RB27B_HUMAN
ID RB27B_HUMAN Reviewed; 218 AA.
AC O00194; B2RAB0; Q9BZB6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Ras-related protein Rab-27B;
DE EC=3.6.5.2 {ECO:0000305|PubMed:30771381};
DE AltName: Full=C25KG;
GN Name=RAB27B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Melanocyte;
RX PubMed=9066979; DOI=10.1006/bmme.1996.2559;
RA Chen D., Guo J., Miki T., Tachibana M., Gahl W.A.;
RT "Molecular cloning and characterization of rab27a and rab27b, novel human
RT rab proteins shared by melanocytes and platelets.";
RL Biochem. Mol. Med. 60:27-37(1997).
RN [2]
RP SEQUENCE REVISION TO 206.
RA Chen D., Gahl W.A.;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11178108; DOI=10.1186/1471-2156-2-2;
RA Ramalho J.S., Tolmachova T., Hume A.N., McGuigan A., Gregory-Evans C.Y.,
RA Huxley C., Seabra M.C.;
RT "Chromosomal mapping, gene structure and characterization of the human and
RT murine RAB27B gene.";
RL BMC Genet. 2:2-2(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [8]
RP PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Platelet;
RX PubMed=2507536; DOI=10.1016/s0021-9258(18)71450-6;
RA Nagata K., Itoh H., Katada T., Takenaka K., Ui M., Kaziro Y., Nozawa Y.;
RT "Purification, identification, and characterization of two GTP-binding
RT proteins with molecular weights of 25,000 and 21,000 in human platelet
RT cytosol. One is the rap1/smg21/Krev-1 protein and the other is a novel GTP-
RT binding protein.";
RL J. Biol. Chem. 264:17000-17005(1989).
RN [9]
RP PROTEIN SEQUENCE OF 2-28; 38-47; 50-64; 68-80 AND 150-184, CLEAVAGE OF
RP INITIATOR METHIONINE, ACETYLATION AT THR-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RA Bienvenut W.V., Claeys D.;
RL Submitted (NOV-2005) to UniProtKB.
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP FUNCTION.
RX PubMed=21775604; DOI=10.1523/jneurosci.0436-11.2011;
RA Huang S.H., Duan S., Sun T., Wang J., Zhao L., Geng Z., Yan J., Sun H.J.,
RA Chen Z.Y.;
RT "JIP3 mediates TrkB axonal anterograde transport and enhances BDNF
RT signaling by directly bridging TrkB with kinesin-1.";
RL J. Neurosci. 31:10602-10614(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DENND10, ACTIVITY
RP REGULATION, AND MUTAGENESIS OF THR-23 AND GLN-78.
RX PubMed=30771381; DOI=10.1016/j.bbamcr.2019.02.006;
RA Zhang J., Zhang K., Qi L., Hu Q., Shen Z., Liu B., Deng J., Zhang C.,
RA Zhang Y.;
RT "DENN domain-containing protein FAM45A regulates the homeostasis of
RT late/multivesicular endosomes.";
RL Biochim. Biophys. Acta 1866:916-929(2019).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 4-201 IN COMPLEX WITH GDP, AND
RP DISULFIDE BOND.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human RAB27B.";
RL Submitted (FEB-2009) to the PDB data bank.
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
CC (PubMed:30771381). Plays a role in NTRK2/TRKB axonal anterograde
CC transport by facilitating the association of NTRK2/TRKB with KLC1
CC (PubMed:21775604). May be involved in targeting uroplakins to
CC urothelial apical membranes (By similarity).
CC {ECO:0000250|UniProtKB:Q8HZJ5, ECO:0000269|PubMed:21775604,
CC ECO:0000269|PubMed:30771381}.
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:0000305|PubMed:30771381};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC Evidence={ECO:0000305|PubMed:30771381};
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:0000305|PubMed:30771381}.
CC -!- SUBUNIT: Interacts with SYTL2, SYTL4, MYRIP and MLPH. Interacts with
CC RPH3A and RPH3A (By similarity). Interacts (GDP-bound form
CC preferentially) with DENND10 (PubMed:30771381).
CC {ECO:0000250|UniProtKB:Q99P58, ECO:0000269|PubMed:30771381}.
CC -!- INTERACTION:
CC O00194; Q03135: CAV1; NbExp=2; IntAct=EBI-10179046, EBI-603614;
CC O00194; P49366: DHPS; NbExp=6; IntAct=EBI-10179046, EBI-741925;
CC O00194; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-10179046, EBI-739467;
CC O00194; Q9BV36: MLPH; NbExp=3; IntAct=EBI-10179046, EBI-7042162;
CC O00194; Q8NFW9: MYRIP; NbExp=3; IntAct=EBI-10179046, EBI-1759414;
CC O00194; Q9Y2J0-2: RPH3A; NbExp=3; IntAct=EBI-10179046, EBI-16808141;
CC O00194; Q9UNE2: RPH3AL; NbExp=3; IntAct=EBI-10179046, EBI-2855824;
CC O00194; Q8TDW5: SYTL5; NbExp=5; IntAct=EBI-10179046, EBI-2939487;
CC O00194; Q8TDW5-2: SYTL5; NbExp=3; IntAct=EBI-10179046, EBI-12243980;
CC -!- SUBCELLULAR LOCATION: Membrane; Lipid-anchor. Late endosome
CC {ECO:0000269|PubMed:30771381}.
CC -!- TISSUE SPECIFICITY: Expressed primarily in testis.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; U57093; AAC51194.2; -; mRNA.
DR EMBL; AF329499; AAK11243.1; -; mRNA.
DR EMBL; AF498954; AAM21102.1; -; mRNA.
DR EMBL; AK314115; BAG36807.1; -; mRNA.
DR EMBL; CH471096; EAW63010.1; -; Genomic_DNA.
DR EMBL; BC027474; AAH27474.1; -; mRNA.
DR CCDS; CCDS11958.1; -.
DR RefSeq; NP_004154.2; NM_004163.4.
DR RefSeq; XP_005266790.1; XM_005266733.1.
DR RefSeq; XP_016881402.1; XM_017025913.1.
DR RefSeq; XP_016881403.1; XM_017025914.1.
DR PDB; 2F7S; X-ray; 2.70 A; A/B=4-201.
DR PDBsum; 2F7S; -.
DR AlphaFoldDB; O00194; -.
DR SMR; O00194; -.
DR BioGRID; 111812; 37.
DR DIP; DIP-48948N; -.
DR IntAct; O00194; 19.
DR STRING; 9606.ENSP00000262094; -.
DR GlyGen; O00194; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00194; -.
DR PhosphoSitePlus; O00194; -.
DR BioMuta; RAB27B; -.
DR OGP; O00194; -.
DR EPD; O00194; -.
DR jPOST; O00194; -.
DR MassIVE; O00194; -.
DR MaxQB; O00194; -.
DR PaxDb; O00194; -.
DR PeptideAtlas; O00194; -.
DR PRIDE; O00194; -.
DR ProteomicsDB; 47773; -.
DR Antibodypedia; 4487; 286 antibodies from 32 providers.
DR DNASU; 5874; -.
DR Ensembl; ENST00000262094.10; ENSP00000262094.4; ENSG00000041353.10.
DR GeneID; 5874; -.
DR KEGG; hsa:5874; -.
DR MANE-Select; ENST00000262094.10; ENSP00000262094.4; NM_004163.4; NP_004154.2.
DR UCSC; uc002lfr.4; human.
DR CTD; 5874; -.
DR DisGeNET; 5874; -.
DR GeneCards; RAB27B; -.
DR HGNC; HGNC:9767; RAB27B.
DR HPA; ENSG00000041353; Tissue enhanced (stomach).
DR MIM; 603869; gene.
DR neXtProt; NX_O00194; -.
DR OpenTargets; ENSG00000041353; -.
DR PharmGKB; PA34118; -.
DR VEuPathDB; HostDB:ENSG00000041353; -.
DR eggNOG; KOG0081; Eukaryota.
DR GeneTree; ENSGT00940000157449; -.
DR HOGENOM; CLU_041217_10_1_1; -.
DR InParanoid; O00194; -.
DR OMA; IGWMRDI; -.
DR OrthoDB; 1190514at2759; -.
DR PhylomeDB; O00194; -.
DR TreeFam; TF312895; -.
DR PathwayCommons; O00194; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR Reactome; R-HSA-8876198; RAB GEFs exchange GTP for GDP on RABs.
