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Q15669 (RHOH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 140. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rho-related GTP-binding protein RhoH
Alternative name(s):
GTP-binding protein TTF
Translocation three four protein
Gene names
Name:RHOH
Synonyms:ARHH, TTF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length191 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.6

Subunit structure

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. Ref.4 Ref.5

Subcellular location

Cytoplasm. Cell membrane; Lipid-anchor; Cytoplasmic side By similarity. Note: Colocalizes together with ZAP70 in the immunological synapse By similarity. Ref.4 Ref.6

Tissue specificity

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. Ref.4 Ref.6

Induction

By CSF2/GM-CSF. Down-regulated by phorbol myristate acetate (PMA). Ref.4 Ref.6

Domain

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

Post-translational modification

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.

Involvement in disease

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

Sequence similarities

Belongs to the small GTPase superfamily. Rho family.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
   Coding sequence diversityChromosomal rearrangement
   LigandGTP-binding
Nucleotide-binding
   PTMLipoprotein
Methylation
Phosphoprotein
Prenylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell differentiation

Non-traceable author statement Ref.4. Source: UniProtKB

mast cell activation

Inferred from electronic annotation. Source: Ensembl

negative regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.4. Source: UniProtKB

negative regulation of catalytic activity

Non-traceable author statement Ref.4. Source: GOC

negative regulation of phosphorylation

Inferred from direct assay Ref.4. Source: GOC

regulation of small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Non-traceable author statement Ref.4. Source: UniProtKB

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.4. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

immunological synapse

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionGTP binding

Inferred from direct assay Ref.4. Source: UniProtKB

GTPase inhibitor activity

Non-traceable author statement Ref.4. Source: UniProtKB

Rho GTPase binding

Non-traceable author statement Ref.4. Source: UniProtKB

kinase inhibitor activity

Inferred from direct assay Ref.4. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 188188Rho-related GTP-binding protein RhoH
PRO_0000198867
Propeptide189 – 1913Removed in mature form By similarity
PRO_0000281218

Regions

Nucleotide binding11 – 188GTP By similarity
Nucleotide binding58 – 625GTP By similarity
Nucleotide binding116 – 1194GTP By similarity
Region73 – 8614Interaction with ZAP70 By similarity
Motif33 – 419Effector region By similarity

Amino acid modifications

Modified residue1881Cysteine methyl ester By similarity
Lipidation1881S-geranylgeranyl cysteine By similarity

Sequences

Sequence LengthMass (Da)Tools
Q15669 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: C5BF8929AD1E59D0

FASTA19121,331
        10         20         30         40         50         60 
MLSSIKCVLV GDSAVGKTSL LVRFTSETFP EAYKPTVYEN TGVDVFMDGI QISLGLWDTA 

        70         80         90        100        110        120 
GNDAFRSIRP LSYQQADVVL MCYSVANHNS FLNLKNKWIG EIRSNLPCTP VLVVATQTDQ 

       130        140        150        160        170        180 
REMGPHRASC VNAMEGKKLA QDVRAKGYLE CSALSNRGVQ QVFECAVRTA VNQARRRNRR 

       190 
RLFSINECKI F 

« Hide

References

« Hide 'large scale' references
[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]"RhoH/TTF negatively regulates leukotriene production in neutrophils."
Daryadel A., Yousefi S., Troi D., Schmid I., Schmidt-Mende J., Mordasini C., Dahinden C.A., Ziemiecki A., Simon H.-U.
J. Immunol. 182:6527-6532(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z35227 mRNA. Translation: CAA84538.1.
AF498975 mRNA. Translation: AAM21122.1.
BC014261 mRNA. Translation: AAH14261.1.
CCDSCCDS3458.1.
PIRI38367.
RefSeqNP_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.
UniGeneHs.654594.
Hs.738915.

3D structure databases

ProteinModelPortalQ15669.
SMRQ15669. Positions 4-171.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106892. 6 interactions.
MINTMINT-1216771.
STRING9606.ENSP00000371219.

Polymorphism databases

DMDM2500200.

Proteomic databases

MaxQBQ15669.
PaxDbQ15669.
PRIDEQ15669.

Protocols and materials databases

DNASU399.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381799; ENSP00000371219; ENSG00000168421.
ENST00000505618; ENSP00000425010; ENSG00000168421.
GeneID399.
KEGGhsa:399.
UCSCuc003guz.2. human.

Organism-specific databases

CTD399.
GeneCardsGC04P040192.
HGNCHGNC:686. RHOH.
HPAHPA030345.
MIM602037. gene.
neXtProtNX_Q15669.
Orphanet324294. T-cell immunodeficiency with epidermodysplasia verruciformis.
PharmGKBPA24979.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233974.
HOVERGENHBG009351.
InParanoidQ15669.
KOK07873.
OMAASCINAI.
OrthoDBEOG7TJ3K0.
PhylomeDBQ15669.
TreeFamTF331219.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ15669.
BgeeQ15669.
CleanExHS_RHOH.
GenevestigatorQ15669.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR003578. Small_GTPase_Rho.
[Graphical view]
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00174. RHO. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51420. RHO. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRhoH.
GenomeRNAi399.
NextBio1673.
PROQ15669.
SOURCESearch...

Entry information

Entry nameRHOH_HUMAN
AccessionPrimary (citable) accession number: Q15669
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 140 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM