Reviewed, UniProtKB/Swiss-Prot P49795 (RGS19_HUMAN)

Names and origin

Protein names

Recommended name:
    Regulator of G-protein signaling 19
      Short name=RGS19
Alternative name(s):
    G-alpha-interacting protein
      Short name=GAIP

Gene names

Name:	RGS19
Synonyms:	GAIP, GNAI3IP

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	217 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G-alpha subfamily 1 members, with the order G(i)a3 > G(i)a1 > G(o)a >> G(z)a/G(i)a2. Activity on G(z)-alpha is inhibited by phosphorylation and palmitoylation of the G-protein.
Subunit structure	Interacts with GIPC PDZ domain.
Subcellular location	Membrane; Lipid-anchor.
Tissue specificity	Highest expression in lung. Placenta, liver and heart also express high levels of GAIP.
Post-translational modification	Fatty acylated. Heavily palmitoylated in the cysteine string motif. Ref.8 Phosphorylated, mainly on serine residues. Ref.9 Ref.12
Sequence similarities	Contains 1 RGS domain.

Ontologies

Keywords
Biological process	Autophagy
Cellular component	Membrane
Molecular function	Signal transduction inhibitor
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Ref.1 Traceable author statement. Source: ProtInc autophagy Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of signal transduction Inferred from electronic annotation. Source: UniProtKB-KW small GTPase mediated signal transduction Traceable author statement. Source: ProtInc
Cellular component	Golgi apparatus Traceable author statement. Source: ProtInc anchored to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.1 Inferred from physical interaction. Source: UniProtKB signal transducer activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Gnai3	P08753	3	EBI-874907,EBI-874897	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 217

217

Regulator of G-protein signaling 19

PRO_0000204229

Regions

Domain

90 – 206

117

RGS

Region

207 – 217

11

Interaction with GIPC

Compositional bias

39 – 49

11

Poly-Cys

Amino acid modifications

Modified residue

24

1

Phosphoserine By similarity

Modified residue

97

1

Phosphoserine Ref.9

Modified residue

151

1

Phosphoserine; by MAPK1 and MAPK3 Ref.12

Experimental info

Mutagenesis

151

1

S → A: Diminishes gap activity towards G(i)-alpha3 and autophagy in colon cancer cells. Ref.12

Sequence conflict

204

1

A → V in AAM12653. Ref.2

Secondary structure

1

.

.

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217

Helix Strand Turn

Details...

Helix

81 – 87

7

Helix

92 – 95

4

Helix

98 – 111

14

Helix

115 – 125

11

Helix

126 – 128

3

Helix

133 – 145

13

Turn

146 – 148

3

Beta strand

150 – 152

3

Helix

160 – 168

9

Beta strand

169 – 171

3

Helix

178 – 191

14

Helix

193 – 196

4

Helix

200 – 203

4

Sequences

	Sequence		Length	Mass (Da)
	P49795-1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 925A5687DC222CBD	FASTA	217	24,636
	10 20 30 40 50 60 MPTPHEAEKQ ITGPEEADRP PSMSSHDTAS PAAPSRNPCC LCWCCCCSCS WNQERRRAWQ 70 80 90 100 110 120 ASRESKLQPL PSCEVCATPS PEEVQSWAQS FDKLMHSPAG RSVFRAFLRT EYSEENMLFW 130 140 150 160 170 180 LACEELKAEA NQHVVDEKAR LIYEDYVSIL SPKEVSLDSR VREGINKKMQ EPSAHTFDDA 190 200 210 QLQIYTLMHR DSYPRFLSSP TYRALLLQGP SQSSSEA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"GAIP, a protein that specifically interacts with the trimeric G protein G alpha i3, is a member of a protein family with a highly conserved core domain." de Vries L., Mousli M., Wurmser A., Farquhar M.G. Proc. Natl. Acad. Sci. U.S.A. 92:11916-11920(1995) [PubMed: 8524874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"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-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Subthalamic nucleus.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood, Placenta and Testis.
[8]	"GAIP is membrane-anchored by palmitoylation and interacts with the activated (GTP-bound) form of G alpha i subunits." de Vries L., Elenko E., Hubler L., Jones T.L.Z., Farquhar M.G. Proc. Natl. Acad. Sci. U.S.A. 93:15203-15208(1996) [PubMed: 8986788] [Abstract] Cited for: PALMITOYLATION.
[9]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97, MASS SPECTROMETRY.
[10]	"Solution structure of human GAIP (Galpha interacting protein): a regulator of G protein signaling." de Alba E., De Vries L., Farquhar M.G., Tjandra N. J. Mol. Biol. 291:927-939(1999) [PubMed: 10452897] [Abstract] Cited for: STRUCTURE BY NMR OF 79-206.
[11]	"RGSZ1, a Gz-selective RGS protein in brain. Structure, membrane association, regulation by Galphaz phosphorylation, and relationship to a Gz GTPase-activating protein subfamily." Wang J., Ducret A., Tu Y., Kozasa T., Aebersold R., Ross E.M. J. Biol. Chem. 273:26014-26025(1998) [PubMed: 9748280] [Abstract] Cited for: INHIBITION.
[12]	"Erk1/2-dependent phosphorylation of Galpha-interacting protein stimulates its GTPase accelerating activity and autophagy in human colon cancer cells." Ogier-Denis E., Pattingre S., El Benna J., Codogno P. J. Biol. Chem. 275:39090-39095(2000) [PubMed: 10993892] [Abstract] Cited for: PHOSPHORYLATION AT SER-151, MUTAGENESIS OF SER-151.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X91809 mRNA. Translation: CAA62919.1.
AF493939 mRNA. Translation: AAM12653.1.
AY585188 mRNA. Translation: AAS94232.1.
BT009804 mRNA. Translation: AAP88806.1.
AK290081 mRNA. Translation: BAF82770.1.
AL590548 Genomic DNA. Translation: CAD11902.1.
CH471077 Genomic DNA. Translation: EAW75166.1.
BC001318 mRNA. Translation: AAH01318.1.
BC054337 mRNA. Translation: AAH54337.1.
BC063010 mRNA. Translation: AAH63010.1.

IPI

IPI00028108.

RefSeq

NP_001034556.1.
NP_005864.1.

UniGene

Hs.422336

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CMZ	NMR	-	A	79-206	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P49795. 2 interactions.

STRING

P49795.

PTM databases

PhosphoSite

P49795.

Proteomic databases

PRIDE

P49795.

Genome annotation databases

Ensembl

ENST00000332298; ENSP00000333194; ENSG00000171700; Homo sapiens. [Genome view]
ENST00000395042; ENSP00000378483; ENSG00000171700; Homo sapiens. [Genome view]

GeneID

10287.

KEGG

hsa:10287.

UCSC

uc002yhy.1. human.

Organism-specific databases

CTD

10287.

GeneCards

GC20M062174.

H-InvDB

HIX0016021.

HGNC

HGNC:13735. RGS19.

MIM

605071. gene.

PharmGKB

PA34370.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P49795.

HOVERGEN

P49795.

OMA

FDKLMHS.

Enzyme and pathway databases

Pathway_Interaction_DB

trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.

Gene expression databases

ArrayExpress

P49795.

Bgee

P49795.

CleanEx

HS_RGS19.

Genevestigator

P49795.

GermOnline

ENSG00000171700. Homo sapiens.

Family and domain databases

InterPro

IPR000342. Regulat_G_prot_signal.
[Graphical view]

Pfam

PF00615. RGS. 1 hit.
[Graphical view]

PRINTS

PR01301. RGSPROTEIN.

ProDom

PD001580. Regl_Gprotein. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00315. RGS. 1 hit.
[Graphical view]

PROSITE

PS50132. RGS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

38976.

SOURCE

Search...

Entry information

Entry name

RGS19_HUMAN

Accession

Primary (citable) accession number: P49795
Secondary accession number(s): A8K216, Q53XN0, Q8TD60

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	November 3, 2009
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.