DR SignaLink; O00194; -.
DR BioGRID-ORCS; 5874; 7 hits in 1076 CRISPR screens.
DR ChiTaRS; RAB27B; human.
DR EvolutionaryTrace; O00194; -.
DR GenomeRNAi; 5874; -.
DR Pharos; O00194; Tbio.
DR PRO; PR:O00194; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O00194; protein.
DR Bgee; ENSG00000041353; Expressed in esophagus squamous epithelium and 180 other tissues.
DR ExpressionAtlas; O00194; baseline and differential.
DR Genevisible; O00194; HS.
DR GO; GO:0098993; C:anchored component of synaptic vesicle membrane; IEA:Ensembl.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0070382; C:exocytic vesicle; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0042470; C:melanosome; IDA:UniProtKB.
DR GO; GO:0032585; C:multivesicular body membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0031088; C:platelet dense granule membrane; TAS:Reactome.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0030140; C:trans-Golgi network transport vesicle; IDA:UniProtKB.
DR GO; GO:0042589; C:zymogen granule membrane; IEA:Ensembl.
DR GO; GO:0003925; F:G protein activity; IEA:UniProtKB-EC.
DR GO; GO:0019003; F:GDP binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR GO; GO:0031489; F:myosin V binding; IPI:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0099641; P:anterograde axonal protein transport; ISS:UniProtKB.
DR GO; GO:0006887; P:exocytosis; IBA:GO_Central.
DR GO; GO:0071985; P:multivesicular body sorting pathway; IMP:UniProtKB.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:UniProtKB.
DR GO; GO:0048488; P:synaptic vesicle endocytosis; IEA:Ensembl.
DR GO; GO:0016192; P:vesicle-mediated transport; IBA:GO_Central.
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 3D-structure; Acetylation; Direct protein sequencing; Disulfide bond;
KW Endosome; GTP-binding; Hydrolase; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.9"
FT CHAIN 2..218
FT /note="Ras-related protein Rab-27B"
FT /id="PRO_0000121224"
FT REGION 194..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 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 BINDING 163..165
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000269|Ref.9"
FT MOD_RES 218
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 216
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 218
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT DISULFID 123..188
FT /evidence="ECO:0000269|Ref.14"
FT VARIANT 92
FT /note="A -> T (in dbSNP:rs9966265)"
FT /id="VAR_051714"
FT MUTAGEN 23
FT /note="T->N: GDP-locked. Increases interaction with
FT DENND10. Disrupts late endocytic pathway homeostasis."
FT /evidence="ECO:0000269|PubMed:30771381"
FT MUTAGEN 78
FT /note="Q->L: GTP-locked. decreases interaction with
FT DENND10."
FT /evidence="ECO:0000269|PubMed:30771381"
FT STRAND 7..16
FT /evidence="ECO:0007829|PDB:2F7S"
FT HELIX 22..30
FT /evidence="ECO:0007829|PDB:2F7S"
FT STRAND 37..54
FT /evidence="ECO:0007829|PDB:2F7S"
FT STRAND 65..77
FT /evidence="ECO:0007829|PDB:2F7S"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:2F7S"
FT STRAND 94..100
FT /evidence="ECO:0007829|PDB:2F7S"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:2F7S"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:2F7S"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2F7S"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2F7S"
FT HELIX 145..154
FT /evidence="ECO:0007829|PDB:2F7S"
FT STRAND 159..162
FT /evidence="ECO:0007829|PDB:2F7S"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:2F7S"
FT HELIX 170..188
FT /evidence="ECO:0007829|PDB:2F7S"
SQ SEQUENCE 218 AA; 24608 MW; 8ED640F0C15EDCD3 CRC64;
MTDGDYDYLI KLLALGDSGV GKTTFLYRYT DNKFNPKFIT TVGIDFREKR VVYNAQGPNG
SSGKAFKVHL QLWDTAGQER FRSLTTAFFR DAMGFLLMFD LTSQQSFLNV RNWMSQLQAN
AYCENPDIVL IGNKADLPDQ REVNERQARE LADKYGIPYF ETSAATGQNV EKAVETLLDL
IMKRMEQCVE KTQIPDTVNG GNSGNLDGEK PPEKKCIC
