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   27-MAR-2024, entry version 157.
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}.
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; 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; 2.
DR   IntAct; Q9D3G9; 1.
DR   STRING; 10090.ENSMUSP00000031106; -.
DR   iPTMnet; Q9D3G9; -.
DR   PhosphoSitePlus; Q9D3G9; -.
DR   EPD; Q9D3G9; -.
DR   MaxQB; Q9D3G9; -.
DR   PaxDb; 10090-ENSMUSP00000031106; -.
DR   ProteomicsDB; 255337; -.
DR   Antibodypedia; 23555; 284 antibodies from 29 providers.
DR   DNASU; 74734; -.
DR   Ensembl; ENSMUST00000031106.8; ENSMUSP00000031106.5; ENSMUSG00000029204.8.
DR   Ensembl; ENSMUST00000201533.2; ENSMUSP00000143810.2; ENSMUSG00000029204.8.
DR   GeneID; 74734; -.
DR   KEGG; mmu:74734; -.
DR   UCSC; uc008xoc.1; mouse.
DR   AGR; MGI:1921984; -.
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; HKWIAEV; -.
DR   OrthoDB; 20499at2759; -.
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 77 CRISPR screens.
DR   PRO; PR:Q9D3G9; -.
DR   Proteomes; UP000000589; Chromosome 5.
DR   RNAct; Q9D3G9; Protein.
DR   Bgee; ENSMUSG00000029204; Expressed in thymus and 85 other cell types or tissues.
DR   ExpressionAtlas; Q9D3G9; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
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:0045576; P:mast cell activation; IDA:UniProtKB.
DR   GO; GO:0043124; P:negative regulation of canonical NF-kappaB signal transduction; ISO:MGI.
DR   GO; GO:0045582; P:positive regulation of T cell differentiation; ISO:MGI.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR   GO; GO:0030217; P:T cell differentiation; IDA:UniProtKB.
DR   CDD; cd00157; Rho; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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   NCBIfam; TIGR00231; small_GTP; 1.
DR   PANTHER; PTHR24072; RHO FAMILY GTPASE; 1.
DR   PANTHER; PTHR24072:SF412; RHO-RELATED GTP-BINDING PROTEIN RHOH; 1.
DR   Pfam; PF00071; Ras; 1.
DR   PRINTS; PR00449; RASTRNSFRMNG.
DR   SMART; SM00175; RAB; 1.
DR   SMART; SM00173; RAS; 1.
DR   SMART; SM00174; RHO; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR   PROSITE; PS51420; RHO; 1.
DR   Genevisible; Q9D3G9; MM.
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
//