Q15669 (RHOH_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 140. History...
Names and origin
|Protein names||Recommended name:|
Rho-related GTP-binding protein RhoH
GTP-binding protein TTF
Translocation three four protein
|Organism||Homo sapiens (Human) [Reference proteome]|
|Taxonomic identifier||9606 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo|
|Sequence length||191 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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
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
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
The region involved in interaction with ZAP70 is a non-canonical immunoreceptor tyrosine-based activation motif (ITAM) By similarity.
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 annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 188||188||Rho-related GTP-binding protein RhoH||PRO_0000198867|
|Propeptide||189 – 191||3||Removed in mature form By similarity||PRO_0000281218|
|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|
|||"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].
|||"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].
|||"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].
|||"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.
|||"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.
|||"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.|
|Z35227 mRNA. Translation: CAA84538.1.|
AF498975 mRNA. Translation: AAM21122.1.
BC014261 mRNA. Translation: AAH14261.1.
|RefSeq||NP_001265288.1. NM_001278359.1. |
3D structure databases
|SMR||Q15669. Positions 4-171. |
Protein-protein interaction databases
|BioGrid||106892. 6 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENST00000381799; ENSP00000371219; ENSG00000168421. |
ENST00000505618; ENSP00000425010; ENSG00000168421.
|UCSC||uc003guz.2. human. |
|HGNC||HGNC:686. RHOH. |
|MIM||602037. gene. |
|Orphanet||324294. T-cell immunodeficiency with epidermodysplasia verruciformis. |
Enzyme and pathway databases
|Reactome||REACT_111102. Signal Transduction. |
Gene expression databases
Family and domain databases
|Gene3D||22.214.171.1240. 1 hit. |
|InterPro||IPR027417. P-loop_NTPase. |
|Pfam||PF00071. Ras. 1 hit. |
|PRINTS||PR00449. RASTRNSFRMNG. |
|SMART||SM00174. RHO. 1 hit. |
|SUPFAM||SSF52540. SSF52540. 1 hit. |
|TIGRFAMs||TIGR00231. small_GTP. 1 hit. |
|PROSITE||PS51420. RHO. 1 hit. |
|Accession||Primary (citable) accession number: Q15669|
|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.|