RAB8A_PONAB
ID RAB8A_PONAB Reviewed; 207 AA.
AC Q5R4A3;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Ras-related protein Rab-8A;
DE EC=3.6.5.2 {ECO:0000250|UniProtKB:P61006};
DE Flags: Precursor;
GN Name=RAB8A;
OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: The small GTPases Rab are key regulators of intracellular
CC membrane trafficking, from the formation of transport vesicles to their
CC fusion with membranes. Rabs cycle between an inactive GDP-bound form
CC and an active GTP-bound form that is able to recruit to membranes
CC different sets of downstream effectors directly responsible for vesicle
CC formation, movement, tethering and fusion. That Rab is involved in
CC polarized vesicular trafficking and neurotransmitter release. Together
CC with RAB11A, RAB3IP, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42
CC and DNMBP promotes transcytosis of PODXL to the apical membrane
CC initiation sites (AMIS), apical surface formation and lumenogenesis.
CC Regulates the compacted morphology of the Golgi (By similarity).
CC Together with MYO5B and RAB11A participates in epithelial cell
CC polarization. Also involved in membrane trafficking to the cilium and
CC ciliogenesis (By similarity). Together with MICALL2, may also regulate
CC adherens junction assembly (By similarity). May play a role in insulin-
CC induced transport to the plasma membrane of the glucose transporter
CC GLUT4 and therefore play a role in glucose homeostasis (By similarity).
CC Involved in autophagy (By similarity). {ECO:0000250|UniProtKB:P35280,
CC ECO:0000250|UniProtKB:P55258, ECO:0000250|UniProtKB:P61006}.
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:P61006};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000250|UniProtKB:P61006};
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 (By similarity). Activated in response to
CC insulin (By similarity). {ECO:0000250|UniProtKB:P35280,
CC ECO:0000250|UniProtKB:P61006}.
CC -!- SUBUNIT: Interacts (GTP-bound form) with MICALL1; regulates RAB8A
CC association with recycling endosomes (By similarity). Interacts with
CC MICALL2; competes with RAB13 and is involved in E-cadherin endocytic
CC recycling (By similarity). Interacts (GTP-bound form) with MICAL1,
CC MICALCL, MICAL3 and EHBP1L1; two molecules of RAB8A can bind to one
CC molecule of the effector protein; ternary complexes of RAB8A, RAB13 and
CC either MICAL1 or EHBP1L1 are possible (By similarity). Interacts (GTP-
CC bound form) with EHBP1 (By similarity). Interacts with EHD1 (By
CC similarity). Interacts with MAP4K2 and SYTL4 (By similarity). Interacts
CC with SGSM1 and SGSM3 (By similarity). Interacts with RABIF, RIMS2,
CC RPH3A and RPH3A (By similarity). Interacts with OPTN (By similarity).
CC Interacts with RAB3IP (By similarity). Interacts with MYO5B (By
CC similarity). Interacts with PIFO (By similarity). Interacts with
CC BIRC6/bruce (By similarity). Interacts with OCRL (By similarity).
CC Interacts with AHI1 (By similarity). Interacts with DCDC1 (By
CC similarity). Interacts with LRRK2; interaction facilitates
CC phosphorylation of Thr-72 (By similarity). Interacts with RAB31P, GDI1,
CC GDI2, CHM, CHML, RABGGTA, RABGGTB, TBC1D15 and INPP5B; these
CC interactions are dependent on Thr-72 not being phosphorylated (By
CC similarity). Interacts with RILPL1 and RILPL2; these interactions are
CC dependent on the phosphorylation of Thr-72 by LRRK2 (By similarity).
