RHOH_HUMAN
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 03-AUG-2022, entry version 200.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Denis C.,
RA Hildebrand M.-P., Lantoine D., Deweindt C., Tilly H., Bastard C.,
RA 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 sequenced by
RT 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH GDI1 AND GDI2, SUBCELLULAR LOCATION, INDUCTION,
RP 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 deficient
RT and modulates activities of other Rho GTPases by an 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 neutrophils.";
RL J. Immunol. 182:6527-6532(2009).
RN [7]
RP FUNCTION, VARIANT EV4 38-TYR--PHE-191 DEL, AND CHARACTERIZATION OF VARIANT
RP EV4 38-TYR--PHE-191 DEL.
RX PubMed=22850876; DOI=10.1172/jci62949;
RA Crequer A., Troeger A., Patin E., Ma C.S., Picard C., Pedergnana V.,
RA Fieschi C., Lim A., Abhyankar A., Gineau L., Mueller-Fleckenstein I.,
RA Schmidt M., Taieb A., Krueger J., Abel L., Tangye S.G., Orth G.,
RA Williams D.A., Casanova J.L., Jouanguy E.;
RT "Human RHOH deficiency causes T cell defects and susceptibility to EV-HPV
RT infections.";
RL J. Clin. Invest. 122:3239-3247(2012).
CC -!- FUNCTION: Negative regulator of hematopoietic progenitor cell
CC proliferation, survival and migration. Critical regulator of thymocyte
CC development and T-cell antigen receptor (TCR) signaling by mediating
CC recruitment and activation of ZAP70. 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 (By similarity). Binds GTP but lacks
CC intrinsic GTPase activity and is resistant to Rho-specific GTPase-
CC activating proteins. Inhibits the activation of NF-kappa-B by TNF and
CC IKKB and the activation of CRK/p38 by TNF. Inhibits activities of RAC1,
CC RHOA and CDC42. Negatively regulates leukotriene production in
CC neutrophils. {ECO:0000250, ECO:0000269|PubMed:11809807,
CC ECO:0000269|PubMed:19414807, ECO:0000269|PubMed:22850876}.
CC -!- SUBUNIT: Interacts with ZAP70 (via SH2 domains) and the interaction is
CC enhanced by its phosphorylation by LCK. Interacts with SYK and the
CC interaction is enhanced by its phosphorylation by FYN (By similarity).
CC Interacts with GDI1 and GDI2. Interacts with PAK5 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q15669; Q8N9N5-2: BANP; NbExp=3; IntAct=EBI-1244971, EBI-11524452;
CC Q15669; P51946: CCNH; NbExp=3; IntAct=EBI-1244971, EBI-741406;
CC Q15669; Q86YD7: FAM90A1; NbExp=3; IntAct=EBI-1244971, EBI-6658203;
CC Q15669; Q8NA54: IQUB; NbExp=3; IntAct=EBI-1244971, EBI-10220600;
CC Q15669; O14713: ITGB1BP1; NbExp=3; IntAct=EBI-1244971, EBI-2127319;
CC Q15669; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-1244971, EBI-2556193;
CC Q15669; O75431: MTX2; NbExp=3; IntAct=EBI-1244971, EBI-7415268;
CC Q15669; Q6IQ23-2: PLEKHA7; NbExp=3; IntAct=EBI-1244971, EBI-12069346;
CC Q15669; O94827-4: PLEKHG5; NbExp=3; IntAct=EBI-1244971, EBI-11980215;
CC Q15669; Q0D2K3: RIPPLY1; NbExp=3; IntAct=EBI-1244971, EBI-10226430;
CC Q15669; Q9BWG6: SCNM1; NbExp=3; IntAct=EBI-1244971, EBI-748391;
CC Q15669; Q92673: SORL1; NbExp=3; IntAct=EBI-1244971, EBI-1171329;
CC Q15669; P51687: SUOX; NbExp=3; IntAct=EBI-1244971, EBI-3921347;
CC Q15669; Q9Y242: TCF19; NbExp=3; IntAct=EBI-1244971, EBI-7413767;
CC Q15669; Q9NQW7-3: XPNPEP1; NbExp=3; IntAct=EBI-1244971, EBI-12079490;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11809807,
CC ECO:0000269|PubMed:19414807}. Cell membrane {ECO:0000250}; Lipid-anchor
CC {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=Colocalizes
CC together with ZAP70 in the immunological synapse. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed only in hematopoietic cells. Present at
CC very high levels in the thymus, less abundant in the spleen, and least
CC abundant in the bone marrow. Expressed at a higher level in the TH1
CC subtype of T-helper cells than in the TH2 subpopulation. Expressed in
CC neutrophils under inflammatory conditions, such as cystic fibrosis,
CC ulcerative colitis and appendicitis. {ECO:0000269|PubMed:11809807,
CC ECO:0000269|PubMed:19414807}.
CC -!- INDUCTION: By CSF2/GM-CSF. Down-regulated by phorbol myristate acetate
CC (PMA). {ECO:0000269|PubMed:11809807, 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 is
CC critical for its function in thymocyte development (By similarity).
CC {ECO:0000250}.
CC -!- DISEASE: Note=A chromosomal aberration involving RHOH is found in a
CC non-Hodgkin lymphoma cell line. Translocation t(3;4)(q27;p11) with
CC BCL6.
