RB27A_RAT
ID RB27A_RAT Reviewed; 221 AA.
AC P23640; Q4KMA7;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Ras-related protein Rab-27A;
DE Short=Rab-27;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P51159};
DE AltName: Full=GTP-binding protein Ram;
DE AltName: Full=Ram p25;
GN Name=Rab27a; Synonyms=Rab27;
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=Megakaryocyte;
RX PubMed=2124544; DOI=10.1016/0014-5793(90)81431-m;
RA Nagata K., Satoh T., Itoh H., Kozasa T., Okano Y., Doi T., Kaziro Y.,
RA Nozawa Y.;
RT "The ram: a novel low molecular weight GTP-binding protein cDNA from a rat
RT megakaryocyte library.";
RL FEBS Lett. 275:29-32(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [3]
RP CHARACTERIZATION, AND MUTAGENESIS.
RX PubMed=1527078; DOI=10.1016/s0021-9258(18)41817-0;
RA Nagata K., Suzuki T., Shibagaki Y., Mizumoto K., Okano Y., Kaziro Y.,
RA Nozawa Y.;
RT "Characterization and site-directed mutagenesis of a low M(r) GTP-binding
RT protein, ram p25, expressed in Escherichia coli.";
RL J. Biol. Chem. 267:19600-19606(1992).
CC -!- FUNCTION: Small GTPase which cycles between active GTP-bound and
CC inactive GDP-bound states. In its active state, binds to a variety of
CC effector proteins to regulate homeostasis of late endocytic pathway,
CC including endosomal positioning, maturation and secretion. Plays a role
CC in cytotoxic granule exocytosis in lymphocytes. Required for both
CC granule maturation and granule docking and priming at the immunologic
CC synapse. {ECO:0000250|UniProtKB:P51159}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.2;
CC Evidence={ECO:0000250|UniProtKB:P51159};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P51159};
CC -!- ACTIVITY REGULATION: Regulated by guanine nucleotide exchange factors
CC (GEFs) which promote the exchange of bound GDP for free GTP, GTPase
CC activating proteins (GAPs) which increase the GTP hydrolysis activity,
CC and GDP dissociation inhibitors which inhibit the dissociation of the
CC nucleotide from the GTPase. Activated by GEFs such as DENND10.
CC {ECO:0000250|UniProtKB:P51159}.
CC -!- SUBUNIT: Binds SYTL1, SLAC2B, MYRIP, SYTL3, SYTL4 and SYTL5. Interacts
CC with RPH3A and RPH3A (By similarity). Binds MLPH and SYTL2. Interacts
CC with UNC13D. Does not interact with the BLOC-3 complex (heterodimer of
CC HPS1 and HPS4) (By similarity). Interacts (GDP-bound form
CC preferentially) with DENND10 (By similarity).
CC {ECO:0000250|UniProtKB:P51159, ECO:0000250|UniProtKB:Q9ERI2}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:P51159}; Lipid-
CC anchor {ECO:0000250|UniProtKB:P51159}. Melanosome
CC {ECO:0000250|UniProtKB:P51159}. Late endosome
CC {ECO:0000250|UniProtKB:P51159}. Lysosome
CC {ECO:0000250|UniProtKB:P51159}. Note=Identified by mass spectrometry in
CC melanosome fractions from stage I to stage IV. Localizes to endosomal
CC exocytic vesicles. {ECO:0000250|UniProtKB:P51159}.
CC -!- TISSUE SPECIFICITY: High levels in eye, intestine, lung, pancreas and
CC spleen, and low or absent in brain, liver, heart, kidney, and skeletal
CC muscle.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; D17352; BAA04167.1; -; mRNA.
DR EMBL; BC098667; AAH98667.1; -; mRNA.
DR PIR; S12959; S12959.
DR RefSeq; NP_059013.1; NM_017317.2.
DR RefSeq; XP_017451353.1; XM_017595864.1.
DR AlphaFoldDB; P23640; -.
DR SMR; P23640; -.
DR STRING; 10116.ENSRNOP00000010012; -.
DR PhosphoSitePlus; P23640; -.
DR jPOST; P23640; -.
DR PaxDb; P23640; -.
DR Ensembl; ENSRNOT00000083957; ENSRNOP00000068946; ENSRNOG00000052499.
DR GeneID; 50645; -.
DR KEGG; rno:50645; -.
DR UCSC; RGD:620918; rat.
DR CTD; 5873; -.
DR RGD; 620918; Rab27a.
DR eggNOG; KOG0081; Eukaryota.
DR GeneTree; ENSGT00940000156218; -.
DR HOGENOM; CLU_041217_10_1_1; -.
DR InParanoid; P23640; -.
DR OMA; CTGANIQ; -.
DR OrthoDB; 1190514at2759; -.
DR PhylomeDB; P23640; -.
DR TreeFam; TF312895; -.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR Reactome; R-RNO-8873719; RAB geranylgeranylation.
DR Reactome; R-RNO-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR PRO; PR:P23640; -.
DR Proteomes; UP000002494; Chromosome 8.
DR Bgee; ENSRNOG00000052499; Expressed in stomach and 19 other tissues.
DR Genevisible; P23640; RN.
DR GO; GO:0016324; C:apical plasma membrane; IDA:RGD.
DR GO; GO:0030425; C:dendrite; ISO:RGD.
DR GO; GO:0070382; C:exocytic vesicle; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISO:RGD.
DR GO; GO:0042470; C:melanosome; ISO:RGD.
DR GO; GO:0032585; C:multivesicular body membrane; ISO:RGD.
DR GO; GO:0001750; C:photoreceptor outer segment; ISO:RGD.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0030667; C:secretory granule membrane; IDA:RGD.
DR GO; GO:0033093; C:Weibel-Palade body; IDA:UniProtKB.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; ISS:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISS:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0031489; F:myosin V binding; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0019882; P:antigen processing and presentation; ISO:RGD.
DR GO; GO:0007596; P:blood coagulation; ISO:RGD.
DR GO; GO:0097278; P:complement-dependent cytotoxicity; ISO:RGD.
DR GO; GO:0043316; P:cytotoxic T cell degranulation; ISO:RGD.
DR GO; GO:0006887; P:exocytosis; ISO:RGD.
DR GO; GO:1990182; P:exosomal secretion; ISO:RGD.
DR GO; GO:0030318; P:melanocyte differentiation; ISO:RGD.
DR GO; GO:0032400; P:melanosome localization; ISO:RGD.
DR GO; GO:0032402; P:melanosome transport; ISO:RGD.
DR GO; GO:0036257; P:multivesicular body organization; ISO:RGD.
DR GO; GO:0071985; P:multivesicular body sorting pathway; ISO:RGD.
DR GO; GO:0043320; P:natural killer cell degranulation; ISO:RGD.
DR GO; GO:0051875; P:pigment granule localization; ISO:RGD.
DR GO; GO:0051904; P:pigment granule transport; ISO:RGD.
DR GO; GO:0043473; P:pigmentation; ISO:RGD.
DR GO; GO:1903435; P:positive regulation of constitutive secretory pathway; ISO:RGD.
DR GO; GO:0045921; P:positive regulation of exocytosis; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0050766; P:positive regulation of phagocytosis; ISO:RGD.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:RGD.
DR GO; GO:1903307; P:positive regulation of regulated secretory pathway; ISO:RGD.
DR GO; GO:0006605; P:protein targeting; ISO:RGD.
DR GO; GO:0016192; P:vesicle-mediated transport; ISO:RGD.
DR CDD; cd04127; Rab27A; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041837; Rab27a/b.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Acetylation; Disulfide bond; Endosome; Exocytosis; GTP-binding; Hydrolase;
KW Lipoprotein; Lysosome; Membrane; Methylation; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P51159"
FT CHAIN 2..221
FT /note="Ras-related protein Rab-27A"
FT /id="PRO_0000121223"
FT MOTIF 38..46
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 16..24
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 74..78
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 133..136
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 163..165
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:P51159"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P51159"
FT MOD_RES 221
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 219
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 221
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT DISULFID 123..188
FT /evidence="ECO:0000250"
FT MUTAGEN 19
FT /note="G->V: No binding of GTP and GDP."
FT /evidence="ECO:0000269|PubMed:1527078"
FT MUTAGEN 41
FT /note="T->S: Increased rates of GTP binding and GDP
FT dissociation."
FT /evidence="ECO:0000269|PubMed:1527078"
FT MUTAGEN 76
FT /note="A->T: Increased rates of GTP binding and GDP
FT dissociation."
FT /evidence="ECO:0000269|PubMed:1527078"
FT MUTAGEN 78
FT /note="Q->L: Increased GTP dissociation and decreased GDP
FT hydrolysis."
FT /evidence="ECO:0000269|PubMed:1527078"
FT MUTAGEN 133
FT /note="N->H: Increased rates of GTP binding and GDP
FT dissociation."
FT /evidence="ECO:0000269|PubMed:1527078"
SQ SEQUENCE 221 AA; 25068 MW; 6A3125DCC4738C80 CRC64;
MSDGDYDYLI KFLALGDSGV GKTSVLYQYT DGKFNSKFIT TVGIDFREKR VVYRANGPDG
TVGRGQRIHL QLWDTAGQER FRSLTTAFFR DAMGFLLLFD LTNEQSFLNV RNWISQLQMH
AYCENPDIVL CGNKSDLEDQ RAVKEEEARE LAEKYGIPYF ETSAANGTNI SQAIEMLLDL
IMKRMERCVD KSWIPEGVVR SNGHTSTDQL SEEKEKGLCG C
