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P49798 (RGS4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Regulator of G-protein signaling 4

Short name=RGP4
Short name=RGS4
Gene names
Name:RGS4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length205 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 205205Regulator of G-protein signaling 4
PRO_0000204185

Regions

Domain62 – 178117RGS

Amino acid modifications

Lipidation21S-palmitoyl cysteine Probable
Lipidation121S-palmitoyl cysteine Probable
Lipidation951S-palmitoyl cysteine Ref.9

Natural variations

Alternative sequence1 – 1818Missing in isoform 5.
VSP_043854
Alternative sequence11M → MYNMMLLIQKRKGIGSQLLR AGEAEGDRGAGTAERSSDWL DGRSWAIKETPTGLAGRRSE DSDNIFTGEEAKYAQSRSHS SSCRISFLLANSKLLNKM in isoform 3.
VSP_043853
Alternative sequence72 – 205134GLAAF…VPQCA → EPGFLHQGRDKPEHARAYNN LL in isoform 4.
VSP_043855
Alternative sequence1731F → S in isoform 2.
VSP_043856
Natural variant1951A → S.
Corresponds to variant rs14665 [ dbSNP | Ensembl ].
VAR_051795

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (B) [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 7713F1F7496A698B

FASTA20523,256
        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 

« Hide

Isoform 2 (A) [UniParc].

Checksum: 6AA52A87496A698B
Show »

FASTA20523,196
Isoform 3 (C) [UniParc].

Checksum: 1D058A564C79BB58
Show »

FASTA30233,919
Isoform 4 [UniParc].

Checksum: 52F755864B24E3FA
Show »

FASTA9310,556
Isoform 5 [UniParc].

Checksum: 33A39E66A6333B5C
Show »

FASTA18721,452

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
PIRS78221.
RefSeqNP_001095915.1. NM_001102445.2.
NP_001106851.1. NM_001113380.1.
NP_001106852.1. NM_001113381.1.
NP_005604.1. NM_005613.5.
UniGeneHs.386726.

3D structure databases

ProteinModelPortalP49798.
SMRP49798. Positions 8-182.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111931. 13 interactions.
DIPDIP-59092N.
STRING9606.ENSP00000397181.

Chemistry

ChEMBLCHEMBL1795091.

PTM databases

PhosphoSiteP49798.

Polymorphism databases

DMDM1710146.

Proteomic databases

PaxDbP49798.
PRIDEP49798.

Protocols and materials databases

DNASU5999.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000367906; ENSP00000356882; ENSG00000117152. [P49798-5]
ENST00000367908; ENSP00000356884; ENSG00000117152. [P49798-4]
ENST00000367909; ENSP00000356885; ENSG00000117152. [P49798-1]
ENST00000421743; ENSP00000397181; ENSG00000117152. [P49798-3]
ENST00000527809; ENSP00000433261; ENSG00000117152. [P49798-5]
GeneID5999.
KEGGhsa:5999.
UCSCuc001gcl.4. human. [P49798-3]
uc009wuy.3. human. [P49798-1]
uc009wuz.3. human. [P49798-4]

Organism-specific databases

CTD5999.
GeneCardsGC01P163038.
HGNCHGNC:10000. RGS4.
HPAHPA030802.
MIM181500. phenotype.
602516. gene.
604906. phenotype.
neXtProtNX_P49798.
Orphanet3140. Schizophrenia.
PharmGKBPA34375.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG318241.
HOGENOMHOG000233512.
HOVERGENHBG013233.
InParanoidP49798.
KOK16449.
OMADCPSLVP.
OrthoDBEOG7VHSZ5.
PhylomeDBP49798.
TreeFamTF315837.

Gene expression databases

ArrayExpressP49798.
BgeeP49798.
CleanExHS_RGS4.
GenevestigatorP49798.

Family and domain databases

Gene3D1.10.196.10. 2 hits.
InterProIPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
[Graphical view]
PfamPF00615. RGS. 1 hit.
[Graphical view]
PRINTSPR01301. RGSPROTEIN.
SMARTSM00315. RGS. 1 hit.
[Graphical view]
SUPFAMSSF48097. SSF48097. 1 hit.
PROSITEPS50132. RGS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiRGS4.
GenomeRNAi5999.
NextBio23389.
PROP49798.
SOURCESearch...

Entry information

Entry nameRGS4_HUMAN
AccessionPrimary (citable) accession number: P49798
Secondary accession number(s): A7XA56 expand/collapse secondary AC list , A7XA58, A7XA59, A7YVV7, B1APZ3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: March 19, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM