LOCUS       NM_002087               2130 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens granulin precursor (GRN), mRNA.
ACCESSION   NM_002087
VERSION     NM_002087.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 2130)
  AUTHORS   Liao,A., Zheng,W., Wang,S., Wang,N., Li,Y., Chen,D. and Wang,Y.
  TITLE     Sortilin is associated with progranulin deficiency and autism-like
            behaviors in valproic acid-induced autism rats
  JOURNAL   CNS Neurosci Ther 30 (9), e70015 (2024)
   PUBMED   39218796
  REMARK    GeneRIF: Sortilin is associated with progranulin deficiency and
            autism-like behaviors in valproic acid-induced autism rats.
REFERENCE   2  (bases 1 to 2130)
  AUTHORS   Huper,L., Steinacker,P., Polyakova,M., Mueller,K., Godulla,J.,
            Herzig,S., Danek,A., Engel,A., Diehl-Schmid,J., Classen,J.,
            Fassbender,K., Fliessbach,K., Jahn,H., Kassubek,J., Kornhuber,J.,
            Landwehrmeyer,B., Lauer,M., Obrig,H., Oeckl,P., Prudlo,J., Saur,D.,
            Anderl-Straub,S., Synofzik,M., Wagner,M., Wiltfang,J.,
            Winkelmann,J., Volk,A.E., Huppertz,H.J., Otto,M. and Schroeter,M.L.
  CONSRTM   FTLD Consortium Germany
  TITLE     Neurofilaments and progranulin are related to atrophy in
            frontotemporal lobar degeneration - A transdiagnostic study
            cross-validating atrophy and fluid biomarkers
  JOURNAL   Alzheimers Dement 20 (7), 4461-4475 (2024)
   PUBMED   38865340
  REMARK    GeneRIF: Neurofilaments and progranulin are related to atrophy in
            frontotemporal lobar degeneration - A transdiagnostic study
            cross-validating atrophy and fluid biomarkers.
REFERENCE   3  (bases 1 to 2130)
  AUTHORS   Zhou,T., Qian,H., Zhang,D., Fang,W., Yao,M., Shi,H., Chen,T.,
            Chai,C. and Guo,B.
  TITLE     PGRN inhibits CD8+T cell recruitment and promotes breast cancer
            progression by up-regulating ICAM-1 on TAM
  JOURNAL   Cancer Immunol Immunother 73 (5), 76 (2024)
   PUBMED   38554213
  REMARK    GeneRIF: PGRN inhibits CD8[+]T cell recruitment and promotes breast
            cancer progression by up-regulating ICAM-1 on TAM.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2130)
  AUTHORS   Capell,A., Fellerer,K. and Haass,C.
  TITLE     Progranulin transcripts with short and long 5' untranslated regions
            (UTRs) are differentially expressed via posttranscriptional and
            translational repression
  JOURNAL   J Biol Chem 289 (37), 25879-25889 (2014)
   PUBMED   25056957
  REMARK    GeneRIF: This revealed a selective repression of progranulin
            translation and a reduction of mRNA levels by the
            219-nucleotide-long 5' UTR.
REFERENCE   5  (bases 1 to 2130)
  AUTHORS   Mole,S.E. and Williams,R.E.
  TITLE     Neuronal Ceroid-Lipofuscinoses - RETIRED CHAPTER, FOR HISTORICAL
            REFERENCE ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301601
REFERENCE   6  (bases 1 to 2130)
  AUTHORS   Hsiung,G.Y.R. and Feldman,H.H.
  TITLE     GRN Frontotemporal Dementia
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301545
REFERENCE   7  (bases 1 to 2130)
  AUTHORS   Klein,C., Lohmann,K., Marras,C. and Munchau,A.
  TITLE     Hereditary Dystonia Overview
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301334
REFERENCE   8  (bases 1 to 2130)
  AUTHORS   Bhandari,V. and Bateman,A.
  TITLE     Structure and chromosomal location of the human granulin gene
  JOURNAL   Biochem Biophys Res Commun 188 (1), 57-63 (1992)
   PUBMED   1417868
REFERENCE   9  (bases 1 to 2130)
  AUTHORS   Plowman,G.D., Green,J.M., Neubauer,M.G., Buckley,S.D.,
            McDonald,V.L., Todaro,G.J. and Shoyab,M.
  TITLE     The epithelin precursor encodes two proteins with opposing
            activities on epithelial cell growth
  JOURNAL   J Biol Chem 267 (18), 13073-13078 (1992)
   PUBMED   1618805
REFERENCE   10 (bases 1 to 2130)
  AUTHORS   Bhandari,V., Palfree,R.G. and Bateman,A.
  TITLE     Isolation and sequence of the granulin precursor cDNA from human
            bone marrow reveals tandem cysteine-rich granulin domains
  JOURNAL   Proc Natl Acad Sci U S A 89 (5), 1715-1719 (1992)
   PUBMED   1542665
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC003043.2.
            
            On Feb 27, 2020 this sequence version replaced NM_002087.3.
            
            Summary: 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.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X62320.1, AK000607.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000053867.8/ ENSP00000053867.2
            RefSeq Select criteria :: based on single protein-coding transcript
            regulatory uORF        :: PMID: 25056957
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-33                AC003043.2         43252-43284         c
            34-178              AC003043.2         39284-39428         c
            179-304             AC003043.2         39035-39160         c
            305-389             AC003043.2         38835-38919         c
            390-502             AC003043.2         38246-38358         c
            503-638             AC003043.2         38009-38144         c
            639-748             AC003043.2         37786-37895         c
            749-875             AC003043.2         37423-37549         c
            876-973             AC003043.2         37126-37223         c
            974-1219            AC003043.2         36791-37036         c
            1220-1453           AC003043.2         36338-36571         c
            1454-1684           AC003043.2         36015-36245         c
            1685-2130           AC003043.2         35480-35925         c
FEATURES             Location/Qualifiers
     source          1..2130
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="17"
                     /map="17q21.31"
     gene            1..2130
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /note="granulin precursor"
                     /db_xref="GeneID:2896"
                     /db_xref="HGNC:HGNC:4601"
                     /db_xref="MIM:138945"
     exon            1..33
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            34..178
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     CDS             41..1822
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /note="PC cell-derived growth factor; progranulin;
                     proepithelin; acrogranin; granulin-epithelin; granulins;
                     glycoprotein 88; glycoprotein of 88 Kda"
                     /codon_start=1
                     /product="progranulin precursor"
                     /protein_id="NP_002078.1"
                     /db_xref="CCDS:CCDS11483.1"
                     /db_xref="GeneID:2896"
                     /db_xref="HGNC:HGNC:4601"
                     /db_xref="MIM:138945"
                     /translation="MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRP
                     LLDKWPTTLSRHLGGPCQVDAHCSAGHSCIFTVSGTSSCCPFPEAVACGDGHHCCPRG
                     FHCSADGRSCFQRSGNNSVGAIQCPDSQFECPDFSTCCVMVDGSWGCCPMPQASCCED
                     RVHCCPHGAFCDLVHTRCITPTGTHPLAKKLPAQRTNRAVALSSSVMCPDARSRCPDG
                     STCCELPSGKYGCCPMPNATCCSDHLHCCPQDTVCDLIQSKCLSKENATTDLLTKLPA
                     HTVGDVKCDMEVSCPDGYTCCRLQSGAWGCCPFTQAVCCEDHIHCCPAGFTCDTQKGT
                     CEQGPHQVPWMEKAPAHLSLPDPQALKRDVPCDNVSSCPSSDTCCQLTSGEWGCCPIP
                     EAVCCSDHQHCCPQGYTCVAEGQCQRGSEIVAGLEKMPARRASLSHPRDIGCDQHTSC
                     PVGQTCCPSLGGSWACCQLPHAVCCEDRQHCCPAGYTCNVKARSCEKEVVSAQPATFL
                     ARSPHVGVKDVECGEGHFCHDNQTCCRDNRQGWACCPYRQGVCCADRRHCCPAGFRCA
