Q15669 (RHOH_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	191 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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: Co-localizes 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	Note=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 component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Chromosomal rearrangement
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	T cell differentiation Non-traceable author statement Ref.4. Source: UniProtKB negative regulation of I-kappaB kinase/NF-kappaB cascade Inferred from direct assay Ref.4. Source: UniProtKB regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome regulation of transcription, DNA-dependent Non-traceable author statement Ref.4. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from direct assay. Source: HPA plasma membrane Traceable author statement. Source: Reactome
Molecular function	GTP 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
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 188	188	Rho-related GTP-binding protein RhoH		PRO_0000198867
	Propeptide	189 – 191	3	Removed in mature form By similarity		PRO_0000281218
Regions
	Nucleotide binding	11 – 18	8	GTP By similarity
	Nucleotide binding	58 – 62	5	GTP By similarity
	Nucleotide binding	116 – 119	4	GTP By similarity
	Region	73 – 86	14	Interaction with ZAP70 By similarity
	Motif	33 – 41	9	Effector region By similarity
Amino acid modifications
	Modified residue	188	1	Cysteine methyl ester By similarity
	Lipidation	188	1	S-geranylgeranyl cysteine By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q15669 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: C5BF8929AD1E59D0	FASTA	191	21,331
	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

References

	« Hide 'large scale' referencesShow '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: 7784061] [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: 15489334] [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: 11809807] [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: 17064668] [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: 19414807] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INDUCTION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z35227 mRNA. Translation: CAA84538.1. AF498975 mRNA. Translation: AAM21122.1. BC014261 mRNA. Translation: AAH14261.1.
IPI	IPI00018882.
PIR	I38367.
RefSeq	NP_004301.1. NM_004310.3.
UniGene	Hs.654594.
3D structure databases
ProteinModelPortal	Q15669.
SMR	Q15669. Positions 2-179.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15669. 1 interaction.
MINT	MINT-1216771.
STRING	Q15669.
Polymorphism databases
DMDM	2500200.
Proteomic databases
PRIDE	Q15669.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000381799; ENSP00000371219; ENSG00000168421.
GeneID	399.
KEGG	hsa:399.
UCSC	uc003guz.2. human.
Organism-specific databases
CTD	399.
GeneCards	GC04P040198.
H-InvDB	HIX0004171.
HGNC	HGNC:686. RHOH.
HPA	HPA030345.
MIM	602037. gene.
neXtProt	NX_Q15669.
PharmGKB	PA24979.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06276.
HOGENOM	HBG745225.
HOVERGEN	HBG009351.
InParanoid	Q15669.
OMA	ASCINAI.
OrthoDB	EOG412M6J.
PhylomeDB	Q15669.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q15669.
Bgee	Q15669.
CleanEx	HS_RHOH.
Genevestigator	Q15669.
GermOnline	ENSG00000168421. Homo sapiens.
Family and domain databases
InterPro	IPR005225. Small_GTP-bd_dom. IPR001806. Small_GTPase. IPR003578. Small_GTPase_Rho. [Graphical view]
KO	K07873.
Pfam	PF00071. Ras. 1 hit. [Graphical view]
PRINTS	PR00449. RASTRNSFRMNG.
SMART	SM00174. RHO. 1 hit. [Graphical view]
TIGRFAMs	TIGR00231. Small_GTP. 1 hit.
PROSITE	PS51420. RHO. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	1673.
SOURCE	Search...

Entry information

Entry name

RHOH_HUMAN

Accession

Primary (citable) accession number: Q15669

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.