RB33B_HUMAN
ID RB33B_HUMAN Reviewed; 229 AA.
AC Q9H082; B2R987; Q4W5B0;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Ras-related protein Rab-33B;
GN Name=RAB33B;
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].
RA Mao Y., Xie Y., Cheng H.;
RT "Molecular cloning and characterization of human RAB33B.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [6]
RP SUBCELLULAR LOCATION.
RX PubMed=18448665; DOI=10.1091/mbc.e07-12-1231;
RA Itoh T., Fujita N., Kanno E., Yamamoto A., Yoshimori T., Fukuda M.;
RT "Golgi-resident small GTPase Rab33B interacts with Atg16L and modulates
RT autophagosome formation.";
RL Mol. Biol. Cell 19:2916-2925(2008).
RN [7]
RP FUNCTION.
RX PubMed=20163571; DOI=10.1111/j.1600-0854.2010.01051.x;
RA Starr T., Sun Y., Wilkins N., Storrie B.;
RT "Rab33b and Rab6 are functionally overlapping regulators of Golgi
RT homeostasis and trafficking.";
RL Traffic 11:626-636(2010).
RN [8]
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 [9]
RP INTERACTION WITH ATG16L1, ACTIVITY REGULATION, AND MUTAGENESIS OF GLN-92.
RX PubMed=21808068; DOI=10.1074/jbc.m111.261115;
RA Nottingham R.M., Ganley I.G., Barr F.A., Lambright D.G., Pfeffer S.R.;
RT "RUTBC1 protein, a Rab9A effector that activates GTP hydrolysis by Rab32
RT and Rab33B proteins.";
RL J. Biol. Chem. 286:33213-33222(2011).
RN [10]
RP INTERACTION WITH RGP1 AND RIC1.
RX PubMed=23091056; DOI=10.1074/jbc.m112.414565;
RA Pusapati G.V., Luchetti G., Pfeffer S.R.;
RT "Ric1-Rgp1 complex is a guanine nucleotide exchange factor for the late
RT Golgi Rab6A GTPase and an effector of the medial Golgi Rab33B GTPase.";
RL J. Biol. Chem. 287:42129-42137(2012).
RN [11]
RP VARIANT SMC2 GLN-46.
RX PubMed=22652534; DOI=10.1136/jmedgenet-2011-100666;
RA Alshammari M.J., Al-Otaibi L., Alkuraya F.S.;
RT "Mutation in RAB33B, which encodes a regulator of retrograde Golgi
RT transport, defines a second Dyggve--Melchior--Clausen locus.";
RL J. Med. Genet. 49:455-461(2012).
RN [12]
RP VARIANT SMC2 LYS-148, AND CHARACTERIZATION OF VARIANT SMC2 LYS-148.
RX PubMed=23042644; DOI=10.1002/humu.22235;
RA Dupuis N., Lebon S., Kumar M., Drunat S., Graul-Neumann L.M., Gressens P.,
RA El Ghouzzi V.;
RT "A novel RAB33B mutation in Smith-McCort dysplasia.";
RL Hum. Mutat. 34:283-286(2013).
CC -!- FUNCTION: Protein transport. Acts, in coordination with RAB6A, to
CC regulate intra-Golgi retrograde trafficking. It is involved in
CC autophagy, acting as a modulator of autophagosome formation.
CC {ECO:0000269|PubMed:20163571}.
CC -!- ACTIVITY REGULATION: Regulated by a guanine nucleotide-exchange factor
CC (GEF) and a GTPase-activating protein (GAP) and alternates between an
CC inactive GDP-bound and an active GTP-bound form. In vitro, SGSM2 acts
CC as its GAP and inactivates it by stimulating its GTPase activity.
CC {ECO:0000269|PubMed:21808068}.
CC -!- SUBUNIT: Interacts with ATG16L1 (PubMed:21808068). Interaction with
CC ATG16L1 is important for autophagosome formation (By similarity).
CC Interacts with ATG16L2; however interaction is approximately hundred
CC times lower than for ATG16L1 (By similarity). Interacts with RIC1 (via
CC C-terminus domain); the interaction is direct with a preference for
CC RAB33B-GTP (PubMed:23091056). Interacts with RGP1 (PubMed:23091056).
