RHOH_MOUSE
ID RHOH_MOUSE Reviewed; 191 AA.
AC Q9D3G9;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Rho-related GTP-binding protein RhoH;
DE Flags: Precursor;
GN Name=Rhoh; Synonyms=Arhh;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15494435; DOI=10.1182/blood-2004-04-1604;
RA Gu Y., Jasti A.C., Jansen M., Siefring J.E.;
RT "RhoH, a hematopoietic-specific Rho GTPase, regulates proliferation,
RT survival, migration, and engraftment of hematopoietic progenitor cells.";
RL Blood 105:1467-1475(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP FUNCTION, INTERACTION WITH ZAP70, SUBCELLULAR LOCATION, PHOSPHORYLATION,
RP MUTAGENESIS OF TYR-73 AND TYR-83, AND DISRUPTION PHENOTYPE.
RX PubMed=17028588; DOI=10.1038/ni1396;
RA Gu Y., Chae H.-D., Siefring J.E., Jasti A.C., Hildeman D.A., Williams D.A.;
RT "RhoH GTPase recruits and activates Zap70 required for T cell receptor
RT signaling and thymocyte development.";
RL Nat. Immunol. 7:1182-1190(2006).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=17119112; DOI=10.1182/blood-2006-04-019034;
RA Dorn T., Kuhn U., Bungartz G., Stiller S., Bauer M., Ellwart J., Peters T.,
RA Scharffetter-Kochanek K., Semmrich M., Laschinger M., Holzmann B.,
RA Klinkert W.E.F., Straten P.T., Kollgaard T., Sixt M., Brakebusch C.;
RT "RhoH is important for positive thymocyte selection and T-cell receptor
RT signaling.";
RL Blood 109:2346-2355(2007).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, INTERACTION WITH SYK, AND TISSUE
RP SPECIFICITY.
RX PubMed=19124738; DOI=10.4049/jimmunol.182.2.957;
RA Oda H., Fujimoto M., Patrick M.S., Chida D., Sato Y., Azuma Y., Aoki H.,
RA Abe T., Suzuki H., Shirai M.;
RT "RhoH plays critical roles in Fc epsilon RI-dependent signal transduction
RT in mast cells.";
RL J. Immunol. 182:957-962(2009).
RN [6]
RP INDUCTION.
RX PubMed=19414807; DOI=10.4049/jimmunol.0803846;
RA Daryadel A., Yousefi S., Troi D., Schmid I., Schmidt-Mende J.,
RA Mordasini C., Dahinden C.A., Ziemiecki A., Simon H.-U.;
RT "RhoH/TTF negatively regulates leukotriene production in neutrophils.";
RL J. Immunol. 182:6527-6532(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Binds GTP but lacks intrinsic GTPase activity and is
CC resistant to Rho-specific GTPase-activating proteins. Inhibits the
CC activation of NF-kappa-B by TNF and IKKB and the activation of CRK/p38
CC by TNF. Inhibits activities of RAC1, RHOA and CDC42. Negatively
CC regulates leukotriene production in neutrophils (By similarity).
CC Negative regulator of hematopoietic progenitor cell proliferation,
CC survival and migration. Critical regulator of thymocyte development and
CC T-cell antigen receptor (TCR) signaling by mediating recruitment and
CC activation of ZAP70 (PubMed:17028588). Required for phosphorylation of
CC CD3Z, membrane translocation of ZAP70 and subsequent activation of the
CC ZAP70-mediated pathways. Essential for efficient beta-selection and
CC positive selection by promoting the ZAP70-dependent phosphorylation of
CC the LAT signalosome during pre-TCR and TCR signaling. Crucial for
CC thymocyte maturation during DN3 to DN4 transition and during positive
CC selection. Plays critical roles in mast cell function by facilitating
CC phosphorylation of SYK in Fc epsilon RI-mediated signal transduction.
CC Essential for the phosphorylation of LAT, LCP2, PLCG1 and PLCG2 and for
CC Ca(2+) mobilization in mast cells. {ECO:0000250,
CC ECO:0000269|PubMed:15494435, ECO:0000269|PubMed:17028588,
CC ECO:0000269|PubMed:17119112, ECO:0000269|PubMed:19124738}.
CC -!- SUBUNIT: Interacts with GDI1 and GDI2 (By similarity). Interacts with
CC ZAP70 (via SH2 domains) and the interaction is enhanced by its
CC phosphorylation by LCK. Interacts with SYK and the interaction is
CC enhanced by its phosphorylation by FYN. {ECO:0000250,
CC ECO:0000269|PubMed:17028588, ECO:0000269|PubMed:19124738}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17028588}. Cell
CC membrane {ECO:0000269|PubMed:17028588}; Lipid-anchor
CC {ECO:0000269|PubMed:17028588}; Cytoplasmic side
CC {ECO:0000269|PubMed:17028588}. Note=Colocalizes together with ZAP70 in
CC the immunological synapse.
CC -!- TISSUE SPECIFICITY: Expression is widespread in hematopoietic cells,
CC including in bone marrow progenitor cells and in differentiated myeloid
CC as well as lymphoid cells. Expressed at high levels in the thymus and
CC mast cells, found in spleen and low-density bone marrow (LDBM) cells
CC and is detected at a low level in neutrophils. In the thymus it is
CC detected in thymocytes of the thymic cortex but not in non-lymphoid
CC cells of fibrovascular and fibroadipose tissues. Expressed in T-cells,
CC B-cells and mast cells. {ECO:0000269|PubMed:15494435,
CC ECO:0000269|PubMed:19124738}.
CC -!- DEVELOPMENTAL STAGE: Expressed at all stages of thymocyte development,
CC with relative peaks at the DN3 and DP stages.
CC {ECO:0000269|PubMed:17119112}.
