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UniProtKB/Swiss-Prot entry P28799


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name GRN_HUMAN
Primary accession number P28799
Secondary accession numbers P23781 P23782 P23783 P23784 Q9BWE7 Q9UCH0
Integrated into Swiss-Prot on December 1, 1992
Sequence was last modified on October 11, 2005 (Sequence version 2)
Annotations were last modified on    July 22, 2008 (Entry version 93)
Name and origin of the protein
Protein name Granulins [Precursor]
Synonyms Proepithelin
PEPI
Contains Acrogranin
Paragranulin
Granulin-1
     (Granulin G)
Granulin-2
     (Granulin F)
Granulin-3
     (Granulin B)
Granulin-4
     (Granulin A)
Granulin-5
     (Granulin C)
Granulin-6
     (Granulin D)
Granulin-7
     (Granulin E)
Gene name
Name: GRN
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
DOI=10.1016/0006-291X(92)92349-3; PubMed=1417868 [NCBI, ExPASy, EBI, Israel, Japan]
Bhandari V., Bateman A.;
"Structure and chromosomal location of the human granulin gene.";
Biochem. Biophys. Res. Commun. 188:57-63(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
TISSUE=Kidney;
PubMed=1618805 [NCBI, ExPASy, EBI, Israel, Japan]
Plowman G.D., Green J.M., Neubauer M.G., Buckley S.D., McDonald V.L., Todaro G.J., Shoyab M.;
"The epithelin precursor encodes two proteins with opposing activities on epithelial cell growth.";
J. Biol. Chem. 267:13073-13078(1992).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
TISSUE=Bone marrow;
PubMed=1542665 [NCBI, ExPASy, EBI, Israel, Japan]
Bhandari V., Palfree R.G.E., Bateman A.;
"Isolation and sequence of the granulin precursor cDNA from human bone marrow reveals tandem cysteine-rich granulin domains.";
Proc. Natl. Acad. Sci. U.S.A. 89:1715-1719(1992).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
Yu W., Gibbs R.A.;
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
TISSUE=Cervix, and Lung;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
PROTEIN SEQUENCE OF 206-233; 281-336; 364-396 AND 442-447.
TISSUE=Leukocyte;
DOI=10.1016/S0006-291X(05)80908-8; PubMed=2268320 [NCBI, ExPASy, EBI, Israel, Japan]
Bateman A., Belcourt D.R., Bennett H.P., Lazure C., Solomon S.;
"Granulins, a novel class of peptide from leukocytes.";
Biochem. Biophys. Res. Commun. 173:1161-1168(1990).
[7]
PROTEIN SEQUENCE OF 281-295.
PubMed=8471426 [NCBI, ExPASy, EBI, Israel, Japan]
Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M.;
"Characterisation of UGP and its relationship with beta-core fragment.";
Br. J. Cancer 67:686-692(1993).
[8]
STRUCTURE BY NMR OF 284-311.
DOI=10.1021/bi992130u; PubMed=10715107 [NCBI, ExPASy, EBI, Israel, Japan]
Tolkatchev D., Ng A., Vranken W., Ni F.;
"Design and solution structure of a well-folded stack of two beta-hairpins based on the amino-terminal fragment of human granulin A.";
Biochemistry 39:2878-2886(2000).
[9]
INVOLVEMENT IN UP-FTD.
DOI=10.1038/nature05016; PubMed=16862116 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"Mutations in progranulin cause tau-negative frontotemporal dementia linked to chromosome 17.";
Nature 442:916-919(2006).
[10]
VARIANT UP-FTD ASP-9.
DOI=10.1002/ana.20963; PubMed=16983685 [NCBI, ExPASy, EBI, Israel, Japan]
Mukherjee O., Pastor P., Cairns N.J., Chakraverty S., Kauwe J.S.K., Shears S., Behrens M.I., Budde J., Hinrichs A.L., Norton J., Levitch D., Taylor-Reinwald L., Gitcho M., Tu P.-H., Tenenholz Grinberg L., Liscic R.M., Armendariz J., Morris J.C., Goate A.M.;
"HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin.";
Ann. Neurol. 60:314-322(2006).
[11]
CHARACTERIZATION OF VARIANT UP-FTD ASP-9.
DOI=10.1002/humu.20681; PubMed=18183624 [NCBI, ExPASy, EBI, Israel, Japan]
Mukherjee O., Wang J., Gitcho M., Chakraverty S., Taylor-Reinwald L., Shears S., Kauwe J.S.K., Norton J., Levitch D., Bigio E.H., Hatanpaa K.J., White C.L., Morris J.C., Cairns N.J., Goate A.;
"Molecular characterization of novel progranulin (GRN) mutations in frontotemporal dementia.";
Hum. Mutat. 29:512-521(2008).
Comments
  • 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.
  • SUBCELLULAR LOCATION: Secreted.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDP28799-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDP28799-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_001837.
  • 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.
  • SIMILARITY: Belongs to the granulin family.
  • WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=GRN";.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X62320; CAA44196.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF055008; AAC09359.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M75161; AAA58617.1; ALT_SEQ; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC000324; AAH00324.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC010577; AAH10577.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR JC1284; GYHU.
RefSeq NP_002078.1; -.
UniGene Hs.514220
3D structure databases
PDB
1G26; NMR; -; A=282-311.[ExPASy / RCSB / EBI]
2JYE; NMR; -; A=281-337.[ExPASy / RCSB / EBI]
2JYV; NMR; -; A=123-179.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1G26; -.
2JYE; -.
2JYV; -.
ModBase P28799.
Protein-protein interaction databases
IntAct P28799; -.
Organism-specific databases
H-InvDB HIX0013882; -.
HGNC HGNC:4601; GRN.
GenAtlas GRN.
HPA HPA008763; -.
MIM 138945; gene. [NCBI / EBI]
607485; phenotype. [NCBI / EBI]
PharmGKB PA24626; -.
GeneCards P28799.
Gene expression databases
CleanEx HS_GRN; -.
GermOnline ENSG00000030582; Homo sapiens.
Ontologies
GO
GO:0008083; Molecular function: growth factor activity (traceable author statement from ProtInc).
GO:0007165; Biological process: signal transduction (non-traceable author statement from ProtInc).
QuickGo view.
Family and domain databases
InterPro IPR015874; 4-disulphide_core.
IPR006150; Cys_repeat_1.
IPR000118; Granulin.
Graphical view of domain structure.
Pfam PF00396; Granulin; 7.
Pfam graphical view of domain structure.
PRINTS PR00003; 4DISULPHCORE.
SMART SM00277; GRAN; 7.
SM00289; WR1; 5.
SMART graphical view of domain structure.
PROSITE PS00799; GRANULINS; 7.
BLOCKS P28799.
Genome annotation databases
Ensembl ENSG00000030582; Homo sapiens. [Contig view]
GeneID 2896; -.
KEGG hsa:2896; -.
Phylogenomic databases
HOVERGEN P28799; -.
Other
LinkHub P28799; -.
SOURCE GRN; Homo sapiens.
ProtoNet P28799.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Cytokine; Direct protein sequencing; Glycoprotein; Polymorphism; Repeat; Secreted; Signal.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
SIGNAL   1     17  17     Potential. 
CHAIN   18    593  576     Acrogranin. PRO_0000012693
PEPTIDE   18    ?47        Paragranulin. PRO_0000012694
PEPTIDE   ?58   ?113        Granulin-1. PRO_0000012695
PEPTIDE   ?123   ?179        Granulin-2. PRO_0000012696
PEPTIDE   206    261  56     Granulin-3. PRO_0000012697
PEPTIDE   281    336  56     Granulin-4. PRO_0000012698
PEPTIDE   364   ?417        Granulin-5. PRO_0000012699
PEPTIDE   442   ?496        Granulin-6. PRO_0000012700
PEPTIDE   ?518   ?573        Granulin-7. PRO_0000012701
CARBOHYD   118    118        N-linked (GlcNAc...) (Potential). 
CARBOHYD   236    236        N-linked (GlcNAc...) (Potential). 
CARBOHYD   265    265        N-linked (GlcNAc...) (Potential). 
CARBOHYD   368    368        N-linked (GlcNAc...). 
CARBOHYD   530    530        N-linked (GlcNAc...) (Potential). 
DISULFID   284    296         
DISULFID   290    306         
VAR_SEQ   377    531        Missing (in isoform 2). VSP_001837
VARIANT   9      9  1     A -> D (in UP-FTD; no significant difference in the total mRNA between cases and controls; although the mutant protein is expressed it is not secreted and appears to be trapped within an intracellular compartment). VAR_044451 
VARIANT   515    515  1     G -> A (in dbSNP:rs25647 [NCBI]). VAR_014830 
CONFLICT   219    219        S -> H (in Ref. 6; AA sequence). 
CONFLICT   290    290        C -> S (in Ref. 7; AA sequence). 
CONFLICT   386    386        W -> H (in Ref. 6; AA sequence). 
CONFLICT   454    454        Q -> G (in Ref. 3; AAA58617). 
STRAND   282    285  4      
STRAND   288    290  3      
STRAND   294    298  5      
STRAND   304    308  5      
Sequence information
Length: 593 AA [This is the length of the unprocessed precursor] Molecular weight: 63544 Da [This is the MW of the unprocessed precursor] CRC64: 4E5947F1B4EDE619 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MWTLVSWVAL TAGLVAGTRC PDGQFCPVAC CLDPGGASYS CCRPLLDKWP TTLSRHLGGP 

