Reviewed, UniProtKB/Swiss-Prot Q16821 (PPR3A_HUMAN)

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

Gene names

Name:	PPP1R3A
Synonyms:	PP1G

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1122 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 proteinBy 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	Defects in PPP1R3A are a cause of susceptibility to noninsulin-dependent diabetes mellitus (NIDDM) [MIM:125853]; also known as diabetes mellitus type II. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. Ref.5 Defects in PPP1R3A are a cause of insulin resistance (Ins resistance).
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
PTM	Phosphoprotein
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.

Notes: No experimental confirmation available.

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	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
	Modified residue	759	1	Phosphothreonine Ref.6
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: dbSNP rs8192687.		VAR_027929
	Natural variant	231	1	C → Y: dbSNP rs7801819.		VAR_027930
	Natural variant	451	1	M → V: dbSNP rs2974942. Ref.2		VAR_027931
	Natural variant	476	1	K → N: dbSNP rs2974944. Ref.2		VAR_027932
	Natural variant	554	1	G → A in a breast cancer sample; somatic mutation. Ref.8		VAR_036287
	Natural variant	748	1	E → K: dbSNP rs4304271.		VAR_027933
	Natural variant	882	1	H → L: dbSNP rs2974938. Ref.2		VAR_027934
	Natural variant	883	1	R → S: dbSNP rs1800000. Ref.1		VAR_019697
	Natural variant	905	1	D → Y in insulin resistance. dbSNP rs1799999. Ref.1 Ref.7		VAR_019698
	Natural variant	931	1	A → E in NIDDM. Ref.5		VAR_019699

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1998. Version 2. Checksum: 4250FB0A4DC0B686	FASTA	1,122	125,837
	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 MQIPCPSSDQ LMAGNLNKKH EGGAKKIEVK 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 DHRQVQELSK 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. Checksum: 16A09845C8C8273A		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., Majer M., Xi T., Norman R.A., Knowler W.C., Bogardus C., Prochazka M. Diabetes 47:1519-1524(1998) [PubMed: 9726244] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, VARIANT INSULIN RESISTANCE TYR-905, VARIANT SER-883. 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: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS VAL-451; ASN-476 AND LEU-882.
[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: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[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: 7926294] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2-1122 (ISOFORM 1), VARIANT NIDDM GLU-931. Tissue: Skeletal muscle.
[6]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-759, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"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., Pedersen O. Hum. Mol. Genet. 4:1313-1320(1995) [PubMed: 7581368] [Abstract] Cited for: VARIANT INSULIN RESISTANCE TYR-905.
[8]	"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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ALA-554.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
PIR	I38127.
RefSeq	NP_002702.2.
UniGene	Hs.458309
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q16821.
Proteomic databases
PRIDE	Q16821.
Genome annotation databases
Ensembl	ENSG00000154415. Homo sapiens. [Contig view]
GeneID	5506.
KEGG	hsa:5506.
Organism-specific databases
GeneCards	GC07M113301.
H-InvDB	HIX0033522.
HGNC	HGNC:9291. PPP1R3A.
MIM	125853. phenotype. 600917. gene.
PharmGKB	PA33651.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q16821.
HOVERGEN	Q16821.
Gene expression databases
ArrayExpress	Q16821.
CleanEx	HS_PPP1R3A.
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 Resources
LinkHub	Q16821.
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:	November 1, 1998
Last modified:	December 16, 2008
This is version 59 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)