P49795 (RGS19_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [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	217 AA.
Sequence status	Complete.
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.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 Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc autophagy Inferred from electronic annotation. Source: UniProtKB-KW small GTPase mediated signal transduction Traceable author statement PubMed 9571244. Source: ProtInc termination of G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	Golgi apparatus Traceable author statement PubMed 9571244. Source: ProtInc brush border Inferred from electronic annotation. Source: Compara clathrin-coated vesicle Inferred from electronic annotation. Source: Compara cytosolic part Inferred from electronic annotation. Source: Compara plasma membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	GTPase activator activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Gnai3	P08753	4	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 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-97, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-151, MUTAGENESIS OF SER-151.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.
CH471077 Genomic DNA. Translation: EAW75167.1.
BC001318 mRNA. Translation: AAH01318.1.
BC054337 mRNA. Translation: AAH54337.1.
BC063010 mRNA. Translation: AAH63010.1.

IPI

IPI00028108.

RefSeq

NP_001034556.1. NM_001039467.1.
NP_005864.1. NM_005873.2.

UniGene

Hs.422336.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P49795.

ModBase

Search...

Protein-protein interaction databases

IntAct

P49795. 3 interactions.

STRING

9606.ENSP00000333194.

PTM databases

PhosphoSite

P49795.

Polymorphism databases

DMDM

1730186.

Proteomic databases

PaxDb

P49795.

PRIDE

P49795.

Protocols and materials databases

DNASU

10287.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000332298; ENSP00000333194; ENSG00000171700.
ENST00000395042; ENSP00000378483; ENSG00000171700.

GeneID

10287.

KEGG

hsa:10287.

UCSC

uc002yhy.3. human.

Organism-specific databases

CTD

10287.

GeneCards

GC20M062704.

HGNC

HGNC:13735. RGS19.

HPA

CAB031925.

MIM

605071. gene.

neXtProt

NX_P49795.

PharmGKB

PA34370.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG258376.

HOGENOM

HOG000233513.

HOVERGEN

HBG013233.

InParanoid

P49795.

KO

K16449.

OMA

FDKLMHS.

OrthoDB

EOG418BPC.

PhylomeDB

P49795.

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

Gene3D

1.10.196.10. 1 hit.

InterPro

IPR000342. Regulat_G_prot_signal.
IPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
[Graphical view]

Pfam

PF00615. RGS. 1 hit.
[Graphical view]

PRINTS

PR01301. RGSPROTEIN.

SMART

SM00315. RGS. 1 hit.
[Graphical view]

SUPFAM

SSF48097. Regulat_G_prot_signal_superfam. 1 hit.

PROSITE

PS50132. RGS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P49795.

ChiTaRS

RGS19. human.

EvolutionaryTrace

P49795.

GenomeRNAi

10287.

NextBio

38976.

SOURCE

Search...

Entry information

Entry name

RGS19_HUMAN

Accession

Primary (citable) accession number: P49795
Secondary accession number(s): A8K216 , E1P5G9, Q53XN0, Q8TD60

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 130 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.