Q9HB90 (RRAGC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-related GTP-binding protein C
Short name=Rag C
Short name=RagC

Alternative name(s):
GTPase-interacting protein 2
TIB929

Gene names

Name:

RRAGC

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	399 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	Guanine nucleotide-binding protein forming heterodimeric Rag complexes required for the amino acid-induced relocalization of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB. This is a crucial step in the activation of the TOR signaling cascade by amino acids. Ref.8
Subunit structure	Forms a heterodimer with RRAGA, in a sequence-independent manner, and RRAGB. Heterodimerization stabilizes proteins of the heterodimer. In complex with RRAGA or RRAGB, interacts with RPTOR; this interaction is particularly efficient with GTP-loaded RRAGB and GDP-loaded RRAGC. Interacts with NOL8. Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGB, is negatively regulated by amino acids and prevents interaction with RPTOR. Ref.2 Ref.6 Ref.7 Ref.11
Subcellular location	Cytoplasm. Nucleus. Lysosome. Note: Predominantly cytoplasmic. May shuttle between the cytoplasm and nucleus, depending on the bound nucleotide state of associated RRAGA. Ref.2 Ref.8
Sequence similarities	Belongs to the GTR/RAG GTP-binding protein family.
Sequence caution	The sequence BAB14548.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Cellular component	Cytoplasm Lysosome Nucleus
Ligand	GTP-binding Nucleotide-binding
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	RNA splicing Non-traceable author statement Ref.2. Source: UniProtKB apoptotic process Non-traceable author statement Ref.2. Source: UniProtKB cell growth Non-traceable author statement Ref.2. Source: UniProtKB cellular protein localization Inferred from sequence or structural similarity. Source: UniProtKB cellular response to amino acid stimulus Inferred from sequence or structural similarity. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement Ref.2. Source: UniProtKB transcription, DNA-dependent Non-traceable author statement Ref.2. Source: UniProtKB
Cellular_component	lysosome Inferred from direct assay Ref.8. Source: UniProtKB nucleus Inferred from direct assay Ref.2. Source: UniProtKB
Molecular_function	GDP binding Inferred from direct assay Ref.2. Source: UniProtKB GTP binding Inferred from direct assay Ref.2. Source: HGNC GTPase activity Inferred from direct assay Ref.2. Source: UniProtKB magnesium ion binding Non-traceable author statement Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
RRAGA	Q7L523	11	EBI-752390,EBI-752376
RRAGB	Q5VZM2	4	EBI-752390,EBI-993049

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.9

Chain

2 – 399

398

Ras-related GTP-binding protein C

PRO_0000239951

Regions

Nucleotide binding

68 – 75

8

GTP By similarity UniProtKB P53290

Nucleotide binding

116 – 120

5

GTP By similarity

Nucleotide binding

178 – 181

4

GTP By similarity UniProtKB P53290

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.9

Modified residue

2

1

Phosphoserine Ref.9

Experimental info

Mutagenesis

75

1

S → L: Increased RPTOR-binding. Ref.7

Mutagenesis

120

1

Q → L: Decreased RPTOR-binding. Ref.7

Sequence conflict

206

1

A → S in AAG45221. Ref.1

Secondary structure

1

.

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399

Helix Strand Turn

Details...

