ca(2+) uptake.
CC {ECO:0000250|UniProtKB:P52306}.
CC -!- FUNCTION: [Isoform 1]: Acts as a GEF (guanine nucleotide exchange
CC factor) for unprenylated RHOA. Chaperones the entry and passage of
CC small GTPases through the prenylation pathway. Recognizes the last
CC amino acid in the GTPase C-terminal CAAX motif with a preference for
CC 'Leu' over 'Met', indicating involvement in the geranylgeranylation
CC pathway. May also recognize prenylated GTPases.
CC {ECO:0000250|UniProtKB:P52306}.
CC -!- FUNCTION: [Isoform 2]: Acts as a GEF (guanine nucleotide exchange
CC factor) for prenylated RHOA. Acts as a GEF for RHOC. Chaperones the
CC downstream trafficking and/or processing of small newly prenylated
CC GTPases. Escorts RAC1 to the nucleus. {ECO:0000250|UniProtKB:P52306}.
CC -!- SUBUNIT: Interacts with RABL3. Interacts with RHOT1.
CC {ECO:0000250|UniProtKB:P52306}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with unprenylated RHOA; the interaction
CC is direct. Interacts with RAP1A. Interacts with KRAS. Interacts with
CC RAC1. Interacts with RAP1B. Preferentially interacts with unprenylated
CC GTPases that will become geranylgeranylated. May also interact with
CC prenylated GTPases. {ECO:0000250|UniProtKB:P52306}.
CC -!- SUBUNIT: [Isoform 2]: Interacts with prenylated RHOA; the interaction
CC is direct and in a 1:1 stoichiometry. Interacts with RAP1A. Interacts
CC with KRAS. Interacts with RAC1. Interacts with RAP1B. Preferentially
CC interacts with prenylated GTPases. {ECO:0000250|UniProtKB:P52306}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:P52306}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P52306}. Mitochondrion
CC {ECO:0000250|UniProtKB:P52306}. Nucleus {ECO:0000250|UniProtKB:P52306}.
CC Note=Nuclear import is dependent on complexing with a GTPase containing
CC a C-terminal polybasic region. {ECO:0000250|UniProtKB:P52306}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q04173-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q04173-2; Sequence=VSP_061496;
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:1901951}.
CC -!- PTM: The N-terminus is blocked. {ECO:0000269|PubMed:1901951}.
CC -!- PTM: Forms covalent cross-links mediated by transglutaminase TGM2,
CC between a glutamine and the epsilon-amino group of a lysine residue,
CC forming homopolymers and heteropolymers.
CC {ECO:0000250|UniProtKB:P52306}.
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DR EMBL; M63325; -; NOT_ANNOTATED_CDS; mRNA.
DR PIR; A39795; A39795.
DR AlphaFoldDB; Q04173; -.
DR SMR; Q04173; -.
DR STRING; 9913.ENSBTAP00000064604; -.
DR PaxDb; 9913-ENSBTAP00000009904; -.
DR PeptideAtlas; Q04173; -.
DR VEuPathDB; HostDB:ENSBTAG00000007522; -.
DR eggNOG; KOG4500; Eukaryota.
DR InParanoid; Q04173; -.
DR Proteomes; UP000009136; Chromosome 6.
DR Bgee; ENSBTAG00000007522; Expressed in myometrium and 107 other cell types or tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0080120; P:CAAX-box protein maturation; ISS:UniProtKB.
DR GO; GO:0034504; P:protein localization to nucleus; ISS:UniProtKB.
DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 3.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR000225; Armadillo.
DR InterPro; IPR040144; RAP1GDS1.
DR PANTHER; PTHR10957; RAP1 GTPASE-GDP DISSOCIATION STIMULATOR 1; 1.
DR PANTHER; PTHR10957:SF2; RAP1 GTPASE-GDP DISSOCIATION STIMULATOR 1; 1.
DR Pfam; PF00514; Arm; 3.
DR SMART; SM00185; ARM; 6.
DR SUPFAM; SSF48371; ARM repeat; 2.
DR PROSITE; PS50176; ARM_REPEAT; 2.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Endoplasmic reticulum; Guanine-nucleotide releasing factor; Mitochondrion;
KW Nucleus; Reference proteome; Repeat.
FT CHAIN 1..608
FT /note="Rap1 GTPase-GDP dissociation stimulator 1"
FT /id="PRO_0000056758"
FT REPEAT 89..131
FT /note="ARM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00259"
FT REPEAT 171..212
FT /note="ARM 2"
FT /evidence="ECO:0000255"
FT REPEAT 348..391
FT /note="ARM 3"
FT /evidence="ECO:0000255"
FT REPEAT 392..432
FT /note="ARM 4"
FT /evidence="ECO:0000250|UniProtKB:P52306"
FT REPEAT 480..520
FT /note="ARM 5"
FT /evidence="ECO:0000250|UniProtKB:P52306"
FT REGION 122..171
FT /note="Prevents binding to prenylated RHOA"
FT /evidence="ECO:0000250|UniProtKB:P52306"
FT MOD_RES 231
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P52306"
FT VAR_SEQ 122..170
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000269|PubMed:1901951"
FT /id="VSP_061496"
FT VARIANT 196
FT /note="K -> N"
FT /evidence="ECO:0000269|Ref.3"
FT VARIANT 385
FT /note="C -> A"
FT /evidence="ECO:0000269|Ref.3"
FT CONFLICT 312..375
FT /note="EGGKGNVFQRVLSWIPSNNHQLQLAGALAIANFARNDGNCIHMVDNGIVEKL
FT MDLLDRHVEDGN -> VTVQHAALSCLRNLAIPVVNKAKMLSAGVTEAVLKFLKSEMPP
FT VQFKLLGTLRMLIDAQMQKLF (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 437..500
FT /note="AAEQLGKNVKLVERLVEWCEAKDHAGVMGESNRLLSALIRHSKSKDVIKTIV
FT QSGGIKHLVTMA -> TSEHVIMQNEALVALALIAALELGTAEKDLESAQLVQILHRLL
FT ADERSAPEIKYNSMVLICAAE (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 608 AA; 66449 MW; 208420DE8D18B9F5 CRC64;
MDNLSDTLKK LKITAVDRTD DSLEGCLDCL LQALTQNNME TSEKIQGSGI LQVFASLLIP
QSSCTAKVAN VIAEIAKNEF MRIPCVDAGL ISPLVQLLNS KDQEVLLQTG RALGNICYDS
HEGRSAVDQA GGAQIVVDHL RSLCSKTDPA SEKLLTVFCG MLMNYSNEKN DSLQAQLINM
GVIPTLVKLL GIHCQKAALT EMCLVAFGNL AELESSKEQF ASTNIAEELV KLFKKQIEHD
KREMVFEVLA PLAENDAIKL QLVESGLVEC LLEIVQQKVD SDKEEDIAEL KTASDLMVLL
LLGDESMQKL FEGGKGNVFQ RVLSWIPSNN HQLQLAGALA IANFARNDGN CIHMVDNGIV
EKLMDLLDRH VEDGNVTVQH AALSCLRNLA IPVVNKAKML SAGVTEAVLK FLKSEMPPVQ
FKLLGTLRML IDAQAEAAEQ LGKNVKLVER LVEWCEAKDH AGVMGESNRL LSALIRHSKS
KDVIKTIVQS GGIKHLVTMA TSEHVIMQNE ALVALALIAA LELGTAEKDL ESAQLVQILH
RLLADERSAP EIKYNSMVLI CALMGSESLH KEVQDLAFLD VVSKLRSHEN KSVAQQASLT
EQRLAVES
//