CC {ECO:0000250|UniProtKB:O35963, ECO:0000269|PubMed:21808068,
CC ECO:0000269|PubMed:23091056}.
CC -!- INTERACTION:
CC Q9H082; Q676U5: ATG16L1; NbExp=3; IntAct=EBI-3048549, EBI-535909;
CC Q9H082; Q8WXA3-4: RUFY2; NbExp=3; IntAct=EBI-3048549, EBI-19117969;
CC Q9H082; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-3048549, EBI-11522811;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:O35963}; Lipid-anchor {ECO:0000305}. Golgi
CC apparatus, cis-Golgi network {ECO:0000269|PubMed:18448665}. Note=Under
CC starvation conditions punctate RAB33B-positive structures are often
CC observed in the cytoplasm. {ECO:0000250|UniProtKB:O35963}.
CC -!- DISEASE: Smith-McCort dysplasia 2 (SMC2) [MIM:615222]: A rare autosomal
CC recessive osteochondrodysplasia with skeletal features identical to
CC those of Dyggve-Melchior-Clausen syndrome, but with normal intelligence
CC and no microcephaly. It is characterized by short limbs and trunk with
CC barrel-shaped chest. The radiographic phenotype includes platyspondyly,
CC generalized abnormalities of the epiphyses and metaphyses, and a
CC distinctive lacy appearance of the iliac crest.
CC {ECO:0000269|PubMed:22652534, ECO:0000269|PubMed:23042644}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
CC {ECO:0000305}.
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DR EMBL; AF350420; AAL83916.1; -; mRNA.
DR EMBL; AL136904; CAB66838.1; -; mRNA.
DR EMBL; AK313685; BAG36434.1; -; mRNA.
DR EMBL; AC114743; AAY40936.1; -; Genomic_DNA.
DR EMBL; BC111977; AAI11978.1; -; mRNA.
DR CCDS; CCDS3747.1; -.
DR RefSeq; NP_112586.1; NM_031296.2.
DR PDB; 6Y09; X-ray; 2.40 A; A/B=30-218.
DR PDB; 6ZAY; X-ray; 2.40 A; A/B=30-218.
DR PDBsum; 6Y09; -.
DR PDBsum; 6ZAY; -.
DR AlphaFoldDB; Q9H082; -.
DR SMR; Q9H082; -.
DR BioGRID; 123654; 36.
DR DIP; DIP-61978N; -.
DR IntAct; Q9H082; 9.
DR MINT; Q9H082; -.
DR STRING; 9606.ENSP00000306496; -.
DR GlyGen; Q9H082; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9H082; -.
DR PhosphoSitePlus; Q9H082; -.
DR BioMuta; RAB33B; -.
DR DMDM; 14916662; -.
DR EPD; Q9H082; -.
DR jPOST; Q9H082; -.
DR MassIVE; Q9H082; -.
DR MaxQB; Q9H082; -.
DR PaxDb; Q9H082; -.
DR PeptideAtlas; Q9H082; -.
DR PRIDE; Q9H082; -.
DR ProteomicsDB; 80216; -.
DR Antibodypedia; 27146; 77 antibodies from 24 providers.
DR DNASU; 83452; -.
DR Ensembl; ENST00000305626.6; ENSP00000306496.5; ENSG00000172007.7.
DR GeneID; 83452; -.
DR KEGG; hsa:83452; -.
DR MANE-Select; ENST00000305626.6; ENSP00000306496.5; NM_031296.3; NP_112586.1.
DR UCSC; uc003ihv.4; human.
DR CTD; 83452; -.
DR DisGeNET; 83452; -.
DR GeneCards; RAB33B; -.
DR HGNC; HGNC:16075; RAB33B.
DR HPA; ENSG00000172007; Low tissue specificity.
DR MalaCards; RAB33B; -.
DR MIM; 605950; gene.
DR MIM; 615222; phenotype.
DR neXtProt; NX_Q9H082; -.
DR OpenTargets; ENSG00000172007; -.
DR Orphanet; 178355; Smith-McCort dysplasia.
DR PharmGKB; PA34125; -.
DR VEuPathDB; HostDB:ENSG00000172007; -.
DR eggNOG; KOG0084; Eukaryota.
DR GeneTree; ENSGT00940000157090; -.
DR HOGENOM; CLU_041217_10_3_1; -.
DR InParanoid; Q9H082; -.
DR OrthoDB; 1081271at2759; -.
DR PhylomeDB; Q9H082; -.
DR TreeFam; TF300097; -.
DR PathwayCommons; Q9H082; -.
DR Reactome; R-HSA-6811438; Intra-Golgi traffic.
DR Reactome; R-HSA-8854214; TBC/RABGAPs.
DR Reactome; R-HSA-8873719; RAB geranylgeranylation.
DR SignaLink; Q9H082; -.
DR SIGNOR; Q9H082; -.
DR BioGRID-ORCS; 83452; 12 hits in 1080 CRISPR screens.
DR ChiTaRS; RAB33B; human.
DR GeneWiki; RAB33B; -.
DR GenomeRNAi; 83452; -.
DR Pharos; Q9H082; Tbio.
DR PRO; PR:Q9H082; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q9H082; protein.
DR Bgee; ENSG00000172007; Expressed in calcaneal tendon and 201 other tissues.
DR ExpressionAtlas; Q9H082; baseline and differential.
DR Genevisible; Q9H082; HS.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0098793; C:presynapse; IEA:Ensembl.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IMP:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; IEA:Ensembl.
DR GO; GO:0006891; P:intra-Golgi vesicle-mediated transport; IMP:UniProtKB.
DR GO; GO:1903434; P:negative regulation of constitutive secretory pathway; IMP:UniProtKB.
DR GO; GO:0034067; P:protein localization to Golgi apparatus; IMP:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0032482; P:Rab protein signal transduction; IEA:InterPro.
DR GO; GO:0017157; P:regulation of exocytosis; IBA:GO_Central.
DR GO; GO:1903358; P:regulation of Golgi organization; IMP:UniProtKB.
DR GO; GO:2000156; P:regulation of retrograde vesicle-mediated transport, Golgi to ER; IMP:UniProtKB.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:UniProtKB.
DR CDD; cd04115; Rab33B_Rab33A; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR041822; Rab33A/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; Autophagy; Disease variant; Dwarfism; Golgi apparatus;
KW GTP-binding; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Prenylation; Protein transport; Reference proteome; Transport.
FT CHAIN 1..229
FT /note="Ras-related protein Rab-33B"
FT /id="PRO_0000121239"
FT BINDING 39..46
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 88..92
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 148..151
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 229
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 227
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 229
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT VARIANT 46
FT /note="K -> Q (in SMC2; dbSNP:rs587776958)"
FT /evidence="ECO:0000269|PubMed:22652534"
FT /id="VAR_068854"
FT VARIANT 148
FT /note="N -> K (in SMC2; strongly inhibits protein
FT expression and may disrupt the Golgi apparatus structure;
FT dbSNP:rs886044716)"
FT /evidence="ECO:0000269|PubMed:23042644"
FT /id="VAR_068855"
FT MUTAGEN 92
FT /note="Q->A: No loss of SGSM2-stimulated GTPase activity."
FT /evidence="ECO:0000269|PubMed:21808068"
FT STRAND 32..40
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 46..55
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 67..77
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 80..89
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:6Y09"
FT TURN 97..99
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 100..104
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 119..123
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 125..135
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 143..148
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 160..169
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:6Y09"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:6Y09"
FT HELIX 188..201
FT /evidence="ECO:0007829|PDB:6Y09"
SQ SEQUENCE 229 AA; 25718 MW; 40D8B1A1D4C6CD85 CRC64;
MAEEMESSLE ASFSSSGAVS GASGFLPPAR SRIFKIIVIG DSNVGKTCLT YRFCAGRFPD
RTEATIGVDF RERAVEIDGE RIKIQLWDTA GQERFRKSMV QHYYRNVHAV VFVYDMTNMA
SFHSLPSWIE ECKQHLLAND IPRILVGNKC DLRSAIQVPT DLAQKFADTH SMPLFETSAK
NPNDNDHVEA IFMTLAHKLK SHKPLMLSQP PDNGIILKPE PKPAMTCWC
