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Protein

Protein phosphatase 1 regulatory subunit 12A

Gene

Ppp1r12a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Key regulator of protein phosphatase 1C (PPP1C). Mediates binding to myosin. As part of the PPP1C complex, involved in dephosphorylation of PLK1. Capable of inhibiting HIF1AN-dependent suppression of HIF1A activity (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-MMU-2565942 Regulation of PLK1 Activity at G2/M Transition
R-MMU-5625740 RHO GTPases activate PKNs
R-MMU-5627123 RHO GTPases activate PAKs

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase 1 regulatory subunit 12A
Alternative name(s):
Myosin phosphatase-targeting subunit 1
Short name:
Myosin phosphatase target subunit 1
Gene namesi
Name:Ppp1r12aImported
Synonyms:Mypt1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1309528 Ppp1r12a

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000670261 – 1029Protein phosphatase 1 regulatory subunit 12AAdd BLAST1029

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei67(3S)-3-hydroxyasparagine; by HIF1ANBy similarity1
Modified residuei100(3S)-3-hydroxyasparagine; by HIF1ANBy similarity1
Modified residuei226(3S)-3-hydroxyasparagine; by HIF1ANBy similarity1
Modified residuei299PhosphoserineCombined sources1
Modified residuei422PhosphoserineBy similarity1
Modified residuei432PhosphoserineBy similarity1
Modified residuei443PhosphothreonineBy similarity1
Modified residuei445Phosphoserine; by NUAK1Combined sources1
Modified residuei446PhosphotyrosineCombined sources1
Modified residuei472Phosphoserine; by NUAK1By similarity1
Modified residuei473Phosphoserine; by CDK1By similarity1
Modified residuei477PhosphoserineBy similarity1
Modified residuei507PhosphoserineBy similarity1
Modified residuei509PhosphoserineBy similarity1
Modified residuei601PhosphoserineBy similarity1
Modified residuei618PhosphoserineBy similarity1
Modified residuei690Phosphoserine; by PKA and PKG; in vitroBy similarity1
Modified residuei693Phosphoserine; by PKA and PKG; in vitroBy similarity1
Modified residuei694Phosphothreonine; by ROCK1, ROCK2, CDC42BP, ZIPK/DAPK3 and RAF1By similarity1
Modified residuei801PhosphoserineCombined sources1
Modified residuei851Phosphoserine; by ROCK2By similarity1
Modified residuei861PhosphoserineCombined sources1
Modified residuei870PhosphoserineCombined sources1
Modified residuei902PhosphoserineBy similarity1
Modified residuei907PhosphoserineBy similarity1
Modified residuei909Phosphoserine; by NUAK1By similarity1
Modified residuei994PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CIT (Rho-associated kinase) (By similarity). Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-694 (By similarity). Phosphorylated on upon DNA damage, probably by ATM or ATR. In vitro, phosphorylation of Ser-693 by PKA and PKG appears to prevent phosphorylation of the inhibitory site Thr-694, probably mediated by PRKG1. Phosphorylation at Ser-445, Ser-472 and Ser-909 by NUAK1 promotes interaction with 14-3-3, leading to inhibit interaction with myosin light chain MLC2, preventing dephosphorylation of MLC2. May be phosphorylated at Thr-694 by DMPK; may inhibit the myosin phosphatase activity (By similarity). Phosphorylated at Ser-473 by CDK1 during mitosis, creating docking sites for the POLO box domains of PLK1. Subsequently, PLK1 binds and phosphorylates PPP1R12A (By similarity).By similarity

Keywords - PTMi

Hydroxylation, Phosphoprotein

Proteomic databases

EPDiQ9DBR7
PaxDbiQ9DBR7
PeptideAtlasiQ9DBR7
PRIDEiQ9DBR7

PTM databases

iPTMnetiQ9DBR7
PhosphoSitePlusiQ9DBR7

Miscellaneous databases

PMAP-CutDBiQ9DBR7

Expressioni

Tissue specificityi

Expressed in striated and vascular smooth muscle, specificcally in type 2a fibers (at protein level). Expression levels are 20-30% higher in developed males than females (at protein level).1 Publication

