ID MYPT1_CHICK Reviewed; 1004 AA.
AC Q90623; Q10727; Q90624;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 24-JAN-2024, entry version 144.
DE RecName: Full=Protein phosphatase 1 regulatory subunit 12A;
DE AltName: Full=130 kDa myosin-binding subunit of smooth muscle myosin phosphatase;
DE AltName: Full=Myosin phosphatase-targeting subunit 1;
DE Short=Myosin phosphatase target subunit 1;
DE AltName: Full=PP1M subunit M110;
DE AltName: Full=Protein phosphatase myosin-binding subunit;
GN Name=PPP1R12A; Synonyms=MBS, MYPT1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PARTIAL PROTEIN SEQUENCE,
RP FUNCTION, SUBUNIT, INTERACTION WITH MYOSIN, AND TISSUE SPECIFICITY.
RC TISSUE=Gizzard;
RX PubMed=7982954; DOI=10.1016/s0021-9258(18)43828-8;
RA Shimizu H., Ito M., Miyahara M., Ichikawa K., Okubo S., Konishi T.,
RA Naka M., Tanaka T., Hirano K., Hartshorne D.J., Nakano T.;
RT "Characterization of the myosin-binding subunit of smooth muscle myosin
RT phosphatase.";
RL J. Biol. Chem. 269:30407-30411(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 681-1004, AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Gizzard;
RX PubMed=7988720; DOI=10.1016/0014-5793(94)01231-8;
RA Chen Y.H., Chen M.X., Alessi D.R., Campbell D.G., Shanahan C., Cohen P.,
RA Cohen P.T.W.;
RT "Molecular cloning of cDNA encoding the 110 kDa and 21 kDa regulatory
RT subunits of smooth muscle protein phosphatase 1M.";
RL FEBS Lett. 356:51-55(1994).
RN [3]
RP PARTIAL PROTEIN SEQUENCE, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP PHOSPHORYLATION AT THR-695 AND THR-850.
RX PubMed=12220642; DOI=10.1016/s0014-5793(02)03175-7;
RA Velasco G., Armstrong C., Morrice N., Frame S., Cohen P.;
RT "Phosphorylation of the regulatory subunit of smooth muscle protein
RT phosphatase 1M at Thr850 induces its dissociation from myosin.";
RL FEBS Lett. 527:101-104(2002).
RN [4]
RP PHOSPHORYLATION AT THR-695 AND THR-850, AND MUTAGENESIS OF THR-695 AND
RP THR-850.
RX PubMed=10601309; DOI=10.1074/jbc.274.52.37385;
RA Feng J., Ito M., Ichikawa K., Isaka N., Nishikawa M., Hartshorne D.J.,
RA Nakano T.;
RT "Inhibitory phosphorylation site for Rho-associated kinase on smooth muscle
RT myosin phosphatase.";
RL J. Biol. Chem. 274:37385-37390(1999).
RN [5]
RP PHOSPHORYLATION BY DMPK.
RX PubMed=11287000; DOI=10.1016/s0014-5793(01)02283-9;
RA Muranyi A., Zhang R., Liu F., Hirano K., Ito M., Epstein H.F.,
RA Hartshorne D.J.;
RT "Myotonic dystrophy protein kinase phosphorylates the myosin phosphatase
RT targeting subunit and inhibits myosin phosphatase activity.";
RL FEBS Lett. 493:80-84(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1-299 IN COMPLEX WITH PPP1CB.
RX PubMed=15164081; DOI=10.1038/nature02582;
RA Terrak M., Kerff F., Langsetmo K., Tao T., Dominguez R.;
RT "Structural basis of protein phosphatase 1 regulation.";
RL Nature 429:780-784(2004).
CC -!- FUNCTION: Regulates myosin phosphatase activity.
CC {ECO:0000269|PubMed:7982954}.
CC -!- SUBUNIT: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC,
CC and one or several targeting or regulatory subunits (By similarity).
CC PPP1R12A mediates binding to myosin. {ECO:0000250,
CC ECO:0000269|PubMed:15164081, ECO:0000269|PubMed:7982954}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O14974}.
CC Cytoplasm, cytoskeleton, stress fiber {ECO:0000250|UniProtKB:O14974}.
CC Note=Also along actomyosin filaments. {ECO:0000250|UniProtKB:O14974}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=M133;
CC IsoId=Q90623-1; Sequence=Displayed;
CC Name=2; Synonyms=M130;
CC IsoId=Q90623-2; Sequence=VSP_035912;
CC -!- TISSUE SPECIFICITY: Detected in brain, lung, aorta, heart, gizzard,
CC stomach, oviduct, spleen, kidney and small intestine.
