PDCD6 programmed cell death 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PDCD6provided by HGNC
Official Full Name: programmed cell death 6provided by HGNC
Primary source: HGNC:HGNC:8765
See related: Ensembl:ENSG00000249915 MIM:601057; AllianceGenome:HGNC:8765
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: ALG2; ALG-2; PEF1B
Summary: This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]
Annotation information: Note: ALG2 (Gene ID: 85365) and PDCD6 (Gene ID: 10016) share the ALG2 symbol/alias in common. ALG2 is a widely used alternative name for programmed cell death 6 (PDCD6), whose synonym is apoptosis-linked gene-2. This can be confused with the official symbol for ALG2, alpha-1,3/1,6-mannosyltransferase (ALG2). [31 May 2018]
Expression: Ubiquitous expression in colon (RPKM 23.5), adrenal (RPKM 21.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5p15.33

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (271646..314974)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (261673..305205)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (271761..315089)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

The Contribution of PDCD6 Polymorphisms to Oral Cancer Risk.
Title: The Contribution of PDCD6 Polymorphisms to Oral Cancer Risk.
ALG2 regulates type I interferon responses by inhibiting STING trafficking.
Title: ALG2 regulates type I interferon responses by inhibiting STING trafficking.
Expression level of NEAT1 differentiates benign and malignant thyroid nodules by regulating NEAT1/miR9/PTEN and NEAT1/miR124/PDCD6 signalling.
Title: Expression level of NEAT1 differentiates benign and malignant thyroid nodules by regulating NEAT1/miR‑9/PTEN and NEAT1/miR‑124/PDCD6 signalling.
PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.
Title: PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.
ALG-2 couples T cell activation and apoptosis by regulating proteasome activity and influencing MCL1 stability.
Title: ALG-2 couples T cell activation and apoptosis by regulating proteasome activity and influencing MCL1 stability.
The low expression of miR-124 can promote the proliferation as well as migration of esophageal cancer cells and inhibit cell apoptosis. The mechanism may be that miR-124 can regulate the expression of PDCD6.
Title: Highly expressed microRNA-124 inhibits migration and promotes apoptosis of esophageal cancer cells by degrading PDCD6.
ALG-2 is predominantly localized to a specialized region of the endoplasmic reticulum (ER), called the ER exit site (ERES), through its interaction with Sec31A. Sec31A is an outer coat protein of coat protein complex II (COPII) and is recruited from the cytosol to the ERES to form COPII-coated transport vesicles
Title: Adaptor functions of the Ca(2+)-binding protein ALG-2 in protein transport from the endoplasmic reticulum.
Up-regulation of miR-20a by HPV16 E6 exerted growth-promoting effects by targeting PDCD6 in cervical carcinoma cells.
Title: Up-regulation of miR-20a by HPV16 E6 exerts growth-promoting effects by targeting PDCD6 in cervical carcinoma cells.
the t(5;21)(p15;q22) translocation could be identified only when what had seemed like a del(21)(qq) in G-banded preparations was examined using FISH and RNA-sequencing directed at finding out what lay behind the 21q-.
Title: RUNX1-PDCD6 fusion resulting from a novel t(5;21)(p15;q22) chromosome translocation in myelodysplastic syndrome secondary to chronic lymphocytic leukemia.
ALG-2 binding to Scotin is strictly calcium dependent, indicating a role of this interaction in calcium signaling pathways
Title: The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane.

Submit: New GeneRIF Correction See all GeneRIFs (60)