Developmental stagei

In neonates, expressed at low levels in striated and smooth muscles. As the animals mature sexually, expression increases 10-20-fold. Pregnancy promotes a 2-3-fold increase in expression in striated, vascular and uterine muscle (at protein level).1 Publication

Gene expression databases

BgeeiENSMUSG00000019907
ExpressionAtlasiQ9DBR7 baseline and differential
GenevisibleiQ9DBR7 MM

Interactioni

Subunit structurei

PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, and one or several targeting or regulatory subunits. PPP1R12A mediates binding to myosin. Interacts with ARHA and CIT (By similarity). Binds PPP1R12B, ROCK1 and IL16. Interacts directly with PRKG1. Non-covalent dimer of 2 dimers; PRKG1-PRKG1 and PPP1R12A-PPP1R12A. Interacts with SMTNL1 (By similarity). Interacts with PPP1CB; the interaction is direct. Interacts (when phosphorylated at Ser-445, Ser-472 and Ser-910) with 14-3-3. Interacts with ROCK1 and ROCK2. Interacts with isoform 1 and isoform 2 of ZIPK/DAPK3. Interacts with RAF1. Interacts with HIF1AN (By similarity). Interacts with NCKAP1L (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Prkg1P0C605-12EBI-1014335,EBI-15699851

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201677, 2 interactors
DIPiDIP-29982N
IntActiQ9DBR7, 7 interactors
MINTiQ9DBR7
STRINGi10090.ENSMUSP00000069257

Structurei

3D structure databases

ProteinModelPortaliQ9DBR7
SMRiQ9DBR7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati39 – 68ANK 1Add BLAST30
Repeati72 – 101ANK 2Add BLAST30
Repeati105 – 134ANK 3Add BLAST30
Repeati138 – 164ANK 4Add BLAST27
Repeati198 – 227ANK 5Add BLAST30
Repeati231 – 260ANK 6Add BLAST30

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni680 – 863Interaction with ROCK2By similarityAdd BLAST184

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi35 – 38KVKF motif4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi335 – 370Glu/Ser-richAdd BLAST36
Compositional biasi771 – 794Ser-richAdd BLAST24

Domaini

Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.By similarity
The KVKF motif mediates interaction with PPP1CB.By similarity

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0505 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00760000119141
HOGENOMiHOG000290648
HOVERGENiHBG052561
InParanoidiQ9DBR7
KOiK06270
OMAiVDNLCDM
OrthoDBiEOG091G12CT
PhylomeDBiQ9DBR7
TreeFamiTF105543

Family and domain databases

CDDicd00204 ANK, 2 hits
Gene3Di1.25.40.20, 2 hits
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR017401 MYPT1/MYPT2/Mbs85
IPR031775 PRKG1_interact
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF15898 PRKG1_interact, 1 hit
PIRSFiPIRSF038141 PP1_12ABC_vert, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 6 hits
SUPFAMiSSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 4 hits

