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GRN granulin precursor [ Homo sapiens (human) ]

Gene ID: 2896, updated on 27-Nov-2024

Summary

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Official Symbol
GRNprovided by HGNC
Official Full Name
granulin precursorprovided by HGNC
Primary source
HGNC:HGNC:4601
See related
Ensembl:ENSG00000030582 MIM:138945; AllianceGenome:HGNC:4601
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
GEP; FTD2; GP88; PEPI; PGRN; CLN11; PCDGF
Summary
Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in bone marrow (RPKM 141.7), lung (RPKM 139.8) and 25 other tissues See more
Orthologs
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Genomic context

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See GRN in Genome Data Viewer
Location:
17q21.31
Exon count:
13
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (44345302..44353106)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (45199297..45207105)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (42422670..42430474)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene solute carrier family 25 member 39 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8588 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12255 Neighboring gene uncharacterized LOC124904009 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12256 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12257 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:42403114-42403965 Neighboring gene CRISPRi-validated cis-regulatory element chr17.2878 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42420716-42421641 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 12260 Neighboring gene Sharpr-MPRA regulatory region 15390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8590 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8591 Neighboring gene family with sequence similarity 171 member A2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42438205-42438805 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:42438806-42439405 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8592 Neighboring gene RPL7L1 pseudogene 5

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Progranulin is a substrate for neutrophil-elastase and proteinase-3 in the airway and its concentration correlates with mediators of airway inflammation in COPD. Ungurs MJ, et al. Am J Physiol Lung Cell Mol Physiol, 2014 Jan 1. PMID 24186875
  2. Molecular signature of disease onset in granulin mutation carriers: a gene expression analysis study. Milanesi E, et al. Neurobiol Aging, 2013 Jul. PMID 23419701
  3. Novel progranulin mutations with reduced serum-progranulin levels in frontotemporal lobar degeneration. Chiang HH, et al. Eur J Hum Genet, 2013 Nov. PMID 23463024, Free PMC Article
  4. Plasma progranulin concentrations are increased in patients with type 2 diabetes and obesity and correlated with insulin resistance. Qu H, et al. Mediators Inflamm, 2013. PMID 23476101, Free PMC Article
  5. GRN Thr272fs clinical heterogeneity: a case with atypical late onset presenting with a dementia with Lewy bodies phenotype. Arosio B, et al. J Alzheimers Dis, 2013. PMID 23478307

See all (604) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.
    Title: Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.
  2. GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.
    Title: GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.
  3. Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.
    Title: Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.
  4. Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.
    Title: Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.
  5. PGRN inhibits CD8[+]T cell recruitment and promotes breast cancer progression by up-regulating ICAM-1 on TAM.
    Title: PGRN inhibits CD8(+)T cell recruitment and promotes breast cancer progression by up-regulating ICAM-1 on TAM.
  6. A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
    Title: A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
  7. Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-alpha pathway in lupus nephritis.
    Title: Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis.
  8. Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1alpha pathway in ARDS.
    Title: Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS.
  9. Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.
    Title: Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.
  10. Progranulin and neuropathological features of Alzheimer's disease: longitudinal study.
    Title: Progranulin and neuropathological features of Alzheimer's disease: longitudinal study.
Submit: New GeneRIF Correction See all GeneRIFs (477)

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

EBI GWAS Catalog

Description
Common variants at 6q22 and 17q21 are associated with intracranial volume.
EBI GWAS Catalog

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
Tat tat Granulin forms stable complexes with cyclin T1 and HIV-1 Tat and inhibits Tat transactivation of the viral LTR promoter PubMed
tat The cysteine rich region of HIV-1 Tat (amino acids 21-37) mediates the binding of Tat to granulin amino acids 206-337 (granulin regions B+A) suggesting a role for granulin growth factors as biologically important extracellular Tat co-factors PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables cytokine activity IEA
Inferred from Electronic Annotation
more info
  
enables growth factor activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein-folding chaperone binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in astrocyte activation involved in immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in lysosomal lumen acidification IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in lysosomal transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in lysosomal transport ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in lysosome organization ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in microglial cell activation involved in immune response ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of microglial cell activation ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in negative regulation of neuron apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of neutrophil activation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of respiratory burst involved in inflammatory response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of angiogenesis ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of aspartic-type peptidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of aspartic-type peptidase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of axon regeneration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of defense response to bacterium ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of endothelial cell migration ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of epithelial cell proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of inflammatory response to wounding ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of lysosome organization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of neuron apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of protein folding ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein stabilization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in signal transduction NAS
Non-traceable Author Statement
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in azurophil granule lumen TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endosome IDA
Inferred from Direct Assay
more info
  
located_in extracellular exosome HDA PubMed 
is_active_in extracellular region IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular region IDA
Inferred from Direct Assay
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in late endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in lysosomal membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in lysosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in trans-Golgi network ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
progranulin
Names
PC cell-derived growth factor
acrogranin
epithelin
glycoprotein 88
glycoprotein of 88 Kda
granulin-epithelin
granulins
proepithelin

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

  1. NG_007886.1 RefSeqGene

    Range
    4964..12984
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_661

mRNA and Protein(s)

  1. NM_002087.4 → NP_002078.1  progranulin precursor

    See identical proteins and their annotated locations for NP_002078.1

    Status: REVIEWED

    Source sequence(s)
    AC003043
    Consensus CDS
    CCDS11483.1
    UniProtKB/Swiss-Prot
    D3DX55, P23781, P23782, P23783, P23784, P28799, Q53HQ8, Q53Y88, Q540U8, Q9BWE7, Q9H8S1, Q9UCH0
    UniProtKB/TrEMBL
    B4DJI2
    Related
    ENSP00000053867.2, ENST00000053867.8
    Conserved Domains (3) summary
    smart00277
    Location:285 → 335
    GRAN; Granulin
    pfam00396
    Location:377 → 415
    Granulin
    cl02546
    Location:62 → 112
    Granulin

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

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    44345302..44353106
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    45199297..45207105
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001012479.1: Suppressed sequence

    Description
    NM_001012479.1: This RefSeq was permanently suppressed because there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P28799.2 GenPept UniProtKB/Swiss-Prot:P28799

Gene LinkOut

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