ID   RHOH_HUMAN              Reviewed;         191 AA.
AC   Q15669;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   08-MAY-2019, entry version 182.
DE   RecName: Full=Rho-related GTP-binding protein RhoH;
DE   AltName: Full=GTP-binding protein TTF;
DE   AltName: Full=Translocation three four protein;
DE   Flags: Precursor;
GN   Name=RHOH; Synonyms=ARHH, TTF;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=7784061;
RA   Dallery E., Galiegue-Zouitina S., Collyn-D'Hooghe M., Quief S.,
RA   Denis C., Hildebrand M.-P., Lantoine D., Deweindt C., Tilly H.,
RA   Bastard C., Kerckaert J.-P.;
RT   "TTF, a gene encoding a novel small G protein, fuses to the lymphoma-
RT   associated LAZ3 gene by t(3;4) chromosomal translocation.";
RL   Oncogene 10:2171-2178(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA   Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT   "cDNA clones of human proteins involved in signal transduction
RT   sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL   Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=B-cell;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION, INTERACTION WITH GDI1 AND GDI2, SUBCELLULAR LOCATION,
RP   INDUCTION, AND TISSUE SPECIFICITY.
RX   PubMed=11809807; DOI=10.1128/MCB.22.4.1158-1171.2002;
RA   Li X., Bu X., Lu B., Avraham H., Flavell R.A., Lim B.;
RT   "The hematopoiesis-specific GTP-binding protein RhoH is GTPase
RT   deficient and modulates activities of other Rho GTPases by an
RT   inhibitory function.";
RL   Mol. Cell. Biol. 22:1158-1171(2002).
RN   [5]
RP   INTERACTION WITH PAK5.
RX   PubMed=17064668; DOI=10.1016/j.bbrc.2006.09.172;
RA   Wu X., Frost J.A.;
RT   "Multiple Rho proteins regulate the subcellular targeting of PAK5.";
RL   Biochem. Biophys. Res. Commun. 351:328-335(2006).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND 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
RT   neutrophils.";
RL   J. Immunol. 182:6527-6532(2009).
CC   -!- FUNCTION: Negative regulator of hematopoietic progenitor cell
CC       proliferation, survival and migration. Critical regulator of
CC       thymocyte development and T-cell antigen receptor (TCR) signaling
CC       by mediating recruitment and activation of ZAP70. Required for
CC       phosphorylation of CD3Z, membrane translocation of ZAP70 and
CC       subsequent activation of the ZAP70-mediated pathways. Essential
CC       for efficient beta-selection and positive selection by promoting
CC       the ZAP70-dependent phosphorylation of the LAT signalosome during
CC       pre-TCR and TCR signaling. Crucial for thymocyte maturation during
CC       DN3 to DN4 transition and during positive selection. Plays
CC       critical roles in mast cell function by facilitating
CC       phosphorylation of SYK in Fc epsilon RI-mediated signal
CC       transduction. Essential for the phosphorylation of LAT, LCP2,
CC       PLCG1 and PLCG2 and for Ca(2+) mobilization in mast cells (By
CC       similarity). 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
CC       CRK/p38 by TNF. Inhibits activities of RAC1, RHOA and CDC42.
CC       Negatively regulates leukotriene production in neutrophils.
CC       {ECO:0000250, ECO:0000269|PubMed:11809807,
CC       ECO:0000269|PubMed:19414807}.
CC   -!- SUBUNIT: Interacts with ZAP70 (via SH2 domains) and the
CC       interaction is enhanced by its phosphorylation by LCK. Interacts
CC       with SYK and the interaction is enhanced by its phosphorylation by
CC       FYN (By similarity). Interacts with GDI1 and GDI2. Interacts with
CC       PAK5 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11809807,
CC       ECO:0000269|PubMed:19414807}. Cell membrane {ECO:0000250}; Lipid-
CC       anchor {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC       Note=Colocalizes together with ZAP70 in the immunological synapse.
