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9  structures 140  species 0  interactions 1181  sequences 18  architectures

Family: Granulin (PF00396)

Summary: Granulin

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Granulin Edit Wikipedia article


Solution structure of the N-terminal sub-domain of human granulin A based on PDB 1g26.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM138945 MGI95832 HomoloGene1577 GeneCards: GRN Gene
RNA expression pattern
PBB GE GRN 211284 s at tn.png
PBB GE GRN 200678 x at tn.png
PBB GE GRN 216041 x at tn.png
More reference expression data
Species Human Mouse
Entrez 2896 14824
Ensembl ENSG00000030582 ENSMUSG00000034708
UniProt P28799 P28798
RefSeq (mRNA) NM_001012479 NM_008175
RefSeq (protein) NP_002078 NP_032201
Location (UCSC) Chr 17:
42.42 – 42.43 Mb
Chr 11:
102.43 – 102.44 Mb
PubMed search [1] [2]
PDB 1g26 EBI.jpg
the solution structure of a well-folded peptide based on the 31-residue amino-terminal subdomain of human granulin a
Symbol Granulin
Pfam PF00396
InterPro IPR000118
SCOP 1pcn

Granulin is a protein that in humans is encoded by the GRN gene.[1][2][3]


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.[3]

Clinical significance[edit]

The human liver fluke (Opisthorchis viverrini) contributes to the development of bile duct (liver) cancer by secreting a granulin-like growth hormone.[4]

Mutations in the GRN gene have been implicated in up to 25% of frontotemporal lobar degeneration, inherited in an autosomal dominant fashion with high penetrance.[5] Several loss-of-function mutations disease-causing mutations in GRN have been identified.[6][7]


Granulin has been shown to interact with Cyclin T1[8] and TRIB3.[9]


  1. ^ Bhandari V, Bateman A (Nov 1992). "Structure and chromosomal location of the human granulin gene". Biochem Biophys Res Commun 188 (1): 57–63. doi:10.1016/0006-291X(92)92349-3. PMID 1417868. 
  2. ^ Zhang H, Serrero G (Dec 1998). "Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor)". Proc Natl Acad Sci U S A 95 (24): 14202–7. Bibcode:1998PNAS...9514202Z. doi:10.1073/pnas.95.24.14202. PMC 24351. PMID 9826678. 
  3. ^ a b "Entrez Gene: GRN granulin". 
  4. ^ Smout MJ, Laha T, Mulvenna J, Sripa B, Suttiprapa S, Jones A, Brindley PJ, Loukas A (October 2009). "A granulin-like growth factor secreted by the carcinogenic liver fluke, Opisthorchis viverrini, promotes proliferation of host cells". PLoS Pathog. 5 (10): e1000611. doi:10.1371/journal.ppat.1000611. PMC 2749447. PMID 19816559. 
  5. ^ MacKenzie, I. R. A. (2007). "The neuropathology and clinical phenotype of FTD with progranulin mutations". Acta Neuropathologica 114 (1): 49–40. doi:10.1007/s00401-007-0223-8. PMID 17458552.  edit
  6. ^ Baker, M.; MacKenzie, I. R.; Pickering-Brown, S. M.; Gass, J.; Rademakers, R.; Lindholm, C.; Snowden, J.; Adamson, J.; Sadovnick, A. D.; Rollinson, S.; Cannon, A.; Dwosh, E.; Neary, D.; Melquist, S.; Richardson, A.; Dickson, D.; Berger, Z.; Eriksen, J.; Robinson, T.; Zehr, C.; Dickey, C. A.; Crook, R.; McGowan, E.; Mann, D.; Boeve, B.; Feldman, H.; Hutton, M. (2006). "Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17". Nature 442 (7105): 916–919. Bibcode:2006Natur.442..916B. doi:10.1038/nature05016. PMID 16862116.  edit
  7. ^ Cruts, M.; Gijselinck, I.; Van Der Zee, J.; Engelborghs, S.; Wils, H.; Pirici, D.; Rademakers, R.; Vandenberghe, R.; Dermaut, B.; Martin, J. J.; Van Duijn, C.; Peeters, K.; Sciot, R.; Santens, P.; De Pooter, T.; Mattheijssens, M.; Van Den Broeck, M.; Cuijt, I.; Vennekens, K. L.; De Deyn, P. P.; Kumar-Singh, S.; Van Broeckhoven, C. (2006). "Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21". Nature 442 (7105): 920–924. Bibcode:2006Natur.442..920C. doi:10.1038/nature05017. PMID 16862115.  edit
  8. ^ Hoque M, Young TM, Lee CG, Serrero G, Mathews MB, Pe'ery T (March 2003). "The growth factor granulin interacts with cyclin T1 and modulates P-TEFb-dependent transcription". Mol. Cell. Biol. 23 (5): 1688–702. doi:10.1128/MCB.23.5.1688-1702.2003. PMC 151712. PMID 12588988. 
  9. ^ Zhou Y, Li L, Liu Q, Xing G, Kuai X, Sun J, Yin X, Wang J, Zhang L, He F (May 2008). "E3 ubiquitin ligase SIAH1 mediates ubiquitination and degradation of TRB3". Cell. Signal. 20 (5): 942–8. doi:10.1016/j.cellsig.2008.01.010. PMID 18276110. 

Further reading[edit]

External links[edit]

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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Granulin Provide feedback

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000118

Metazoan granulins [PUBMED:1542665] are a family of cysteine-rich peptides of about 6 Kd which may have multiple biological activity. A precursor protein (known as acrogranin) potentially encodes seven different forms of granulin (grnA to grnG) which are probably released by post-translational proteolytic processing. Granulins are evolutionary related to a PMP-D1, a peptide extracted from the pars intercerebralis of migratory locusts [PUBMED:1740125]. A schematic representation of the structure of a granulin is shown below:

'C': conserved cysteine probably involved in a disulphide bond.

In plants a granulin domain is often associated with the C terminus of cysteine proteases belong to the MEROPS peptidase family C1, subfamily C1A (papain).

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Curation and family details

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Seed source: Prosite
Previous IDs: granulin;
Type: Family
Author: Finn RD
Number in seed: 94
Number in full: 1181
Average length of the domain: 43.50 aa
Average identity of full alignment: 48 %
Average coverage of the sequence by the domain: 31.13 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.9 20.9
Trusted cut-off 22.5 21.2
Noise cut-off 20.7 20.8
Model length: 43
Family (HMM) version: 13
Download: download the raw HMM for this family

Species distribution

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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Granulin domain has been found. There are 9 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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