PPP1R15B protein phosphatase 1 regulatory subunit 15B [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPP1R15Bprovided by HGNC
Official Full Name: protein phosphatase 1 regulatory subunit 15Bprovided by HGNC
Primary source: HGNC:HGNC:14951
See related: Ensembl:ENSG00000158615 MIM:613257; AllianceGenome:HGNC:14951
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CREP; MSSGM2
Summary: This gene encodes a protein phosphatase I-interacting protein that promotes the dephosphorylation of eukaryotic translation initiation factor 2A to regulate translation under conditions of cellular stress. The transcribed messenger RNA contains two upstream open reading frames (ORFs) that repress translation of the main protein coding ORF under normal conditions, while the protein coding ORF is expressed at high levels in response to stress. Continual translation of the mRNA under conditions of eukaryotic translation initiation factor 2A inactivation is thought to create a feedback loop for reactivation of the gene during recovery from stress. In addition, it has been shown that this protein plays a role in membrane traffic that is independent of translation and that it is required for exocytosis from erythroleukemia cells. Allelic variants of this gene are associated with microcephaly, short stature, and impaired glucose metabolism. [provided by RefSeq, Feb 2016]
Expression: Ubiquitous expression in bone marrow (RPKM 43.3), gall bladder (RPKM 18.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q32.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (204395826..204411817, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (203660566..203676419, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (204372509..204380945, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B.
Title: Recruitment of trimeric eIF2 by phosphatase non-catalytic subunit PPP1R15B.
The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).
Title: The PPP1R15 Family of eIF2-alpha Phosphatase Targeting Subunits (GADD34 and CReP).
An integrative pan-cancer analysis illustrating the key role of LRP11 in cervical cancer.
Title: An integrative pan-cancer analysis illustrating the key role of LRP11 in cervical cancer.
Substrate recognition determinants of human eIF2alpha phosphatases.
Title: Substrate recognition determinants of human eIF2α phosphatases.
p97-mediated degradation, together with a reduction in CReP synthesis, is essential for timely stress-induced reduction of CReP levels and, consequently, for robust eIF2alpha phosphorylation to enforce the stress response.
Title: AP-SWATH Reveals Direct Involvement of VCP/p97 in Integrated Stress Response Signaling Through Facilitating CReP/PPP1R15B Degradation.
Whole-exome sequencing identified a homozygous missense mutation, c.1972G>A; p.Arg658Cys, in protein phosphatase 1, regulatory subunit 15b (PPP1R15B)
Title: Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability.
the first homozygous mutation in the PPP1R15B gene encoding the regulatory subunit of an eIF2alpha-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly
Title: A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.
CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer
Title: CIP2A regulates cancer metabolism and CREB phosphorylation in non-small cell lung cancer.
the mammalian traffic machinery co-opts p-eIF2alpha and CReP, regulators of translation initiation.
Title: A subunit of eukaryotic translation initiation factor 2α-phosphatase (CreP/PPP1R15B) regulates membrane traffic.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Microcephaly, short stature, and impaired glucose metabolism 2 MedGen: C4225195 OMIM: 616817 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2279 (e-PCR)
- UniSTS:473907

D1S1423 (e-PCR)
- UniSTS:149619

SHGC-76198 (e-PCR)
- UniSTS:4213

D1S1425 (e-PCR)
- UniSTS:149621

SHGC-84724 (e-PCR)
- UniSTS:104119

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein phosphatase regulator activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in ER overload response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of PERK-mediated unfolded protein response	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of translation	IEA Inferred from Electronic Annotation more info
involved_in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor more info
part_of protein phosphatase type 1 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of protein phosphatase type 1 complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein phosphatase type 1 complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: protein phosphatase 1 regulatory subunit 15B

Names: protein phosphatase 1, regulatory (inhibitor) subunit 15B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_046737.1 RefSeqGene

Range

5001..13437

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_032833.5 → NP_116222.4 protein phosphatase 1 regulatory subunit 15B

See identical proteins and their annotated locations for NP_116222.4

Status: REVIEWED

Source sequence(s)

AL606489, KF459739

Consensus CDS

CCDS1445.1

UniProtKB/Swiss-Prot

Q53GQ4, Q5SWA1, Q658M2, Q6P156, Q96SN1

UniProtKB/TrEMBL

B4E0U9

Related

ENSP00000356156.4, ENST00000367188.5

Conserved Domains (2) summary

pfam10472
Location:1 → 410

CReP_N; eIF2-alpha phosphatase phosphorylation constitutive repressor

pfam10488
Location:413 → 699

PP1c_bdg; Phosphatase-1 catalytic subunit binding region

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

204395826..204411817 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005245551.6 → XP_005245608.2 protein phosphatase 1 regulatory subunit 15B isoform X1

UniProtKB/TrEMBL

A0A8I5KSH1, B4E0U9

Related

ENSP00000508814.1, ENST00000693720.1

Conserved Domains (2) summary

pfam10472
Location:1 → 410

CReP_N; eIF2-alpha phosphatase phosphorylation constitutive repressor

pfam10488
Location:413 → 636

PP1c_bdg; Phosphatase-1 catalytic subunit binding region
XM_047432518.1 → XP_047288474.1 protein phosphatase 1 regulatory subunit 15B isoform X1

UniProtKB/TrEMBL

A0A8I5KSH1, B4E0U9

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

203660566..203676419 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054339268.1 → XP_054195243.1 protein phosphatase 1 regulatory subunit 15B isoform X1

UniProtKB/TrEMBL

A0A8I5KSH1, B4E0U9
XM_054339269.1 → XP_054195244.1 protein phosphatase 1 regulatory subunit 15B isoform X1

UniProtKB/TrEMBL

A0A8I5KSH1, B4E0U9