P49798 (RGS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Regulator of G-protein signaling 4
Short name=RGP4
Short name=RGS4

Gene names

Name:

RGS4

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	205 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. Activity on G(z)-alpha is inhibited by phosphorylation of the G-protein. Activity on G(z)-alpha and G(i)-alpha-1 is inhibited by palmitoylation of the G-protein.
Tissue specificity	Expressed in brain and heart. Expressed in brain at protein level. Expressed in prefontal and visual cortex. Isoform 4 and isoform 5 are expressed ubiquitously. Isoform 1, isoform 2 and isoform 3 are not expressed in the cerebellum. Ref.2
Post-translational modification	Palmitoylated on Cys-2 and/or Cys-12. Ref.9 Phosphorylated by cyclic GMP-dependent protein kinase By similarity.
Involvement in disease	Schizophrenia 9 (SCZD9) [MIM:604906]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.11 Ref.12
Sequence similarities	Contains 1 RGS domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Schizophrenia
Molecular function	Signal transduction inhibitor
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inactivation of MAPK activity Traceable author statement Ref.1. Source: ProtInc regulation of G-protein coupled receptor protein signaling pathway Traceable author statement PubMed 10747990. Source: ProtInc termination of G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome cytosol 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 calmodulin binding Traceable author statement PubMed 10747990. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: May be produced by alternative promoter usage.

Isoform 1 (identifier: P49798-1)

Also known as: B;

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: P49798-2)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     173-173: F → S

Isoform 3 (identifier: P49798-3)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MYNMMLLIQK...LANSKLLNKM

Isoform 4 (identifier: P49798-4)

The sequence of this isoform differs from the canonical sequence as follows:
     72-205: GLAAFKAFLK...DCASLVPQCA → EPGFLHQGRDKPEHARAYNNLL

Isoform 5 (identifier: P49798-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 205	205	Regulator of G-protein signaling 4		PRO_0000204185
Regions
	Domain	62 – 178	117	RGS
Amino acid modifications
	Lipidation	2	1	S-palmitoyl cysteine Probable
	Lipidation	12	1	S-palmitoyl cysteine Probable
	Lipidation	95	1	S-palmitoyl cysteine Ref.9
Natural variations
	Alternative sequence	1 – 18	18	Missing in isoform 5.		VSP_043854
	Alternative sequence	1	1	M → MYNMMLLIQKRKGIGSQLLR AGEAEGDRGAGTAERSSDWL DGRSWAIKETPTGLAGRRSE DSDNIFTGEEAKYAQSRSHS SSCRISFLLANSKLLNKM in isoform 3.		VSP_043853
	Alternative sequence	72 – 205	134	GLAAF…VPQCA → EPGFLHQGRDKPEHARAYNN LL in isoform 4.		VSP_043855
	Alternative sequence	173	1	F → S in isoform 2.		VSP_043856
	Natural variant	195	1	A → S. Corresponds to variant rs14665 [ dbSNP | Ensembl ].		VAR_051795