CC       {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Expressed only in hematopoietic cells. Present
CC       at very high levels in the thymus, less abundant in the spleen,
CC       and least abundant in the bone marrow. Expressed at a higher level
CC       in the TH1 subtype of T-helper cells than in the TH2
CC       subpopulation. Expressed in neutrophils under inflammatory
CC       conditions, such as cystic fibrosis, ulcerative colitis and
CC       appendicitis. {ECO:0000269|PubMed:11809807,
CC       ECO:0000269|PubMed:19414807}.
CC   -!- INDUCTION: By CSF2/GM-CSF. Down-regulated by phorbol myristate
CC       acetate (PMA). {ECO:0000269|PubMed:11809807,
CC       ECO:0000269|PubMed:19414807}.
CC   -!- DOMAIN: The region involved in interaction with ZAP70 is a non-
CC       canonical immunoreceptor tyrosine-based activation motif (ITAM).
CC       {ECO:0000250}.
CC   -!- PTM: Phosphorylated on tyrosine by LCK. Phosphorylated by FYN.
CC       Phosphorylation enhances the interactions with ZAP70 and SYK and
CC       is critical for its function in thymocyte development (By
CC       similarity). {ECO:0000250}.
CC   -!- DISEASE: Note=A chromosomal aberration involving RHOH is found in
CC       a non-Hodgkin lymphoma cell line. Translocation t(3;4)(q27;p11)
CC       with BCL6.
CC   -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/RHOHID93.html";
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DR   EMBL; Z35227; CAA84538.1; -; mRNA.
DR   EMBL; AF498975; AAM21122.1; -; mRNA.
DR   EMBL; BC014261; AAH14261.1; -; mRNA.
DR   CCDS; CCDS3458.1; -.
DR   PIR; I38367; I38367.
DR   RefSeq; NP_001265288.1; NM_001278359.1.
DR   RefSeq; NP_001265289.1; NM_001278360.1.
DR   RefSeq; NP_001265290.1; NM_001278361.1.
DR   RefSeq; NP_001265291.1; NM_001278362.1.
DR   RefSeq; NP_001265292.1; NM_001278363.1.
DR   RefSeq; NP_001265293.1; NM_001278364.1.
DR   RefSeq; NP_001265294.1; NM_001278365.1.
DR   RefSeq; NP_001265295.1; NM_001278366.1.
DR   RefSeq; NP_001265296.1; NM_001278367.1.
DR   RefSeq; NP_001265297.1; NM_001278368.1.
DR   RefSeq; NP_001265298.1; NM_001278369.1.
DR   RefSeq; NP_004301.1; NM_004310.4.
DR   RefSeq; XP_011511994.1; XM_011513692.1.
DR   RefSeq; XP_016863677.1; XM_017008188.1.
DR   RefSeq; XP_016863678.1; XM_017008189.1.
DR   SMR; Q15669; -.
DR   BioGrid; 106892; 5.
DR   IntAct; Q15669; 14.
DR   MINT; Q15669; -.
DR   STRING; 9606.ENSP00000371219; -.
DR   iPTMnet; Q15669; -.
DR   PhosphoSitePlus; Q15669; -.
DR   BioMuta; RHOH; -.
DR   DMDM; 2500200; -.
DR   PaxDb; Q15669; -.
DR   PeptideAtlas; Q15669; -.
DR   PRIDE; Q15669; -.
DR   ProteomicsDB; 60699; -.
DR   DNASU; 399; -.
DR   Ensembl; ENST00000381799; ENSP00000371219; ENSG00000168421.
DR   Ensembl; ENST00000505618; ENSP00000425010; ENSG00000168421.
DR   Ensembl; ENST00000610353; ENSP00000480192; ENSG00000168421.
DR   Ensembl; ENST00000613272; ENSP00000480772; ENSG00000168421.
DR   Ensembl; ENST00000614836; ENSP00000478248; ENSG00000168421.
DR   Ensembl; ENST00000615083; ENSP00000480379; ENSG00000168421.
DR   Ensembl; ENST00000615577; ENSP00000481566; ENSG00000168421.
DR   Ensembl; ENST00000617441; ENSP00000482947; ENSG00000168421.
DR   Ensembl; ENST00000619474; ENSP00000481746; ENSG00000168421.
DR   Ensembl; ENST00000622175; ENSP00000481836; ENSG00000168421.
DR   GeneID; 399; -.
DR   KEGG; hsa:399; -.
DR   CTD; 399; -.
DR   DisGeNET; 399; -.
DR   GeneCards; RHOH; -.
DR   HGNC; HGNC:686; RHOH.
DR   HPA; HPA030345; -.
DR   MalaCards; RHOH; -.
DR   MIM; 602037; gene.
DR   neXtProt; NX_Q15669; -.
DR   OpenTargets; ENSG00000168421; -.
DR   Orphanet; 324294; T-cell immunodeficiency with epidermodysplasia verruciformis.
DR   PharmGKB; PA24979; -.
DR   eggNOG; KOG0393; Eukaryota.
DR   eggNOG; COG1100; LUCA.
DR   GeneTree; ENSGT00940000160078; -.
DR   HOGENOM; HOG000233974; -.
DR   InParanoid; Q15669; -.
DR   KO; K07873; -.
DR   OMA; QQVFEYA; -.
DR   OrthoDB; 1091615at2759; -.
DR   PhylomeDB; Q15669; -.
DR   TreeFam; TF331219; -.
DR   BRENDA; 3.6.5.2; 2681.
DR   Reactome; R-HSA-194840; Rho GTPase cycle.
DR   ChiTaRS; RHOH; human.
DR   GeneWiki; RhoH; -.
DR   GenomeRNAi; 399; -.
DR   PRO; PR:Q15669; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   Bgee; ENSG00000168421; Expressed in 116 organ(s), highest expression level in leukocyte.
DR   ExpressionAtlas; Q15669; baseline and differential.
DR   Genevisible; Q15669; HS.
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:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0001772; C:immunological synapse; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005525; F:GTP binding; IDA:UniProtKB.
DR   GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR   GO; GO:0005095; F:GTPase inhibitor activity; NAS:UniProtKB.
DR   GO; GO:0019210; F:kinase inhibitor activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR   GO; GO:0017048; F:Rho GTPase binding; NAS:UniProtKB.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IBA:GO_Central.
DR   GO; GO:0007015; P:actin filament organization; 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; IEA:Ensembl.
DR   GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
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:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR   GO; GO:0007266; P:Rho protein signal transduction; IBA:GO_Central.
DR   GO; GO:0030217; P:T cell differentiation; NAS:UniProtKB.
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   Pfam; PF00071; Ras; 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; Chromosomal rearrangement; Complete proteome;
KW   Cytoplasm; GTP-binding; Lipoprotein; Membrane; Methylation;
KW   Nucleotide-binding; Phosphoprotein; Prenylation; Reference proteome.
FT   CHAIN         1    188       Rho-related GTP-binding protein RhoH.
FT                                /FTId=PRO_0000198867.
FT   PROPEP      189    191       Removed in mature form. {ECO:0000250}.
FT                                /FTId=PRO_0000281218.
FT   NP_BIND      11     18       GTP. {ECO:0000250}.
FT   NP_BIND      58     62       GTP. {ECO:0000250}.
FT   NP_BIND     116    119       GTP. {ECO:0000250}.
FT   REGION       73     86       Interaction with ZAP70. {ECO:0000250}.
FT   MOTIF        33     41       Effector region. {ECO:0000250}.
FT   MOD_RES     188    188       Cysteine methyl ester. {ECO:0000250}.
FT   LIPID       188    188       S-geranylgeranyl cysteine. {ECO:0000250}.
SQ   SEQUENCE   191 AA;  21331 MW;  C5BF8929AD1E59D0 CRC64;
     MLSSIKCVLV GDSAVGKTSL LVRFTSETFP EAYKPTVYEN TGVDVFMDGI QISLGLWDTA
     GNDAFRSIRP LSYQQADVVL MCYSVANHNS FLNLKNKWIG EIRSNLPCTP VLVVATQTDQ
     REMGPHRASC VNAMEGKKLA QDVRAKGYLE CSALSNRGVQ QVFECAVRTA VNQARRRNRR
     RLFSINECKI F
//