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Q9DBR7 (MYPT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 112. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Protein phosphatase 1 regulatory subunit 12A
Alternative name(s):
Myosin phosphatase-targeting subunit 1
Short name=Myosin phosphatase target subunit 1
Gene names
Name:Ppp1r12a
Synonyms:Mypt1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1029 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, and one or several targeting or regulatory subunits. PPP1R12A mediates binding to myosin. Binds PPP1R12B, ROCK1 and IL16 By similarity. Interacts with ARHA and CIT. Interacts directly with PRKG1. Non-covalent dimer of 2 dimers; PRKG1-PRKG1 and PPP1R12A-PPP1R12A. Interacts with PPP1CB; the interaction is direct. Interacts (when phosphorylated at Ser-445, Ser-472 and Ser-909) with 14-3-3 By similarity. Interacts with SMTNL1. Interacts with ZIPK/DAPK3 By similarity. Interacts with RAF1 By similarity. Interacts with HIF1AN By similarity. Ref.5 Ref.7

Subcellular location

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

Tissue specificity

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). Ref.7

Developmental stage

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). Ref.7

Domain

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.

Post-translational modification

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. Ref.5

Sequence similarities

Contains 6 ANK repeats.

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityAlternative splicing
   DomainANK repeat
Repeat
   PTMHydroxylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcentrosome organization

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic nuclear division

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of catalytic activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

protein dephosphorylation

Inferred from mutant phenotype PubMed 17369396. Source: MGI

regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of myosin-light-chain-phosphatase activity

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of nucleocytoplasmic transport

Inferred from mutant phenotype PubMed 17369396. Source: MGI

   Cellular_componentPTW/PP1 phosphatase complex

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

contractile fiber

Inferred from electronic annotation. Source: Ensembl

kinetochore

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_function14-3-3 protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

enzyme inhibitor activity

Inferred from sequence or structural similarity. Source: UniProtKB

phosphatase regulator activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9DBR7-1)

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: Q9DBR7-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10291029Protein phosphatase 1 regulatory subunit 12A
PRO_0000067026

Regions

Repeat39 – 6830ANK 1
Repeat72 – 10130ANK 2
Repeat105 – 13430ANK 3
Repeat138 – 16427ANK 4
Repeat198 – 22730ANK 5
Repeat231 – 26030ANK 6
Region680 – 863184Interaction with ROCK2 By similarity
Motif35 – 384KVKF motif
Compositional bias335 – 37036Glu/Ser-rich
Compositional bias771 – 79424Ser-rich

Amino acid modifications

Modified residue671(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residue1001(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residue2261(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residue2991Phosphoserine By similarity
Modified residue4221Phosphoserine By similarity
Modified residue4321Phosphoserine By similarity
Modified residue4431Phosphothreonine
Modified residue4451Phosphoserine; alternate Ref.6
Modified residue4451Phosphoserine; by NUAK1; alternate Probable
Modified residue4721Phosphoserine; by NUAK1 By similarity
Modified residue4731Phosphoserine; by CDK1 By similarity
Modified residue4771Phosphoserine By similarity
Modified residue5071Phosphoserine
Modified residue6011Phosphoserine By similarity
Modified residue6661Phosphoserine
Modified residue6901Phosphoserine; by PKA and PKG; in vitro By similarity
Modified residue6931Phosphoserine; by PKA and PKG; in vitro By similarity
Modified residue6941Phosphothreonine; by ROCK1, ROCK2, CDC42BP, ZIPK/DAPK3 and RAF1
Modified residue8511Phosphoserine; by ROCK2 By similarity
Modified residue8611Phosphoserine By similarity
Modified residue8701Phosphoserine
Modified residue9091Phosphoserine; by NUAK1 Probable
Modified residue9941Phosphoserine By similarity

Natural variations

Alternative sequence985 – 102945ERRAL…SKLSK → VAGKSQYLLGGTKSSRKKNI in isoform 2.
VSP_038478

Sequences

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

Last modified December 15, 2009. Version 2.
Checksum: C466573AC1DFC81F

FASTA1,029114,996
        10         20         30         40         50         60 
MKMADAKQKR NEQLKRWIGS ETDLEPPVVK RQKTKVKFDD GAVFLAACSS GDTDEVLKLL 

        70         80         90        100        110        120 
HRGADINYAN VDGLTALHQA CIDDNVDMVK FLVENGANIN QPDNEGWIPL HAAASCGYLD 

       130        140        150        160        170        180 
IAEFLIGQGA HVGAVNSEGD TPLDIAEEEA MEELLQNEVN RQGVDIEAAR KEEERVMLRD 

       190        200        210        220        230        240 
ARQWLNSGHI SDVRHAKSGG TALHVAAAKG YTEVLKLLIQ AGYDVNIKDY DGWTPLHAAA 

       250        260        270        280        290        300 
HWGKEEACRI LVDNLCDMET VNKVGQTAFD VADEDILGYL EELQKKQTLL HSEKRDKKSP 

       310        320        330        340        350        360 
LIESTANMEN NQPQKAFKNK ETLIIEPEKN ASRIESLEHE KADEEEEGKK DESSCSSEED 

       370        380        390        400        410        420 
EEDDSESEAE TDKTKPMASV SNAHTSSTQA APAAVTAPTL SSNQGTPTSP VKKFPISTTK 