                     ARGTKCLRREAPRWDAPLRDPALRQLL"
     exon            179..304
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            305..389
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            390..502
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            503..638
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            639..748
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            749..875
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            876..973
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            974..1219
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            1220..1453
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            1454..1684
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     exon            1685..2130
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2107..2112
                     /regulatory_class="polyA_signal_sequence"
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /note="hexamer: AATAAA"
     polyA_site      2130
                     /gene="GRN"
                     /gene_synonym="CLN11; FTD2; GEP; GP88; PCDGF; PEPI; PGRN"
                     /note="major polyA site"
ORIGIN      
        1 gctgctgccc aaggaccgcg gagtcggacg caggcagacc atgtggaccc tggtgagctg
       61 ggtggcctta acagcagggc tggtggctgg aacgcggtgc ccagatggtc agttctgccc
      121 tgtggcctgc tgcctggacc ccggaggagc cagctacagc tgctgccgtc cccttctgga
      181 caaatggccc acaacactga gcaggcatct gggtggcccc tgccaggttg atgcccactg
      241 ctctgccggc cactcctgca tctttaccgt ctcagggact tccagttgct gccccttccc
      301 agaggccgtg gcatgcgggg atggccatca ctgctgccca cggggcttcc actgcagtgc
      361 agacgggcga tcctgcttcc aaagatcagg taacaactcc gtgggtgcca tccagtgccc
      421 tgatagtcag ttcgaatgcc cggacttctc cacgtgctgt gttatggtcg atggctcctg
      481 ggggtgctgc cccatgcccc aggcttcctg ctgtgaagac agggtgcact gctgtccgca
      541 cggtgccttc tgcgacctgg ttcacacccg ctgcatcaca cccacgggca cccaccccct
      601 ggcaaagaag ctccctgccc agaggactaa cagggcagtg gccttgtcca gctcggtcat
      661 gtgtccggac gcacggtccc ggtgccctga tggttctacc tgctgtgagc tgcccagtgg
      721 gaagtatggc tgctgcccaa tgcccaacgc cacctgctgc tccgatcacc tgcactgctg
      781 cccccaagac actgtgtgtg acctgatcca gagtaagtgc ctctccaagg agaacgctac
      841 cacggacctc ctcactaagc tgcctgcgca cacagtgggg gatgtgaaat gtgacatgga
      901 ggtgagctgc ccagatggct atacctgctg ccgtctacag tcgggggcct ggggctgctg
      961 cccttttacc caggctgtgt gctgtgagga ccacatacac tgctgtcccg cggggtttac
     1021 gtgtgacacg cagaagggta cctgtgaaca ggggccccac caggtgccct ggatggagaa
     1081 ggccccagct cacctcagcc tgccagaccc acaagccttg aagagagatg tcccctgtga
     1141 taatgtcagc agctgtccct cctccgatac ctgctgccaa ctcacgtctg gggagtgggg
     1201 ctgctgtcca atcccagagg ctgtctgctg ctcggaccac cagcactgct gcccccaggg
     1261 ctacacgtgt gtagctgagg ggcagtgtca gcgaggaagc gagatcgtgg ctggactgga
     1321 gaagatgcct gcccgccggg cttccttatc ccaccccaga gacatcggct gtgaccagca
     1381 caccagctgc ccggtggggc agacctgctg cccgagcctg ggtgggagct gggcctgctg
     1441 ccagttgccc catgctgtgt gctgcgagga tcgccagcac tgctgcccgg ctggctacac
     1501 ctgcaacgtg aaggctcgat cctgcgagaa ggaagtggtc tctgcccagc ctgccacctt
     1561 cctggcccgt agccctcacg tgggtgtgaa ggacgtggag tgtggggaag gacacttctg
     1621 ccatgataac cagacctgct gccgagacaa ccgacagggc tgggcctgct gtccctaccg
     1681 ccagggcgtc tgttgtgctg atcggcgcca ctgctgtcct gctggcttcc gctgcgcagc
     1741 caggggtacc aagtgtttgc gcagggaggc cccgcgctgg gacgcccctt tgagggaccc
     1801 agccttgaga cagctgctgt gagggacagt actgaagact ctgcagccct cgggacccca
     1861 ctcggagggt gccctctgct caggcctccc tagcacctcc ccctaaccaa attctccctg
     1921 gaccccattc tgagctcccc atcaccatgg gaggtggggc ctcaatctaa ggccttccct
     1981 gtcagaaggg ggttgtggca aaagccacat tacaagctgc catcccctcc ccgtttcagt
     2041 ggaccctgtg gccaggtgct tttccctatc cacaggggtg tttgtgtgtg tgcgcgtgtg
     2101 cgtttcaata aagtttgtac actttcttaa
//
