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Protein

Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform

Gene

PPP2R5D

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

Functioni

The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.

GO - Molecular functioni

  • phosphoprotein phosphatase activity Source: UniProtKB
  • protein phosphatase activator activity Source: GO_Central
  • protein phosphatase regulator activity Source: ProtInc
  • protein serine/threonine phosphatase activity Source: Reactome

GO - Biological processi

Enzyme and pathway databases

ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163685 Integration of energy metabolism
R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024 DARPP-32 events
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-432142 Platelet sensitization by LDL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-5673000 RAF activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877 Mitotic Prometaphase
R-HSA-70171 Glycolysis
SignaLinkiQ14738
SIGNORiQ14738

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform
Alternative name(s):
PP2A B subunit isoform B'-delta
PP2A B subunit isoform B56-delta
PP2A B subunit isoform PR61-delta
PP2A B subunit isoform R5-delta
Gene namesi
Name:PPP2R5D
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000112640.14
HGNCiHGNC:9312 PPP2R5D
MIMi601646 gene
neXtProtiNX_Q14738

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal dominant 35 (MRD35)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mental retardation, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period.
See also OMIM:616355
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073708198E → K in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 2 PublicationsCorresponds to variant dbSNP:rs863225082EnsemblClinVar.1
Natural variantiVAR_074491200E → K in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 1 PublicationCorresponds to variant dbSNP:rs863225079EnsemblClinVar.1
Natural variantiVAR_073709201P → R in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 2 PublicationsCorresponds to variant dbSNP:rs876657383EnsemblClinVar.1
Natural variantiVAR_074492207W → R in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 1 PublicationCorresponds to variant dbSNP:rs869320691EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi5528
MalaCardsiPPP2R5D
MIMi616355 phenotype
OpenTargetsiENSG00000112640
Orphaneti457279 Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome
PharmGKBiPA33676

Polymorphism and mutation databases

BioMutaiPPP2R5D
DMDMi7387495

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000714521 – 602Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoformAdd BLAST602

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei63PhosphothreonineCombined sources1
Modified residuei88PhosphoserineCombined sources1
Modified residuei89PhosphoserineCombined sources1
Modified residuei90PhosphoserineCombined sources1
Modified residuei573PhosphoserineCombined sources1
Modified residuei598PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ14738
MaxQBiQ14738
PaxDbiQ14738
PeptideAtlasiQ14738
PRIDEiQ14738

PTM databases

iPTMnetiQ14738
PhosphoSitePlusiQ14738

Expressioni

Tissue specificityi

Isoform Delta-2 is widely expressed. Isoform Delta-1 is highly expressed in brain.

Inductioni

By retinoic acid; in neuroblastoma cell lines.

Gene expression databases

BgeeiENSG00000112640 Expressed in 227 organ(s), highest expression level in dorsal plus ventral thalamus
CleanExiHS_PPP2R5D
ExpressionAtlasiQ14738 baseline and differential
GenevisibleiQ14738 HS

Organism-specific databases

HPAiHPA029045
HPA029046

Interactioni

Subunit structurei

PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi111520, 84 interactors
DIPiDIP-29961N
ELMiQ14738
IntActiQ14738, 35 interactors
MINTiQ14738
STRINGi9606.ENSP00000417963

Structurei

3D structure databases

ProteinModelPortaliQ14738
SMRiQ14738
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati37 – 3812
Repeati39 – 4022
Repeati41 – 4232
Repeati43 – 4442
Repeati45 – 4652
Repeati47 – 486; approximate2
Repeati49 – 507; approximate2
Repeati51 – 5282

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni37 – 528 X 2 AA approximate tandem repeats of Q-PAdd BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi523 – 530SH3-binding; class ISequence analysis8
Motifi548 – 565Nuclear localization signalSequence analysisAdd BLAST18

Sequence similaritiesi

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2085 Eukaryota
ENOG410XQJW LUCA
GeneTreeiENSGT00550000074525
HOVERGENiHBG000009
InParanoidiQ14738
KOiK11584
OMAiDECSHEY
OrthoDBiEOG091G06HU
PhylomeDBiQ14738
TreeFamiTF105556

Family and domain databases

Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR002554 PP2A_B56
PANTHERiPTHR10257 PTHR10257, 1 hit
PfamiView protein in Pfam
PF01603 B56, 1 hit
PIRSFiPIRSF028043 PP2A_B56, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform Delta-1 (identifier: Q14738-1) [UniParc]FASTAAdd to basket

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
MPYKLKKEKE PPKVAKCTAK PSSSGKDGGG ENTEEAQPQP QPQPQPQAQS
60 70 80 90 100
QPPSSNKRPS NSTPPPTQLS KIKYSGGPQI VKKERRQSSS RFNLSKNREL
110 120 130 140 150
QKLPALKDSP TQEREELFIQ KLRQCCVLFD FVSDPLSDLK FKEVKRAGLN
160 170 180 190 200
EMVEYITHSR DVVTEAIYPE AVTMFSVNLF RTLPPSSNPT GAEFDPEEDE
210 220 230 240 250
PTLEAAWPHL QLVYEFFLRF LESPDFQPNI AKKYIDQKFV LALLDLFDSE
260 270 280 290 300
DPRERDFLKT ILHRIYGKFL GLRAYIRRQI NHIFYRFIYE TEHHNGIAEL
310 320 330 340 350
LEILGSIING FALPLKEEHK MFLIRVLLPL HKVKSLSVYH PQLAYCVVQF
360 370 380 390 400
LEKESSLTEP VIVGLLKFWP KTHSPKEVMF LNELEEILDV IEPSEFSKVM
410 420 430 440 450
EPLFRQLAKC VSSPHFQVAE RALYYWNNEY IMSLISDNAA RVLPIMFPAL
460 470 480 490 500
YRNSKSHWNK TIHGLIYNAL KLFMEMNQKL FDDCTQQYKA EKQKGRFRMK
510 520 530 540 550
EREEMWQKIE ELARLNPQYP MFRAPPPLPP VYSMETETPT AEDIQLLKRT
560 570 580 590 600
VETEAVQMLK DIKKEKVLLR RKSELPQDVY TIKALEAHKR AEEFLTASQE

AL
Length:602
Mass (Da):69,992
Last modified:November 1, 1996 - v1
Checksum:iF15F71AF4E565387
GO
Isoform Delta-2 (identifier: Q14738-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-116: Missing.

Show »
Length:570
Mass (Da):66,181
Checksum:i978213A7CD1B21A5
GO
Isoform Delta-3 (identifier: Q14738-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     11-116: Missing.

Show »
Length:496
Mass (Da):58,453
Checksum:iA57661F8B20731CB
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PFR3E9PFR3_HUMAN
Serine/threonine-protein phosphatas...
PPP2R5D
594Annotation score:
H0Y8C4H0Y8C4_HUMAN
Serine/threonine-protein phosphatas...
PPP2R5D
504Annotation score:
H7C5Q9H7C5Q9_HUMAN
Serine/threonine-protein phosphatas...
PPP2R5D
154Annotation score:
H7C5Z1H7C5Z1_HUMAN
Serine/threonine-protein phosphatas...
PPP2R5D
111Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06941453P → S Found in a patient with delayed psychomotor development, no speech and cataracts; no effect on binding to subunit PPP2CA; no effect on binding to subunit PPP2R1A. 2 PublicationsCorresponds to variant dbSNP:rs757369209EnsemblClinVar.1
Natural variantiVAR_073708198E → K in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 2 PublicationsCorresponds to variant dbSNP:rs863225082EnsemblClinVar.1
Natural variantiVAR_074491200E → K in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 1 PublicationCorresponds to variant dbSNP:rs863225079EnsemblClinVar.1
Natural variantiVAR_073709201P → R in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 2 PublicationsCorresponds to variant dbSNP:rs876657383EnsemblClinVar.1
Natural variantiVAR_074492207W → R in MRD35; decreases binding to subunit PPP2CA; decreases binding to subunit PPP2R1A. 1 PublicationCorresponds to variant dbSNP:rs869320691EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00511011 – 116Missing in isoform Delta-3. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_00511185 – 116Missing in isoform Delta-2. 3 PublicationsAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76702 mRNA Translation: AAB69751.1
AB000634 mRNA Translation: BAA20381.1
AB000635 mRNA Translation: BAA20382.1
D78360 mRNA Translation: BAA11372.1
AK290604 mRNA Translation: BAF83293.1
AB451342 mRNA Translation: BAG70156.1
AB451357 mRNA Translation: BAG70171.1
AL136304 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04133.1
BC010692 mRNA Translation: AAH10692.1
BC001095 mRNA Translation: AAH01095.1
BC001175 mRNA Translation: AAH01175.1
CCDSiCCDS43464.1 [Q14738-3]
CCDS4878.1 [Q14738-1]
CCDS55002.1 [Q14738-2]
PIRiS68686
RefSeqiNP_001257405.1, NM_001270476.1
NP_006236.1, NM_006245.3 [Q14738-1]
NP_851307.1, NM_180976.2 [Q14738-2]
NP_851308.1, NM_180977.2 [Q14738-3]
UniGeneiHs.533308

Genome annotation databases

EnsembliENST00000394110; ENSP00000377669; ENSG00000112640 [Q14738-2]
ENST00000461010; ENSP00000420674; ENSG00000112640 [Q14738-3]
ENST00000485511; ENSP00000417963; ENSG00000112640 [Q14738-1]
GeneIDi5528
KEGGihsa:5528
UCSCiuc003oth.5 human [Q14738-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L76702 mRNA Translation: AAB69751.1
AB000634 mRNA Translation: BAA20381.1
AB000635 mRNA Translation: BAA20382.1
D78360 mRNA Translation: BAA11372.1
AK290604 mRNA Translation: BAF83293.1
AB451342 mRNA Translation: BAG70156.1
AB451357 mRNA Translation: BAG70171.1
AL136304 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX04133.1
BC010692 mRNA Translation: AAH10692.1
BC001095 mRNA Translation: AAH01095.1
BC001175 mRNA Translation: AAH01175.1
CCDSiCCDS43464.1 [Q14738-3]
CCDS4878.1 [Q14738-1]
CCDS55002.1 [Q14738-2]
PIRiS68686
RefSeqiNP_001257405.1, NM_001270476.1
NP_006236.1, NM_006245.3 [Q14738-1]
NP_851307.1, NM_180976.2 [Q14738-2]
NP_851308.1, NM_180977.2 [Q14738-3]
UniGeneiHs.533308

