Q92963 (RIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	219 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.11
Enzyme regulation	Alternate 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.
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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Ligand	GTP-binding Nucleotide-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	neurotrophin TRK receptor signaling pathway Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome
Cellular_component	plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	GTP binding Traceable author statement Ref.1. Source: ProtInc GTPase activity Inferred from electronic annotation. Source: InterPro calmodulin binding Traceable author statement Ref.2. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RLF	Q13129	3	EBI-365845,EBI-958266

Alternative products

This entry describes 2 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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 219	219	GTP-binding protein Rit1		PRO_0000082725
Regions
	Nucleotide binding	28 – 35	8	GTP By similarity
	Nucleotide binding	75 – 79	5	GTP By similarity
	Nucleotide binding	134 – 137	4	GTP By similarity
Natural variations
	Alternative sequence	1 – 36	36	Missing in isoform 2.		VSP_045306
Experimental info
	Mutagenesis	35	1	S → N: Dominant negative. Loss of interaction with MLLT4, RLF and RALGDS. Ref.4
	Mutagenesis	53	1	T → S: Loss of interaction with MLLT4, RLF and RALGDS; when associated with L-79. Ref.4
	Mutagenesis	55	1	E → G: Loss of interaction with MLLT4, but not with RLF and RALGDS; when associated with L-79. Ref.4
	Mutagenesis	79	1	Q → 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		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 7F957871F836AE92	FASTA	219	25,145
	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
	Isoform 2 [UniParc]. Checksum: 61CFC2E07B180267	FASTA	183	21,633
	10 20 30 40 50 60 MTMQFISHRF PEDHDPTIED AYKIRIRIDD EPANLDILDT AGQAEFTAMR DQYMRAGEGF 70 80 90 100 110 120 IICYSITDRR SFHEVREFKQ LIYRVRRTDD TPVVLVGNKS DLKQLRQVTK EEGLALAREF 130 140 150 160 170 180 SCPFFETSAA YRYYIDDVFH ALVREIRRKE KEAVLAMEKK SKPKNSVWKR LKSPFRKKKD SVT

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
+	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.
IPI	IPI00144289.
RefSeq	NP_001243749.1. NM_001256820.1. NP_008843.1. NM_006912.5.
UniGene	Hs.491234.
3D structure databases
ProteinModelPortal	Q92963.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92963. 9 interactions.
STRING	9606.ENSP00000357306.
PTM databases
PhosphoSite	Q92963.
Polymorphism databases
DMDM	38258628.
Proteomic databases
PaxDb	Q92963.
PRIDE	Q92963.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000368323; ENSP00000357306; ENSG00000143622. ENST00000539040; ENSP00000441950; ENSG00000143622.
GeneID	6016.
KEGG	hsa:6016.
UCSC	uc001fmh.1. human.
Organism-specific databases
CTD	6016.
GeneCards	GC01M155867.
HGNC	HGNC:10023. RIT1.
HPA	HPA053249.
MIM	609591. gene.
neXtProt	NX_Q92963.
PharmGKB	PA35528.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1100.
HOGENOM	HOG000233973.
HOVERGEN	HBG009351.
InParanoid	Q92963.
KO	K07832.
OrthoDB	EOG4VDQ0C.
PhylomeDB	Q92963.
Enzyme and pathway databases
Pathway_Interaction_DB	trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q92963.
Bgee	Q92963.
CleanEx	HS_RIT1.
Genevestigator	Q92963.
GermOnline	ENSG00000143622. Homo sapiens.
Family and domain databases
InterPro	IPR027417. P-loop_NTPase. IPR005225. Small_GTP-bd_dom. IPR001806. Small_GTPase. IPR020849. Small_GTPase_Ras. [Graphical view]
PANTHER	PTHR24070. PTHR24070. 1 hit.
Pfam	PF00071. Ras. 1 hit. [Graphical view]
PRINTS	PR00449. RASTRNSFRMNG.
SMART	SM00173. RAS. 1 hit. [Graphical view]
SUPFAM	SSF52540. SSF52540. 1 hit.
TIGRFAMs	TIGR00231. small_GTP. 1 hit.
PROSITE	PS51421. RAS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6016.
NextBio	23471.
SOURCE	Search...

Entry information

Entry name

RIT1_HUMAN

Accession

Primary (citable) accession number: Q92963
Secondary accession number(s): B4DQE8 , O00646, O00720, Q5VY90

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 31, 2003
Last sequence update:	February 1, 1997
Last modified:	May 29, 2013
This is version 113 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.