RHBT3_HUMAN
ID RHBT3_HUMAN Reviewed; 611 AA.
AC O94955; A0PJA4; A8K1W9; Q8IW06;
DT 28-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2007, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Rho-related BTB domain-containing protein 3;
DE EC=3.6.1.-;
GN Name=RHOBTB3; Synonyms=KIAA0878;
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], VARIANT ASP-262, AND TISSUE SPECIFICITY.
RX PubMed=12426103; DOI=10.1016/s0378-1119(02)00980-0;
RA Ramos S., Khademi F., Somesh B.P., Rivero F.;
RT "Genomic organization and expression profile of the small GTPases of the
RT RhoBTB family in human and mouse.";
RL Gene 298:147-157(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASP-262.
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 MRNA], AND VARIANT GLN-20.
RC TISSUE=Brain, and Muscle;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, BIOPHYSICOCHEMICAL PROPERTIES, ATP-BINDING,
RP INTERACTION WITH RAB9A; RAB9B AND M6PRBP1, AND MUTAGENESIS OF ASN-138;
RP ALA-498; ASP-532; ILE-533 AND 608-CYS--MET-611.
RX PubMed=19490898; DOI=10.1016/j.cell.2009.03.043;
RA Espinosa E.J., Calero M., Sridevi K., Pfeffer S.R.;
RT "RhoBTB3: a Rho GTPase-family ATPase required for endosome to Golgi
RT transport.";
RL Cell 137:938-948(2009).
CC -!- FUNCTION: Rab9-regulated ATPase required for endosome to Golgi
CC transport. Involved in transport vesicle docking at the Golgi complex,
CC possibly by participating in release M6PRBP1/TIP47 from vesicles to
CC permit their efficient docking and fusion at the Golgi. Specifically
CC binds Rab9, but not other Rab proteins. Has low intrinsic ATPase
CC activity due to autoinhibition, which is relieved by Rab9.
CC {ECO:0000269|PubMed:19490898}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=48 uM for ATP {ECO:0000269|PubMed:19490898};
CC -!- SUBUNIT: Interacts with RAB9A and RAB9B (at lower level compared to
CC RAB9A-binding). Interacts with M6PRBP1/TIP47.
CC {ECO:0000269|PubMed:19490898}.
CC -!- INTERACTION:
CC O94955; O14503: BHLHE40; NbExp=7; IntAct=EBI-2367123, EBI-711810;
CC O94955; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-2367123, EBI-2349927;
CC O94955; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-2367123, EBI-8638439;
CC O94955; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-2367123, EBI-1055254;
CC O94955; Q96JM7-2: L3MBTL3; NbExp=3; IntAct=EBI-2367123, EBI-11985629;
CC O94955; Q9UPG8: PLAGL2; NbExp=3; IntAct=EBI-2367123, EBI-2876622;
CC O94955; Q93062: RBPMS; NbExp=4; IntAct=EBI-2367123, EBI-740322;
CC O94955; Q96SF7: TBX15; NbExp=3; IntAct=EBI-2367123, EBI-10191361;
CC O94955; Q5T124: UBXN11; NbExp=4; IntAct=EBI-2367123, EBI-746004;
CC O94955; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-2367123, EBI-11975223;
CC O94955; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-2367123, EBI-527853;
CC O94955; P24408: RAB9A; Xeno; NbExp=5; IntAct=EBI-2367123, EBI-1646050;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000269|PubMed:19490898}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in neural and cardiac
CC tissues, pancreas, placenta and testis. {ECO:0000269|PubMed:12426103}.
CC -!- DOMAIN: Although predicted to be a GTP-binding protein because of the
CC presence of a Rho-like region, binds and hydrolyzes ATP. In contrast to
CC Rho-like proteins, the conserved Asp residue in position 138 in the G4
CC region is replaced by an Asn, decreasing the ability to bind GTP.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74901.2; Type=Erroneous initiation; Evidence={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; AB020685; BAA74901.2; ALT_INIT; mRNA.
DR EMBL; AK290034; BAF82723.1; -; mRNA.
DR EMBL; BC020231; AAH20231.1; -; mRNA.
DR EMBL; BC041337; AAH41337.1; -; mRNA.
DR CCDS; CCDS4077.1; -.
DR RefSeq; NP_055714.3; NM_014899.3.
DR AlphaFoldDB; O94955; -.
DR SMR; O94955; -.
DR BioGRID; 116510; 131.
DR IntAct; O94955; 30.
DR STRING; 9606.ENSP00000369318; -.
DR GlyConnect; 1717; 2 N-Linked glycans (1 site).
DR GlyGen; O94955; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; O94955; -.
DR PhosphoSitePlus; O94955; -.
DR BioMuta; RHOBTB3; -.
DR EPD; O94955; -.
DR jPOST; O94955; -.
DR MassIVE; O94955; -.
DR MaxQB; O94955; -.
DR PaxDb; O94955; -.
DR PeptideAtlas; O94955; -.
DR PRIDE; O94955; -.
DR ProteomicsDB; 50576; -.
DR Antibodypedia; 636; 136 antibodies from 26 providers.
DR DNASU; 22836; -.
DR Ensembl; ENST00000379982.8; ENSP00000369318.3; ENSG00000164292.13.
DR GeneID; 22836; -.
DR KEGG; hsa:22836; -.
DR MANE-Select; ENST00000379982.8; ENSP00000369318.3; NM_014899.4; NP_055714.3.
DR UCSC; uc003klm.4; human.
DR CTD; 22836; -.
DR DisGeNET; 22836; -.
DR GeneCards; RHOBTB3; -.
DR HGNC; HGNC:18757; RHOBTB3.
DR HPA; ENSG00000164292; Low tissue specificity.
DR MIM; 607353; gene.
DR neXtProt; NX_O94955; -.
DR OpenTargets; ENSG00000164292; -.
DR PharmGKB; PA38679; -.
DR VEuPathDB; HostDB:ENSG00000164292; -.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00850000132411; -.
DR HOGENOM; CLU_029897_0_0_1; -.
DR InParanoid; O94955; -.
DR OMA; MSVNIVA; -.
DR OrthoDB; 338031at2759; -.
DR PhylomeDB; O94955; -.
DR TreeFam; TF323347; -.
DR PathwayCommons; O94955; -.
DR Reactome; R-HSA-6811440; Retrograde transport at the Trans-Golgi-Network.
DR Reactome; R-HSA-9706019; RHOBTB3 ATPase cycle.
DR SABIO-RK; O94955; -.
DR SignaLink; O94955; -.
DR BioGRID-ORCS; 22836; 13 hits in 1115 CRISPR screens.
DR ChiTaRS; RHOBTB3; human.
DR GeneWiki; RHOBTB3; -.
DR GenomeRNAi; 22836; -.
DR Pharos; O94955; Tbio.
DR PRO; PR:O94955; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O94955; protein.
DR Bgee; ENSG00000164292; Expressed in adrenal tissue and 212 other tissues.
DR ExpressionAtlas; O94955; baseline and differential.
DR Genevisible; O94955; HS.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032588; C:trans-Golgi network membrane; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0031267; F:small GTPase binding; IPI:UniProtKB.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0008360; P:regulation of cell shape; IBA:GO_Central.
DR GO; GO:0042147; P:retrograde transport, endosome to Golgi; IMP:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR Gene3D; 3.30.710.10; -; 2.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR031260; RhoBTB3.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003578; Small_GTPase_Rho.
DR PANTHER; PTHR24072; PTHR24072; 1.
DR PANTHER; PTHR24072:SF139; PTHR24072:SF139; 1.
DR Pfam; PF00651; BTB; 2.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00225; BTB; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF54695; SSF54695; 2.
DR PROSITE; PS50097; BTB; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Golgi apparatus; Hydrolase; Nucleotide-binding;
KW Reference proteome; Repeat; Transport.
FT CHAIN 1..611
FT /note="Rho-related BTB domain-containing protein 3"
FT /id="PRO_0000198964"
FT DOMAIN 254..356
FT /note="BTB 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT DOMAIN 420..487
FT /note="BTB 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REGION 1..175
FT /note="Rho-like"
FT REGION 420..611
FT /note="Interaction with Rab9"
FT VARIANT 20
FT /note="R -> Q (in dbSNP:rs17855649)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_030490"
FT VARIANT 21
FT /note="P -> R (in dbSNP:rs2302980)"
FT /id="VAR_018481"
FT VARIANT 262
FT /note="N -> D (in dbSNP:rs34899)"
FT /evidence="ECO:0000269|PubMed:10048485,
FT ECO:0000269|PubMed:12426103"
FT /id="VAR_018482"
FT MUTAGEN 138
FT /note="N->D: Abolishes ATP-binding."
FT /evidence="ECO:0000269|PubMed:19490898"
FT MUTAGEN 498
FT /note="A->T: Abolishes interaction with RAB9A."
FT /evidence="ECO:0000269|PubMed:19490898"
FT MUTAGEN 532
FT /note="D->E: Abolishes interaction with RAB9A."
FT /evidence="ECO:0000269|PubMed:19490898"
FT MUTAGEN 533
FT /note="I->K: Abolishes interaction with RAB9A."
FT /evidence="ECO:0000269|PubMed:19490898"
FT MUTAGEN 608..611
FT /note="Missing: Does not affect subcellular location,
FT suggesting this protein is not prenylated."
FT /evidence="ECO:0000269|PubMed:19490898"
SQ SEQUENCE 611 AA; 69413 MW; 430ED42327AF08B6 CRC64;
MSIHIVALGN EGDTFHQDNR PSGLIRTYLG RSPLVSGDES SLLLNAASTV ARPVFTEYQA
SAFGNVKLVV HDCPVWDIFD SDWYTSRNLI GGADIIVIKY NVNDKFSFHE VKDNYIPVIK
RALNSVPVII AAVGTRQNEE LPCTCPLCTS DRGSCVSTTE GIQLAKELGA TYLELHSLDD
FYIGKYFGGV LEYFMIQALN QKTSEKMKKR KMSNSFHGIR PPQLEQPEKM PVLKAEASHY
NSDLNNLLFC CQCVDVVFYN PNLKKVVEAH KIVLCAVSHV FMLLFNVKSP TDIQDSSIIR
TTQDLFAINR DTAFPGASHE SSGNPPLRVI VKDALFCSCL SDILRFIYSG AFQWEELEED
IRKKLKDSGD VSNVIEKVKC ILKTPGKINC LRNCKTYQAR KPLWFYNTSL KFFLNKPMLA
DVVFEIQGTT VPAHRAILVA RCEVMAAMFN GNYMEAKSVL IPVYGVSKET FLSFLEYLYT
DSCCPAGIFQ AMCLLICAEM YQVSRLQHIC ELFIITQLQS MPSRELASMN LDIVDLLKKA
KFHHSDCLST WLLHFIATNY LIFSQKPEFQ DLSVEERSFV EKHRWPSNMY LKQLAEYRKY
IHSRKCRCLV M
