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Q15669

- RHOH_HUMAN

UniProt

Q15669 - RHOH_HUMAN

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Protein

Rho-related GTP-binding protein RhoH

Gene

RHOH

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Negative regulator of hematopoietic progenitor cell proliferation, survival and migration. Critical regulator of thymocyte development and T-cell antigen receptor (TCR) signaling by mediating recruitment and activation of ZAP70. Required for phosphorylation of CD3Z, membrane translocation of ZAP70 and subsequent activation of the ZAP70-mediated pathways. Essential for efficient beta-selection and positive selection by promoting the ZAP70-dependent phosphorylation of the LAT signalosome during pre-TCR and TCR signaling. Crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Plays critical roles in mast cell function by facilitating phosphorylation of SYK in Fc epsilon RI-mediated signal transduction. Essential for the phosphorylation of LAT, LCP2, PLCG1 and PLCG2 and for Ca2+ mobilization in mast cells By similarity. Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Inhibits the activation of NF-kappa-B by TNF and IKKB and the activation of CRK/p38 by TNF. Inhibits activities of RAC1, RHOA and CDC42. Negatively regulates leukotriene production in neutrophils.By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi11 – 188GTPBy similarity
Nucleotide bindingi58 – 625GTPBy similarity
Nucleotide bindingi116 – 1194GTPBy similarity

GO - Molecular functioni

  1. GTPase inhibitor activity Source: UniProtKB
  2. GTP binding Source: UniProtKB
  3. kinase inhibitor activity Source: UniProtKB
  4. Rho GTPase binding Source: UniProtKB

GO - Biological processi

  1. mast cell activation Source: Ensembl
  2. negative regulation of catalytic activity Source: GOC
  3. negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  4. negative regulation of phosphorylation Source: GOC
  5. regulation of small GTPase mediated signal transduction Source: Reactome
  6. regulation of transcription, DNA-templated Source: UniProtKB
  7. small GTPase mediated signal transduction Source: Reactome
  8. T cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_11051. Rho GTPase cycle.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho-related GTP-binding protein RhoH
Alternative name(s):
GTP-binding protein TTF
Translocation three four protein
Gene namesi
Name:RHOH
Synonyms:ARHH, TTF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:686. RHOH.

Subcellular locationi

Cytoplasm 2 Publications. Cell membrane By similarity; Lipid-anchor By similarity; Cytoplasmic side By similarity
Note: Colocalizes together with ZAP70 in the immunological synapse.By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. immunological synapse Source: Ensembl
  4. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving RHOH is found in a non-Hodgkin lymphoma cell line. Translocation t(3;4)(q27;p11) with BCL6.

Organism-specific databases

Orphaneti324294. T-cell immunodeficiency with epidermodysplasia verruciformis.
PharmGKBiPA24979.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 188188Rho-related GTP-binding protein RhoHPRO_0000198867Add
BLAST
Propeptidei189 – 1913Removed in mature formBy similarityPRO_0000281218

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei188 – 1881Cysteine methyl esterBy similarity
Lipidationi188 – 1881S-geranylgeranyl cysteineBy similarity

Post-translational modificationi

Phosphorylated on tyrosine by LCK. Phosphorylated by FYN. Phosphorylation enhances the interactions with ZAP70 and SYK and is critical for its function in thymocyte development By similarity.By similarity

Keywords - PTMi

Lipoprotein, Methylation, Phosphoprotein, Prenylation

Proteomic databases

PaxDbiQ15669.
PRIDEiQ15669.

Expressioni

Tissue specificityi

Expressed only in hematopoietic cells. Present at very high levels in the thymus, less abundant in the spleen, and least abundant in the bone marrow. Expressed at a higher level in the TH1 subtype of T-helper cells than in the TH2 subpopulation. Expressed in neutrophils under inflammatory conditions, such as cystic fibrosis, ulcerative colitis and appendicitis.2 Publications

Inductioni

By CSF2/GM-CSF. Down-regulated by phorbol myristate acetate (PMA).2 Publications

Gene expression databases

BgeeiQ15669.
CleanExiHS_RHOH.
ExpressionAtlasiQ15669. baseline and differential.
GenevestigatoriQ15669.

Organism-specific databases

HPAiHPA030345.

Interactioni

Subunit structurei

Interacts with ZAP70 (via SH2 domains) and the interaction is enhanced by its phosphorylation by LCK. Interacts with SYK and the interaction is enhanced by its phosphorylation by FYN By similarity. Interacts with GDI1 and GDI2. Interacts with PAK7/PAK5 By similarity.By similarity

Protein-protein interaction databases

BioGridi106892. 6 interactions.
MINTiMINT-1216771.
STRINGi9606.ENSP00000371219.

Structurei

3D structure databases

ProteinModelPortaliQ15669.
SMRiQ15669. Positions 4-171.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni73 – 8614Interaction with ZAP70By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi33 – 419Effector regionBy similarity

Domaini

The region involved in interaction with ZAP70 is a non-canonical immunoreceptor tyrosine-based activation motif (ITAM).By similarity

Sequence similaritiesi

Belongs to the small GTPase superfamily. Rho family.Curated

Phylogenomic databases

eggNOGiCOG1100.
HOGENOMiHOG000233974.
HOVERGENiHBG009351.
InParanoidiQ15669.
KOiK07873.
OMAiASCINAI.
OrthoDBiEOG7TJ3K0.
PhylomeDBiQ15669.
TreeFamiTF331219.

Family and domain databases

Gene3Di3.40.50.300. 1 hit.
InterProiIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
[Graphical view]
PfamiPF00071. Ras. 1 hit.
[Graphical view]
PRINTSiPR00449. RASTRNSFRMNG.
SMARTiSM00174. RHO. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
TIGRFAMsiTIGR00231. small_GTP. 1 hit.
PROSITEiPS51420. RHO. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15669-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MLSSIKCVLV GDSAVGKTSL LVRFTSETFP EAYKPTVYEN TGVDVFMDGI
60 70 80 90 100
QISLGLWDTA GNDAFRSIRP LSYQQADVVL MCYSVANHNS FLNLKNKWIG
110 120 130 140 150
EIRSNLPCTP VLVVATQTDQ REMGPHRASC VNAMEGKKLA QDVRAKGYLE
160 170 180 190
CSALSNRGVQ QVFECAVRTA VNQARRRNRR RLFSINECKI F
Length:191
Mass (Da):21,331
Last modified:November 1, 1997 - v1
Checksum:iC5BF8929AD1E59D0
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z35227 mRNA. Translation: CAA84538.1.
AF498975 mRNA. Translation: AAM21122.1.
BC014261 mRNA. Translation: AAH14261.1.
CCDSiCCDS3458.1.
PIRiI38367.
RefSeqiNP_001265288.1. NM_001278359.1.
NP_001265289.1. NM_001278360.1.
NP_001265290.1. NM_001278361.1.
NP_001265291.1. NM_001278362.1.
NP_001265292.1. NM_001278363.1.
NP_001265293.1. NM_001278364.1.
NP_001265294.1. NM_001278365.1.
NP_001265295.1. NM_001278366.1.
NP_001265296.1. NM_001278367.1.
NP_001265297.1. NM_001278368.1.
NP_001265298.1. NM_001278369.1.
NP_004301.1. NM_004310.4.
XP_006714076.1. XM_006714013.1.
UniGeneiHs.654594.
Hs.738915.

Genome annotation databases

EnsembliENST00000381799; ENSP00000371219; ENSG00000168421.
ENST00000505618; ENSP00000425010; ENSG00000168421.
ENST00000610353; ENSP00000480192; ENSG00000168421.
ENST00000613272; ENSP00000480772; ENSG00000168421.
ENST00000614836; ENSP00000478248; ENSG00000168421.
ENST00000615083; ENSP00000480379; ENSG00000168421.
ENST00000615577; ENSP00000481566; ENSG00000168421.
ENST00000617441; ENSP00000482947; ENSG00000168421.
ENST00000619474; ENSP00000481746; ENSG00000168421.
ENST00000622175; ENSP00000481836; ENSG00000168421.
GeneIDi399.
KEGGihsa:399.
UCSCiuc003guz.2. human.

Polymorphism databases

DMDMi2500200.

Keywords - Coding sequence diversityi

Chromosomal rearrangement

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
Z35227 mRNA. Translation: CAA84538.1 .
AF498975 mRNA. Translation: AAM21122.1 .
BC014261 mRNA. Translation: AAH14261.1 .
CCDSi CCDS3458.1.
PIRi I38367.
RefSeqi NP_001265288.1. NM_001278359.1.
NP_001265289.1. NM_001278360.1.
NP_001265290.1. NM_001278361.1.
NP_001265291.1. NM_001278362.1.
NP_001265292.1. NM_001278363.1.
NP_001265293.1. NM_001278364.1.
NP_001265294.1. NM_001278365.1.
NP_001265295.1. NM_001278366.1.
NP_001265296.1. NM_001278367.1.
NP_001265297.1. NM_001278368.1.
NP_001265298.1. NM_001278369.1.
NP_004301.1. NM_004310.4.
XP_006714076.1. XM_006714013.1.
UniGenei Hs.654594.
Hs.738915.

3D structure databases

ProteinModelPortali Q15669.
SMRi Q15669. Positions 4-171.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 106892. 6 interactions.
MINTi MINT-1216771.
STRINGi 9606.ENSP00000371219.

Polymorphism databases

DMDMi 2500200.

Proteomic databases

PaxDbi Q15669.
PRIDEi Q15669.

Protocols and materials databases

DNASUi 399.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000381799 ; ENSP00000371219 ; ENSG00000168421 .
ENST00000505618 ; ENSP00000425010 ; ENSG00000168421 .
ENST00000610353 ; ENSP00000480192 ; ENSG00000168421 .
ENST00000613272 ; ENSP00000480772 ; ENSG00000168421 .
ENST00000614836 ; ENSP00000478248 ; ENSG00000168421 .
ENST00000615083 ; ENSP00000480379 ; ENSG00000168421 .
ENST00000615577 ; ENSP00000481566 ; ENSG00000168421 .
ENST00000617441 ; ENSP00000482947 ; ENSG00000168421 .
ENST00000619474 ; ENSP00000481746 ; ENSG00000168421 .
ENST00000622175 ; ENSP00000481836 ; ENSG00000168421 .
GeneIDi 399.
KEGGi hsa:399.
UCSCi uc003guz.2. human.

Organism-specific databases

CTDi 399.
GeneCardsi GC04P040192.
HGNCi HGNC:686. RHOH.
HPAi HPA030345.
MIMi 602037. gene.
neXtProti NX_Q15669.
Orphaneti 324294. T-cell immunodeficiency with epidermodysplasia verruciformis.
PharmGKBi PA24979.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG1100.
HOGENOMi HOG000233974.
HOVERGENi HBG009351.
InParanoidi Q15669.
KOi K07873.
OMAi ASCINAI.
OrthoDBi EOG7TJ3K0.
PhylomeDBi Q15669.
TreeFami TF331219.

Enzyme and pathway databases

Reactomei REACT_11051. Rho GTPase cycle.

Miscellaneous databases

GeneWikii RhoH.
GenomeRNAii 399.
NextBioi 1673.
PROi Q15669.
SOURCEi Search...

Gene expression databases

Bgeei Q15669.
CleanExi HS_RHOH.
ExpressionAtlasi Q15669. baseline and differential.
Genevestigatori Q15669.

Family and domain databases

Gene3Di 3.40.50.300. 1 hit.
InterProi IPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
[Graphical view ]
Pfami PF00071. Ras. 1 hit.
[Graphical view ]
PRINTSi PR00449. RASTRNSFRMNG.
SMARTi SM00174. RHO. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
TIGRFAMsi TIGR00231. small_GTP. 1 hit.
PROSITEi PS51420. RHO. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "TTF, a gene encoding a novel small G protein, fuses to the lymphoma-associated LAZ3 gene by t(3;4) chromosomal translocation."
    Dallery E., Galiegue-Zouitina S., Collyn-D'Hooghe M., Quief S., Denis C., Hildebrand M.-P., Lantoine D., Deweindt C., Tilly H., Bastard C., Kerckaert J.-P.
    Oncogene 10:2171-2178(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Puhl H.L. III, Ikeda S.R., Aronstam R.S.
    Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: B-cell.
  4. "The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function."
    Li X., Bu X., Lu B., Avraham H., Flavell R.A., Lim B.
    Mol. Cell. Biol. 22:1158-1171(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GDI1 AND GDI2, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
  5. "Multiple Rho proteins regulate the subcellular targeting of PAK5."
    Wu X., Frost J.A.
    Biochem. Biophys. Res. Commun. 351:328-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PAK7.
  6. Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.

Entry informationi

Entry nameiRHOH_HUMAN
AccessioniPrimary (citable) accession number: Q15669
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: October 29, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3