Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q92963 (RIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
GTP-binding protein Rit1
Alternative name(s):
Ras-like protein expressed in many tissues
Ras-like without CAAX protein 1
Gene names
Name:RIT1
Synonyms:RIBB, RIT, ROC1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length219 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation. Ref.11 Ref.12

Enzyme regulation

Alternates between an inactive form bound to GDP and an active form bound to GTP.

Subunit structure

Interacts with MLLT4, the C-terminal domain of RALGDS and RLF, but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-bound form. Strongly interacts with BRAF, but only weakly with RAF1. BARF and RAF1 association is dependent upon the GTP-bound state. Interacts with RGL3 By similarity. Ref.4 Ref.11

Subcellular location

Cell membrane.

Tissue specificity

Expressed in many tissues.

Involvement in disease

Noonan syndrome 8 (NS8) [MIM:615355]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Miscellaneous

Stimulation of the NGF and EGF receptor signaling pathways results in rapid and prolonged activation.

Shows rapid uncatalyzed guanine nucleotide dissociation rates, which are much faster than those of most Ras subfamily members.

Sequence similarities

Belongs to the small GTPase superfamily. Ras family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RLFQ131293EBI-365845,EBI-958266

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92963-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q92963-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
Isoform 3 (identifier: Q92963-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MERWLFLGATEEGPKRTM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 219219GTP-binding protein Rit1
PRO_0000082725

Regions

Nucleotide binding28 – 358GTP By similarity
Nucleotide binding75 – 795GTP By similarity
Nucleotide binding134 – 1374GTP By similarity

Natural variations

Alternative sequence1 – 3636Missing in isoform 2.
VSP_045306
Alternative sequence11M → MERWLFLGATEEGPKRTM in isoform 3.
VSP_047114
Natural variant351S → T Probable disease-associated mutation found in patients with features of Noonan syndrome. Ref.12
VAR_070149
Natural variant571A → G in NS8; results in increased ELK1 transcriptional activation. Ref.12
VAR_070150
Natural variant811E → G in NS8; results in increased ELK1 transcriptional activation. Ref.12
VAR_070151
Natural variant821F → L in NS8; results in increased ELK1 transcriptional activation. Ref.12
VAR_070152
Natural variant821F → V Probable disease-associated mutation found in patients with features of Noonan syndrome. Ref.12
VAR_070153
Natural variant831T → P Probable disease-associated mutation found in patients with features of Noonan syndrome. Ref.12
VAR_070154
Natural variant891Y → H Probable disease-associated mutation found in patients with features of Noonan syndrome. Ref.12
VAR_070155
Natural variant901M → I Probable disease-associated mutation found in patients with features of Noonan syndrome. Ref.12
VAR_070156
Natural variant951G → A in NS8; results in increased ELK1 transcriptional activation. Ref.12
VAR_070157

Experimental info

Mutagenesis351S → N: Dominant negative. Loss of interaction with MLLT4, RLF and RALGDS. Ref.4
Mutagenesis531T → S: Loss of interaction with MLLT4, RLF and RALGDS; when associated with L-79. Ref.4
Mutagenesis551E → G: Loss of interaction with MLLT4, but not with RLF and RALGDS; when associated with L-79. Ref.4
Mutagenesis791Q → L: Constitutively active. Dramatic reduction of the rate of GTP hydrolysis. Loss of interaction with MLLT4, RLF and RALGDS; when associated with S-53. Loss of interaction with MLLT4; when associated with G-55. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 7F957871F836AE92

FASTA21925,145
        10         20         30         40         50         60 
MDSGTRPVGS CCSSPAGLSR EYKLVMLGAG GVGKSAMTMQ FISHRFPEDH DPTIEDAYKI 

        70         80         90        100        110        120 
RIRIDDEPAN LDILDTAGQA EFTAMRDQYM RAGEGFIICY SITDRRSFHE VREFKQLIYR 

       130        140        150        160        170        180 
VRRTDDTPVV LVGNKSDLKQ LRQVTKEEGL ALAREFSCPF FETSAAYRYY IDDVFHALVR 

       190        200        210 
EIRRKEKEAV LAMEKKSKPK NSVWKRLKSP FRKKKDSVT 

« Hide

Isoform 2 [UniParc].

Checksum: 61CFC2E07B180267
Show »

FASTA18321,633
Isoform 3 [UniParc].