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

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

NoName (e-PCR)
- UniSTS:482564

D8S2279 (e-PCR)
- UniSTS:473907

D5S1924E (e-PCR)
- UniSTS:153916

RH65518 (e-PCR)
- UniSTS:86108

D5S2300E (e-PCR)
- UniSTS:154508

L28364 (e-PCR)
- UniSTS:24218

SGC34338 (e-PCR)
- UniSTS:45504

RH47205 (e-PCR)
- UniSTS:61664

Readthrough PDCD6-AHRR

Readthrough gene: PDCD6-AHRR, Included gene: AHRR

Clone Names

MGC9123, FLJ14113, FLJ42309, FLJ46208, MGC111017, MGC119050

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables calcium-dependent protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables calcium-dependent protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables magnesium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein heterodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein-macromolecule adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein-membrane adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ubiquitin-like ligase-substrate adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in COPII vesicle coating	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in apoptotic signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to heat	IDA Inferred from Direct Assay more info	PubMed
involved_in endoplasmic reticulum to Golgi vesicle-mediated transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intracellular protein transport	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of TOR signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of vascular endothelial growth factor receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in neural crest cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural crest formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cysteine-type endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endothelial cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of protein monoubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to calcium ion	IDA Inferred from Direct Assay more info	PubMed
involved_in response to calcium ion	ISS Inferred from Sequence or Structural Similarity more info
involved_in vascular endothelial growth factor receptor-2 signaling pathway	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of COPII vesicle coat	IDA Inferred from Direct Assay more info	PubMed
part_of Cul3-RING ubiquitin ligase complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum exit site	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum exit site	IMP Inferred from Mutant Phenotype more info	PubMed
located_in endoplasmic reticulum membrane	IEA Inferred from Electronic Annotation more info
located_in endosome	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: programmed cell death protein 6

Names: apoptosis-linked gene 2 protein homolog; probable calcium-binding protein ALG-2

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.

mRNA and Protein(s)

NM_001267556.2 → NP_001254485.1 programmed cell death protein 6 isoform 2

See identical proteins and their annotated locations for NP_001254485.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AK223366, BC012384, BC110291

Consensus CDS

CCDS58940.1

UniProtKB/TrEMBL

Q53FC3

Related

ENSP00000423815.1, ENST00000507528.5

Conserved Domains (1) summary

cd16183
Location:27 → 189

EFh_PEF_ALG-2; EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins
NM_001267557.2 → NP_001254486.1 programmed cell death protein 6 isoform 3

See identical proteins and their annotated locations for NP_001254486.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two consecutive exons in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AK223366, BC012384, BG390506

Consensus CDS

CCDS75222.1

UniProtKB/TrEMBL

A0A087WZ38

Related

ENSP00000482332.1, ENST00000618970.4

Conserved Domains (2) summary

cd15897
Location:27 → 54

EFh_PEF; EF-hand motif [structural motif]

cl25352
Location:27 → 123

EFh_PEF; The penta-EF hand (PEF) family
NM_001267558.2 → NP_001254487.1 programmed cell death protein 6 isoform 4

See identical proteins and their annotated locations for NP_001254487.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and initiates translation at a downstream, in-frame start codon, compared to variant 1. The encoded isoform (4) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

BC012384, DB495449

Consensus CDS

CCDS75223.1

UniProtKB/TrEMBL

A0A024QZ42

Related

ENSP00000485024.1, ENST00000614778.4

Conserved Domains (2) summary

cd15897
Location:24 → 54

EFh_PEF; EF-hand motif [structural motif]

cl25352
Location:1 → 121

EFh_PEF; The penta-EF hand (PEF) family
NM_001267559.2 → NP_001254488.1 programmed cell death protein 6 isoform 5

See identical proteins and their annotated locations for NP_001254488.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks two consecutive exons in the coding region, which results in a frameshift, compared to variant 1. The encoded isoform (5) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AK223366, BC012384, CR983268

Consensus CDS

CCDS58941.1

UniProtKB/TrEMBL

A0A6Q8PH81

Related

ENSP00000422085.1, ENST00000505221.5

Conserved Domains (2) summary

cd15897
Location:27 → 56

EFh_PEF; EF-hand motif [structural motif]

cl25352
Location:27 → 69

EFh_PEF; The penta-EF hand (PEF) family
NM_013232.4 → NP_037364.1 programmed cell death protein 6 isoform 1

See identical proteins and their annotated locations for NP_037364.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AK223366, BC012384

Consensus CDS

CCDS3854.1

UniProtKB/Swiss-Prot

B2RD16, E7ESR3, O75340, Q2YDC2, Q5TZS0

UniProtKB/TrEMBL

Q53FC3

Related

ENSP00000264933.4, ENST00000264933.9

Conserved Domains (1) summary

cd16183
Location:27 → 191

EFh_PEF_ALG-2; EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins

RNA

NR_073609.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks several exons and includes an alternate 3' terminal exon, compared to variant 1. This variant (6) is represented as non-coding because the predicted ORF does not meet quality criteria for a protein coding locus with longer protein data.

Source sequence(s)

AK223366, AW300963, BC050597

Related

ENST00000509581.5