CC {ECO:0000269|PubMed:7982954}.
CC -!- PTM: Phosphorylated by CIT (Rho-associated kinase) and by ROCK2 on
CC serine and threonine residues. Phosphorylation at Thr-695 leads to
CC inhibition of myosin phosphatase activity. Phosphorylation at Thr-850
CC abolishes myosin binding. May be phosphorylated at Thr-695 by DMPK; may
CC inhibit the myosin phosphatase activity. {ECO:0000269|PubMed:10601309,
CC ECO:0000269|PubMed:11287000, ECO:0000269|PubMed:12220642}.
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DR EMBL; D37985; BAA07201.1; -; mRNA.
DR EMBL; D37986; BAA07202.1; -; mRNA.
DR EMBL; S74623; AAB32730.1; -; mRNA.
DR PIR; A55142; A55142.
DR RefSeq; NP_990454.1; NM_205123.1. [Q90623-1]
DR RefSeq; XP_015133641.1; XM_015278155.1.
DR RefSeq; XP_015133841.1; XM_015278355.1. [Q90623-2]
DR PDB; 1S70; X-ray; 2.70 A; B=1-299.
DR PDBsum; 1S70; -.
DR AlphaFoldDB; Q90623; -.
DR BMRB; Q90623; -.
DR SMR; Q90623; -.
DR BioGRID; 676290; 1.
DR ELM; Q90623; -.
DR IntAct; Q90623; 1.
DR STRING; 9031.ENSGALP00000016789; -.
DR iPTMnet; Q90623; -.
DR PaxDb; 9031-ENSGALP00000016789; -.
DR Ensembl; ENSGALT00000065339; ENSGALP00000055263; ENSGALG00000010325. [Q90623-1]
DR Ensembl; ENSGALT00010032131.1; ENSGALP00010018921.1; ENSGALG00010013333.1. [Q90623-1]
DR Ensembl; ENSGALT00015038312; ENSGALP00015022440; ENSGALG00015015710. [Q90623-1]
DR GeneID; 396020; -.
DR KEGG; gga:396020; -.
DR CTD; 4659; -.
DR VEuPathDB; HostDB:geneid_396020; -.
DR eggNOG; KOG0505; Eukaryota.
DR GeneTree; ENSGT00940000156120; -.
DR InParanoid; Q90623; -.
DR PhylomeDB; Q90623; -.
DR BRENDA; 3.1.3.53; 1306.
DR Reactome; R-GGA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-GGA-5627123; RHO GTPases activate PAKs.
DR EvolutionaryTrace; Q90623; -.
DR PRO; PR:Q90623; -.
DR Proteomes; UP000000539; Chromosome 1.
DR Bgee; ENSGALG00000010325; Expressed in colon and 13 other cell types or tissues.
DR ExpressionAtlas; Q90623; baseline and differential.
DR GO; GO:0031672; C:A band; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0072357; C:PTW/PP1 phosphatase complex; ISS:UniProtKB.
DR GO; GO:0001725; C:stress fiber; IEA:UniProtKB-SubCell.
DR GO; GO:0030018; C:Z disc; ISS:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; ISS:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IBA:GO_Central.
DR GO; GO:0019208; F:phosphatase regulator activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:InterPro.
DR GO; GO:0030155; P:regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0035507; P:regulation of myosin-light-chain-phosphatase activity; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd21944; IPD_MYPT1; 1.
DR Gene3D; 6.10.140.390; -; 1.
DR Gene3D; 6.10.250.1820; -; 1.
DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 2.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR017401; MYPT1/MYPT2/Mbs85.
DR InterPro; IPR031775; PRKG1_interact.
DR PANTHER; PTHR24179; PROTEIN PHOSPHATASE 1 REGULATORY SUBUNIT 12; 1.
DR PANTHER; PTHR24179:SF20; PROTEIN PHOSPHATASE 1 REGULATORY SUBUNIT 12A; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF15898; PRKG1_interact; 1.
DR PIRSF; PIRSF038141; PP1_12ABC_vert; 1.
DR SMART; SM00248; ANK; 6.
DR SUPFAM; SSF48403; Ankyrin repeat; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Phosphoprotein; Reference proteome; Repeat.