       430        440        450        460        470        480 
ISPKEEERKD ESPASWRLGL RKTGSYGALA EISASKEAQK EKDTAGVMRS ASSPRLSSSL 

       490        500        510        520        530        540 
DNKEKEKDNK GTRLAYVTPT IPRRLASTSD IEEKENRESS SLRTSSSYTR RKWEDDLKKN 

       550        560        570        580        590        600 
SSINEGSTYH RSCSFGRRQD DLISCSVPST TSTPTVTSAA GLQRSLPSST STAAKTPPGS 

       610        620        630        640        650        660 
SSAGTQSSTS NRLWAEDSTE KEKDSAPTAV TIPVAPTVVN AAAPSTTTLT TTTAGTVSEV 

       670        680        690        700        710        720 
RERRRSYLTP VRDEESESQR KARSRQARQS RRSTQGVTLT DLQEAEKTIG RSRSTRTREQ 

       730        740        750        760        770        780 
ENEEKEKEEK EKQDKEKQEE KKESEASRED EYKQKYSRTY DETYTRYRPV STSSSSAPSS 

       790        800        810        820        830        840 
SSLSTLGSTL YASSQLNRPN SLVGITSAYS RGLAKENERE GEKKEEEKEG EDKSQPKSIR 

       850        860        870        880        890        900 
ERRRPREKRR STGVSFWTQD SDENEQERQS DTEDGSSKRE TQTDSVSRYD SSSTSSSDRY 

       910        920        930        940        950        960 
DSLLGRSASY SYLEDRKPYS SRLEKDDSTD FKKLYEQILA ENEKLKAQLH DTNMELTDLK 

       970        980        990       1000       1010       1020 
LQLEKATQRQ ERFADRSQLE MEKRERRALE RRISEMEEEL KMLPDLKADN QRLKDENGAL 


IRVISKLSK 

« Hide

Isoform 2 [UniParc].

Checksum: 1CF7118111B85BF1
Show »

FASTA1,004111,809

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Lung and Urinary bladder.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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.
[4]"Molecular cloning and analysis of the 5'-flanking region of human MYPT1 gene."
Machida H., Ito M., Okamoto R., Shiraki K., Isaka N., Hartshorne D.J., Nakano T.
Biochim. Biophys. Acta 1517:424-429(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-79.
[5]"Regulation of myosin phosphatase by Rho and Rho-associated kinase (Rho-kinase)."
Kimura K., Ito M., Amano M., Chihara K., Fukata Y., Nakafuku M., Yamamori B., Feng J., Nakano T., Okawa K., Iwamatsu A., Kaibuchi K.
Science 273:245-248(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH ARHA AND CIT.
[6]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[7]"Smoothelin-like 1 protein regulates myosin phosphatase-targeting subunit 1 expression during sexual development and pregnancy."
Lontay B., Bodoor K., Weitzel D.H., Loiselle D., Fortner C., Lengyel S., Zheng D., Devente J., Hickner R., Haystead T.A.
J. Biol. Chem. 285:29357-29366(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SMTNL1, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS36052.1. [Q9DBR7-2]
RefSeqNP_082168.1. NM_027892.2. [Q9DBR7-2]
XP_006513389.1. XM_006513326.1. [Q9DBR7-1]
UniGeneMm.422959.
Mm.489819.

3D structure databases

ProteinModelPortalQ9DBR7.
SMRQ9DBR7. Positions 1-291, 656-712.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-29982N.
IntActQ9DBR7. 3 interactions.
MINTMINT-4102998.
STRING10090.ENSMUSP00000100915.

PTM databases

PhosphoSiteQ9DBR7.

Proteomic databases

MaxQBQ9DBR7.
PaxDbQ9DBR7.
PRIDEQ9DBR7.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000070663; ENSMUSP00000069257; ENSMUSG00000019907. [Q9DBR7-2]
GeneID17931.
KEGGmmu:17931.
UCSCuc007gzc.1. mouse. [Q9DBR7-2]
uc007gzd.1. mouse. [Q9DBR7-1]

Organism-specific databases

CTD4659.
MGIMGI:1309528. Ppp1r12a.

Phylogenomic databases

eggNOGCOG0666.
GeneTreeENSGT00730000110434.
HOGENOMHOG000290648.
HOVERGENHBG052561.
InParanoidQ05A74.
KOK06270.
OMATDKQTTT.
OrthoDBEOG7060Q5.
PhylomeDBQ9DBR7.
TreeFamTF105543.

Gene expression databases

BgeeQ9DBR7.
GenevestigatorQ9DBR7.

Family and domain databases

Gene3D1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR017401. Pase-1_reg_su_12A/B/C_euk.
[Graphical view]
PfamPF12796. Ank_2. 2 hits.
[Graphical view]
PIRSFPIRSF038141. PP1_12ABC_vert. 1 hit.
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 6 hits.
[Graphical view]
SUPFAMSSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPPP1R12A. mouse.
NextBio292815.
PMAP-CutDBQ9DBR7.
PROQ9DBR7.
SOURCESearch...

Entry information

Entry nameMYPT1_MOUSE
AccessionPrimary (citable) accession number: Q9DBR7
Secondary accession number(s): Q05A74, Q8CBV2, Q99NB6
Entry history
Integrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: December 15, 2009
Last modified: July 9, 2014
This is version 112 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

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