Reactome | UniProt:O14974 PPP1R12A

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UniProt:O14974 PPP1R12A Show undefined attributes

chain	chain:1-1030
checksum	EA43E9BFF5DA08FF
comment	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.SUBUNIT 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. Interacts with NCKAP1L (PubMed:16417406).INTERACTION Also along actomyosin filaments.ALTERNATIVE PRODUCTS Expressed in striated muscles, specifically in type 2a fibers (at protein level).DEVELOPMENTAL STAGE Induced by 2-fold during pregnancy, including in abdominus rectus muscle.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.DOMAIN The KVKF motif mediates interaction with PPP1CB.PTM Phosphorylated by CIT (Rho-associated kinase) (By similarity). Phosphorylated cooperatively by ROCK1 and CDC42BP on Thr-696. Phosphorylated on upon DNA damage, probably by ATM or ATR. In vitro, phosphorylation of Ser-695 by PKA and PKG appears to prevent phosphorylation of the inhibitory site Thr-696, probably mediated by PRKG1. Phosphorylation at Ser-445, Ser-472 and Ser-910 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-696 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.DISEASE The disease is caused by variants affecting the gene represented in this entry.SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence.SEQUENCE CAUTION Contaminating sequence. Potential poly-A sequence.
created	[InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference	[DatabaseIdentifier:11497450] ENSEMBL:ENSG00000058272 [DatabaseIdentifier:11606277] ENSEMBL:ENSP00000446855 [DatabaseIdentifier:11606276] ENSEMBL:ENSP00000416769 [DatabaseIdentifier:11606275] ENSEMBL:ENSP00000389168 [DatabaseIdentifier:11606274] ENSEMBL:ENSP00000261207 [DatabaseIdentifier:11606273] ENSEMBL:ENSP00000449514 [DatabaseIdentifier:11728973] ENSEMBL:ENST00000546369 [DatabaseIdentifier:11728974] ENSEMBL:ENST00000437004 [DatabaseIdentifier:11728975] ENSEMBL:ENST00000450142 [DatabaseIdentifier:11728976] ENSEMBL:ENST00000261207 [DatabaseIdentifier:11728972] ENSEMBL:ENST00000550107 [DatabaseIdentifier:11790802] GeneCards:PPP1R12A [DatabaseIdentifier:11806740] GlyGen:O14974 [DatabaseIdentifier:11843806] HPA:ENSG00000058272-PPP1R12A [DatabaseIdentifier:12128422] OpenTargets:ENSG00000058272 [DatabaseIdentifier:12204845] PDB:5HUZ [DatabaseIdentifier:12204846] PDB:2KJY [DatabaseIdentifier:12249893] PRO:O14974 [DatabaseIdentifier:12288644] Pharos - Targets:O14974 [DatabaseIdentifier:12423120] RefSeq:NP_001231921.1 [DatabaseIdentifier:12423118] RefSeq:NP_001231919.1 [DatabaseIdentifier:12423119] RefSeq:NP_001137357.1 [DatabaseIdentifier:12423121] RefSeq:NP_002471.1 [DatabaseIdentifier:12423117] RefSeq:NP_001137358.1
databaseName	UniProt
dbId	150515
description	recommendedName: Protein phosphatase 1 regulatory subunit 12A alternativeName: Myosin phosphatase-targeting subunit 1 shortName: Myosin phosphatase target subunit 1 alternativeName: Protein phosphatase myosin-binding subunit
displayName	UniProt:O14974 PPP1R12A
geneName	PPP1R12A MBS MYPT1
identifier	O14974
isSequenceChanged	false
keyword	3D-structure Alternative splicing ANK repeat Cytoplasm Cytoskeleton Direct protein sequencing Disease variant Hydroxylation Phosphoprotein Proteomics identification Reference proteome Repeat
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	PPP1R12A