FT CHAIN 1..1004
FT /note="Protein phosphatase 1 regulatory subunit 12A"
FT /id="PRO_0000355556"
FT REPEAT 39..68
FT /note="ANK 1"
FT REPEAT 72..101
FT /note="ANK 2"
FT REPEAT 105..134
FT /note="ANK 3"
FT REPEAT 138..164
FT /note="ANK 4"
FT REPEAT 198..227
FT /note="ANK 5"
FT REPEAT 231..260
FT /note="ANK 6"
FT REGION 35..38
FT /note="Important for interaction with PPP1CB"
FT REGION 291..920
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 303..331
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..355
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..413
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..431
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 539..613
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 637..658
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 659..685
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 707..765
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 766..811
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 812..839
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 859..883
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 884..911
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 695
FT /note="Phosphothreonine; by ROCK2"
FT /evidence="ECO:0000269|PubMed:10601309,
FT ECO:0000269|PubMed:12220642"
FT MOD_RES 850
FT /note="Phosphothreonine; by ROCK2"
FT /evidence="ECO:0000269|PubMed:10601309,
FT ECO:0000269|PubMed:12220642"
FT VAR_SEQ 512..552
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7982954"
FT /id="VSP_035912"
FT MUTAGEN 695
FT /note="T->A: Reduces phosphorylation. Reduces
FT phosphorylation on serine and threonine residues by 80%;
FT when associated with A-850."
FT /evidence="ECO:0000269|PubMed:10601309"
FT MUTAGEN 850
FT /note="T->A: Reduces phosphorylation. Reduces
FT phosphorylation on serine and threonine residues by 80%;
FT when associated with A-695."
FT /evidence="ECO:0000269|PubMed:10601309"
FT HELIX 4..19
FT /evidence="ECO:0007829|PDB:1S70"
FT TURN 20..22
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 40..50
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 53..62
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 76..82
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 86..94
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 109..116
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 119..127
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 149..162
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 166..187
FT /evidence="ECO:0007829|PDB:1S70"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 212..219
FT /evidence="ECO:0007829|PDB:1S70"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 235..241
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 245..253
FT /evidence="ECO:0007829|PDB:1S70"
FT TURN 268..270
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:1S70"
FT HELIX 278..286
FT /evidence="ECO:0007829|PDB:1S70"
SQ SEQUENCE 1004 AA; 111606 MW; 7ED870DB87046929 CRC64;
MKMADAKQKR NEQLKRWIGS ETDLEPPVVK RKKTKVKFDD GAVFLAACSS GDTEEVLRLL
ERGADINYAN VDGLTALHQA CIDDNVDMVK FLVENGANIN QPDNEGWIPL HAAASCGYLD
IAEYLISQGA HVGAVNSEGD TPLDIAEEEA MEELLQNEVN RQGVDIEAAR KEEERIMLRD
ARQWLNSGHI NDVRHAKSGG TALHVAAAKG YTEVLKLLIQ ARYDVNIKDY DGWTPLHAAA
HWGKEEACRI LVENLCDMEA VNKVGQTAFD VADEDILGYL EELQKKQNLL HSEKREKKSP
LIESTANLDN NQTQKTFKNK ETLIMEQEKN ASSIESLEHE KADEEEEGKK DESSCSSEEE
EDDDSESEAE TDKAKTLANA NTTSTQSASM TAPSVAGGQG TPTSPLKKFP TSTTKVSPKE
EERKDESPAS WRLGLRKTGS YGALAEITAS KEAQKEKDSA GVIRSASSPR LSSSLDNKEK
EKDGKGTRLA YVAPTIPRRL ASTSDIDEKE NRDSSASSIR SGSSYARRKW EEDVKKNSLN
EGPTSLNTSY QRSGSFGRRQ DDLVSSNVPS TASTVTSSAG LQKTLPASAN TTTKSTTGST
SAGVQSSTSN RLWAEDSTEK EKDSVPTAVT VPVAPSVVNA AATTTAMTTA TSGTVSSTSE
VRERRRSYLT PVRDEESESQ RKARSRQARQ SRRSTQGVTL TDLQEAEKTI GRSRSTRTRE
QENEEKEKEE KEKQDKEKQE EKKESETKDD DYRQRYSRTV EEPYHRYRPT STSTSTSSTS
SLSTSTSSLS SSSQLNRPNS LIGITSAYSR SGTKESEREG GKKEEEKEED KSQPKSIRER
RRPREKRRST GVSFWTQDSD ENEQEHQSDS EEGTNKKETQ SDSLSRYDTG SLSVSSGDRY
DSAQGRSGSQ SYLEDRKPYC SRLEKEDSTD FKKLYEQILA ENEKLKAQLH DTNMELTDLK
LQLEKTTQRQ ERFADRSLLE MEKRVSGKSQ YLLGGKKSSR KKDI
//