        70         80         90        100        110        120 
CQVDAHCSAG HSCIFTVSGT SSCCPFPEAV ACGDGHHCCP RGFHCSADGR SCFQRSGNNS 

       130        140        150        160        170        180 
VGAIQCPDSQ FECPDFSTCC VMVDGSWGCC PMPQASCCED RVHCCPHGAF CDLVHTRCIT 

       190        200        210        220        230        240 
PTGTHPLAKK LPAQRTNRAV ALSSSVMCPD ARSRCPDGST CCELPSGKYG CCPMPNATCC 

       250        260        270        280        290        300 
SDHLHCCPQD TVCDLIQSKC LSKENATTDL LTKLPAHTVG DVKCDMEVSC PDGYTCCRLQ 

       310        320        330        340        350        360 
SGAWGCCPFT QAVCCEDHIH CCPAGFTCDT QKGTCEQGPH QVPWMEKAPA HLSLPDPQAL 

       370        380        390        400        410        420 
KRDVPCDNVS SCPSSDTCCQ LTSGEWGCCP IPEAVCCSDH QHCCPQGYTC VAEGQCQRGS 

       430        440        450        460        470        480 
EIVAGLEKMP ARRASLSHPR DIGCDQHTSC PVGQTCCPSL GGSWACCQLP HAVCCEDRQH 

       490        500        510        520        530        540 
CCPAGYTCNV KARSCEKEVV SAQPATFLAR SPHVGVKDVE CGEGHFCHDN QTCCRDNRQG 

       550        560        570        580        590 
WACCPYRQGV CCADRRHCCP AGFRCAARGT KCLRREAPRW DAPLRDPALR QLL 

P28799 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
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