CC -!- DISEASE: Epidermodysplasia verruciformis 4 (EV4) [MIM:618307]: A form
CC of epidermodysplasia verruciformis, a rare genodermatosis associated
CC with a high risk of skin carcinoma that results from an abnormal
CC susceptibility to infection by specific human papillomaviruses,
CC including the oncogenic HPV5. Infection leads to the early development
CC of disseminated flat wart-like and pityriasis versicolor-like skin
CC lesions. Cutaneous Bowen's carcinomas in situ and invasive squamous
CC cell carcinomas develop in about half of the patients, mainly on sun-
CC exposed skin areas. EV4 patients have decreased number of naive T
CC cells, increased memory and effector T cells, and impaired T-cell
CC receptor signaling. EV4 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:22850876}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rho family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/RHOHID93.html";
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; 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 AlphaFoldDB; Q15669; -.
DR SMR; Q15669; -.
DR BioGRID; 106892; 504.
DR IntAct; Q15669; 20.
DR MINT; Q15669; -.
DR STRING; 9606.ENSP00000371219; -.
DR GlyGen; Q15669; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15669; -.
DR PhosphoSitePlus; Q15669; -.
DR BioMuta; RHOH; -.
DR DMDM; 2500200; -.
DR jPOST; Q15669; -.
DR MassIVE; Q15669; -.
DR PaxDb; Q15669; -.
DR PeptideAtlas; Q15669; -.
DR PRIDE; Q15669; -.
DR ProteomicsDB; 60699; -.
DR Antibodypedia; 23555; 262 antibodies from 29 providers.
DR DNASU; 399; -.
DR Ensembl; ENST00000381799.10; ENSP00000371219.4; ENSG00000168421.13.
DR Ensembl; ENST00000505618.5; ENSP00000425010.1; ENSG00000168421.13.
DR Ensembl; ENST00000610353.4; ENSP00000480192.1; ENSG00000168421.13.
DR Ensembl; ENST00000613272.4; ENSP00000480772.1; ENSG00000168421.13.
DR Ensembl; ENST00000614836.1; ENSP00000478248.1; ENSG00000168421.13.
DR Ensembl; ENST00000615083.4; ENSP00000480379.1; ENSG00000168421.13.
DR Ensembl; ENST00000615577.4; ENSP00000481566.1; ENSG00000168421.13.
DR Ensembl; ENST00000617441.4; ENSP00000482947.1; ENSG00000168421.13.
DR Ensembl; ENST00000619474.4; ENSP00000481746.1; ENSG00000168421.13.
DR Ensembl; ENST00000622175.4; ENSP00000481836.1; ENSG00000168421.13.
DR GeneID; 399; -.
DR KEGG; hsa:399; -.
DR MANE-Select; ENST00000381799.10; ENSP00000371219.4; NM_004310.5; NP_004301.1.
DR CTD; 399; -.
DR DisGeNET; 399; -.
DR GeneCards; RHOH; -.
DR HGNC; HGNC:686; RHOH.
DR HPA; ENSG00000168421; Tissue enhanced (bone marrow, lymphoid tissue).
DR MalaCards; RHOH; -.
DR MIM; 602037; gene.
DR MIM; 618307; phenotype.
DR neXtProt; NX_Q15669; -.
DR OpenTargets; ENSG00000168421; -.
DR Orphanet; 324294; T-cell immunodeficiency with epidermodysplasia verruciformis.
DR PharmGKB; PA24979; -.
DR VEuPathDB; HostDB:ENSG00000168421; -.
DR eggNOG; KOG0393; Eukaryota.
DR GeneTree; ENSGT00940000160078; -.
DR HOGENOM; CLU_041217_21_3_1; -.
DR InParanoid; Q15669; -.
DR OMA; NKWIAEI; -.
DR OrthoDB; 1091615at2759; -.
DR PhylomeDB; Q15669; -.
DR TreeFam; TF331219; -.
DR BRENDA; 3.6.5.2; 2681.
DR PathwayCommons; Q15669; -.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR SignaLink; Q15669; -.
DR SIGNOR; Q15669; -.
DR BioGRID-ORCS; 399; 22 hits in 1072 CRISPR screens.
DR ChiTaRS; RHOH; human.
DR GeneWiki; RhoH; -.
DR GenomeRNAi; 399; -.
DR Pharos; Q15669; Tbio.
DR PRO; PR:Q15669; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q15669; protein.
DR Bgee; ENSG00000168421; Expressed in bone marrow cell and 113 other tissues.
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:0031410; C:cytoplasmic vesicle; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central.
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:0031267; F:small GTPase binding; NAS:UniProtKB.
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; IEA:Ensembl.
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; IDA:UniProtKB.
DR GO; GO:0045582; P:positive regulation of T cell differentiation; IMP:UniProtKB.
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:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; NAS: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; Chromosomal rearrangement; Cytoplasm; Disease variant;
KW GTP-binding; Lipoprotein; Membrane; Methylation; Nucleotide-binding;
KW Phosphoprotein; Prenylation; Reference proteome.
FT CHAIN 1..188
FT /note="Rho-related GTP-binding protein RhoH"
FT /id="PRO_0000198867"
FT PROPEP 189..191
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000281218"
FT REGION 73..86
FT /note="Interaction with ZAP70"
FT /evidence="ECO:0000250"
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 VARIANT 38..191
FT /note="Missing (in EV4; loss-of-function variant resulting
FT in impaired T-cell differentiation; unable to rescue T-cell
FT lymphopenia in RHOH knockout mice; no protein detected in
FT patient cells; results in defective TCR signaling in
FT patient cells)"
FT /evidence="ECO:0000269|PubMed:22850876"
FT /id="VAR_081933"
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
