Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
9  structures 140  species 0  interactions 1181  sequences 18  architectures

Family: Granulin (PF00396)

Summary: Granulin

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Granulin". More...

Granulin Edit Wikipedia article

Granulin

Solution structure of the N-terminal sub-domain of human granulin A based on PDB 1g26.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols GRN; CLN11; GEP; GP88; PCDGF; PEPI; PGRN
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
Orthologs
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]
Granulin
PDB 1g26 EBI.jpg
the solution structure of a well-folded peptide based on the 31-residue amino-terminal subdomain of human granulin a
Identifiers
Symbol Granulin
Pfam PF00396
InterPro IPR000118
PROSITE PDOC00634
SCOP 1pcn
SUPERFAMILY 1pcn

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

Structure[edit]

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.

Function[edit]

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]

Interactions[edit]

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

References[edit]

  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]


This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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:

       xxxCxxxxxCxxxxxCCxxxxxxxxCCxxxxxxCCxxxxxCCxxxxxCxxxxxxCx
'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...

Loading domain graphics...

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(94)
Full
(1181)
Representative proteomes NCBI
(1067)
Meta
(2)
RP15
(196)
RP35
(261)
RP55
(377)
RP75
(509)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(94)
Full
(1181)
Representative proteomes NCBI
(1067)
Meta
(2)
RP15
(196)
RP35
(261)
RP55
(377)
RP75
(509)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(94)
Full
(1181)
Representative proteomes NCBI
(1067)
Meta
(2)
RP15
(196)
RP35
(261)
RP55
(377)
RP75
(509)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

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:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

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

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

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.

Loading structure mapping...