Checksum: B6B991C6D3668388
Show »

FASTA23627,148

References

« Hide 'large scale' references
[1]"Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of ras proteins."
Lee C.H.J., Della N.G., Chew C.E., Zack D.J.
J. Neurosci. 16:6784-6794(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"RIC, a calmodulin-binding Ras-like GTPase."
Wes P.D., Yu M., Montell C.
EMBO J. 15:5839-5848(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Characterization of new small G proteins in the Ras subfamily."
Kawasaki H., Housman D.E., Graybiel A.M.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[4]"Biochemical characterization of the Ras-related GTPases Rit and Rin."
Shao H., Kadono-Okuda K., Finlin B.S., Andres D.A.
Arch. Biochem. Biophys. 371:207-219(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, INTERACTION WITH MLLT4; RALGDS AND RLF, MUTAGENESIS OF SER-35; THR-53; GLU-55 AND GLN-79.
Tissue: Retina.
[5]"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 (MAR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Esophagus.
[7]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[8]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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] (ISOFORM 1).
[11]"Rit contributes to nerve growth factor-induced neuronal differentiation via activation of B-Raf-extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades."
Shi G.-X., Andres D.A.
Mol. Cell. Biol. 25:830-846(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BRAF AND RAF1.
[12]"Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome."
Aoki Y., Niihori T., Banjo T., Okamoto N., Mizuno S., Kurosawa K., Ogata T., Takada F., Yano M., Ando T., Hoshika T., Barnett C., Ohashi H., Kawame H., Hasegawa T., Okutani T., Nagashima T., Hasegawa S. expand/collapse author list , Funayama R., Nagashima T., Nakayama K., Inoue S., Watanabe Y., Ogura T., Matsubara Y.
Am. J. Hum. Genet. 93:173-180(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANTS NS8 GLY-57; GLY-81; LEU-82 AND ALA-95, CHARACTERIZATION OF VARIANTS NS8 GLY-57; GLY-81; LEU-82 AND ALA-95, VARIANTS THR-35; VAL-82; PRO-83 HIS-89 AND ILE-90.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U71203 mRNA. Translation: AAB42213.1.
Y07566 mRNA. Translation: CAA68851.1.
U78165 mRNA. Translation: AAB64246.1.
AF084462 mRNA. Translation: AAD13021.1.
AF493923 mRNA. Translation: AAM12637.1.
AK298768 mRNA. Translation: BAG60910.1.
AK314239 mRNA. Translation: BAG36908.1.
CR407639 mRNA. Translation: CAG28567.1.
AL139128, AL355388 Genomic DNA. Translation: CAH69943.1.
AL355388, AL139128 Genomic DNA. Translation: CAH72621.1.
CH471121 Genomic DNA. Translation: EAW53024.1.
BC104186 mRNA. Translation: AAI04187.1.
BC104187 mRNA. Translation: AAI04188.1.
RefSeqNP_001243749.1. NM_001256820.1.
NP_001243750.1. NM_001256821.1.
NP_008843.1. NM_006912.5.
UniGeneHs.491234.

3D structure databases

ProteinModelPortalQ92963.
SMRQ92963. Positions 21-217.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111948. 10 interactions.
IntActQ92963. 10 interactions.
STRING9606.ENSP00000357306.

PTM databases

PhosphoSiteQ92963.

Polymorphism databases

DMDM38258628.

Proteomic databases

PaxDbQ92963.
PRIDEQ92963.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368322; ENSP00000357305; ENSG00000143622. [Q92963-3]
ENST00000368323; ENSP00000357306; ENSG00000143622. [Q92963-1]
ENST00000539040; ENSP00000441950; ENSG00000143622. [Q92963-2]
GeneID6016.
KEGGhsa:6016.
UCSCuc001fmh.2. human. [Q92963-1]

Organism-specific databases

CTD6016.
GeneCardsGC01M155867.
HGNCHGNC:10023. RIT1.
HPAHPA053249.
MIM609591. gene.
615355. phenotype.
neXtProtNX_Q92963.
Orphanet648. Noonan syndrome.
PharmGKBPA35528.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1100.
HOGENOMHOG000233973.
HOVERGENHBG009351.
InParanoidQ92963.
KOK07832.
OMALKSPFRK.
OrthoDBEOG7QVM41.
PhylomeDBQ92963.
TreeFamTF315072.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ92963.
BgeeQ92963.
CleanExHS_RIT1.
GenevestigatorQ92963.

Family and domain databases

Gene3D3.40.50.300. 1 hit.
InterProIPR027417. P-loop_NTPase.
IPR005225. Small_GTP-bd_dom.
IPR001806. Small_GTPase.
IPR020849. Small_GTPase_Ras.
[Graphical view]
PANTHERPTHR24070. PTHR24070. 1 hit.
PfamPF00071. Ras. 1 hit.
[Graphical view]
PRINTSPR00449. RASTRNSFRMNG.
SMARTSM00173. RAS. 1 hit.
[Graphical view]
SUPFAMSSF52540. SSF52540. 1 hit.
TIGRFAMsTIGR00231. small_GTP. 1 hit.
PROSITEPS51421. RAS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRIT1.
GenomeRNAi6016.
NextBio23471.
PROQ92963.
SOURCESearch...

Entry information

Entry nameRIT1_HUMAN
AccessionPrimary (citable) accession number: Q92963
Secondary accession number(s): B4DQE8 expand/collapse secondary AC list , O00646, O00720, Q5VY89, Q5VY90
Entry history
Integrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 123 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM