Q16821 (PPR3A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein phosphatase 1 regulatory subunit 3A

Alternative name(s):
Protein phosphatase 1 glycogen-associated regulatory subunit
Protein phosphatase type-1 glycogen targeting subunit
Short name=RG1

Gene names

Name:	PPP1R3A
Synonyms:	PP1G

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	1122 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase By similarity.
Subunit structure	Interacts with PPP1CC catalytic subunit of PP1, and associates with glycogen By similarity.
Subcellular location	Membrane; Single-pass membrane protein By similarity.
Tissue specificity	Skeletal muscle and heart. Ref.1
Domain	The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes.
Post-translational modification	Phosphorylation at Ser-46 by ISPK stimulates the dephosphorylation of glycogen synthase and phosphorylase kinase By similarity.
Involvement in disease	Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.5
Sequence similarities	Contains 1 CBM21 (carbohydrate binding type-21) domain.
Sequence caution	The sequence AAS07492.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glycogen metabolism
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus Disease mutation
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glycogen metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane 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: Q16821-1)

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: Q16821-2)

The sequence of this isoform differs from the canonical sequence as follows:
     60-74: GTRRVSFADSFGFNL → ERTRAGACKTMERSS
     75-1122: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1122	1122	Protein phosphatase 1 regulatory subunit 3A		PRO_0000071500
Regions
	Transmembrane	1078 – 1098	21	Helical; Potential
	Domain	122 – 230	109	CBM21
	Motif	62 – 65	4	PP1-binding motif
Amino acid modifications
	Modified residue	38	1	Phosphoserine; by GSK3 By similarity
	Modified residue	42	1	Phosphoserine; by GSK3 By similarity
	Modified residue	46	1	Phosphoserine; by PKA and ISPK By similarity
	Modified residue	65	1	Phosphoserine; by PKA By similarity
	Modified residue	261	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	60 – 74	15	GTRRV…FGFNL → ERTRAGACKTMERSS in isoform 2.		VSP_011585
	Alternative sequence	75 – 1122	1048	Missing in isoform 2.		VSP_011586
	Natural variant	45	1	G → S. Corresponds to variant rs8192687 [ dbSNP | Ensembl ].		VAR_027929
	Natural variant	231	1	C → Y. Corresponds to variant rs7801819 [ dbSNP | Ensembl ].		VAR_027930
	Natural variant	451	1	V → M. Ref.1 Ref.3 Ref.4 Ref.5 Corresponds to variant rs2974942 [ dbSNP | Ensembl ].		VAR_027931
	Natural variant	476	1	N → K. Ref.1 Ref.3 Ref.4 Ref.5 Corresponds to variant rs2974944 [ dbSNP | Ensembl ].		VAR_027932
	Natural variant	554	1	G → A in a breast cancer sample; somatic mutation. Ref.7		VAR_036287
	Natural variant	627	1	R → K. Corresponds to variant rs35067467 [ dbSNP | Ensembl ].		VAR_057128
	Natural variant	748	1	E → K. Corresponds to variant rs4304271 [ dbSNP | Ensembl ].		VAR_027933
	Natural variant	882	1	L → H. Ref.1 Ref.3 Ref.4 Ref.5 Corresponds to variant rs2974938 [ dbSNP | Ensembl ].		VAR_027934
	Natural variant	883	1	R → S. Ref.1 Corresponds to variant rs1800000 [ dbSNP | Ensembl ].		VAR_019697
	Natural variant	905	1	D → Y Common polymorphism; can be associated with insulin resistance. Ref.1 Ref.6 Corresponds to variant rs1799999 [ dbSNP | Ensembl ].		VAR_019698
	Natural variant	931	1	A → E in NIDDM. Ref.5 Corresponds to variant rs35449651 [ dbSNP | Ensembl ].		VAR_019699

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 15, 2010. Version 3. Checksum: FACB2CEA7C00E75B	FASTA	1,122	125,767
	10 20 30 40 50 60 MEPSEVPSQI SKDNFLEVPN LSDSLCEDEE VTFQPGFSPQ PSRRGSDSSE DIYLDTPSSG 70 80 90 100 110 120 TRRVSFADSF GFNLVSVKEF DCWELPSAST TFDLGTDIFH TEEYVLAPLF DLPSSKEDLM 130 140 150 160 170 180 QQLQIQKAIL ESTESLLGST SIKGIIRVLN VSFEKLVYVR MSLDDWQTHY DILAEYVPNS 190 200 210 220 230 240 CDGETDQFSF KIVLVPPYQK DGSKVEFCIR YETSVGTFWS NNNGTNYTFI CQKKEQEPEP 250 260 270 280 290 300 VKPWKEVPNR QIKGCLKVKS SKEESSVTSE ENNFENPKNT DTYIPTIICS HEDKEDLEAS 310 320 330 340 350 360 NRNVKDVNRE HDEHNEKELE LMINQHLIRT RSTASRDERN TFSTDPVNFP NKAEGLEKKQ 370 380 390 400 410 420 IHGEICTDLF QRSLSPSSSA ESSVKGDFYC NEKYSSGDDC THQPSEETTS NMGEIKPSLG 430 440 450 460 470 480 DTSSDELVQL HTGSKEVLDD NANPAHGNGT VQIPCPSSDQ LMAGNLNKKH EGGAKNIEVK 490 500 510 520 530 540 DLGCLRRDFH SDTSACLKES TEEGSSKEDY YGNGKDDEEQ RIYLGVNEKQ RKNFQTILHD 550 560 570 580 590 600 QERKMGNPKI SVAGIGASNR DLATLLSEHT AIPTRAITAD VSHSPRTNLS WEEAVLTPEH 610 620 630 640 650 660 HHLTSEGSAL GGITGQVCSS RTGNVLRNDY LFQVEEKSGG INSEDQDNSP QHKQSWNVLE 670 680 690 700 710 720 SQGKSRENKT NITEHIKGQT DCEDVWGKRD NTRSLKATTE ELFTCQETVC CELSSLADHG 730 740 750 760 770 780 ITEKAEAGTA YIIKTTSEST PESMSAREKA IIAKLPQETA RSDRPIEVKE TAFDPHEGRN 790 800 810 820 830 840 DDSHYTLCQR DTVGVIYDND FEKESRLGIC NVRVDEMEKE ETMSMYNPRK THDREKCGTG 850 860 870 880 890 900 NITSVEESSW VITEYQKATS KLDLQLGMLP TDKTVFSENR DLRQVQELSK KTDSDAIVHS 910 920 930 940 950 960 AFNSDTNRAP QNSSPFSKHH TEISVSTNEQ AIAVENAVTT MASQPISTKS ENICNSTREI 970 980 990 1000 1010 1020 QGIEKHPYPE SKPEEVSRSS GIVTSGSRKE RCIGQIFQTE EYSVEKSLGP MILINKPLEN 1030 1040 1050 1060 1070 1080 MEEARHENEG LVSSGQSLYT SGEKESDSSA STSLPVEESQ AQGNESLFSK YTNSKIPYFL 1090 1100 1110 1120 LFLIFLITVY HYDLMIGLTF YVLSLSWLSW EEGRQKESVK KK
	Isoform 2 [UniParc]. Checksum: 16A09845C8C8273A	FASTA	74	8,187
	10 20 30 40 50 60 MEPSEVPSQI SKDNFLEVPN LSDSLCEDEE VTFQPGFSPQ PSRRGSDSSE DIYLDTPSSE 70 RTRAGACKTM ERSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes." Xia J., Scherer S.W., Cohen P.T.W., Majer M., Xi T., Norman R.A., Knowler W.C., Bogardus C., Prochazka M. Diabetes 47:1519-1524(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, VARIANTS MET-451; LYS-476; HIS-882; SER-883 AND TYR-905. Tissue: Skeletal muscle.
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS MET-451; LYS-476 AND HIS-882.
[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), VARIANTS MET-451; LYS-476 AND HIS-882.
[5]	"Sequence of the human glycogen-associated regulatory subunit of type I protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with non-insulin-dependent diabetes." Chen Y.H., Hansen L., Chen M.X., Bjorbaek C., Vestergaard H., Hansen T., Cohen P.T.W., Pederson O. Diabetes 43:1234-1241(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-1122 (ISOFORM 1), VARIANTS MET-451; LYS-476 AND HIS-882, VARIANT NIDDM GLU-931. Tissue: Skeletal muscle.
[6]	"A widespread amino acid polymorphism at codon 905 of the glycogen-associated regulatory subunit of protein phosphatase-1 is associated with insulin resistance and hypersecretion of insulin." Hansen L., Hansen T., Vestergaard H., Bjorbaek C., Echwald S.M., Clausen J.O., Chen Y.H., Chen M.X., Cohen P.T.W., Pedersen O. Hum. Mol. Genet. 4:1313-1320(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TYR-905.
[7]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-554.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF024578, AF024576, AF024577 Genomic DNA. Translation: AAB94596.1. AF024579 mRNA. Translation: AAB94597.1. AC092465 Genomic DNA. Translation: AAS07492.1. Sequence problems. AC093598 Genomic DNA. Translation: AAP22361.1. CH236947 Genomic DNA. Translation: EAL24370.1. BC126451 mRNA. Translation: AAI26452.1. BC126453 mRNA. Translation: AAI26454.1. X78578 mRNA. Translation: CAA55316.1.
IPI	IPI00003091. IPI00012532.
PIR	I38127.
RefSeq	NP_002702.2. NM_002711.3.
UniGene	Hs.458309.
3D structure databases
ProteinModelPortal	Q16821.
SMR	Q16821. Positions 110-230.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16821. 1 interaction.
STRING	9606.ENSP00000284601.
Protein family/group databases
CAZy	CBM21. Carbohydrate-Binding Module Family 21.
PTM databases
PhosphoSite	Q16821.
Polymorphism databases
DMDM	298286906.
Proteomic databases
PaxDb	Q16821.
PRIDE	Q16821.
Protocols and materials databases
DNASU	5506.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000284601; ENSP00000284601; ENSG00000154415. ENST00000284602; ENSP00000284602; ENSG00000154415.
GeneID	5506.
KEGG	hsa:5506.
UCSC	uc010ljy.1. human.
Organism-specific databases
CTD	5506.
GeneCards	GC07M113516.
H-InvDB	HIX0033522.
HGNC	HGNC:9291. PPP1R3A.
MIM	125853. phenotype. 600917. gene.
neXtProt	NX_Q16821.
PharmGKB	PA33651.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG288354.
HOVERGEN	HBG053657.
InParanoid	Q16821.
KO	K07189.
OMA	AFDPHEG.
OrthoDB	EOG412M6H.
PhylomeDB	Q16821.
Enzyme and pathway databases
Pathway_Interaction_DB	insulin_glucose_pathway. Insulin-mediated glucose transport.
Gene expression databases
ArrayExpress	Q16821.
Bgee	Q16821.
CleanEx	HS_PPP1R3A.
Genevestigator	Q16821.
GermOnline	ENSG00000154415. Homo sapiens.
Family and domain databases
InterPro	IPR005036. CBM_21. [Graphical view]
Pfam	PF03370. CBM_21. 1 hit. [Graphical view]
PROSITE	PS51159. CBM21. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5506.
NextBio	21300.
SOURCE	Search...

Entry information

Entry name

PPR3A_HUMAN

Accession

Primary (citable) accession number: Q16821
Secondary accession number(s): A0AVQ2 , A4D0T6, O43476, Q75LN8, Q7KYM8, Q86UI6

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2004
Last sequence update:	June 15, 2010
Last modified:	May 1, 2013
This is version 97 of the entry and version 3 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.