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Protein

Protein phosphatase 1B

Gene

PPM1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Enzyme with a broad specificity. Dephosphorylates CDK2 and CDK6 in vitro. Dephosphorylates PRKAA1 and PRKAA2. Inhibits TBK1-mediated antiviral signaling by dephosphorylating it at 'Ser-172'. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.2 Publications

Catalytic activityi

[a protein]-serine/threonine phosphate + H2O = [a protein]-serine/threonine + phosphate.

Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium or manganese ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi60Manganese 1By similarity1
Metal bindingi60Manganese 2Combined sources1 Publication1
Metal bindingi61Manganese 1; via carbonyl oxygenBy similarity1
Metal bindingi243Manganese 2Combined sources1 Publication1
Metal bindingi286Manganese 2Combined sources1 Publication1

GO - Molecular functioni

GO - Biological processi

  • negative regulation of defense response to virus Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of interferon-beta production Source: UniProtKB
  • negative regulation of NF-kappaB import into nucleus Source: UniProtKB
  • N-terminal protein myristoylation Source: UniProtKB
  • peptidyl-threonine dephosphorylation Source: UniProtKB
  • protein dephosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Ligandi

Magnesium, Manganese, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS06439-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
SIGNORiO75688.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein phosphatase 1B (EC:3.1.3.16)
Alternative name(s):
Protein phosphatase 2C isoform beta
Short name:
PP2C-beta
Gene namesi
Name:PPM1B
Synonyms:PP2CB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:9276. PPM1B.

Subcellular locationi

  • Cytoplasmcytosol 1 Publication
  • Membrane By similarity; Lipid-anchor By similarity

  • Note: Weakly associates at the membrane and N-myristoylation mediates the membrane localization.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi5495.
MalaCardsiPPM1B.
OpenTargetsiENSG00000138032.
Orphaneti163693. 2p21 microdeletion syndrome.
PharmGKBiPA33604.

Chemistry databases

ChEMBLiCHEMBL2845.

Polymorphism and mutation databases

BioMutaiPPM1B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000577462 – 479Protein phosphatase 1BAdd BLAST478

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi2N-myristoyl glycine1 Publication1
Cross-linki12Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
Cross-linki142Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)
Modified residuei386PhosphoserineCombined sources1

Post-translational modificationi

Isgylation negatively regulates its activity.1 Publication
N-myristoylation is essential for the recognition of its substrates for dephosphorylation.By similarity

Keywords - PTMi

Isopeptide bond, Lipoprotein, Myristate, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO75688.
PaxDbiO75688.
PeptideAtlasiO75688.
PRIDEiO75688.

PTM databases

DEPODiO75688.
iPTMnetiO75688.
PhosphoSitePlusiO75688.

Expressioni

Tissue specificityi

Highly expressed in heart and skeletal muscle.

Gene expression databases

BgeeiENSG00000138032.
CleanExiHS_PPM1B.
ExpressionAtlasiO75688. baseline and differential.
GenevisibleiO75688. HS.

Organism-specific databases

HPAiHPA016745.

Interactioni

Subunit structurei

Monomer (By similarity). Interacts with PAK6. Interacts with the phosphorylated form of IKBKB/IKKB.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ARRB1P494074EBI-1047039,EBI-743313
ARRB2P321214EBI-1047039,EBI-714559
ISG15P051612EBI-1047039,EBI-746466

Protein-protein interaction databases

BioGridi111490. 67 interactors.
IntActiO75688. 26 interactors.
MINTiMINT-2841839.
STRINGi9606.ENSP00000282412.

Chemistry databases

BindingDBiO75688.