Beta strand

63 – 69

7

Helix

74 – 82

9

Helix

87 – 92

6

Beta strand

100 – 104

5

Beta strand

112 – 116

5

Helix

130 – 135

6

Beta strand

138 – 145

8

Helix

151 – 167

17

Beta strand

172 – 178

7

Helix

180 – 182

3

Helix

185 – 205

21

Beta strand

213 – 218

6

Helix

224 – 235

12

Sequences

	Sequence		Length	Mass (Da)
	Q9HB90 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 35B3171253CC69CF	FASTA	399	44,224
	10 20 30 40 50 60 MSLQYGAEET PLAGSYGAAD SFPKDFGYGV EEEEEEAAAA GGGVGAGAGG GCGPGGADSS 70 80 90 100 110 120 KPRILLMGLR RSGKSSIQKV VFHKMSPNET LFLESTNKIY KDDISNSSFV NFQIWDFPGQ 130 140 150 160 170 180 MDFFDPTFDY EMIFRGTGAL IYVIDAQDDY MEALTRLHIT VSKAYKVNPD MNFEVFIHKV 190 200 210 220 230 240 DGLSDDHKIE TQRDIHQRAN DDLADAGLEK LHLSFYLTSI YDHSIFEAFS KVVQKLIPQL 250 260 270 280 290 300 PTLENLLNIF ISNSGIEKAF LFDVVSKIYI ATDSSPVDMQ SYELCCDMID VVIDVSCIYG 310 320 330 340 350 360 LKEDGSGSAY DKESMAIIKL NNTTVLYLKE VTKFLALVCI LREESFERKG LIDYNFHCFR 370 380 390 KAIHEVFEVG VTSHRSCGHQ TSASSLKALT HNGTPRNAI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Adenovirus immunoregulatory genes and their cellular targets." Horwitz M.S. Virology 279:1-8(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B." Sekiguchi T., Hirose E., Nakashima N., Ii M., Nishimoto T. J. Biol. Chem. 276:7246-7257(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH RRAGA AND RRAGB, SUBCELLULAR LOCATION, GTP-BINDING.
[3]	"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].
[4]	"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]. Tissue: Lymph.
[5]	"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] OF 266-399. Tissue: Ovary.
[6]	"A novel human nucleolar protein, Nop132, binds to the G proteins, RRAG A/C/D." Sekiguchi T., Todaka Y., Wang Y., Hirose E., Nakashima N., Nishimoto T. J. Biol. Chem. 279:8343-8350(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NOL8 AND RRAGA.
[7]	"The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1." Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C., Bar-Peled L., Sabatini D.M. Science 320:1496-1501(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RPTOR, MUTAGENESIS OF SER-75 AND GLN-120.
[8]	"Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids." Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M. Cell 141:290-303(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, CLEAVAGE OF INITIATOR METHIONINE. Tissue: Cervix carcinoma.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"SH3BP4 is a negative regulator of amino acid-Rag GTPase-mTORC1 signaling." Kim Y.M., Stone M., Hwang T.H., Kim Y.G., Dunlevy J.R., Griffin T.J., Kim D.H. Mol. Cell 46:833-846(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SH3BP4.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF323609 mRNA. Translation: AAG45221.1.
AF272035 mRNA. Translation: AAG32662.1.
AL139260 Genomic DNA. Translation: CAI23049.1.
BC016668 mRNA. Translation: AAH16668.1.
AK023373 mRNA. Translation: BAB14548.1. Different initiation.

IPI

IPI00300585.

RefSeq

NP_001258780.1. NM_001271851.1.
NP_071440.1. NM_022157.3.

UniGene

Hs.532461.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3LLU	X-ray	1.40	A	60-237	[»]

ProteinModelPortal

Q9HB90.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9HB90. 11 interactions.

MINT

MINT-1451634.

STRING

9606.ENSP00000362092.

PTM databases

PhosphoSite

Q9HB90.

Polymorphism databases

DMDM

74752776.

Proteomic databases

PaxDb

Q9HB90.

PeptideAtlas

Q9HB90.

PRIDE

Q9HB90.

Protocols and materials databases

DNASU

64121.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000373001; ENSP00000362092; ENSG00000116954.

GeneID

64121.

KEGG

hsa:64121.

UCSC

uc001ccq.2. human.

Organism-specific databases

CTD

64121.

GeneCards

GC01M039303.

HGNC

HGNC:19902. RRAGC.

HPA

HPA018247.

MIM

608267. gene.

neXtProt

NX_Q9HB90.

PharmGKB

PA134862062.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG250062.

HOGENOM

HOG000203695.

HOVERGEN

HBG059482.

InParanoid

Q9HB90.

KO

K16186.

OMA

EVGVASH.

OrthoDB

EOG4CG08D.

PhylomeDB

Q9HB90.

Gene expression databases

ArrayExpress

Q9HB90.

Bgee

Q9HB90.

CleanEx

HS_RRAGC.

Genevestigator

Q9HB90.

GermOnline

ENSG00000116954. Homo sapiens.

Family and domain databases

InterPro

IPR006762. Gtr1_RagA.
IPR027417. P-loop_NTPase.
[Graphical view]

PANTHER

PTHR11259. PTHR11259. 1 hit.

Pfam

PF04670. Gtr1_RagA. 1 hit.
[Graphical view]

SUPFAM

SSF52540. SSF52540. 1 hit.

ProtoNet

Search...

Other

ChiTaRS

RRAGC. human.

EvolutionaryTrace

Q9HB90.

GenomeRNAi

64121.

NextBio

65996.

SOURCE

Search...

Entry information

Entry name

RRAGC_HUMAN

Accession

Primary (citable) accession number: Q9HB90
Secondary accession number(s): Q9H202, Q9H8Q8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2006
Last sequence update:	March 1, 2001
Last modified:	May 29, 2013
This is version 92 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.