otherIdentifier	11733074_s_at 11733075_a_at 11733076_x_at 11733077_a_at 11733078_a_at 16767932 201602_PM_s_at 201602_s_at 201603_PM_at 201603_at 201604_PM_s_at 201604_s_at 3463569 3463570 3463572 3463573 3463574 3463575 3463578 3463579 3463580 3463581 3463582 3463584 3463585 3463586 3463587 3463590 3463593 3463594 3463595 3463596 3463597 3463598 3463599 3463600 3463601 3463603 3463605 3463606 3463607 3463608 3463609 3463610 3463613 3463614 3463615 3463618 3463620 3463621 3463623 3463627 3463628 3463629 3463631 3463632 3463641 3463651 3463652 3463653 3463654 40438_at 4659 79022_at 7965123 A_23_P204564 A_24_P364412 A_24_P56252 GE499062 GE57421 GO:0000278 GO:0000776 GO:0001725 GO:0004857 GO:0005515 GO:0005654 GO:0005730 GO:0005737 GO:0005813 GO:0005815 GO:0005829 GO:0005856 GO:0005886 GO:0005925 GO:0006355 GO:0006470 GO:0007098 GO:0007165 GO:0015629 GO:0017020 GO:0019208 GO:0019901 GO:0030018 GO:0030155 GO:0031672 GO:0043086 GO:0043226 GO:0043292 GO:0045944 GO:0046822 GO:0048812 GO:0071466 GO:0071889 GO:0072357 GO:0098772 HMNXSV003029505 HMNXSV003055085 Hs.16533.0.S1_3p_a_at Hs.16533.0.S3_3p_at PH_hs_0024292 TC12001766.hg g4505316_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-419070] PPP1R12A [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5668956] p-T696-PPP1R12A [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-419079] p-T696,S852-PPP1R12A [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-3002801] p-S473-PPP1R12A [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000058272] ENSEMBL:ENSG00000058272 PPP1R12A [ReferenceDNASequence:12701244] UCSC:O14974 PPP1R12A [ReferenceDNASequence:11362983] BioGPS Gene:4659 PPP1R12A [ReferenceDNASequence:11394340] COSMIC - genes:PPP1R12A PPP1R12A [ReferenceDNASequence:11418307] CTD Gene:4659 PPP1R12A [ReferenceDNASequence:11430402] dbSNP Gene:4659 PPP1R12A [ReferenceDNASequence:11822465] HGNC:7618 PPP1R12A [ReferenceDNASequence:11901781] KEGG:hsa:4659 PPP1R12A [ReferenceDNASequence:11992772] Monarch:4659 PPP1R12A [ReferenceDNASequence:12076865] NCBI Gene:4659 PPP1R12A [ReferenceDNASequence:12113185] OMIM:602021 PPP1R12A
referenceTranscript	[ReferenceRNASequence:12604704] RefSeq:NM_001244992.1 PPP1R12A [ReferenceRNASequence:12604703] RefSeq:NM_001244990.2 PPP1R12A [ReferenceRNASequence:12604705] RefSeq:NM_001143885.2 PPP1R12A [ReferenceRNASequence:12604706] RefSeq:NM_001143886.2 PPP1R12A [ReferenceRNASequence:12604707] RefSeq:NM_002480.3 PPP1R12A
schemaClass	ReferenceGeneProduct
secondaryIdentifier	MYPT1_HUMAN B4DZ09 F8VWB4 Q2NKL4 Q569H0 Q86WU3 Q8NFR6 Q9BYH0
sequenceLength	1030
species	[Species:48887] Homo sapiens
stId	uniprot:O14974
url	http://purl.uniprot.org/uniprot/O14974

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-419070] PPP1R12A [cytosol] [EntityWithAccessionedSequence:R-HSA-5668956] p-T696-PPP1R12A [cytosol] [EntityWithAccessionedSequence:R-HSA-419079] p-T696,S852-PPP1R12A [cytosol] [EntityWithAccessionedSequence:R-HSA-3002801] p-S473-PPP1R12A [nucleoplasm]
(referenceSequence)	[ModifiedResidue:419078] O-phospho-L-threonine at 696 [ModifiedResidue:419077] O-phospho-L-serine at 852 [ModifiedResidue:3002799] O-phospho-L-serine at 473
(interactor)	[UndirectedInteraction:11148073] UniProt:P13569 <-> UniProt:O14974 (IntAct) [UndirectedInteraction:11168443] UniProt:P01100 <-> UniProt:O14974 (IntAct) [UndirectedInteraction:11215723] UniProt:O18734 <-> UniProt:O14974 (IntAct) [UndirectedInteraction:11243617] UniProt:P61981 <-> UniProt:O14974 (IntAct) [UndirectedInteraction:11288519] UniProt:P63104 <-> UniProt:O14974 (IntAct)