Description: Homo sapiens granulin (GRN), mRNA. RefSeq Summary (NM_002087): 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]. Sequence Note: The RefSeq transcript and protein were derived from genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments. Transcript (Including UTRs) Position: hg19 chr17:42,422,491-42,430,470 Size: 7,980 Total Exon Count: 13 Strand: + Coding Region Position: hg19 chr17:42,426,533-42,430,166 Size: 3,634 Coding Exon Count: 12
ID:GRN_HUMAN DESCRIPTION: RecName: Full=Granulins; AltName: Full=Proepithelin; Short=PEPI; Contains: RecName: Full=Acrogranin; Contains: RecName: Full=Paragranulin; Contains: RecName: Full=Granulin-1; AltName: Full=Granulin G; Contains: RecName: Full=Granulin-2; AltName: Full=Granulin F; Contains: RecName: Full=Granulin-3; AltName: Full=Granulin B; Contains: RecName: Full=Granulin-4; AltName: Full=Granulin A; Contains: RecName: Full=Granulin-5; AltName: Full=Granulin C; Contains: RecName: Full=Granulin-6; AltName: Full=Granulin D; Contains: RecName: Full=Granulin-7; AltName: Full=Granulin E; Flags: Precursor; FUNCTION: Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling. FUNCTION: Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth. INTERACTION: O00555:CACNA1A; NbExp=2; IntAct=EBI-747754, EBI-766279; SUBCELLULAR LOCATION: Secreted. TISSUE SPECIFICITY: In myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts, and very strongly in epithelial cell lines. Present in inflammatory cells and bone marrow. Highest levels in kidney. PTM: Granulins are disulfide bridged. DISEASE: Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:607485]; also known as tau- negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease. DISEASE: Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:614706]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material. SIMILARITY: Belongs to the granulin family. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GRNID40757ch17q21.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GRN";
Frontotemporal Dementia Johannes Carolus Magnus Schlachetzki , et al. Journal of neurology 2009 256(12):2043-51, Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients., Journal of neurology 2009 256(12):2043-51.
[PubMed 19618231]
Frontotemporal Lobar Degeneration Daniela Galimberti , et al. Journal of Alzheimers disease 2010 19(1):171-7, GRN variability contributes to sporadic frontotemporal lobar degeneration., Journal of Alzheimers disease 2010 19(1):171-7.
[PubMed 20061636]
GRN rs4792938 CC genotype represents a susceptibility factor for the development of FTLD in individuals who do not carry GRN causal mutations
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P28799
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.