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 27-MAR-2024, entry version 189. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 38. DR DIP; DIP-61978N; -. DR IntAct; Q9H082; 10. DR MINT; Q9H082; -. DR STRING; 9606.ENSP00000306496; -. DR GlyCosmos; Q9H082; 1 site, 1 glycan. 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; 9606-ENSP00000306496; -. DR PeptideAtlas; Q9H082; -. DR ProteomicsDB; 80216; -. DR Pumba; Q9H082; -. DR Antibodypedia; 27146; 95 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 AGR; HGNC:16075; -. 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; 8685at2759; -. 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; 14 hits in 1157 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 203 other cell types or tissues. DR ExpressionAtlas; Q9H082; baseline and differential. 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; P-loop containing nucleotide triphosphate hydrolases; 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 NCBIfam; TIGR00231; small_GTP; 1. DR PANTHER; PTHR47978; -; 1. DR PANTHER; PTHR47978:SF66; RAS-RELATED PROTEIN RAB-33B; 1. DR Pfam; PF00071; Ras; 1. DR PRINTS; PR00449; RASTRNSFRMNG. DR SMART; SM00175; RAB; 1. DR SMART; SM00176; RAN; 1. DR SMART; SM00173; RAS; 1. DR SMART; SM00174; RHO; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS51419; RAB; 1. DR Genevisible; Q9H082; HS. 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 //