Q86X27 (RGPS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras-specific guanine nucleotide-releasing factor RalGPS2

Alternative name(s):
Ral GEF with PH domain and SH3-binding motif 2
RalA exchange factor RalGPS2

Gene names

Name:

RALGPS2

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 › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	583 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide exchange factor for the small GTPase RALA. May be involved in cytoskeletal organization. May also be involved in the stimulation of transcription in a Ras-independent fashion By similarity.
Subunit structure	Interacts with the SH3 domains of GRB2 and PLCG1 By similarity. Interacts with RALA By similarity.
Subcellular location	Cytoplasm By similarity. Cell membrane By similarity. Note: Associates with membranes through the PH domain By similarity.
Domain	The PH domain mediates binding to phosphatidylinositol 4,5-bisphosphate By similarity.
Involvement in disease	RALGPS2 is a potential candidate gene for susceptibility to Alzheimer disease linked to 1q24. Ref.5
Sequence similarities	Contains 1 PH domain. Contains 1 Ras-GEF domain.
Sequence caution	The sequence CAH71098.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI21919.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI21925.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Alzheimer disease
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	small GTPase mediated signal transduction Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86X27-1)

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: Q86X27-2)

The sequence of this isoform differs from the canonical sequence as follows:
     280-583: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 583	583	Ras-specific guanine nucleotide-releasing factor RalGPS2		PRO_0000322600
Regions
	Domain	49 – 287	239	Ras-GEF
	Domain	457 – 569	113	PH
	Region	459 – 583	125	Required for stimulation of nucleotide exchange by RALA By similarity
	Motif	324 – 327	4	PXXP
Amino acid modifications
	Modified residue	308	1	Phosphoserine Ref.7
	Modified residue	311	1	Phosphoserine Ref.7
	Modified residue	326	1	Phosphothreonine Ref.7 Ref.9
	Modified residue	329	1	Phosphoserine Ref.7 Ref.9
Natural variations
	Alternative sequence	280 – 583	304	Missing in isoform 2.		VSP_031971
	Natural variant	225	1	N → S. Corresponds to variant rs35161510 [ dbSNP | Ensembl ].		VAR_039468