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9DBR7-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKMADAKQKR NEQLKRWIGS ETDLEPPVVK RQKTKVKFDD GAVFLAACSS
60 70 80 90 100
GDTDEVLKLL HRGADINYAN VDGLTALHQA CIDDNVDMVK FLVENGANIN
110 120 130 140 150
QPDNEGWIPL HAAASCGYLD IAEFLIGQGA HVGAVNSEGD TPLDIAEEEA
160 170 180 190 200
MEELLQNEVN RQGVDIEAAR KEEERVMLRD ARQWLNSGHI SDVRHAKSGG
210 220 230 240 250
TALHVAAAKG YTEVLKLLIQ AGYDVNIKDY DGWTPLHAAA HWGKEEACRI
260 270 280 290 300
LVDNLCDMET VNKVGQTAFD VADEDILGYL EELQKKQTLL HSEKRDKKSP
310 320 330 340 350
LIESTANMEN NQPQKAFKNK ETLIIEPEKN ASRIESLEHE KADEEEEGKK
360 370 380 390 400
DESSCSSEED EEDDSESEAE TDKTKPMASV SNAHTSSTQA APAAVTAPTL
410 420 430 440 450
SSNQGTPTSP VKKFPISTTK ISPKEEERKD ESPASWRLGL RKTGSYGALA
460 470 480 490 500
EISASKEAQK EKDTAGVMRS ASSPRLSSSL DNKEKEKDNK GTRLAYVTPT
510 520 530 540 550
IPRRLASTSD IEEKENRESS SLRTSSSYTR RKWEDDLKKN SSINEGSTYH
560 570 580 590 600
RSCSFGRRQD DLISCSVPST TSTPTVTSAA GLQRSLPSST STAAKTPPGS
610 620 630 640 650
SSAGTQSSTS NRLWAEDSTE KEKDSAPTAV TIPVAPTVVN AAAPSTTTLT
660 670 680 690 700
TTTAGTVSEV RERRRSYLTP VRDEESESQR KARSRQARQS RRSTQGVTLT
710 720 730 740 750
DLQEAEKTIG RSRSTRTREQ ENEEKEKEEK EKQDKEKQEE KKESEASRED
760 770 780 790 800
EYKQKYSRTY DETYTRYRPV STSSSSAPSS SSLSTLGSTL YASSQLNRPN
810 820 830 840 850
SLVGITSAYS RGLAKENERE GEKKEEEKEG EDKSQPKSIR ERRRPREKRR
860 870 880 890 900
STGVSFWTQD SDENEQERQS DTEDGSSKRE TQTDSVSRYD SSSTSSSDRY
910 920 930 940 950
DSLLGRSASY SYLEDRKPYS SRLEKDDSTD FKKLYEQILA ENEKLKAQLH
960 970 980 990 1000
DTNMELTDLK LQLEKATQRQ ERFADRSQLE MEKRERRALE RRISEMEEEL
1010 1020
KMLPDLKADN QRLKDENGAL IRVISKLSK
Length:1,029
Mass (Da):114,996
Last modified:December 15, 2009 - v2
Checksum:iC466573AC1DFC81F
GO
Isoform 2 (identifier: Q9DBR7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     985-1029: ERRALERRISEMEEELKMLPDLKADNQRLKDENGALIRVISKLSK → VAGKSQYLLGGTKSSRKKNI

Show »
Length:1,004
Mass (Da):111,809
Checksum:i1CF7118111B85BF1
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038478985 – 1029ERRAL…SKLSK → VAGKSQYLLGGTKSSRKKNI in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK035230 mRNA Translation: BAC28990.1
AK004785 mRNA Translation: BAB23563.1
CH466539 Genomic DNA Translation: EDL21703.1
BC125381 mRNA Translation: AAI25382.1
BC137630 mRNA Translation: AAI37631.1
AB042280 Genomic DNA Translation: BAB39108.1
CCDSiCCDS36052.1 [Q9DBR7-2]
RefSeqiNP_082168.1, NM_027892.2 [Q9DBR7-2]
XP_006513389.1, XM_006513326.3 [Q9DBR7-1]
UniGeneiMm.422959
Mm.440002
Mm.489819

Genome annotation databases

EnsembliENSMUST00000070663; ENSMUSP00000069257; ENSMUSG00000019907 [Q9DBR7-2]
ENSMUST00000219263; ENSMUSP00000151842; ENSMUSG00000019907 [Q9DBR7-1]
GeneIDi17931
KEGGimmu:17931
UCSCiuc007gzc.1 mouse [Q9DBR7-2]
uc007gzd.1 mouse [Q9DBR7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMYPT1_MOUSE
AccessioniPrimary (citable) accession number: Q9DBR7
Secondary accession number(s): Q05A74, Q8CBV2, Q99NB6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: December 15, 2009
Last modified: March 28, 2018
This is version 148 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
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Main funding by: National Institutes of Health