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Details for messenger / hormone: Granulin-1

EndoNet ID: ENH01089

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Synonyms

  • granulin E
  • granulin D
  • granulin C
  • granulin A
  • granulin B
  • granulin F
  • granulin G
  • Granulins
  • Granulin-1
  • Proepithelin
  • PEPI
  • GRN
  • Progranulin
  • PGRN

General information

  • FTD in these families results from PGRN haploinsufficiency rather than the accumulation of mutant protein [1]
  • Frontotemporal dementia (FTD) population, 5–10% of patients were found to have mutations in PGRN...PGRN expression is also substantially increased in Alzheimer's disease. [1]
  • PGRN is an important modulator of wound healing in peripheral tissues.The secreted protein accelerates neutrophil and macrophage activity, and promotes the neovascularization of damaged tissue. [1]
  • PGRN in the hypothalamus is highly regulated by androgens during critical periods of virilization in the CNS. [1]

Classification

Hormone function

  • homeostasis
    • cardiovascular control
    • development and growth
      • growth stimulation
      • immune response
        • activation

        Chemical classification

        • hormone
          • genome-encoded
            • cytokines
              • granulin family

          Composition

          Granulin-1

          Sequence 
          GGPCQVDAH CSAGHSCIF TVSGTSSCC 
PFPEAVACG DGHHCCPRG FHCSADGRS 
CF

          Granulin-6

          Sequence 
          IGCDQHTSC PVGQTCCPS LGGSWACCQ 
LPHAVCCED RQHCCPAGY TCNVKARSC 
E

          Granulin-2

          Sequence 
          AIQCPDSQF ECPDFSTCC VMVDGSWGC 
CPMPQASCC EDRVHCCPH GAFCDLVHT 
RCI

          Granulin-3

          • Granulin-3 works as an antagonist to Granulin-4 by inhibiting the proliferation.
          Sequence 
          VMCPDARSR CPDGSTCCE LPSGKYGCC 
PMPNATCCS DHLHCCPQD TVCDLIQSK 
CL

          Granulin-4

          • Granulin-4 provides growth of the epithelial cell line A431.p
          Sequence 
          DVKCDMEVS CPDGYTCCR LQSGAWGCC 
PFTQAVCCE DHIHCCPAG FTCDTQKGT 
CE

          Granulin-5

          Sequence 
          VPCDNVSSC PSSDTCCQL TSGEWGCCP 
IPEAVCCSD HQHCCPQGY TCVAEGQCQ

          Paragranulin

          Sequence 
          TRCPDGQFC PVACCLDPG GASYSCCRP 
LLD

          Granulin-7

          Sequence 
          DVECGEGHF CHDNQTCCR DNRQGWACC 
PYRQGVCCA DRRHCCPAG FRCAARGTK 
CL

          Acrogranin; Progranulin

          • Elastase and other extracellular proteases can cleave PGRN within the linker regions [2]
          • Undergoes alternate splicing with exon skipping. [1]
          Sequence 
          TRCPDGQFC PVACCLDPG GASYSCCRP 
LLDKWPTTL SRHLGGPCQ VDAHCSAGH 
SCIFTVSGT SSCCPFPEA VACGDGHHC 
CPRGFHCSA DGRSCFQRS GNNSVGAIQ 
CPDSQFECP DFSTCCVMV DGSWGCCPM 
PQASCCEDR VHCCPHGAF CDLVHTRCI 
TPTGTHPLA KKLPAQRTN RAVALSSSV 
MCPDARSRC PDGSTCCEL PSGKYGCCP 
MPNATCCSD HLHCCPQDT VCDLIQSKC 
LSKENATTD LLTKLPAHT VGDVKCDME 
VSCPDGYTC CRLQSGAWG CCPFTQAVC 
CEDHIHCCP AGFTCDTQK GTCEQGPHQ 
VPWMEKAPA HLSLPDPQA LKRDVPCDN 
VSSCPSSDT CCQLTSGEW GCCPIPEAV 
CCSDHQHCC PQGYTCVAE GQCQRGSEI 
VAGLEKMPA RRASLSHPR DIGCDQHTS 
CPVGQTCCP SLGGSWACC QLPHAVCCE 
DRQHCCPAG YTCNVKARS CEKEVVSAQ 
PATFLARSP HVGVKDVEC GEGHFCHDN 
QTCCRDNRQ GWACCPYRQ GVCCADRRH 
CCPAGFRCA ARGTKCLRR EAPRWDAPL 
RDPALRQLL

          Links to other resources

          UniProt P28799-1
          Ensembl ENST00000053867
          KEGG hsa:2896

          • Anatomical structure: epithelial_cell

          • Anatomical structure: hematopoietic_stem_cell

            • PGRN is highly expressed by cells with a high mitotic rate and low expression is found in tissues with less proliferative activity. [1]

          • Anatomical structure: lymphoid_tissue

          • Anatomical structure: mucosa_of_gastric_wall

          • Anatomical structure: spleen

          • Anatomical structure: skin

          • Anatomical structure: leukocyte

          • Anatomical structure: prosencephalon

          • Anatomical structure: olfactory_bulb

          • Anatomical structure: spinal_cord

          • Anatomical structure: Purkinje_cell

          • Anatomical structure: pyramidal_layer_of_hippocampus

          • Anatomical structure: pyramidal_layer_of_hippocampus

          Targets

          CellTLR9
          bronchial epithelial cell Present
          cholangiocyte Present
          dendritic cell in lymphoid tissues Present
          Influences
          • ↑ IFN-alpha
          • ↑ IFN-beta
          epithelial cell with microvilli Present
          lung Present
          lymph node Present
          macrophage Present
          Influences
          • ↑ IL-1 beta
          monocyte Present
          neutrophil granulocyte Present
          spleen Present
          tonsil Present
          Reference