PACS1 phosphofurin acidic cluster sorting protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PACS1provided by HGNC
Official Full Name: phosphofurin acidic cluster sorting protein 1provided by HGNC
Primary source: HGNC:HGNC:30032
See related: Ensembl:ENSG00000175115 MIM:607492; AllianceGenome:HGNC:30032
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: SHMS; MRD17
Summary: This gene encodes a protein with a putative role in the localization of trans-Golgi network (TGN) membrane proteins. Mouse and rat homologs have been identified and studies of the homologous rat protein indicate a role in directing TGN localization of furin by binding to the protease's phosphorylated cytosolic domain. In addition, the human protein plays a role in HIV-1 Nef-mediated downregulation of cell surface MHC-I molecules to the TGN, thereby enabling HIV-1 to escape immune surveillance. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in testis (RPKM 20.8), lymph node (RPKM 16.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.1-q13.2

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (66070272..66244744)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (66064409..66238837)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (65837743..66012215)

Chromosome 11 - NC_000011.10 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?

Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
Title: Do PACS1 variants impeding adaptor protein binding predispose to syndromic intellectual disability?
Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot-spot: Two additional Italian patients.
Title: Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot-spot: Two additional Italian patients.
Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.
Title: Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.
Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37-PACS1-PACS2 axis.
Title: Coloboma may be a shared feature in a spectrum of disorders caused by mutations in the WDR37-PACS1-PACS2 axis.
Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.
Title: Prenatal and postnatal diagnosis of Schuurs-Hoeijmakers syndrome: Case series and review of the literature.
Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.
Title: Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.
The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.
Title: The multifunctional protein PACS-1 is required for HDAC2- and HDAC3-dependent chromatin maturation and genomic stability.
Using whole exome sequencing (WES), we identified eight additional individuals with the same p.Arg203Trp missense variant in PACS1 that we demonstrated were de novo in seven individuals with available parental DNA.
Title: Association of the missense variant p.Arg203Trp in PACS1 as a cause of intellectual disability and seizures.
PCAF and ADA3 transcriptionally regulate PACS1 and PACS1 is a key regulator of BAX/BAK oligomerization and the intrinsic (mitochondrial) pathway to apoptosis.
Title: Epigenetic control of mitochondrial cell death through PACS1-mediated regulation of BAX/BAK oligomerization.
Protein adaptation and the expanding roles of the PACS1 and PACS2 proteins in tissue homeostasis and disease has been summarized. (Review)
Title: Caught in the act - protein adaptation and the expanding roles of the PACS proteins in tissue homeostasis and disease.

Submit: New GeneRIF Correction See all GeneRIFs (22)

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
Schuurs-Hoeijmakers syndrome MedGen: C3554343 OMIM: 615009 GeneReviews: PACS1 Neurodevelopmental Disorder	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2021-12-14) ClinGen Genome Curation Page Haploinsufficency No evidence available (Last evaluated 2021-12-14) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	Interaction of HIV-1 Nef with PACS-1 occurs in cellular endosomes with markers RAB5 and LAMP-1	PubMed
	nef	HIV-1 Nef-induced downregulation of MHC-I expression and MHC-I targeting to the trans-Golgi network (TGN) require the binding of Nef (amino acid residues 62-65) to PACS-1, a molecule that controls the TGN localization of the cellular protein furin	PubMed
	nef	Pro78 and helix alphaB (residues 104-119) in HIV-1 Nef are required for the binding between PACS-1 and Nef	PubMed
	nef	Amino-acid residues 181-195 in the FBR region of PACS-1 bind to HIV-1 Nef and alanine-scanning analysis reveals that amino acids N188, K189, and Q195 are required for the binding between PACS-1 and Nef	PubMed
	nef	PACS-1S278A mutant blocks the association of Nef with Hck on cell membrane, while wild-type PACS-1 has no effect	PubMed
Rev	rev	Depletion of PACS1 inhibits HIV-1 Rev activity, leading to reduced HIV-1 p24 expression from the Rev-mediated reporter plasmid	PubMed
capsid	gag	Depletion of PACS1 inhibits HIV-1 Rev activity, leading to reduced HIV-1 p24 expression from the Rev-mediated reporter plasmid	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S913 (e-PCR), detects polymorphism
- UniSTS:28973

152L21att (e-PCR)
- UniSTS:265275

3F (e-PCR)
- UniSTS:265276

4f (e-PCR)
- UniSTS:265277

D11S913 (e-PCR), detects polymorphism
- UniSTS:2112

CA21601 (e-PCR)
- UniSTS:265280

CA64681 (e-PCR)
- UniSTS:265281

GT7681 (e-PCR)
- UniSTS:265282

A001T38 (e-PCR)
- UniSTS:109

RH18211 (e-PCR)
- UniSTS:10116

PACS1__5810 (e-PCR)
- UniSTS:464524

D11S3746 (e-PCR)
- UniSTS:152976

RH12046 (e-PCR)
- UniSTS:40348

RH65425 (e-PCR)
- UniSTS:35002

Gene Ontology Provided by GOA

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

Process	Evidence Code	Pubs
involved_in lymphocyte homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to Golgi apparatus	IEA Inferred from Electronic Annotation more info
involved_in protein localization to plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in COPI-coated vesicle	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info

General protein information

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Preferred Names: phosphofurin acidic cluster sorting protein 1

Names: PACS-1; cytosolic sorting protein PACS-1

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_033900.1 RefSeqGene

Range

4920..179392

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_018026.4 → NP_060496.2 phosphofurin acidic cluster sorting protein 1

See identical proteins and their annotated locations for NP_060496.2

Status: REVIEWED

Source sequence(s)

AK096644, AP006287, BC010096, BQ772654

Consensus CDS

CCDS8129.1

UniProtKB/Swiss-Prot

Q6PJY6, Q6PKB6, Q6VY07, Q7Z590, Q7Z5W4, Q8N8K6, Q96MW0, Q9NW92, Q9ULP5

Related

ENSP00000316454.4, ENST00000320580.9

Conserved Domains (1) summary

pfam10254
Location:548 → 960

Pacs-1; PACS-1 cytosolic sorting protein

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_000011.10 Reference GRCh38.p14 Primary Assembly

Range

66070272..66244744

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011545164.3 → XP_011543466.1 phosphofurin acidic cluster sorting protein 1 isoform X2

Conserved Domains (1) summary

pfam10254
Location:435 → 847

Pacs-1; PACS-1 cytosolic sorting protein
XM_011545162.2 → XP_011543464.2 phosphofurin acidic cluster sorting protein 1 isoform X1

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

66064409..66238837

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054369345.1 → XP_054225320.1 phosphofurin acidic cluster sorting protein 1 isoform X2
XM_054369344.1 → XP_054225319.1 phosphofurin acidic cluster sorting protein 1 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_178178.1: Suppressed sequence

Description

NM_178178.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.