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Q10728 (MYPT1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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):
MBSP
Myosin phosphatase-targeting subunit 1
Short name=Myosin phosphatase target subunit 1
Protein phosphatase myosin-binding subunit
Protein phosphatase subunit 1M
Short name=PP-1M
Serine/threonine protein phosphatase PP1 smooth muscle regulatory subunit M110
Gene names
Name:Ppp1r12a
Synonyms:Mbs, Mypt1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1032 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. Ref.2

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. Interacts with PPP1CB; the interaction is direct. Interacts (when phosphorylated at Ser-445, Ser-472 and Ser-912) with 14-3-3 By similarity. Interacts with ARHA and CIT. Interacts directly with PRKG1. Non-covalent dimer of 2 dimers; PRKG1-PRKG1 and PPP1R12A-PPP1R12A By similarity. Interacts with SMTNL1 By similarity. Interacts with ROCK1 and ROCK2. Interacts with ZIPK/DAPK3 By similarity. Interacts with RAF1 By similarity. Interacts with HIF1AN By similarity. Ref.4 Ref.5 Ref.8

Subcellular location

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

Tissue specificity

Smooth muscle. Detected in aorta, portal vein, stomach, intestine, bladder and lung. Ref.3

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 on upon DNA damage, probably by ATM or ATR By similarity. Phosphorylated by CIT (Rho-associated kinase). Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-697. In vitro, phosphorylation of Ser-696 by PKA and PKG appears to prevent phosphorylation of the inhibitory site Thr-697, probably mediated by PRKG1 By similarity. Phosphorylated on upon DNA damage, probably by ATM or ATR By similarity. Phosphorylated by CIT (Rho-associated kinase). Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-697. May be phosphorylated at Thr-697 by DMPK; may inhibit the myosin phosphatase activity. 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.4 Ref.5 Ref.6 Ref.8

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

mitosis

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 sequence or structural similarity. Source: UniProtKB

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

   Cellular_componentPTW/PP1 phosphatase complex

Inferred from sequence or structural similarity. Source: UniProtKB

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

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

phosphoprotein phosphatase activity

Inferred from direct assay Ref.2. Source: RGD

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MPRIPQ6WCQ16EBI-918263,EBI-1022605From a different organism.
NF2P352402EBI-918263,EBI-1014472From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q10728-1)

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: Q10728-2)

The sequence of this isoform differs from the canonical sequence as follows:
     608-667: Missing.
Isoform 3 (identifier: Q10728-3)

The sequence of this isoform differs from the canonical sequence as follows:
     552-607: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10321032Protein phosphatase 1 regulatory subunit 12A
PRO_0000067027

Regions

Repeat39 – 6830ANK 1
Repeat72 – 10130ANK 2
Repeat105 – 13430ANK 3
Repeat138 – 16427ANK 4
Repeat198 – 22730ANK 5
Repeat231 – 26030ANK 6
Region683 – 866184Interaction with ROCK2
Motif35 – 384KVKF motif

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 By similarity
Modified residue4451Phosphoserine; by NUAK1 By similarity
Modified residue4721Phosphoserine; by NUAK1 By similarity
Modified residue4731Phosphoserine; by CDK1 By similarity
Modified residue4771Phosphoserine By similarity
Modified residue5071Phosphoserine By similarity
Modified residue6011Phosphoserine By similarity
Modified residue6691Phosphoserine By similarity
Modified residue6931Phosphoserine; by PKA and PKG; in vitro By similarity
Modified residue6961Phosphoserine; by PKA and PKG; in vitro By similarity
Modified residue6971Phosphothreonine; by ROCK1; ROCK2; CDC42BP; ZIPK/DAPK3 and RAF1 Ref.5 Ref.6
Modified residue8541Phosphoserine; by ROCK2 Ref.5
Modified residue8641Phosphoserine By similarity
Modified residue8731Phosphoserine By similarity
Modified residue9121Phosphoserine; by NUAK1 Probable
Modified residue9971Phosphoserine Ref.7

Natural variations

Alternative sequence552 – 60756Missing in isoform 3.
VSP_009255
Alternative sequence608 – 66760Missing in isoform 2.
VSP_009254

Experimental info

Sequence conflict111N → R in AAA92961. Ref.2
Sequence conflict3161T → N in AAA92961. Ref.2
Sequence conflict4241K → E in AAA92961. Ref.2
Sequence conflict5791A → P in AAA92961. Ref.2
Sequence conflict6821Q → H in AAA92961. Ref.2

Sequences

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

Last modified January 16, 2004. Version 2.
Checksum: 43B9FC1569CD5DDB

FASTA1,032115,283
        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 KEEERIMLRD 

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

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

       310        320        330        340        350        360 
LIESTANMEN NQPQKTFKNK ETLIIEPEKN ASRIESLEQE KADEEEEGKK DESSCSSEED 

       370        380        390        400        410        420 
EEDDSESEAE TDKTKPMASV TNAHTASTQA APAAVTTPTL SSNQGTPTSP VKKFPTSTTK 

       430        440        450        460        470        480 
ISPKEEERKD ESPASWRLGL RKTGSYGALA EITASKEAQK EKDTAGVIRS ASSPRLSSSL 

       490        500        510        520        530        540 
DNKEKEKDNK GTRLAYVAPT IPRRLGSTSD IEEKENRESS NLRTSSSYTR RKWEDDLKKN 

       550        560        570        580        590        600 
SSINEGSTYH RSCSFGRRQD DLISCSVPST TSTPTVTSAA GLQKSFLSST STTAKTPPGS 

       610        620        630        640        650        660 
SPAGTQSSTS NRLWAEDSTE KEKDSAPTAA TILVAPTVVS AAASSTTALT TTTAGTLSST 

       670        680        690        700        710        720 
SEVRERRRSY LTPVRDEESE SQRKARSRQA RQSRRSTQGV TLTDLQEAEK TIGRSRSTRT 

       730        740        750        760        770        780 
REQENEEKDK EEKEKQDKEK QEEKKESEVS REDEYKQKYS RTYDETYARY RPVSTSSSST 

       790        800        810        820        830        840 
PSSSSLSTLG SSLYASSQLN RPNSLVGITS AYSRGLTKDN EREGEKKEEE KEGEDKSQPK 

       850        860        870        880        890        900 
SIRERRRPRE KRRSTGVSFW TQDSDENEQE RQSDTEDGSS KRDTQTDSVS RYDSSSTSSS 

       910        920        930        940        950        960 
DRYDSLLGRS ASYSYLEERK PYGSRLEKDD STDFKKLYEQ ILAENEKLKA QLHDTNMELT 

       970        980        990       1000       1010       1020 
DLKLQLEKAT QRQERFADRS LLEMEKRERR ALERRISEME EELKMLPDLK ADNQRLKDEN 

      1030 
GALIRVISKL SK 

« Hide

Isoform 2 [UniParc].

Checksum: C9C80CD420FCE751
Show »

FASTA972109,116
Isoform 3 [UniParc].

Checksum: 9C25C0117ED89661
Show »

FASTA976109,720

References

« Hide 'large scale' references
[1]"Molecular cloning of cDNA encoding the 110 kDa and 21 kDa regulatory subunits of smooth muscle protein phosphatase 1M."
Chen Y.H., Chen M.X., Alessi D.R., Campbell D.G., Shanahan C., Cohen P., Cohen P.T.W.
FEBS Lett. 356:51-55(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Tissue: Aorta.
[2]"Molecular cloning and functional expression of a recombinant 72.5 kDa fragment of the 110 kDa regulatory subunit of smooth muscle protein phosphatase 1M."
Haystead C.M.M., Gailly P., Somlyo A.P., Somlyo A.V., Haystead T.A.J.
FEBS Lett. 377:123-127(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 11-728 (ISOFORM 2), FUNCTION.
Strain: Wistar.
Tissue: Kidney.
[3]"A myosin phosphatase targeting subunit isoform transition defines a smooth muscle developmental phenotypic switch."
Dirksen W.P., Vladic F., Fisher S.A.
Am. J. Physiol. 278:C589-C600(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 490-665 (ISOFORM 1), TISSUE SPECIFICITY, ALTERNATIVE SPLICING.
Strain: Sprague-Dawley.
[4]"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.
[5]"Phosphorylation of myosin-binding subunit (MBS) of myosin phosphatase by Rho-kinase in vivo."
Kawano Y., Fukata Y., Oshiro N., Amano M., Nakamura T., Ito M., Matsumura F., Inagaki M., Kaibuchi K.
J. Cell Biol. 147:1023-1038(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-697 AND SER-854, INTERACTION WITH ROCK1.
[6]"Zipper-interacting protein kinase induces Ca(2+)-free smooth muscle contraction via myosin light chain phosphorylation."
Niiro N., Ikebe M.
J. Biol. Chem. 276:29567-29574(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-697 BY ZIPK/DAPK3.
[7]"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-997, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]"ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells."
Wang Y., Zheng X.R., Riddick N., Bryden M., Baur W., Zhang X., Surks H.K.
Circ. Res. 104:531-540(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH ROCK1 AND ROCK2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S74907 mRNA. Translation: AAB32731.1.
U50185 mRNA. Translation: AAA92961.1.
AF110176 Genomic DNA. Translation: AAD34326.1.
PIRS68418.
RefSeqNP_446342.1. NM_053890.1.
XP_006241377.1. XM_006241315.1.
UniGeneRn.162937.
Rn.220285.

3D structure databases

ProteinModelPortalQ10728.
SMRQ10728. Positions 1-291.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ10728. 4 interactions.
MINTMINT-4596910.
STRING10116.ENSRNOP00000062297.

PTM databases

PhosphoSiteQ10728.

Proteomic databases

PaxDbQ10728.
PRIDEQ10728.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID116670.
KEGGrno:116670.
UCSCRGD:620013. rat. [Q10728-1]

Organism-specific databases

CTD4659.
RGD620013. Ppp1r12a.

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000290648.
HOVERGENHBG052561.
InParanoidQ10728.
KOK06270.
PhylomeDBQ10728.

Gene expression databases

GenevestigatorQ10728.

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

NextBio619487.
PROQ10728.

Entry information

Entry nameMYPT1_RAT
AccessionPrimary (citable) accession number: Q10728
Secondary accession number(s): Q62937, Q9WU33
Entry history
Integrated into UniProtKB/Swiss-Prot: January 16, 2004
Last sequence update: January 16, 2004
Last modified: April 16, 2014
This is version 120 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