Structurei

Secondary structure

1479
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 19Combined sources11
Beta strandi22 – 31Combined sources10
Beta strandi33 – 35Combined sources3
Beta strandi38 – 46Combined sources9
Turni47 – 49Combined sources3
Beta strandi50 – 63Combined sources14
Helixi66 – 80Combined sources15
Turni83 – 85Combined sources3
Helixi99 – 118Combined sources20
Turni121 – 123Combined sources3
Beta strandi134 – 139Combined sources6
Beta strandi141 – 151Combined sources11
Beta strandi153 – 158Combined sources6
Beta strandi161 – 165Combined sources5
Helixi174 – 182Combined sources9
Turni193 – 195Combined sources3
Helixi205 – 207Combined sources3
Helixi215 – 217Combined sources3
Beta strandi218 – 221Combined sources4
Beta strandi225 – 230Combined sources6
Beta strandi235 – 241Combined sources7
Helixi243 – 246Combined sources4
Helixi251 – 262Combined sources12
Helixi268 – 281Combined sources14
Beta strandi288 – 294Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P8EX-ray1.82A/B2-297[»]
ProteinModelPortaliO75688.
SMRiO75688.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75688.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 295PPM-type phosphatasePROSITE-ProRule annotationAdd BLAST273

Sequence similaritiesi

Belongs to the PP2C family.Curated
Contains 1 PPM-type phosphatase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0697. Eukaryota.
COG0631. LUCA.
GeneTreeiENSGT00740000115384.
HOGENOMiHOG000233895.
HOVERGENiHBG053647.
InParanoidiO75688.
KOiK04461.
OMAiEKVCNWV.
OrthoDBiEOG091G0AJQ.
PhylomeDBiO75688.
TreeFamiTF313590.

Family and domain databases

Gene3Di1.10.10.430. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR012911. PP2C_C.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
PF07830. PP2C_C. 1 hit.
[Graphical view]
SMARTiSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81601. SSF81601. 1 hit.
SSF81606. SSF81606. 1 hit.
PROSITEiPS01032. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform Beta-1 (identifier: O75688-1) [UniParc]FASTAAdd to basket
Also known as: Beta-X, PPM1B2

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
MGAFLDKPKT EKHNAHGAGN GLRYGLSSMQ GWRVEMEDAH TAVVGIPHGL
60 70 80 90 100
EDWSFFAVYD GHAGSRVANY CSTHLLEHIT TNEDFRAAGK SGSALELSVE
110 120 130 140 150
NVKNGIRTGF LKIDEYMRNF SDLRNGMDRS GSTAVGVMIS PKHIYFINCG
160 170 180 190 200
DSRAVLYRNG QVCFSTQDHK PCNPREKERI QNAGGSVMIQ RVNGSLAVSR
210 220 230 240 250
ALGDYDYKCV DGKGPTEQLV SPEPEVYEIL RAEEDEFIIL ACDGIWDVMS
260 270 280 290 300
NEELCEYVKS RLEVSDDLEN VCNWVVDTCL HKGSRDNMSI VLVCFSNAPK
310 320 330 340 350
VSDEAVKKDS ELDKHLESRV EEIMEKSGEE GMPDLAHVMR ILSAENIPNL
360 370 380 390 400
PPGGGLAGKR NVIEAVYSRL NPHRESDGAS DEAEESGSQG KLVEALRQMR
410 420 430 440 450
INHRGNYRQL LEEMLTSYRL AKVEGEESPA EPAATATSSN SDAGNPVTMQ
460 470
ESHTESESGL AELDSSNEDA GTKMSGEKI
Length:479
Mass (Da):52,643
Last modified:November 1, 1998 - v1
Checksum:iA3A5797AD263DFBD
GO
Isoform Beta-2 (identifier: O75688-2) [UniParc]FASTAAdd to basket
Also known as: PPM1B1

The sequence of this isoform differs from the canonical sequence as follows:
     379-387: ASDEAEESG → GAGDLEDPW
     388-479: Missing.

Show »
Length:387
Mass (Da):42,771
Checksum:i56A644A4E5E2B12B
GO
Isoform Beta-X (identifier: O75688-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-287: Missing.

Show »
Length:192
Mass (Da):20,753
Checksum:i46FA14838483534F
GO
Isoform 4 (identifier: O75688-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     379-380: AS → QK
     381-387: Missing.
     388-479: Missing.

Show »
Length:380
Mass (Da):42,086
Checksum:iE5C00B5FF4278013
GO
Isoform 5 (identifier: O75688-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     322-327: EIMEKS → GKTNAF
     328-380: Missing.
     381-387: Missing.
     388-479: Missing.

Show »
Length:327
Mass (Da):36,313
Checksum:iE38A263FCF7F1692
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0410851 – 287Missing in isoform Beta-X. 1 PublicationAdd BLAST287
Alternative sequenceiVSP_043641322 – 327EIMEKS → GKTNAF in isoform 5. 1 Publication6
Alternative sequenceiVSP_043642328 – 380Missing in isoform 5. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_005087379 – 387ASDEAEESG → GAGDLEDPW in isoform Beta-2. 4 Publications9
Alternative sequenceiVSP_043643379 – 380AS → QK in isoform 4. 1 Publication2
Alternative sequenceiVSP_043644381 – 387Missing in isoform 4 and isoform 5. 1 Publication7
Alternative sequenceiVSP_005088388 – 479Missing in isoform Beta-2, isoform 4 and isoform 5. 4 PublicationsAdd BLAST92

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ005801 mRNA. Translation: CAA06704.1.
AF294792 mRNA. Translation: AAG02232.1.
AJ271832 mRNA. Translation: CAC27992.1.
AJ271835 mRNA. Translation: CAC27993.1.
DQ023508 mRNA. Translation: AAY89639.1.
DQ023509 mRNA. Translation: AAY89640.1.
DQ023510 mRNA. Translation: AAY89641.1.
AF136972 mRNA. Translation: AAG49433.1.
AL833035 mRNA. Translation: CAH56319.1.
AC013717 Genomic DNA. Translation: AAX88954.1.
AC019129 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAX00282.1.
CH471053 Genomic DNA. Translation: EAX00283.1.
BC012002 mRNA. Translation: AAH12002.1.
BC064381 mRNA. Translation: AAH64381.1.
CCDSiCCDS1816.1. [O75688-2]
CCDS1817.1. [O75688-1]
CCDS1818.1. [O75688-3]
CCDS46271.1. [O75688-4]
RefSeqiNP_001028729.1. NM_001033557.2. [O75688-4]
NP_002697.1. NM_002706.5. [O75688-1]
NP_808907.1. NM_177968.3. [O75688-2]
NP_808908.1. NM_177969.3. [O75688-3]
UniGeneiHs.416769.

Genome annotation databases

EnsembliENST00000282412; ENSP00000282412; ENSG00000138032. [O75688-1]
ENST00000345249; ENSP00000326089; ENSG00000138032. [O75688-3]
ENST00000378551; ENSP00000367813; ENSG00000138032. [O75688-2]
ENST00000409432; ENSP00000387287; ENSG00000138032. [O75688-4]
GeneIDi5495.
KEGGihsa:5495.
UCSCiuc002rtt.4. human. [O75688-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ005801 mRNA. Translation: CAA06704.1.
AF294792 mRNA. Translation: AAG02232.1.
AJ271832 mRNA. Translation: CAC27992.1.
AJ271835 mRNA. Translation: CAC27993.1.
DQ023508 mRNA. Translation: AAY89639.1.
DQ023509 mRNA. Translation: AAY89640.1.
DQ023510 mRNA. Translation: AAY89641.1.
AF136972 mRNA. Translation: AAG49433.1.
AL833035 mRNA. Translation: CAH56319.1.
AC013717 Genomic DNA. Translation: AAX88954.1.
AC019129 Genomic DNA. No translation available.
CH471053 Genomic DNA. Translation: EAX00282.1.
CH471053 Genomic DNA. Translation: EAX00283.1.
BC012002 mRNA. Translation: AAH12002.1.
BC064381 mRNA. Translation: AAH64381.1.
CCDSiCCDS1816.1. [O75688-2]
CCDS1817.1. [O75688-1]
CCDS1818.1. [O75688-3]
CCDS46271.1. [O75688-4]
RefSeqiNP_001028729.1. NM_001033557.2. [O75688-4]
NP_002697.1. NM_002706.5. [O75688-1]
NP_808907.1. NM_177968.3. [O75688-2]
NP_808908.1. NM_177969.3. [O75688-3]
UniGeneiHs.416769.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P8EX-ray1.82A/B2-297[»]
ProteinModelPortaliO75688.
SMRiO75688.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111490. 67 interactors.
IntActiO75688. 26 interactors.
MINTiMINT-2841839.
STRINGi9606.ENSP00000282412.

Chemistry databases

BindingDBiO75688.
ChEMBLiCHEMBL2845.

PTM databases

DEPODiO75688.
iPTMnetiO75688.
PhosphoSitePlusiO75688.

Polymorphism and mutation databases

BioMutaiPPM1B.

Proteomic databases

EPDiO75688.
PaxDbiO75688.
PeptideAtlasiO75688.
PRIDEiO75688.

Protocols and materials databases

DNASUi5495.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000282412; ENSP00000282412; ENSG00000138032. [O75688-1]
ENST00000345249; ENSP00000326089; ENSG00000138032. [O75688-3]
ENST00000378551; ENSP00000367813; ENSG00000138032. [O75688-2]
ENST00000409432; ENSP00000387287; ENSG00000138032. [O75688-4]
GeneIDi5495.
KEGGihsa:5495.
UCSCiuc002rtt.4. human. [O75688-1]

Organism-specific databases

CTDi5495.
DisGeNETi5495.
GeneCardsiPPM1B.
HGNCiHGNC:9276. PPM1B.
HPAiHPA016745.
MalaCardsiPPM1B.
MIMi603770. gene.
neXtProtiNX_O75688.
OpenTargetsiENSG00000138032.
Orphaneti163693. 2p21 microdeletion syndrome.
PharmGKBiPA33604.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0697. Eukaryota.
COG0631. LUCA.
GeneTreeiENSGT00740000115384.
HOGENOMiHOG000233895.
HOVERGENiHBG053647.
InParanoidiO75688.
KOiK04461.
OMAiEKVCNWV.
OrthoDBiEOG091G0AJQ.
PhylomeDBiO75688.
TreeFamiTF313590.

Enzyme and pathway databases

BioCyciZFISH:HS06439-MONOMER.
ReactomeiR-HSA-1169408. ISG15 antiviral mechanism.
SIGNORiO75688.

Miscellaneous databases

ChiTaRSiPPM1B. human.
EvolutionaryTraceiO75688.
GeneWikiiPPM1B.
GenomeRNAii5495.
PROiO75688.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138032.
CleanExiHS_PPM1B.
ExpressionAtlasiO75688. baseline and differential.
GenevisibleiO75688. HS.

Family and domain databases

Gene3Di1.10.10.430. 1 hit.
3.60.40.10. 1 hit.
InterProiIPR015655. PP2C.
IPR000222. PP2C_BS.
IPR012911. PP2C_C.
IPR001932. PPM-type_phosphatase_dom.
[Graphical view]
PANTHERiPTHR13832. PTHR13832. 1 hit.
PfamiPF00481. PP2C. 1 hit.
PF07830. PP2C_C. 1 hit.
[Graphical view]
SMARTiSM00332. PP2Cc. 1 hit.
[Graphical view]
SUPFAMiSSF81601. SSF81601. 1 hit.
SSF81606. SSF81606. 1 hit.
PROSITEiPS01032. PPM_1. 1 hit.
PS51746. PPM_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPPM1B_HUMAN
AccessioniPrimary (citable) accession number: O75688
Secondary accession number(s): Q461Q2
, Q4J6C1, Q4J6C2, Q658R4, Q96ER6, Q9HAY8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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.