Reviewed, UniProtKB/Swiss-Prot Q15669 (RHOH_HUMAN)

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) [Complete proteome]

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.5
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. Ref.4
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.5
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.5
Induction	By granulocyte macrophage colony-stimulating factor (GM-CSF). Down-regulated by phorbol myristate acetate (PMA). Ref.4 Ref.5
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 component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Chromosomal rearrangement
Ligand	GTP-binding Nucleotide-binding
PTM	Lipoprotein Methylation Phosphoprotein Prenylation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	T cell differentiation Ref.4 Non-traceable author statement. Source: UniProtKB negative regulation of I-kappaB kinase/NF-kappaB cascade Ref.4 Inferred from direct assay. Source: UniProtKB regulation of transcription Ref.4 Non-traceable author statement. Source: UniProtKB small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Ref.4 Inferred from direct assay. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	GTP binding Ref.4 Inferred from direct assay. Source: UniProtKB GTPase inhibitor activity Ref.4 Non-traceable author statement. Source: UniProtKB Rho GTPase binding Ref.4 Non-traceable author statement. Source: UniProtKB kinase inhibitor activity Ref.4 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CNKSR1	Q969H4	1	EBI-1244971,EBI-741671

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)
	Q15669-1 [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]	"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.
UniGene	Hs.654594
3D structure databases
SMR	Q15669. Positions 2-170.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15669. 1 interaction.
STRING	Q15669.
Proteomic databases
PRIDE	Q15669.
Genome annotation databases
Ensembl	ENST00000381799; ENSP00000371219; ENSG00000168421; Homo sapiens. [Genome view]
GeneID	399.
KEGG	hsa:399.
UCSC	uc003guz.2. human.
Organism-specific databases
CTD	399.
GeneCards	GC04P039875.
H-InvDB	HIX0004171.
HGNC	HGNC:686. RHOH.
MIM	602037. gene.
PharmGKB	PA24979.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG06276.
HOGENOM	HBG745225.
HOVERGEN	Q15669.
InParanoid	Q15669.
OMA	RASCVNA.
OrthoDB	EOG9VT8HJ.
PhylomeDB	Q15669.
Enzyme and pathway databases
Reactome	REACT_11044. Signaling by Rho GTPases.
Gene expression databases
ArrayExpress	Q15669.
Bgee	Q15669.
CleanEx	HS_RHOH.
Genevestigator	Q15669.
GermOnline	ENSG00000168421. Homo sapiens.
Family and domain databases
InterPro	IPR003578. GTPase_Rho. IPR013753. Ras. IPR001806. Ras_GTPase. IPR005225. Small_GTP_bd. [Graphical view]
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 Resources
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:	February 9, 2010
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.