GRN granulin [Homo sapiens] - Gene

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Summary

Official Symbol: GRNprovided by HGNC
Official Full Name: granulinprovided by HGNC
Primary source: HGNC:4601
See related: Ensembl:ENSG00000030582; HPRD:00733; MIM:138945
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; 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]

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Genomic context

Location :: 17q21.32

Sequence :: Chromosome: 17; NC_000017.10 (42422491..42430470)

See GRN in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Occurrence of GRN mutations in Tuscany, Central Italy, confirming that genetic variations in this gene could be a considerable genetic cause of frontotemporal lobar degeneration.
Title: Progranulin genetic screening in frontotemporal lobar degeneration patients from central Italy.
Progranulin proteins were overexpressed in breast cancer. Progranulin may be a valuable marker for assessing the metastasis and prognosis of breast cancer, and could provide the basis for new combination regimens with antiangiogenic activity
Title: Clinicopathologic and prognostic implications of progranulin in breast carcinoma.
Lysophosphatidic acid activation of PGRN involving the ERK pathway is critical to promote MDA-MB-231 breast cancer cell invasion.
Title: Progranulin stimulated by LPA promotes the migration of aggressive breast cancer cells.
This study suggested that GRN mutation possible cause of the Frontotemporal lobar degeneration.
Title: From genotype to phenotype: two cases of genetic frontotemporal lobar degeneration with premorbid bipolar disorder.
This study suggested that GRN mutation carriers have normal or borderline CSF biomarkers regardless of the clinical presentation and the speci fi ctype of mutation.
Title: Cerebrospinal fluid biomarkers in Progranulin mutations carriers.
Here we show that progranulin deficit increased cell cycle activity in immortalized lymphocytes.
Title: Alteration in cell cycle-related proteins in lymphoblasts from carriers of the c.709-1G>A PGRN mutation associated with FTLD-TDP dementia.
Patterns of atrophy therefore differed across subjects with C9ORF72, tau and progranulin mutations and sporadic frontotemporal dementia
Title: Neuroimaging signatures of frontotemporal dementia genetics: C9ORF72, tau, progranulin and sporadics.
The miRNA family of ncRNAs showed distinct expression patterns in post-mortem brain tissue of FTLD-TDP patients carrying loss-of function mutations in PGRN compared to FTLD-TDP patients without known mutations.
Title: Altered microRNA expression in frontotemporal lobar degeneration with TDP-43 pathology caused by progranulin mutations.
Data show that plasma progranulin levels were reduced in a subgroup of patients with autism.
Title: Low plasma progranulin levels in children with autism.
Data suggest that circulating IL-6 is increased in progranulin (PGRN)-mutated frontotemporal lobar degeneration (FTLD) patients, as compared to both PGRN non-mutated FTLD patients and controls.
Title: Loss of function mutations in the progranulin gene are related to pro-inflammatory cytokine dysregulation in frontotemporal lobar degeneration patients.

Submit: New GeneRIF Correction See all (157)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Frontotemporal lobar degeneration with ubiquitin-positive inclusions