CC -!- DOMAIN: The region involved in interaction with ZAP70 is a non-
CC canonical immunoreceptor tyrosine-based activation motif (ITAM).
CC -!- PTM: Phosphorylated on tyrosine by LCK. Phosphorylated by FYN.
CC Phosphorylation enhances the interactions with ZAP70 and SYK and is
CC critical for its function in thymocyte development.
CC {ECO:0000269|PubMed:17028588}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice have smaller thymuses than wild-
CC type animals, and T-cell lymphopenia due to defects in T-cell
CC maturation and population expansion in the thymus (PubMed:17028588).
CC Mice show impaired passive systemic anaphylaxis and histamine release
CC upon challenge with the specific antigen. {ECO:0000269|PubMed:17028588,
CC ECO:0000269|PubMed:17119112, ECO:0000269|PubMed:19124738}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC {ECO:0000305}.
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DR EMBL; AK017885; BAB30987.1; -; mRNA.
DR CCDS; CCDS39100.1; -.
DR RefSeq; NP_001074574.1; NM_001081105.1.
DR RefSeq; XP_011239081.1; XM_011240779.2.
DR AlphaFoldDB; Q9D3G9; -.
DR SMR; Q9D3G9; -.
DR BioGRID; 216981; 1.
DR IntAct; Q9D3G9; 1.
DR STRING; 10090.ENSMUSP00000031106; -.
DR iPTMnet; Q9D3G9; -.
DR PhosphoSitePlus; Q9D3G9; -.
DR EPD; Q9D3G9; -.
DR MaxQB; Q9D3G9; -.
DR PaxDb; Q9D3G9; -.
DR PRIDE; Q9D3G9; -.
DR ProteomicsDB; 255337; -.
DR Antibodypedia; 23555; 262 antibodies from 29 providers.
DR DNASU; 74734; -.
DR Ensembl; ENSMUST00000031106; ENSMUSP00000031106; ENSMUSG00000029204.
DR Ensembl; ENSMUST00000201533; ENSMUSP00000143810; ENSMUSG00000029204.
DR GeneID; 74734; -.
DR KEGG; mmu:74734; -.
DR UCSC; uc008xoc.1; mouse.
DR CTD; 399; -.
DR MGI; MGI:1921984; Rhoh.
DR VEuPathDB; HostDB:ENSMUSG00000029204; -.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00940000160078; -.
DR HOGENOM; CLU_041217_21_3_1; -.
DR InParanoid; Q9D3G9; -.
DR OMA; NKWIAEI; -.
DR OrthoDB; 1091615at2759; -.
DR PhylomeDB; Q9D3G9; -.
DR TreeFam; TF331219; -.
DR BRENDA; 3.6.5.2; 3474.
DR Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR BioGRID-ORCS; 74734; 2 hits in 72 CRISPR screens.
DR PRO; PR:Q9D3G9; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q9D3G9; protein.
DR Bgee; ENSMUSG00000029204; Expressed in thymus and 84 other tissues.
DR ExpressionAtlas; Q9D3G9; baseline and differential.
DR Genevisible; Q9D3G9; MM.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0042995; C:cell projection; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
DR GO; GO:0001772; C:immunological synapse; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; ISO:MGI.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0019210; F:kinase inhibitor activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0007015; P:actin filament organization; IBA:GO_Central.
DR GO; GO:0030031; P:cell projection assembly; IBA:GO_Central.
DR GO; GO:0030865; P:cortical cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0043652; P:engulfment of apoptotic cell; IBA:GO_Central.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IBA:GO_Central.
DR GO; GO:0045576; P:mast cell activation; IDA:UniProtKB.
DR GO; GO:0008045; P:motor neuron axon guidance; IBA:GO_Central.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:MGI.
DR GO; GO:0016601; P:Rac protein signal transduction; IBA:GO_Central.
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:1902622; P:regulation of neutrophil migration; IBA:GO_Central.
DR GO; GO:0030217; P:T cell differentiation; IDA: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 InterPro; IPR003578; Small_GTPase_Rho.
DR PANTHER; PTHR24072; PTHR24072; 1.
DR Pfam; PF00071; Ras; 1.
DR SMART; SM00174; RHO; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51420; RHO; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..188
FT /note="Rho-related GTP-binding protein RhoH"
FT /id="PRO_0000198868"
FT PROPEP 189..191
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281219"
FT REGION 73..86
FT /note="Interaction with ZAP70"
FT /evidence="ECO:0000269|PubMed:17028588"
FT MOTIF 33..41
FT /note="Effector region"
FT /evidence="ECO:0000250"
FT BINDING 11..18
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 58..62
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 116..119
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 188
FT /note="Cysteine methyl ester"
FT /evidence="ECO:0000250"
FT LIPID 188
FT /note="S-geranylgeranyl cysteine"
FT /evidence="ECO:0000250"
FT MUTAGEN 73
FT /note="Y->F: Abolishes interaction with ZAP70; when
FT associated with F-83."
FT /evidence="ECO:0000269|PubMed:17028588"
FT MUTAGEN 83
FT /note="Y->F: Abolishes interaction with ZAP70; when
FT associated with F-73."
FT /evidence="ECO:0000269|PubMed:17028588"
SQ SEQUENCE 191 AA; 21324 MW; 18845201F647D539 CRC64;
MLSSIKCVLV GDSAVGKTSL LVRFTSETFP EAYKPTVYEN TGVDVFMDGI QISLGLWDTA
GNDAFRSIRP LSYQQADVVL MCYSVANHNS FLNLKNKWIS EIRSNLPCTP VLVVATQTDQ
REVGPHRASC INAIEGKRLA QDVRAKGYLE CSALSNRGVQ QVFECAVRTA VNQARRRNRR
KLFSINECKI F