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (B) [UniParc]. Last modified October 1, 1996. Version 1. Checksum: 7713F1F7496A698B	FASTA	205	23,256
	10 20 30 40 50 60 MCKGLAGLPA SCLRSAKDMK HRLGFLLQKS DSCEHNSSHN KKDKVVICQR VSQEEVKKWA 70 80 90 100 110 120 ESLENLISHE CGLAAFKAFL KSEYSEENID FWISCEEYKK IKSPSKLSPK AKKIYNEFIS 130 140 150 160 170 180 VQATKEVNLD SCTREETSRN MLEPTITCFD EAQKKIFNLM EKDSYRRFLK SRFYLDLVNP 190 200 SSCGAEKQKG AKSSADCASL VPQCA
	Isoform 2 (A) [UniParc]. Checksum: 6AA52A87496A698B	FASTA	205	23,196
	10 20 30 40 50 60 MCKGLAGLPA SCLRSAKDMK HRLGFLLQKS DSCEHNSSHN KKDKVVICQR VSQEEVKKWA 70 80 90 100 110 120 ESLENLISHE CGLAAFKAFL KSEYSEENID FWISCEEYKK IKSPSKLSPK AKKIYNEFIS 130 140 150 160 170 180 VQATKEVNLD SCTREETSRN MLEPTITCFD EAQKKIFNLM EKDSYRRFLK SRSYLDLVNP 190 200 SSCGAEKQKG AKSSADCASL VPQCA
	Isoform 3 (C) [UniParc]. Checksum: 1D058A564C79BB58	FASTA	302	33,919
	10 20 30 40 50 60 MYNMMLLIQK RKGIGSQLLR AGEAEGDRGA GTAERSSDWL DGRSWAIKET PTGLAGRRSE 70 80 90 100 110 120 DSDNIFTGEE AKYAQSRSHS SSCRISFLLA NSKLLNKMCK GLAGLPASCL RSAKDMKHRL 130 140 150 160 170 180 GFLLQKSDSC EHNSSHNKKD KVVICQRVSQ EEVKKWAESL ENLISHECGL AAFKAFLKSE 190 200 210 220 230 240 YSEENIDFWI SCEEYKKIKS PSKLSPKAKK IYNEFISVQA TKEVNLDSCT REETSRNMLE 250 260 270 280 290 300 PTITCFDEAQ KKIFNLMEKD SYRRFLKSRF YLDLVNPSSC GAEKQKGAKS SADCASLVPQ CA
	Isoform 4 [UniParc]. Checksum: 52F755864B24E3FA	FASTA	93	10,556
	10 20 30 40 50 60 MCKGLAGLPA SCLRSAKDMK HRLGFLLQKS DSCEHNSSHN KKDKVVICQR VSQEEVKKWA 70 80 90 ESLENLISHE CEPGFLHQGR DKPEHARAYN NLL
	Isoform 5 [UniParc]. Checksum: 33A39E66A6333B5C	FASTA	187	21,452
	10 20 30 40 50 60 MKHRLGFLLQ KSDSCEHNSS HNKKDKVVIC QRVSQEEVKK WAESLENLIS HECGLAAFKA 70 80 90 100 110 120 FLKSEYSEEN IDFWISCEEY KKIKSPSKLS PKAKKIYNEF ISVQATKEVN LDSCTREETS 130 140 150 160 170 180 RNMLEPTITC FDEAQKKIFN LMEKDSYRRF LKSRFYLDLV NPSSCGAEKQ KGAKSSADCA SLVPQCA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family." Druey K.M., Blumer K.J., Kang V.H., Kehrl J.H. Nature 379:742-746(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Full length cloning and expression analysis of splice variants of regulator of G-protein signaling RGS4 in human and murine brain." Ding L., Mychaleckyj J.C., Hegde A.N. Gene 401:46-60(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 5), ALTERNATIVE SPLICING (ISOFORM 4), TISSUE SPECIFICITY.
[3]	"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). Tissue: Brain and Uterus.
[4]	"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 (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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] (ISOFORMS 1; 3 AND 5). Tissue: Hippocampus, Thalamus and Trachea.
[6]	"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].
[7]	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].
[8]	"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: Brain.
[9]	"Palmitoylation of a conserved cysteine in the regulator of G protein signaling (RGS) domain modulates the GTPase-activating activity of RGS4 and RGS10." Tu Y., Popov S., Slaughter C., Ross E.M. J. Biol. Chem. 274:38260-38267(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-2; CYS-12 AND CYS-95.
[10]	"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.
[11]	"Association and linkage analyses of RGS4 polymorphisms in schizophrenia." Chowdari K.V., Mirnics K., Semwal P., Wood J., Lawrence E., Bhatia T., Deshpande S.N., Thelma B.K., Ferrell R.E., Middleton F.A., Devlin B., Levitt P., Lewis D.A., Nimgaonkar V.L. Hum. Mol. Genet. 11:1373-1380(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9.
[12]	"Confirming RGS4 as a susceptibility gene for schizophrenia." Morris D.W., Rodgers A., McGhee K.A., Schwaiger S., Scully P., Quinn J., Meagher D., Waddington J.L., Gill M., Corvin A.P. Am. J. Med. Genet. B Neuropsychiatr. Genet. 125:50-53(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U27768 mRNA. Translation: AAC50395.1. DQ346662 mRNA. Translation: ABC94590.1. DQ346663 mRNA. Translation: ABC94591.1. DQ346664 mRNA. Translation: ABC94592.1. EF054877 mRNA. Translation: ABL74968.1. AK093959 mRNA. No translation available. AK295540 mRNA. Translation: BAG58449.1. AK296240 mRNA. Translation: BAG58958.1. AK312250 mRNA. Translation: BAG35182.1. AF493928 mRNA. Translation: AAM12642.1. BT007025 mRNA. Translation: AAP35671.1. AL583850 Genomic DNA. Translation: CAH73766.1. AL583850 Genomic DNA. Translation: CAH73767.1. AL583850 Genomic DNA. Translation: CAH73768.1. CH471067 Genomic DNA. Translation: EAW90727.1. CH471067 Genomic DNA. Translation: EAW90728.1. BC000737 mRNA. Translation: AAH00737.1. BC051869 mRNA. Translation: AAH51869.1.
IPI	IPI00028112. IPI00477871.
PIR	S78221.
RefSeq	NP_001095915.1. NM_001102445.2. NP_001106851.1. NM_001113380.1. NP_001106852.1. NM_001113381.1. NP_005604.1. NM_005613.5.
UniGene	Hs.386726.
3D structure databases
ProteinModelPortal	P49798.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-59092N.
STRING	9606.ENSP00000397181.
PTM databases
PhosphoSite	P49798.
Polymorphism databases
DMDM	1710146.
Proteomic databases
PaxDb	P49798.
PRIDE	P49798.
Protocols and materials databases
DNASU	5999.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000367906; ENSP00000356882; ENSG00000117152. ENST00000367908; ENSP00000356884; ENSG00000117152. ENST00000367909; ENSP00000356885; ENSG00000117152. ENST00000421743; ENSP00000397181; ENSG00000117152. ENST00000527809; ENSP00000433261; ENSG00000117152.
GeneID	5999.
KEGG	hsa:5999.
UCSC	uc009wuy.3. human.
Organism-specific databases
CTD	5999.
GeneCards	GC01P163038.
HGNC	HGNC:10000. RGS4.
HPA	HPA030802.
MIM	181500. phenotype. 602516. gene. 604906. phenotype.
neXtProt	NX_P49798.
Orphanet	3140. Schizophrenia.
PharmGKB	PA34375.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG318241.
HOGENOM	HOG000233512.
HOVERGEN	HBG013233.
InParanoid	P49798.
KO	K16449.
OMA	DCPSLVP.
OrthoDB	EOG4PK297.
PhylomeDB	P49798.
Gene expression databases
ArrayExpress	P49798.
Bgee	P49798.
CleanEx	HS_RGS4.
Genevestigator	P49798.
GermOnline	ENSG00000117152. Homo sapiens.
Family and domain databases
Gene3D	1.10.196.10. 2 hits.
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
ChEMBL	CHEMBL1795091.
GenomeRNAi	5999.
NextBio	23389.
SOURCE	Search...

Entry information

Entry name

RGS4_HUMAN

Accession

Primary (citable) accession number: P49798
Secondary accession number(s): A7XA56 , A7XA58, A7XA59, A7YVV7, B1APZ3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	May 1, 2013
This is version 123 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.