MIM: 607485

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HIV-1 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 Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_002078.1	NP_001231.2	CCNT1	BIND	PubMed	Cyclin T1 interacts with granulin.
NP_002078.1	NP_056842.1	HIV2gp5	BIND	PubMed	HIV-2 Tat interacts with granulin.
NP_002078.1	NP_002106.1	HK3	BIND	PubMed	HKIII interacts with granulin precursor. This interaction was modeled on a demonstrated interaction between rat HKIII and human granulin precursor.
NP_002078.1	AAQ98597.1	tat	BIND	PubMed	Tat interacts with granulin.
NP_002078.1			BIND	PubMed	P-TEFb interacts with and phosphorylates granulin.
P28799	P54259	ATN1	HPRD	PubMed
P28799	O60563	CCNT1	HPRD	PubMed
P28799	P50750	CDK9	HPRD	PubMed
P28799	P80370	DLK1	HPRD	PubMed
P28799	P08246	ELANE	HPRD	PubMed
P28799	Q96AQ9	FAM131C	HPRD	PubMed
P28799	Growth factor independent 1B	GFI1B	HPRD	PubMed
P28799	P52790	HK3	HPRD	PubMed
P28799	P49639	HOXA1	HPRD	PubMed
P28799	P98160	HSPG2	HPRD	PubMed
P28799	P03973	SLPI	HPRD	PubMed
P28799	O15198	SMAD9	HPRD	PubMed
P28799	O95985	TOP3B	HPRD	PubMed
BioGRID:109153	BioGRID:112221	ATXN7	BioGRID	PubMed	Two-hybrid
BioGRID:109153	BioGRID:107227	CACNA1A	BioGRID	PubMed	Two-hybrid
BioGRID:109153	BioGRID:107343	CCNT1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:109153	BioGRID:107459	CDK9	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109153	BioGRID:114316	DLK1	BioGRID	PubMed	Two-hybrid
BioGRID:109153	BioGRID:131523	FAM131C	BioGRID	PubMed	Two-hybrid
BioGRID:109153	BioGRID:109348	HK3	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:109153	BioGRID:109438	HOXA1	BioGRID	PubMed	Two-hybrid
BioGRID:109153	BioGRID:116982	SIRT3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:109153	BioGRID:112475	SLPI	BioGRID	PubMed	Affinity Capture-Western
BioGRID:109153	BioGRID:112761	TAT	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:109153	BioGRID:114452	TOP3B	BioGRID	PubMed	Two-hybrid
BioGRID:109153	BioGRID:121756	TRIB3	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:109153	BioGRID:113269	VHL	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
cytokine activity	IEA Inferred from Electronic Annotation more info
growth factor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
blastocyst hatching	IEA Inferred from Electronic Annotation more info
embryo implantation	IEA Inferred from Electronic Annotation more info
positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
signal transduction	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
extracellular region	IEA Inferred from Electronic Annotation more info
extracellular space	IEA Inferred from Electronic Annotation more info
intracellular membrane-bounded organelle	IDA Inferred from Direct Assay more info	PubMed
mitochondrion	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: granulins

Names: granulins; acrogranin; progranulin; proepithelin; granulin-epithelin; PC cell-derived growth factor

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NCBI Reference Sequences (RefSeq)

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_007886.1 RefSeqGene

Range

5001..12980

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002087.2 → NP_002078.1 granulins precursor

Status: REVIEWED

Source sequence(s)

AF055008, BC000324

Consensus CDS

CCDS11483.1

UniProtKB/Swiss-Prot

P28799

Related

ENSP00000053867, ENST00000053867

Conserved Domains (1) summary

cl02546
Location:285 – 335
Blast Score: 165

Granulin; Granulin

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

42422491..42430470

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

38186768..38194753

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC003043.2 (35484..43462)	None
genomic	CH471178.2	EAW51599.1
		EAW51600.1
		EAW51601.1
mRNA	AF055008.1	AAC09359.1
mRNA	AK000607.1	None
mRNA	AK023348.1	BAB14535.1
mRNA	AK222522.1	BAD96242.1
mRNA	AK296090.1	BAG58844.1
mRNA	AK303830.1	BAG64777.1
mRNA	AY124489.1	AAM94026.1
mRNA	BC000324.2	AAH00324.1
mRNA	BC010577.2	AAH10577.1
mRNA	BT006844.1	AAP35490.1
mRNA	M75161.1	AAA58617.1
mRNA	X62320.1	CAA44196.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P28799.2	GenPept	UniProtKB/Swiss-Prot:P28799
Q53HQ8	GenPept	UniProtKB/TrEMBL:Q53HQ8
Q9H8S1	GenPept	UniProtKB/TrEMBL:Q9H8S1