CC Interacts with DZIP1; prevents inhibition by the GDP-dissociation
CC inhibitor GDI2 (By similarity). {ECO:0000250|UniProtKB:P55258,
CC ECO:0000250|UniProtKB:P61006}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P55258};
CC Lipid-anchor {ECO:0000250|UniProtKB:P55258}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P55258}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P61006}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P61006}. Cell projection, cilium
CC {ECO:0000250|UniProtKB:P61006}. Cytoplasmic vesicle, phagosome membrane
CC {ECO:0000250|UniProtKB:P61006, ECO:0000250|UniProtKB:Q92930}; Lipid-
CC anchor {ECO:0000250|UniProtKB:Q92930}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q92930}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome, centriole
CC {ECO:0000250|UniProtKB:P55258}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000250|UniProtKB:P55258}. Midbody
CC {ECO:0000250|UniProtKB:P61006}. Cytoplasm
CC {ECO:0000250|UniProtKB:P61006}. Note=Colocalizes with OPTN at the Golgi
CC complex and in vesicular structures close to the plasma membrane. In
CC the GDP-bound form, present in the perinuclear region. Shows a
CC polarized distribution to distal regions of cell protrusions in the
CC GTP-bound form. Colocalizes with PARD3, PRKCI, EXOC5, OCLN, PODXL and
CC RAB11A in apical membrane initiation sites (AMIS) during the generation
CC of apical surface and lumenogenesis. Localizes to tubular recycling
CC endosome. Recruited to phagosomes containing S.aureus or Mycobacterium
CC (By similarity). Non-phosphorylated RAB8A predominantly localizes to
CC the cytoplasm whereas phosphorylated RAB8A localizes to the membrane
CC (By similarity). {ECO:0000250|UniProtKB:P61006}.
CC -!- PTM: Phosphorylation of Thr-72 in the switch II region by LRRK2
CC prevents the association of RAB regulatory proteins, including CHM,
CC CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.
CC {ECO:0000250|UniProtKB:P61006}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; CR861352; CAH93413.1; -; mRNA.
DR RefSeq; NP_001127003.1; NM_001133531.1.
DR AlphaFoldDB; Q5R4A3; -.
DR SMR; Q5R4A3; -.
DR STRING; 9601.ENSPPYP00000010852; -.
DR GeneID; 100174026; -.
DR KEGG; pon:100174026; -.
DR CTD; 4218; -.
DR eggNOG; KOG0078; Eukaryota.
DR InParanoid; Q5R4A3; -.
DR OrthoDB; 1426655at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005814; C:centriole; IEA:UniProtKB-SubCell.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISS:UniProtKB.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0055038; C:recycling endosome membrane; ISS:UniProtKB.
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; IEA:InterPro.
DR GO; GO:0031267; F:small GTPase binding; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB.
DR GO; GO:0007030; P:Golgi organization; ISS:UniProtKB.
DR GO; GO:0061512; P:protein localization to cilium; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
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 2: Evidence at transcript level;
KW Autophagy; Cell membrane; Cell projection; Cilium biogenesis/degradation;
KW Cytoplasm; Cytoplasmic vesicle; Cytoskeleton; Endosome; Golgi apparatus;
KW GTP-binding; Hydrolase; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..204
FT /note="Ras-related protein Rab-8A"
FT /id="PRO_0000260748"
FT PROPEP 205..207
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000370796"
FT MOTIF 37..45
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 15..22
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 17..22
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61006"
FT BINDING 34..40
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61006"
FT BINDING 63..67
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61006,
FT ECO:0000250|UniProtKB:Q9H0U4"
FT BINDING 121..124
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61006"
FT BINDING 152..154
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P61006,
FT ECO:0000250|UniProtKB:Q9H0U4"
FT MOD_RES 72
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P61006"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61006"
FT MOD_RES 185
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P61006"
FT MOD_RES 204
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000255"
FT LIPID 204
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
SQ SEQUENCE 207 AA; 23721 MW; EB42DAF5565CCC3A CRC64;
MAKTYDYLFK LLLIGDSGVG KTCVLFRFSE DAFNSTFIST IGIDFKIRTI ELDGKRIKLQ
IWDTAGQERF RTITTAYYRG AMGIMLVYDI TNEKSFDNIR NWIRNIEEHA SADVEKMILG
NKRDVNDKRQ VSKERGEKLA LDYGIKFMET SAKANINVEN AFFTLARDIK AKMDKKLEGN
SPQGSNQGVK ITPDQQKRSS FFRCVLL