3D structure databases

ProteinModelPortaliQ14738
SMRiQ14738
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111520, 84 interactors
DIPiDIP-29961N
ELMiQ14738
IntActiQ14738, 35 interactors
MINTiQ14738
STRINGi9606.ENSP00000417963

PTM databases

iPTMnetiQ14738
PhosphoSitePlusiQ14738

Polymorphism and mutation databases

BioMutaiPPP2R5D
DMDMi7387495

Proteomic databases

EPDiQ14738
MaxQBiQ14738
PaxDbiQ14738
PeptideAtlasiQ14738
PRIDEiQ14738

Protocols and materials databases

DNASUi5528
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000394110; ENSP00000377669; ENSG00000112640 [Q14738-2]
ENST00000461010; ENSP00000420674; ENSG00000112640 [Q14738-3]
ENST00000485511; ENSP00000417963; ENSG00000112640 [Q14738-1]
GeneIDi5528
KEGGihsa:5528
UCSCiuc003oth.5 human [Q14738-1]

Organism-specific databases

CTDi5528
DisGeNETi5528
EuPathDBiHostDB:ENSG00000112640.14
GeneCardsiPPP2R5D
HGNCiHGNC:9312 PPP2R5D
HPAiHPA029045
HPA029046
MalaCardsiPPP2R5D
MIMi601646 gene
616355 phenotype
neXtProtiNX_Q14738
OpenTargetsiENSG00000112640
Orphaneti457279 Intellectual disability-macrocephaly-hypotonia-behavioral abnormalities syndrome
PharmGKBiPA33676
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2085 Eukaryota
ENOG410XQJW LUCA
GeneTreeiENSGT00550000074525
HOVERGENiHBG000009
InParanoidiQ14738
KOiK11584
OMAiDECSHEY
OrthoDBiEOG091G06HU
PhylomeDBiQ14738
TreeFamiTF105556

Enzyme and pathway databases

ReactomeiR-HSA-141444 Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163685 Integration of energy metabolism
R-HSA-163767 PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024 DARPP-32 events
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-196299 Beta-catenin phosphorylation cascade
R-HSA-198753 ERK/MAPK targets
R-HSA-202670 ERKs are inactivated
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2500257 Resolution of Sister Chromatid Cohesion
R-HSA-389513 CTLA4 inhibitory signaling
R-HSA-432142 Platelet sensitization by LDL
R-HSA-4641262 Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716 Misspliced GSK3beta mutants stabilize beta-catenin
R-HSA-5358747 S33 mutants of beta-catenin aren't phosphorylated
R-HSA-5358749 S37 mutants of beta-catenin aren't phosphorylated
R-HSA-5358751 S45 mutants of beta-catenin aren't phosphorylated
R-HSA-5358752 T41 mutants of beta-catenin aren't phosphorylated
R-HSA-5467337 APC truncation mutants have impaired AXIN binding
R-HSA-5467340 AXIN missense mutants destabilize the destruction complex
R-HSA-5467348 Truncations of AMER1 destabilize the destruction complex
R-HSA-5663220 RHO GTPases Activate Formins
R-HSA-5673000 RAF activation
R-HSA-5675221 Negative regulation of MAPK pathway
R-HSA-6811558 PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-68877 Mitotic Prometaphase
R-HSA-70171 Glycolysis
SignaLinkiQ14738
SIGNORiQ14738

Miscellaneous databases

GeneWikiiPPP2R5D
GenomeRNAii5528
PROiPR:Q14738
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112640 Expressed in 227 organ(s), highest expression level in dorsal plus ventral thalamus
CleanExiHS_PPP2R5D
ExpressionAtlasiQ14738 baseline and differential
GenevisibleiQ14738 HS

Family and domain databases

Gene3Di1.25.10.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR002554 PP2A_B56
PANTHERiPTHR10257 PTHR10257, 1 hit
PfamiView protein in Pfam
PF01603 B56, 1 hit
PIRSFiPIRSF028043 PP2A_B56, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
ProtoNetiSearch...

Entry informationi

Entry namei2A5D_HUMAN
AccessioniPrimary (citable) accession number: Q14738
Secondary accession number(s): A8K3I9
, B5BUA6, O00494, O00696, Q15171, Q5TC39
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: November 7, 2018
This is version 194 of the entry and version 1 of the sequence. See 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

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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