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2003. Version 1. Checksum: B6D85A8ACBEBED15	FASTA	583	65,167
	10 20 30 40 50 60 MDLMNGQASS VNIAATASEK SSSSESLSDK GSELKKSFDA VVFDVLKVTP EEYAGQITLM 70 80 90 100 110 120 DVPVFKAIQP DELSSCGWNK KEKYSSAPNA VAFTRRFNHV SFWVVREILH AQTLKIRAEV 130 140 150 160 170 180 LSHYIKTAKK LYELNNLHAL MAVVSGLQSA PIFRLTKTWA LLSRKDKTTF EKLEYVMSKE 190 200 210 220 230 240 DNYKRLRDYI SSLKMTPCIP YLGIYLSDLT YIDSAYPSTG SILENEQRSN LMNNILRIIS 250 260 270 280 290 300 DLQQSCEYDI PMLPHVQKYL NSVQYIEELQ KFVEDDNYKL SLKIEPGTST PRSAASREDL 310 320 330 340 350 360 VGPEVGASPQ SGRKSVAAEG ALLPQTPPSP RNLIPHGHRK CHSLGYNFIH KMNTAEFKSA 370 380 390 400 410 420 TFPNAGPRHL LDDSVMEPHA PSRGQAESST LSSGISIGSS DGSELSEETS WPAFERNRLY 430 440 450 460 470 480 HSLGPVTRVA RNGYRSHMKA SSSAESEDLA VHLYPGAVTI QGVLRRKTLL KEGKKPTVAS 490 500 510 520 530 540 WTKYWAALCG TQLFYYAAKS LKATERKHFK STSNKNVSVI GWMVMMADDP EHPDLFLLTD 550 560 570 580 SEKGNSYKFQ AGNRMNAMLW FKHLSAACQS NKQQVPTNLM TFE
	Isoform 2 [UniParc]. Checksum: 92195039C78F56EA	FASTA	279	31,856
	10 20 30 40 50 60 MDLMNGQASS VNIAATASEK SSSSESLSDK GSELKKSFDA VVFDVLKVTP EEYAGQITLM 70 80 90 100 110 120 DVPVFKAIQP DELSSCGWNK KEKYSSAPNA VAFTRRFNHV SFWVVREILH AQTLKIRAEV 130 140 150 160 170 180 LSHYIKTAKK LYELNNLHAL MAVVSGLQSA PIFRLTKTWA LLSRKDKTTF EKLEYVMSKE 190 200 210 220 230 240 DNYKRLRDYI SSLKMTPCIP YLGIYLSDLT YIDSAYPSTG SILENEQRSN LMNNILRIIS 250 260 270 DLQQSCEYDI PMLPHVQKYL NSVQYIEELQ KFVEDDNYK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] (ISOFORM 2). Tissue: Embryo.
[2]	"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].
[3]	Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases 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] (ISOFORM 1). Tissue: Testis.
[5]	"A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population." Liu F., Arias-Vasquez A., Sleegers K., Aulchenko Y.S., Kayser M., Sanchez-Juan P., Feng B.J., Bertoli-Avella A.M., van Swieten J., Axenovich T.I., Heutink P., van Broeckhoven C., Oostra B.A., van Duijn C.M. Am. J. Hum. Genet. 81:17-31(2007) [PubMed] [Europe PMC] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN ALZHEIMER DISEASE.
[6]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: T-cell.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-308; SER-311; THR-326 AND SER-329, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-326 AND SER-329, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK001106 mRNA. Translation: BAA91506.1. AL162255, AL355520 Genomic DNA. Translation: CAH71096.1. AL162255, AL355520 Genomic DNA. Translation: CAH71097.1. AL162255, AL355520 Genomic DNA. Translation: CAH71098.1. Sequence problems. AL355520, AL162255 Genomic DNA. Translation: CAI21918.1. AL355520, AL162255 Genomic DNA. Translation: CAI21919.1. Sequence problems. AL355520, AL162255 Genomic DNA. Translation: CAI21920.1. AL355520 Genomic DNA. Translation: CAI21925.1. Sequence problems. CH471067 Genomic DNA. Translation: EAW91028.1. CH471067 Genomic DNA. Translation: EAW91029.1. BC047391 mRNA. Translation: AAH47391.1.
RefSeq	NP_689876.2. NM_152663.4.
UniGene	Hs.632485. Hs.657592.
3D structure databases
ProteinModelPortal	Q86X27.
SMR	Q86X27. Positions 43-286, 459-572.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	120413. 5 interactions.
IntAct	Q86X27. 2 interactions.
MINT	MINT-1631677.
STRING	9606.ENSP00000356607.
PTM databases
PhosphoSite	Q86X27.
Polymorphism databases
DMDM	74750518.
Proteomic databases
PaxDb	Q86X27.
PRIDE	Q86X27.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367635; ENSP00000356607; ENSG00000116191. [Q86X27-1]
GeneID	55103.
KEGG	hsa:55103.
UCSC	uc001gly.1. human. [Q86X27-2] uc001glz.3. human. [Q86X27-1]
Organism-specific databases
CTD	55103.
GeneCards	GC01P178694.
HGNC	HGNC:30279. RALGPS2.
HPA	HPA027143. HPA028328.
neXtProt	NX_Q86X27.
PharmGKB	PA134864387.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG275669.
HOGENOM	HOG000008021.
HOVERGEN	HBG059258.
InParanoid	Q86X27.
OMA	YGHRKCH.
OrthoDB	EOG70KGP7.
PhylomeDB	Q86X27.
TreeFam	TF352150.
Gene expression databases
Bgee	Q86X27.
CleanEx	HS_RALGPS2.
Genevestigator	Q86X27.
Family and domain databases
Gene3D	1.10.840.10. 1 hit. 2.30.29.30. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR001849. Pleckstrin_homology. IPR008937. Ras_GEF. IPR023578. Ras_GEF_dom. IPR001895. RasGRF_CDC25. [Graphical view]
PANTHER	PTHR23113. PTHR23113. 1 hit.
Pfam	PF00617. RasGEF. 1 hit. [Graphical view]
SMART	SM00233. PH. 1 hit. SM00147. RasGEF. 1 hit. [Graphical view]
SUPFAM	SSF48366. SSF48366. 1 hit.
PROSITE	PS50003. PH_DOMAIN. 1 hit. PS50009. RASGEF_CAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	RALGPS2. human.
GenomeRNAi	55103.
NextBio	58700.
PRO	Q86X27.

Entry information

Entry name

RGPS2_HUMAN

Accession

Primary (citable) accession number: Q86X27
Secondary accession number(s): Q5T5Z1, Q5VZ67, Q9NW78

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 26, 2008
Last sequence update:	June 1, 2003
Last modified:	April 16, 2014
This is version 108 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.