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UniProtKB - Q9DBR7 (MYPT1_MOUSE)

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Protein

Protein phosphatase 1 regulatory subunit 12A

Gene

Ppp1r12a

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1309528. Ppp1r12a.

Subcellular locationi

  • Cytoplasm By similarity

    • Note: Along actomyosin filaments and stress fibers.By similarity

GO - Cellular componenti

  • A band Source: UniProtKB
  • actin cytoskeleton Source: MGI
  • centrosome Source: UniProtKB
  • contractile fiber Source: MGI
  • cytosol Source: MGI
  • focal adhesion Source: MGI
  • kinetochore Source: UniProtKB
  • PTW/PP1 phosphatase complex Source: UniProtKB
  • Z disc Source: UniProtKB
Complete GO annotation...

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.
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

GO - Molecular functioni

Complete GO annotation...

Protein-protein interaction databases

BioGridi201677. 1 interactor.
DIPiDIP-29982N.
IntActiQ9DBR7. 4 interactors.
MINTiMINT-4102998.
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.
IPR031775. PRKG1_interact.
PfamiView protein in Pfam
PF12796. Ank_2. 2 hits.
PF15898. PRKG1_interact. 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: July 5, 2017
This is version 141 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot