ID   GRN_HUMAN               Reviewed;         593 AA.
AC   P28799; D3DX55; P23781; P23782; P23783; P23784; Q53HQ8; Q53Y88; Q540U8;
AC   Q9BWE7; Q9H8S1; Q9UCH0;
DT   01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 2.
DT   27-MAR-2024, entry version 236.
DE   RecName: Full=Progranulin {ECO:0000303|PubMed:16862116};
DE            Short=PGRN {ECO:0000303|PubMed:16862116};
DE   AltName: Full=Acrogranin {ECO:0000250|UniProtKB:P28798};
DE   AltName: Full=Epithelin precursor {ECO:0000303|PubMed:1618805};
DE   AltName: Full=Glycoprotein of 88 Kda {ECO:0000250|UniProtKB:P28798};
DE            Short=GP88;
DE            Short=Glycoprotein 88;
DE   AltName: Full=Granulin precursor {ECO:0000303|PubMed:1542665};
DE   AltName: Full=PC cell-derived growth factor {ECO:0000250|UniProtKB:P28798};
DE            Short=PCDGF {ECO:0000303|Ref.4};
DE   AltName: Full=Proepithelin {ECO:0000303|PubMed:12526812, ECO:0000303|PubMed:1618805};
DE            Short=PEPI {ECO:0000303|PubMed:12526812};
DE   Contains:
DE     RecName: Full=Paragranulin;
DE   Contains:
DE     RecName: Full=Granulin-1;
DE     AltName: Full=Granulin G;
DE   Contains:
DE     RecName: Full=Granulin-2;
DE     AltName: Full=Granulin F;
DE   Contains:
DE     RecName: Full=Granulin-3;
DE     AltName: Full=Epithelin-2 {ECO:0000250|UniProtKB:P23785};
DE     AltName: Full=Granulin B;
DE   Contains:
DE     RecName: Full=Granulin-4;
DE     AltName: Full=Epithelin-1 {ECO:0000250|UniProtKB:P23785};
DE     AltName: Full=Granulin A;
DE   Contains:
DE     RecName: Full=Granulin-5;
DE     AltName: Full=Granulin C;
DE   Contains:
DE     RecName: Full=Granulin-6;
DE     AltName: Full=Granulin D;
DE   Contains:
DE     RecName: Full=Granulin-7;
DE     AltName: Full=Granulin E;
DE   Flags: Precursor;
GN   Name=GRN {ECO:0000312|HGNC:HGNC:4601};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND SEQUENCE REVISION.
RX   PubMed=1417868; DOI=10.1016/0006-291x(92)92349-3;
RA   Bhandari V., Bateman A.;
RT   "Structure and chromosomal location of the human granulin gene.";
RL   Biochem. Biophys. Res. Commun. 188:57-63(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RX   PubMed=1618805; DOI=10.1016/s0021-9258(18)42382-4;
RA   Plowman G.D., Green J.M., Neubauer M.G., Buckley S.D., McDonald V.L.,
RA   Todaro G.J., Shoyab M.;
RT   "The epithelin precursor encodes two proteins with opposing activities on
RT   epithelial cell growth.";
RL   J. Biol. Chem. 267:13073-13078(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC   TISSUE=Bone marrow;
RX   PubMed=1542665; DOI=10.1073/pnas.89.5.1715;
RA   Bhandari V., Palfree R.G.E., Bateman A.;
RT   "Isolation and sequence of the granulin precursor cDNA from human bone
RT   marrow reveals tandem cysteine-rich granulin domains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:1715-1719(1992).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Lu R., Tian C., Serrero G.;
RT   "PCDGF sequence from lambda phage human Jurkat T cell cDNA library
RT   (Clontech).";
RL   Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RA   Yu W., Gibbs R.A.;
RL   Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Ovary;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Adipose tissue;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Cervix, and Lung;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [11]
RP   PROTEIN SEQUENCE OF 51-62; 122-131; 351-357; 361-367; 435-446 AND 517-526,
RP   INTERACTION WITH SLPI, PROTEOLYTIC CLEAVAGE, AND FUNCTION.
RX   PubMed=12526812; DOI=10.1016/s0092-8674(02)01141-8;
RA   Zhu J., Nathan C., Jin W., Sim D., Ashcroft G.S., Wahl S.M., Lacomis L.,
RA   Erdjument-Bromage H., Tempst P., Wright C.D., Ding A.;
RT   "Conversion of proepithelin to epithelins: roles of SLPI and elastase in
RT   host defense and wound repair.";
RL   Cell 111:867-878(2002).
RN   [12]
RP   PROTEIN SEQUENCE OF 206-233; 281-336; 364-396 AND 442-447.
RC   TISSUE=Leukocyte;
RX   PubMed=2268320; DOI=10.1016/s0006-291x(05)80908-8;
RA   Bateman A., Belcourt D.R., Bennett H.P., Lazure C., Solomon S.;
RT   "Granulins, a novel class of peptide from leukocytes.";
RL   Biochem. Biophys. Res. Commun. 173:1161-1168(1990).
RN   [13]
RP   PROTEIN SEQUENCE OF 281-295.
RX   PubMed=8471426; DOI=10.1038/bjc.1993.127;
RA   Kardana A., Bagshawe K.D., Coles B., Read D., Taylor M.;
RT   "Characterisation of UGP and its relationship with beta-core fragment.";
RL   Br. J. Cancer 67:686-692(1993).
RN   [14]
RP   INVOLVEMENT IN UP-FTD.
RX   PubMed=16862116; DOI=10.1038/nature05016;
RA   Baker M., Mackenzie I.R., Pickering-Brown S.M., Gass J., Rademakers R.,
RA   Lindholm C., Snowden J., Adamson J., Sadovnick A.D., Rollinson S.,
RA   Cannon A., Dwosh E., Neary D., Melquist S., Richardson A., Dickson D.,
RA   Berger Z., Eriksen J., Robinson T., Zehr C., Dickey C.A., Crook R.,
RA   McGowan E., Mann D., Boeve B., Feldman H., Hutton M.;
RT   "Mutations in progranulin cause tau-negative frontotemporal dementia linked
RT   to chromosome 17.";
RL   Nature 442:916-919(2006).
RN   [15]
RP   FUNCTION.
RX   PubMed=18378771; DOI=10.1083/jcb.200712039;
RA   Van Damme P., Van Hoecke A., Lambrechts D., Vanacker P., Bogaert E.,
RA   van Swieten J., Carmeliet P., Van Den Bosch L., Robberecht W.;
RT   "Progranulin functions as a neurotrophic factor to regulate neurite
RT   outgrowth and enhance neuronal survival.";
RL   J. Cell Biol. 181:37-41(2008).
RN   [16]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-265.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [17]
RP   GLYCOSYLATION AT ASN-118; ASN-265; ASN-368 AND ASN-530.
RX   PubMed=20188224; DOI=10.1016/j.jprot.2010.02.013;
RA   Songsrirote K., Li Z., Ashford D., Bateman A., Thomas-Oates J.;
RT   "Development and application of mass spectrometric methods for the analysis
RT   of progranulin N-glycosylation.";
RL   J. Proteomics 73:1479-1490(2010).
RN   [18]
RP   INTERACTION WITH SORT1, AND SUBCELLULAR LOCATION.
RX   PubMed=21092856; DOI=10.1016/j.neuron.2010.09.034;
RA   Hu F., Padukkavidana T., Vaegter C.B., Brady O.A., Zheng Y.,
RA   Mackenzie I.R., Feldman H.H., Nykjaer A., Strittmatter S.M.;
RT   "Sortilin-mediated endocytosis determines levels of the frontotemporal
RT   dementia protein, progranulin.";
RL   Neuron 68:654-667(2010).
RN   [19]
RP   INVOLVEMENT IN CLN11.
RX   PubMed=22608501; DOI=10.1016/j.ajhg.2012.04.021;
RA   Smith K.R., Damiano J., Franceschetti S., Carpenter S., Canafoglia L.,
RA   Morbin M., Rossi G., Pareyson D., Mole S.E., Staropoli J.F., Sims K.B.,
RA   Lewis J., Lin W.L., Dickson D.W., Dahl H.H., Bahlo M., Berkovic S.F.;
RT   "Strikingly different clinicopathological phenotypes determined by
RT   progranulin-mutation dosage.";
RL   Am. J. Hum. Genet. 90:1102-1107(2012).
RN   [20]
RP   SUBUNIT.
RX   PubMed=23364791; DOI=10.1074/jbc.m112.441949;
RA   Nguyen A.D., Nguyen T.A., Cenik B., Yu G., Herz J., Walther T.C.,
RA   Davidson W.S., Farese R.V. Jr.;
RT   "Secreted progranulin is a homodimer and is not a component of high density
RT   lipoproteins (HDL).";
RL   J. Biol. Chem. 288:8627-8635(2013).
RN   [21]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [22]
RP   INTERACTION WITH PSAP, AND SUBCELLULAR LOCATION.
RX   PubMed=26370502; DOI=10.1083/jcb.201502029;
RA   Zhou X., Sun L., Bastos de Oliveira F., Qi X., Brown W.J., Smolka M.B.,
RA   Sun Y., Hu F.;
RT   "Prosaposin facilitates sortilin-independent lysosomal trafficking of
RT   progranulin.";
RL   J. Cell Biol. 210:991-1002(2015).
RN   [23]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25944712; DOI=10.1002/pmic.201400617;
RA   Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA   Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT   "N-terminome analysis of the human mitochondrial proteome.";
RL   Proteomics 15:2519-2524(2015).
RN   [24]
RP   INTERACTION WITH GBA1 AND HSPA1A.
RX   PubMed=27789271; DOI=10.1016/j.ebiom.2016.10.010;
RA   Jian J., Tian Q.Y., Hettinghouse A., Zhao S., Liu H., Wei J., Grunig G.,
RA   Zhang W., Setchell K.D.R., Sun Y., Overkleeft H.S., Chan G.L., Liu C.J.;
RT   "Progranulin Recruits HSP70 to beta-Glucocerebrosidase and Is Therapeutic
RT   Against Gaucher Disease.";
RL   EBioMedicine 13:212-224(2016).
RN   [25]
RP   FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=28073925; DOI=10.1093/hmg/ddx011;
RA   Tanaka Y., Suzuki G., Matsuwaki T., Hosokawa M., Serrano G., Beach T.G.,
RA   Yamanouchi K., Hasegawa M., Nishihara M.;
RT   "Progranulin regulates lysosomal function and biogenesis through
RT   acidification of lysosomes.";
RL   Hum. Mol. Genet. 26:969-988(2017).
RN   [26]
RP   FUNCTION, AND INTERACTION WITH CTSD.
RX   PubMed=28453791; DOI=10.1093/hmg/ddx162;
RA   Beel S., Moisse M., Damme M., De Muynck L., Robberecht W.,
RA   Van Den Bosch L., Saftig P., Van Damme P.;
RT   "Progranulin functions as a cathepsin D chaperone to stimulate axonal
RT   outgrowth in vivo.";
RL   Hum. Mol. Genet. 26:2850-2863(2017).
RN   [27]
RP   PROTEOLYTIC CLEAVAGE BY CTSL AND ELANE, IDENTIFICATION BY MASS
RP   SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX   PubMed=28743268; DOI=10.1186/s13024-017-0196-6;
RA   Lee C.W., Stankowski J.N., Chew J., Cook C.N., Lam Y.W., Almeida S.,
RA   Carlomagno Y., Lau K.F., Prudencio M., Gao F.B., Bogyo M., Dickson D.W.,
RA   Petrucelli L.;
RT   "The lysosomal protein cathepsin L is a progranulin protease.";
RL   Mol. Neurodegener. 12:55-55(2017).
RN   [28]
RP   FUNCTION, INTERACTION WITH PSAP AND SORT1, AND SUBCELLULAR LOCATION.
RX   PubMed=28541286; DOI=10.1038/ncomms15277;
RA   Zhou X., Sun L., Bracko O., Choi J.W., Jia Y., Nana A.L., Brady O.A.,
RA   Hernandez J.C.C., Nishimura N., Seeley W.W., Hu F.;
RT   "Impaired prosaposin lysosomal trafficking in frontotemporal lobar
RT   degeneration due to progranulin mutations.";
RL   Nat. Commun. 8:15277-15277(2017).
RN   [29]
RP   STRUCTURE BY NMR OF 284-311.
RX   PubMed=10715107; DOI=10.1021/bi992130u;
RA   Tolkatchev D., Ng A., Vranken W., Ni F.;
RT   "Design and solution structure of a well-folded stack of two beta-hairpins
RT   based on the amino-terminal fragment of human granulin A.";
RL   Biochemistry 39:2878-2886(2000).
RN   [30]
RP   STRUCTURE BY NMR OF 123-179; 281-337 AND 364-417, AND DISULFIDE BONDS.
RX   PubMed=18359860; DOI=10.1110/ps.073295308;
RA   Tolkatchev D., Malik S., Vinogradova A., Wang P., Chen Z., Xu P.,
RA   Bennett H.P., Bateman A., Ni F.;
RT   "Structure dissection of human progranulin identifies well-folded
RT   granulin/epithelin modules with unique functional activities.";
RL   Protein Sci. 17:711-724(2008).
RN   [31]
RP   VARIANT UP-FTD ASP-9.
RX   PubMed=16983685; DOI=10.1002/ana.20963;
RA   Mukherjee O., Pastor P., Cairns N.J., Chakraverty S., Kauwe J.S.K.,
RA   Shears S., Behrens M.I., Budde J., Hinrichs A.L., Norton J., Levitch D.,
RA   Taylor-Reinwald L., Gitcho M., Tu P.-H., Tenenholz Grinberg L.,
RA   Liscic R.M., Armendariz J., Morris J.C., Goate A.M.;
RT   "HDDD2 is a familial frontotemporal lobar degeneration with ubiquitin-
RT   positive, tau-negative inclusions caused by a missense mutation in the
RT   signal peptide of progranulin.";
RL   Ann. Neurol. 60:314-322(2006).
RN   [32]
RP   CHARACTERIZATION OF VARIANT UP-FTD ASP-9.
RX   PubMed=18183624; DOI=10.1002/humu.20681;
RA   Mukherjee O., Wang J., Gitcho M., Chakraverty S., Taylor-Reinwald L.,
RA   Shears S., Kauwe J.S.K., Norton J., Levitch D., Bigio E.H., Hatanpaa K.J.,
RA   White C.L., Morris J.C., Cairns N.J., Goate A.;
RT   "Molecular characterization of novel progranulin (GRN) mutations in
RT   frontotemporal dementia.";
RL   Hum. Mutat. 29:512-521(2008).
RN   [33]
RP   VARIANTS TRP-19; TRP-55; THR-69; ASN-119 DEL; TYR-120; MET-182; SER-221;
RP   LEU-275; ASN-376; LEU-398; GLN-433; ALA-515 AND HIS-564.
RX   PubMed=20020531; DOI=10.1002/humu.21152;
RA   Guerreiro R.J., Washecka N., Hardy J., Singleton A.;
RT   "A thorough assessment of benign genetic variability in GRN and MAPT.";
RL   Hum. Mutat. 31:E1126-E1140(2010).
CC   -!- FUNCTION: Secreted protein that acts as a key regulator of lysosomal
CC       function and as a growth factor involved in inflammation, wound healing
CC       and cell proliferation (PubMed:28541286, PubMed:28073925,
CC       PubMed:18378771, PubMed:28453791, PubMed:12526812). Regulates protein
CC       trafficking to lysosomes and, also the activity of lysosomal enzymes
CC       (PubMed:28453791, PubMed:28541286). Facilitates also the acidification
CC       of lysosomes, causing degradation of mature CTSD by CTSB
CC       (PubMed:28073925). In addition, functions as a wound-related growth
CC       factor that acts directly on dermal fibroblasts and endothelial cells
CC       to promote division, migration and the formation of capillary-like
CC       tubule structures (By similarity). Also promotes epithelial cell
CC       proliferation by blocking TNF-mediated neutrophil activation preventing
CC       release of oxidants and proteases (PubMed:12526812). Moreover,
CC       modulates inflammation in neurons by preserving neurons survival,
CC       axonal outgrowth and neuronal integrity (PubMed:18378771).
CC       {ECO:0000250|UniProtKB:P28798, ECO:0000269|PubMed:12526812,
CC       ECO:0000269|PubMed:18378771, ECO:0000269|PubMed:28073925,
CC       ECO:0000269|PubMed:28453791, ECO:0000269|PubMed:28541286}.
CC   -!- FUNCTION: [Granulin-4]: Promotes proliferation of the epithelial cell
CC       line A431 in culture.
CC   -!- FUNCTION: [Granulin-3]: Inhibits epithelial cell proliferation and
CC       induces epithelial cells to secrete IL-8.
CC       {ECO:0000269|PubMed:12526812}.
CC   -!- FUNCTION: [Granulin-7]: Stabilizes CTSD through interaction with CTSD
CC       leading to maintain its aspartic-type peptidase activity.
CC       {ECO:0000269|PubMed:28453791}.
CC   -!- SUBUNIT: Progranulin is secreted as a homodimer (PubMed:23364791).
CC       Interacts with SLPI; interaction protects progranulin from proteolysis
CC       (PubMed:12526812). Interacts (via region corresponding to granulin-7
CC       peptide) with CTSD; stabilizes CTSD and increases its proteolytic
CC       activity (PubMed:28453791). Interacts (via region corresponding to
CC       granulin-7 peptide) with SORT1; this interaction mediates endocytosis
CC       and lysosome delivery of progranulin; interaction occurs at the
CC       neuronal cell surface in a stressed nervous system (PubMed:21092856).
CC       Interacts with PSAP; facilitates lysosomal delivery of progranulin from
CC       the extracellular space and the biosynthetic pathway (PubMed:26370502).
CC       Forms a complex with PSAP and M6PR; PSAP bridges the binding between
CC       progranulin and M6PR (PubMed:26370502). Forms a complex with PSAP and
CC       SORT1; progranulin bridges the interaction between PSAP and SORT1;
CC       facilitates lysosomal targeting of PSAP via SORT1; interaction enhances
CC       PSAP uptake in primary cortical neurons (PubMed:28541286). Interacts
CC       (via regions corresponding to granulin-2 and granulin-7 peptides) with
CC       GBA1; this interaction prevents aggregation of GBA1-SCARB2 complex via
CC       interaction with HSPA1A upon stress (PubMed:27789271). Interacts (via
CC       region corresponding to granulin-7 peptide) with HSPA1A; mediates
CC       recruitment of HSPA1A to GBA1 and prevents GBA1 aggregation in response
CC       to stress (PubMed:27789271). {ECO:0000269|PubMed:12526812,
CC       ECO:0000269|PubMed:21092856, ECO:0000269|PubMed:23364791,
CC       ECO:0000269|PubMed:26370502, ECO:0000269|PubMed:27789271,
CC       ECO:0000269|PubMed:28453791, ECO:0000269|PubMed:28541286}.
CC   -!- INTERACTION:
CC       P28799; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-747754, EBI-10173507;
CC       P28799; Q9UIJ7: AK3; NbExp=3; IntAct=EBI-747754, EBI-3916527;
CC       P28799; Q9NYG5: ANAPC11; NbExp=3; IntAct=EBI-747754, EBI-2130187;
CC       P28799; D3DTF8: APLN; NbExp=3; IntAct=EBI-747754, EBI-22002556;
CC       P28799; Q8N6T3: ARFGAP1; NbExp=3; IntAct=EBI-747754, EBI-716933;
CC       P28799; Q8N6T3-3: ARFGAP1; NbExp=3; IntAct=EBI-747754, EBI-10694449;
CC       P28799; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-747754, EBI-14199987;
CC       P28799; Q96DX5-3: ASB9; NbExp=3; IntAct=EBI-747754, EBI-25843552;
CC       P28799; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-747754, EBI-10254793;
CC       P28799; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-747754, EBI-9089489;
CC       P28799; P46379-2: BAG6; NbExp=3; IntAct=EBI-747754, EBI-10988864;
CC       P28799; Q16611: BAK1; NbExp=3; IntAct=EBI-747754, EBI-519866;
CC       P28799; Q8IXM2: BAP18; NbExp=3; IntAct=EBI-747754, EBI-4280811;
CC       P28799; Q14457: BECN1; NbExp=3; IntAct=EBI-747754, EBI-949378;
CC       P28799; Q96LC9: BMF; NbExp=3; IntAct=EBI-747754, EBI-3919268;
CC       P28799; Q9GZL8: BPESC1; NbExp=3; IntAct=EBI-747754, EBI-25861458;
CC       P28799; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-747754, EBI-2837444;
CC       P28799; Q9Y297: BTRC; NbExp=3; IntAct=EBI-747754, EBI-307461;
CC       P28799; Q8TAB5: C1orf216; NbExp=3; IntAct=EBI-747754, EBI-747505;
CC       P28799; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-747754, EBI-7317823;
CC       P28799; Q6P5X5-2: C22orf39; NbExp=3; IntAct=EBI-747754, EBI-10692329;
CC       P28799; Q53FE4: C4orf17; NbExp=3; IntAct=EBI-747754, EBI-715110;
CC       P28799; Q9BRJ6: C7orf50; NbExp=3; IntAct=EBI-747754, EBI-751612;
CC       P28799; O00555: CACNA1A; NbExp=2; IntAct=EBI-747754, EBI-766279;
CC       P28799; Q96NX5: CAMK1G; NbExp=3; IntAct=EBI-747754, EBI-3920838;
CC       P28799; O75808: CAPN15; NbExp=3; IntAct=EBI-747754, EBI-6149008;
CC       P28799; Q8N5R6: CCDC33; NbExp=3; IntAct=EBI-747754, EBI-740841;
CC       P28799; P50750-2: CDK9; NbExp=3; IntAct=EBI-747754, EBI-12029902;
CC       P28799; O14646-2: CHD1; NbExp=3; IntAct=EBI-747754, EBI-10961487;
CC       P28799; Q9Y3D0: CIAO2B; NbExp=3; IntAct=EBI-747754, EBI-744045;
CC       P28799; Q99967: CITED2; NbExp=3; IntAct=EBI-747754, EBI-937732;
CC       P28799; Q9Y240: CLEC11A; NbExp=3; IntAct=EBI-747754, EBI-3957044;
CC       P28799; Q96DZ5: CLIP3; NbExp=3; IntAct=EBI-747754, EBI-12823145;
CC       P28799; Q16740: CLPP; NbExp=3; IntAct=EBI-747754, EBI-1056029;
CC       P28799; Q9BT09: CNPY3; NbExp=3; IntAct=EBI-747754, EBI-2835965;
CC       P28799; Q6PJW8-3: CNST; NbExp=3; IntAct=EBI-747754, EBI-25836090;
CC       P28799; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-747754, EBI-350590;
CC       P28799; Q9UGL9: CRCT1; NbExp=3; IntAct=EBI-747754, EBI-713677;
CC       P28799; Q02930-3: CREB5; NbExp=3; IntAct=EBI-747754, EBI-10192698;
CC       P28799; Q49AN0: CRY2; NbExp=3; IntAct=EBI-747754, EBI-2212355;
CC       P28799; P01040: CSTA; NbExp=3; IntAct=EBI-747754, EBI-724303;
CC       P28799; P07339: CTSD; NbExp=4; IntAct=EBI-747754, EBI-2115097;
CC       P28799; P42830: CXCL5; NbExp=3; IntAct=EBI-747754, EBI-12175919;
CC       P28799; Q8TB03: CXorf38; NbExp=3; IntAct=EBI-747754, EBI-12024320;
CC       P28799; P00167: CYB5A; NbExp=3; IntAct=EBI-747754, EBI-1047284;
CC       P28799; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-747754, EBI-3867333;
CC       P28799; Q16643: DBN1; NbExp=5; IntAct=EBI-747754, EBI-351394;
CC       P28799; Q5TAQ9-2: DCAF8; NbExp=3; IntAct=EBI-747754, EBI-25842815;
CC       P28799; Q9P1A6-3: DLGAP2; NbExp=3; IntAct=EBI-747754, EBI-12019838;
CC       P28799; Q07687: DLX2; NbExp=3; IntAct=EBI-747754, EBI-3908234;
CC       P28799; Q9NQL9: DMRT3; NbExp=3; IntAct=EBI-747754, EBI-9679045;
CC       P28799; P49184: DNASE1L1; NbExp=3; IntAct=EBI-747754, EBI-20894690;
CC       P28799; Q16610: ECM1; NbExp=3; IntAct=EBI-747754, EBI-947964;
CC       P28799; O75530-2: EED; NbExp=3; IntAct=EBI-747754, EBI-11132357;
CC       P28799; O60841: EIF5B; NbExp=3; IntAct=EBI-747754, EBI-928530;
CC       P28799; Q6UXG2-3: ELAPOR1; NbExp=3; IntAct=EBI-747754, EBI-12920100;
CC       P28799; Q8TE68-3: EPS8L1; NbExp=3; IntAct=EBI-747754, EBI-21574901;
CC       P28799; Q9H6S3: EPS8L2; NbExp=3; IntAct=EBI-747754, EBI-3940939;
CC       P28799; O15540: FABP7; NbExp=3; IntAct=EBI-747754, EBI-10697159;
CC       P28799; Q9UNN5: FAF1; NbExp=3; IntAct=EBI-747754, EBI-718246;
CC       P28799; Q6SJ93: FAM111B; NbExp=3; IntAct=EBI-747754, EBI-6309082;
CC       P28799; Q96AQ9: FAM131C; NbExp=4; IntAct=EBI-747754, EBI-741921;
CC       P28799; Q5TZK3: FAM74A6; NbExp=3; IntAct=EBI-747754, EBI-10247271;
CC       P28799; Q5HYJ3-3: FAM76B; NbExp=6; IntAct=EBI-747754, EBI-11956087;
CC       P28799; Q17RN3: FAM98C; NbExp=3; IntAct=EBI-747754, EBI-5461838;
CC       P28799; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-747754, EBI-8468186;
CC       P28799; Q9NW38: FANCL; NbExp=3; IntAct=EBI-747754, EBI-2339898;
CC       P28799; Q53R41: FASTKD1; NbExp=3; IntAct=EBI-747754, EBI-3957005;
CC       P28799; Q8NFZ0: FBH1; NbExp=3; IntAct=EBI-747754, EBI-724767;
CC       P28799; Q9UBX5: FBLN5; NbExp=3; IntAct=EBI-747754, EBI-947897;
CC       P28799; P15976-2: GATA1; NbExp=3; IntAct=EBI-747754, EBI-9090198;
CC       P28799; P23769-2: GATA2; NbExp=3; IntAct=EBI-747754, EBI-21856389;
CC       P28799; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-747754, EBI-8799578;
CC       P28799; P10075: GLI4; NbExp=3; IntAct=EBI-747754, EBI-14061927;
CC       P28799; O76003: GLRX3; NbExp=9; IntAct=EBI-747754, EBI-374781;
CC       P28799; Q9Y223-2: GNE; NbExp=6; IntAct=EBI-747754, EBI-11975289;
CC       P28799; Q9HBQ8: GOLGA2P5; NbExp=3; IntAct=EBI-747754, EBI-22000587;
CC       P28799; Q7Z602: GPR141; NbExp=3; IntAct=EBI-747754, EBI-21649723;
CC       P28799; Q9Y4H4: GPSM3; NbExp=3; IntAct=EBI-747754, EBI-347538;
CC       P28799; O75409: H2AP; NbExp=3; IntAct=EBI-747754, EBI-6447217;
CC       P28799; Q6NXT2: H3-5; NbExp=3; IntAct=EBI-747754, EBI-2868501;
CC       P28799; P68431: H3C12; NbExp=3; IntAct=EBI-747754, EBI-79722;
CC       P28799; A8K0U2: hCG_2001421; NbExp=3; IntAct=EBI-747754, EBI-25843825;
CC       P28799; Q03014: HHEX; NbExp=3; IntAct=EBI-747754, EBI-747421;
CC       P28799; P49639: HOXA1; NbExp=18; IntAct=EBI-747754, EBI-740785;
CC       P28799; P09017: HOXC4; NbExp=3; IntAct=EBI-747754, EBI-3923226;
CC       P28799; P22692: IGFBP4; NbExp=3; IntAct=EBI-747754, EBI-2831948;
CC       P28799; Q14005-2: IL16; NbExp=3; IntAct=EBI-747754, EBI-17178971;
CC       P28799; Q9NXX0: ILF3; NbExp=3; IntAct=EBI-747754, EBI-743980;
CC       P28799; Q9UNL4: ING4; NbExp=3; IntAct=EBI-747754, EBI-2866661;
CC       P28799; Q8IXL9: IQCF2; NbExp=3; IntAct=EBI-747754, EBI-10238842;
CC       P28799; Q9Y6F6-3: IRAG1; NbExp=3; IntAct=EBI-747754, EBI-25840037;
CC       P28799; Q86U28: ISCA2; NbExp=3; IntAct=EBI-747754, EBI-10258659;
CC       P28799; Q14145: KEAP1; NbExp=3; IntAct=EBI-747754, EBI-751001;
CC       P28799; Q12756: KIF1A; NbExp=3; IntAct=EBI-747754, EBI-2679809;
CC       P28799; Q9UIH9: KLF15; NbExp=3; IntAct=EBI-747754, EBI-2796400;
CC       P28799; P57682: KLF3; NbExp=4; IntAct=EBI-747754, EBI-8472267;
CC       P28799; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-747754, EBI-714379;
CC       P28799; O76011: KRT34; NbExp=3; IntAct=EBI-747754, EBI-1047093;
CC       P28799; Q07627: KRTAP1-1; NbExp=3; IntAct=EBI-747754, EBI-11959885;
CC       P28799; Q9BYS1: KRTAP1-5; NbExp=3; IntAct=EBI-747754, EBI-11741292;
CC       P28799; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-747754, EBI-10172290;
CC       P28799; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-747754, EBI-10171774;
CC       P28799; Q8IUC1: KRTAP11-1; NbExp=3; IntAct=EBI-747754, EBI-1052037;
CC       P28799; P59990: KRTAP12-1; NbExp=3; IntAct=EBI-747754, EBI-10210845;
CC       P28799; Q52LG2: KRTAP13-2; NbExp=3; IntAct=EBI-747754, EBI-11953846;
CC       P28799; Q3SY46: KRTAP13-3; NbExp=3; IntAct=EBI-747754, EBI-10241252;
CC       P28799; Q3LI76: KRTAP15-1; NbExp=3; IntAct=EBI-747754, EBI-11992140;
CC       P28799; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-747754, EBI-10241353;
CC       P28799; Q6PEX3: KRTAP26-1; NbExp=8; IntAct=EBI-747754, EBI-3957672;
CC       P28799; P26371: KRTAP5-9; NbExp=3; IntAct=EBI-747754, EBI-3958099;
CC       P28799; Q3LI64: KRTAP6-1; NbExp=3; IntAct=EBI-747754, EBI-12111050;
CC       P28799; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-747754, EBI-11962084;
CC       P28799; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-747754, EBI-10261141;
CC       P28799; Q14847-2: LASP1; NbExp=3; IntAct=EBI-747754, EBI-9088686;
CC       P28799; O95447: LCA5L; NbExp=3; IntAct=EBI-747754, EBI-8473670;
CC       P28799; Q5T7P2: LCE1A; NbExp=3; IntAct=EBI-747754, EBI-11962058;
CC       P28799; Q5T7P3: LCE1B; NbExp=3; IntAct=EBI-747754, EBI-10245913;
CC       P28799; Q5T752: LCE1D; NbExp=3; IntAct=EBI-747754, EBI-11741311;
CC       P28799; Q5T753: LCE1E; NbExp=3; IntAct=EBI-747754, EBI-11955335;
CC       P28799; Q5TA79: LCE2A; NbExp=3; IntAct=EBI-747754, EBI-10246607;
CC       P28799; O14633: LCE2B; NbExp=3; IntAct=EBI-747754, EBI-11478468;
CC       P28799; Q5TA82: LCE2D; NbExp=3; IntAct=EBI-747754, EBI-10246750;
CC       P28799; Q5T5A8: LCE3C; NbExp=3; IntAct=EBI-747754, EBI-10245291;
CC       P28799; Q5T5B0: LCE3E; NbExp=3; IntAct=EBI-747754, EBI-10245456;
CC       P28799; Q5TA78: LCE4A; NbExp=4; IntAct=EBI-747754, EBI-10246358;
CC       P28799; Q9UPM6: LHX6; NbExp=3; IntAct=EBI-747754, EBI-10258746;
CC       P28799; Q68G74: LHX8; NbExp=3; IntAct=EBI-747754, EBI-8474075;
CC       P28799; A2RU56: LOC401296; NbExp=3; IntAct=EBI-747754, EBI-9088215;
CC       P28799; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-747754, EBI-749562;
CC       P28799; Q14693: LPIN1; NbExp=3; IntAct=EBI-747754, EBI-5278370;
CC       P28799; Q6Q4G3-4: LVRN; NbExp=3; IntAct=EBI-747754, EBI-25862057;
CC       P28799; Q9UDY8-2: MALT1; NbExp=3; IntAct=EBI-747754, EBI-12056869;
CC       P28799; Q9GZQ8: MAP1LC3B; NbExp=3; IntAct=EBI-747754, EBI-373144;
CC       P28799; Q99683: MAP3K5; NbExp=3; IntAct=EBI-747754, EBI-476263;
CC       P28799; P61244-4: MAX; NbExp=3; IntAct=EBI-747754, EBI-25848049;
CC       P28799; O95243-2: MBD4; NbExp=3; IntAct=EBI-747754, EBI-6448717;
CC       P28799; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-747754, EBI-16439278;
CC       P28799; P41218: MNDA; NbExp=3; IntAct=EBI-747754, EBI-2829677;
CC       P28799; Q86VF5-3: MOGAT3; NbExp=3; IntAct=EBI-747754, EBI-25840143;
CC       P28799; Q9Y2R5: MRPS17; NbExp=3; IntAct=EBI-747754, EBI-1046443;
CC       P28799; O43196-4: MSH5; NbExp=3; IntAct=EBI-747754, EBI-25860238;
CC       P28799; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-747754, EBI-10699187;
CC       P28799; Q96A32: MYL11; NbExp=3; IntAct=EBI-747754, EBI-1390771;
CC       P28799; Q9NPC7: MYNN; NbExp=3; IntAct=EBI-747754, EBI-3446748;
CC       P28799; O15069: NACAD; NbExp=3; IntAct=EBI-747754, EBI-7108375;
CC       P28799; Q99608: NDN; NbExp=3; IntAct=EBI-747754, EBI-718177;
CC       P28799; Q9P032: NDUFAF4; NbExp=3; IntAct=EBI-747754, EBI-2606839;
CC       P28799; Q12986: NFX1; NbExp=3; IntAct=EBI-747754, EBI-2130062;
CC       P28799; Q8N5V2: NGEF; NbExp=3; IntAct=EBI-747754, EBI-718372;
CC       P28799; Q9UBE8: NLK; NbExp=7; IntAct=EBI-747754, EBI-366978;
CC       P28799; Q96AM0: NLRP1; NbExp=3; IntAct=EBI-747754, EBI-25860999;
CC       P28799; Q6IAD4: NOTCH1; NbExp=3; IntAct=EBI-747754, EBI-25860267;
CC       P28799; Q14995: NR1D2; NbExp=3; IntAct=EBI-747754, EBI-6144053;
CC       P28799; Q7Z417: NUFIP2; NbExp=10; IntAct=EBI-747754, EBI-1210753;
CC       P28799; O43482: OIP5; NbExp=3; IntAct=EBI-747754, EBI-536879;
CC       P28799; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-747754, EBI-1058491;
CC       P28799; P32242: OTX1; NbExp=10; IntAct=EBI-747754, EBI-740446;
CC       P28799; Q15077: P2RY6; NbExp=3; IntAct=EBI-747754, EBI-10235794;
CC       P28799; P07237: P4HB; NbExp=4; IntAct=EBI-747754, EBI-395883;
CC       P28799; O75781-2: PALM; NbExp=3; IntAct=EBI-747754, EBI-16399860;
CC       P28799; Q9NR21-5: PARP11; NbExp=3; IntAct=EBI-747754, EBI-17159452;
CC       P28799; Q86SE9-2: PCGF5; NbExp=3; IntAct=EBI-747754, EBI-25861637;
CC       P28799; O15534: PER1; NbExp=3; IntAct=EBI-747754, EBI-2557276;
CC       P28799; Q96FX8: PERP; NbExp=3; IntAct=EBI-747754, EBI-17183069;
CC       P28799; Q96LB9: PGLYRP3; NbExp=3; IntAct=EBI-747754, EBI-12339509;
CC       P28799; Q9BWX1: PHF7; NbExp=3; IntAct=EBI-747754, EBI-4307517;
CC       P28799; A2BDE7: PHLDA1; NbExp=3; IntAct=EBI-747754, EBI-14084211;
CC       P28799; O75925: PIAS1; NbExp=3; IntAct=EBI-747754, EBI-629434;
CC       P28799; Q9BZM1: PLA2G12A; NbExp=3; IntAct=EBI-747754, EBI-3916751;
CC       P28799; Q58EX7-2: PLEKHG4; NbExp=3; IntAct=EBI-747754, EBI-21503705;
CC       P28799; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-747754, EBI-12891828;
CC       P28799; Q9Y342: PLLP; NbExp=3; IntAct=EBI-747754, EBI-3919291;
CC       P28799; Q8TBJ4: PLPPR1; NbExp=3; IntAct=EBI-747754, EBI-18063495;
CC       P28799; Q9H1D9: POLR3F; NbExp=3; IntAct=EBI-747754, EBI-710067;
CC       P28799; Q12837: POU4F2; NbExp=6; IntAct=EBI-747754, EBI-17236143;
CC       P28799; P09565: PP9974; NbExp=3; IntAct=EBI-747754, EBI-10196507;
CC       P28799; P54646: PRKAA2; NbExp=3; IntAct=EBI-747754, EBI-1383852;
CC       P28799; O43741: PRKAB2; NbExp=4; IntAct=EBI-747754, EBI-1053424;
CC       P28799; P11908: PRPS2; NbExp=3; IntAct=EBI-747754, EBI-4290895;
CC       P28799; P07602: PSAP; NbExp=5; IntAct=EBI-747754, EBI-716699;
CC       P28799; P40306: PSMB10; NbExp=3; IntAct=EBI-747754, EBI-603329;
CC       P28799; P28062-2: PSMB8; NbExp=3; IntAct=EBI-747754, EBI-372312;
CC       P28799; Q8TBK9: PTMA; NbExp=3; IntAct=EBI-747754, EBI-1056327;
CC       P28799; Q8WUK0: PTPMT1; NbExp=3; IntAct=EBI-747754, EBI-7199479;
CC       P28799; Q14671: PUM1; NbExp=3; IntAct=EBI-747754, EBI-948453;
CC       P28799; Q7Z7K5: PXN; NbExp=3; IntAct=EBI-747754, EBI-25841978;
CC       P28799; P47897: QARS1; NbExp=3; IntAct=EBI-747754, EBI-347462;
CC       P28799; Q96PK6: RBM14; NbExp=3; IntAct=EBI-747754, EBI-954272;
CC       P28799; Q96PM5-4: RCHY1; NbExp=3; IntAct=EBI-747754, EBI-21252376;
CC       P28799; Q8TCX5: RHPN1; NbExp=3; IntAct=EBI-747754, EBI-746325;
CC       P28799; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-747754, EBI-25829984;
CC       P28799; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-747754, EBI-749039;
CC       P28799; Q9UBS8: RNF14; NbExp=3; IntAct=EBI-747754, EBI-2130308;
CC       P28799; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-747754, EBI-751555;
CC       P28799; P62244: RPS15A; NbExp=3; IntAct=EBI-747754, EBI-347895;
CC       P28799; Q66K80: RUSC1-AS1; NbExp=3; IntAct=EBI-747754, EBI-10248967;
CC       P28799; Q8N488: RYBP; NbExp=3; IntAct=EBI-747754, EBI-752324;
CC       P28799; Q969E2: SCAMP4; NbExp=3; IntAct=EBI-747754, EBI-4403649;
CC       P28799; P34741: SDC2; NbExp=3; IntAct=EBI-747754, EBI-1172957;
CC       P28799; P60896: SEM1; NbExp=3; IntAct=EBI-747754, EBI-79819;
CC       P28799; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-747754, EBI-9089805;
CC       P28799; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-747754, EBI-745901;
CC       P28799; Q13530: SERINC3; NbExp=3; IntAct=EBI-747754, EBI-1045571;
CC       P28799; O43765: SGTA; NbExp=7; IntAct=EBI-747754, EBI-347996;
CC       P28799; Q9NUL5-3: SHFL; NbExp=3; IntAct=EBI-747754, EBI-22000547;
CC       P28799; O60902-3: SHOX2; NbExp=3; IntAct=EBI-747754, EBI-9092164;
CC       P28799; Q9GZS3: SKIC8; NbExp=3; IntAct=EBI-747754, EBI-358545;
CC       P28799; O15198-2: SMAD9; NbExp=3; IntAct=EBI-747754, EBI-12273450;
CC       P28799; P49901: SMCP; NbExp=3; IntAct=EBI-747754, EBI-750494;
CC       P28799; Q9HCE7-2: SMURF1; NbExp=3; IntAct=EBI-747754, EBI-9845742;
CC       P28799; Q96DI7: SNRNP40; NbExp=3; IntAct=EBI-747754, EBI-538492;
CC       P28799; Q99523: SORT1; NbExp=3; IntAct=EBI-747754, EBI-1057058;
CC       P28799; A0A024R4B0: SPATA3; NbExp=3; IntAct=EBI-747754, EBI-14123856;
CC       P28799; Q6RVD6: SPATA8; NbExp=3; IntAct=EBI-747754, EBI-8635958;
CC       P28799; P20155: SPINK2; NbExp=3; IntAct=EBI-747754, EBI-10200479;
CC       P28799; Q8N865: SPMIP4; NbExp=3; IntAct=EBI-747754, EBI-10174456;
CC       P28799; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-747754, EBI-7082156;
CC       P28799; O43597: SPRY2; NbExp=3; IntAct=EBI-747754, EBI-742487;
CC       P28799; Q9C004: SPRY4; NbExp=3; IntAct=EBI-747754, EBI-354861;
CC       P28799; Q6PJ21: SPSB3; NbExp=3; IntAct=EBI-747754, EBI-3937206;
CC       P28799; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-747754, EBI-357085;
CC       P28799; Q8NBJ7: SUMF2; NbExp=3; IntAct=EBI-747754, EBI-723091;
CC       P28799; Q17RD7-3: SYT16; NbExp=3; IntAct=EBI-747754, EBI-25861603;
CC       P28799; Q5VWN6: TASOR2; NbExp=3; IntAct=EBI-747754, EBI-745958;
CC       P28799; P17735: TAT; NbExp=3; IntAct=EBI-747754, EBI-12046643;
CC       P28799; Q86VP1: TAX1BP1; NbExp=3; IntAct=EBI-747754, EBI-529518;
CC       P28799; P62380: TBPL1; NbExp=3; IntAct=EBI-747754, EBI-716225;
CC       P28799; Q8IYN2: TCEAL8; NbExp=3; IntAct=EBI-747754, EBI-2116184;
CC       P28799; Q13569: TDG; NbExp=3; IntAct=EBI-747754, EBI-348333;
CC       P28799; P28347-2: TEAD1; NbExp=3; IntAct=EBI-747754, EBI-12151837;
CC       P28799; Q8NA77: TEX19; NbExp=3; IntAct=EBI-747754, EBI-13323487;
CC       P28799; O60830: TIMM17B; NbExp=3; IntAct=EBI-747754, EBI-2372529;
CC       P28799; Q04724: TLE1; NbExp=3; IntAct=EBI-747754, EBI-711424;
CC       P28799; Q08117-2: TLE5; NbExp=3; IntAct=EBI-747754, EBI-11741437;
CC       P28799; Q8N0U2: TMEM61; NbExp=3; IntAct=EBI-747754, EBI-25830583;
CC       P28799; Q53NU3: tmp_locus_54; NbExp=3; IntAct=EBI-747754, EBI-10242677;
CC       P28799; Q71RG4-4: TMUB2; NbExp=3; IntAct=EBI-747754, EBI-25831574;
CC       P28799; P19438: TNFRSF1A; NbExp=4; IntAct=EBI-747754, EBI-299451;
CC       P28799; P20333: TNFRSF1B; NbExp=5; IntAct=EBI-747754, EBI-358983;
CC       P28799; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-747754, EBI-17716262;
CC       P28799; Q9BVS5: TRMT61B; NbExp=3; IntAct=EBI-747754, EBI-3197877;
CC       P28799; Q96Q11-3: TRNT1; NbExp=3; IntAct=EBI-747754, EBI-25861172;
CC       P28799; Q9Y3Q8: TSC22D4; NbExp=3; IntAct=EBI-747754, EBI-739485;
CC       P28799; O14817: TSPAN4; NbExp=3; IntAct=EBI-747754, EBI-8652667;
CC       P28799; A0A024RCB9: TSSC4; NbExp=3; IntAct=EBI-747754, EBI-25860845;
CC       P28799; Q99614: TTC1; NbExp=3; IntAct=EBI-747754, EBI-742074;
CC       P28799; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-747754, EBI-9090990;
CC       P28799; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-747754, EBI-9088812;
CC       P28799; Q9BRU9: UTP23; NbExp=3; IntAct=EBI-747754, EBI-5457544;
CC       P28799; Q6EMK4: VASN; NbExp=3; IntAct=EBI-747754, EBI-10249550;
CC       P28799; P45880: VDAC2; NbExp=3; IntAct=EBI-747754, EBI-354022;
CC       P28799; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-747754, EBI-2850578;
CC       P28799; Q8NEZ2-2: VPS37A; NbExp=3; IntAct=EBI-747754, EBI-10270911;
CC       P28799; P58304: VSX2; NbExp=3; IntAct=EBI-747754, EBI-6427899;
CC       P28799; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-747754, EBI-12040603;
CC       P28799; Q8IY57-5: YAF2; NbExp=3; IntAct=EBI-747754, EBI-12111538;
CC       P28799; O95070: YIF1A; NbExp=3; IntAct=EBI-747754, EBI-2799703;
CC       P28799; P25490: YY1; NbExp=4; IntAct=EBI-747754, EBI-765538;
CC       P28799; O43167-2: ZBTB24; NbExp=3; IntAct=EBI-747754, EBI-25842419;
CC       P28799; Q9NTW7: ZFP64; NbExp=3; IntAct=EBI-747754, EBI-711679;
CC       P28799; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-747754, EBI-2602314;
CC       P28799; Q15973: ZNF124; NbExp=3; IntAct=EBI-747754, EBI-2555767;
CC       P28799; P52744: ZNF138; NbExp=3; IntAct=EBI-747754, EBI-10746567;
CC       P28799; Q9UJW8-4: ZNF180; NbExp=3; IntAct=EBI-747754, EBI-12055755;
CC       P28799; Q16600: ZNF239; NbExp=3; IntAct=EBI-747754, EBI-8787052;
CC       P28799; Q8WUU4: ZNF296; NbExp=3; IntAct=EBI-747754, EBI-8834821;
CC       P28799; Q8N895: ZNF366; NbExp=3; IntAct=EBI-747754, EBI-2813661;
CC       P28799; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-747754, EBI-12010736;
CC       P28799; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-747754, EBI-25831733;
CC       P28799; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-747754, EBI-10486136;
CC       P28799; Q96C55: ZNF524; NbExp=3; IntAct=EBI-747754, EBI-10283126;
CC       P28799; Q68EA5: ZNF57; NbExp=3; IntAct=EBI-747754, EBI-8490788;
CC       P28799; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-747754, EBI-10172590;
CC       P28799; Q96I27-2: ZNF625; NbExp=3; IntAct=EBI-747754, EBI-12038525;
CC       P28799; Q96N77-2: ZNF641; NbExp=3; IntAct=EBI-747754, EBI-12939666;
CC       P28799; Q9BS34: ZNF670; NbExp=3; IntAct=EBI-747754, EBI-745276;
CC       P28799; Q9H7X3: ZNF696; NbExp=3; IntAct=EBI-747754, EBI-11090299;
CC       P28799; Q5TEC3: ZNF697; NbExp=3; IntAct=EBI-747754, EBI-25845217;
CC       P28799; Q6NX45: ZNF774; NbExp=3; IntAct=EBI-747754, EBI-10251462;
CC       P28799; Q3KP31: ZNF791; NbExp=3; IntAct=EBI-747754, EBI-2849119;
CC       P28799; Q16670: ZSCAN26; NbExp=3; IntAct=EBI-747754, EBI-3920053;
CC       P28799; O15535: ZSCAN9; NbExp=3; IntAct=EBI-747754, EBI-751531;
CC       P28799; A0A384ME25; NbExp=3; IntAct=EBI-747754, EBI-10211777;
CC       P28799; Q7L8T7; NbExp=3; IntAct=EBI-747754, EBI-25831943;
CC       P28799; Q7Z783; NbExp=3; IntAct=EBI-747754, EBI-9088990;
CC       P28799; P09022: Hoxa1; Xeno; NbExp=2; IntAct=EBI-747754, EBI-3957603;
CC       P28799-2; D3DTF8: APLN; NbExp=3; IntAct=EBI-25860013, EBI-22002556;
CC       P28799-2; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-25860013, EBI-718459;
CC       P28799-2; A0A024R9H7: CCDC26; NbExp=3; IntAct=EBI-25860013, EBI-10271580;
CC       P28799-2; P50750-2: CDK9; NbExp=3; IntAct=EBI-25860013, EBI-12029902;
CC       P28799-2; Q02930-3: CREB5; NbExp=3; IntAct=EBI-25860013, EBI-10192698;
CC       P28799-2; P80370: DLK1; NbExp=3; IntAct=EBI-25860013, EBI-21555397;
CC       P28799-2; O14531: DPYSL4; NbExp=3; IntAct=EBI-25860013, EBI-719542;
CC       P28799-2; Q92997: DVL3; NbExp=3; IntAct=EBI-25860013, EBI-739789;
CC       P28799-2; O15540: FABP7; NbExp=3; IntAct=EBI-25860013, EBI-10697159;
CC       P28799-2; Q96AQ9: FAM131C; NbExp=3; IntAct=EBI-25860013, EBI-741921;
CC       P28799-2; Q5HYJ3-3: FAM76B; NbExp=3; IntAct=EBI-25860013, EBI-11956087;
CC       P28799-2; Q8N7T0: hCG_1820408; NbExp=3; IntAct=EBI-25860013, EBI-25858908;
CC       P28799-2; P49639: HOXA1; NbExp=3; IntAct=EBI-25860013, EBI-740785;
CC       P28799-2; Q5TA79: LCE2A; NbExp=3; IntAct=EBI-25860013, EBI-10246607;
CC       P28799-2; Q8IXL7-2: MSRB3; NbExp=3; IntAct=EBI-25860013, EBI-10699187;
CC       P28799-2; Q14995: NR1D2; NbExp=3; IntAct=EBI-25860013, EBI-6144053;
CC       P28799-2; P09565: PP9974; NbExp=3; IntAct=EBI-25860013, EBI-10196507;
CC       P28799-2; Q14671: PUM1; NbExp=3; IntAct=EBI-25860013, EBI-948453;
CC       P28799-2; Q7Z7K5: PXN; NbExp=3; IntAct=EBI-25860013, EBI-25841978;
CC       P28799-2; Q969E2: SCAMP4; NbExp=3; IntAct=EBI-25860013, EBI-4403649;
CC       P28799-2; P34741: SDC2; NbExp=3; IntAct=EBI-25860013, EBI-1172957;
CC       P28799-2; Q9NTG7: SIRT3; NbExp=3; IntAct=EBI-25860013, EBI-724621;
CC       P28799-2; O95416: SOX14; NbExp=3; IntAct=EBI-25860013, EBI-9087806;
CC       P28799-2; A0A024R4B0: SPATA3; NbExp=3; IntAct=EBI-25860013, EBI-14123856;
CC       P28799-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25860013, EBI-5235340;
CC       P28799-2; P17735: TAT; NbExp=3; IntAct=EBI-25860013, EBI-12046643;
CC       P28799-2; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-25860013, EBI-3923210;
CC       P28799-2; Q71RG4-4: TMUB2; NbExp=3; IntAct=EBI-25860013, EBI-25831574;
CC       P28799-2; Q9Y2B4: TP53TG5; NbExp=3; IntAct=EBI-25860013, EBI-21870909;
CC       P28799-2; P25490: YY1; NbExp=3; IntAct=EBI-25860013, EBI-765538;
CC       P28799-2; Q9C0A1: ZFHX2; NbExp=3; IntAct=EBI-25860013, EBI-25850811;
CC       P28799-2; Q9UJW8-4: ZNF180; NbExp=3; IntAct=EBI-25860013, EBI-12055755;
CC       P28799-2; Q8N895: ZNF366; NbExp=3; IntAct=EBI-25860013, EBI-2813661;
CC       P28799-2; A0A087WZY1; NbExp=3; IntAct=EBI-25860013, EBI-13387614;
CC       P28799-2; Q7L8T7; NbExp=3; IntAct=EBI-25860013, EBI-25831943;
CC       PRO_0000012695; P07339: CTSD; NbExp=2; IntAct=EBI-21335602, EBI-2115097;
CC       PRO_0000012696; P07339: CTSD; NbExp=2; IntAct=EBI-21335615, EBI-2115097;
CC       PRO_0000012697; P07339: CTSD; NbExp=2; IntAct=EBI-21335629, EBI-2115097;
CC       PRO_0000012698; P07339: CTSD; NbExp=2; IntAct=EBI-21335642, EBI-2115097;
CC       PRO_0000012699; P07339: CTSD; NbExp=2; IntAct=EBI-21335656, EBI-2115097;
CC       PRO_0000012700; P07339: CTSD; NbExp=2; IntAct=EBI-21335669, EBI-2115097;
CC       PRO_0000012701; P07339: CTSD; NbExp=2; IntAct=EBI-21335682, EBI-2115097;
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21092856,
CC       ECO:0000269|PubMed:26370502}. Lysosome {ECO:0000269|PubMed:21092856,
CC       ECO:0000269|PubMed:26370502, ECO:0000269|PubMed:28073925,
CC       ECO:0000269|PubMed:28541286, ECO:0000269|PubMed:28743268}.
CC       Note=Endocytosed by SORT1 and delivred to lysosomes (PubMed:21092856,
CC       PubMed:28073925). Targeted to lysosome by PSAP via M6PR and LRP1, in
CC       both biosynthetic and endocytic pathways (PubMed:26370502,
CC       PubMed:28073925). Co-localized with GBA1 in the intracellular
CC       trafficking compartments until to lysosome (By similarity).
CC       {ECO:0000250|UniProtKB:P28798, ECO:0000269|PubMed:21092856,
CC       ECO:0000269|PubMed:26370502, ECO:0000269|PubMed:28073925}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P28799-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P28799-2; Sequence=VSP_001837;
CC       Name=3;
CC         IsoId=P28799-3; Sequence=VSP_053472, VSP_053473;
CC   -!- TISSUE SPECIFICITY: In myelogenous leukemic cell lines of promonocytic,
CC       promyelocytic, and proerythroid lineage, in fibroblasts, and very
CC       strongly in epithelial cell lines. Present in inflammatory cells and
CC       bone marrow. Highest levels in kidney.
CC   -!- INDUCTION: Increased in response to lysosome alkalization.
CC       {ECO:0000269|PubMed:28073925}.
CC   -!- PTM: Cleaved by ELANE; proteolysis is blocked by SLPI and is
CC       concentration- and time-dependent and induces CXCL8/IL-8 production;
CC       granulin-3 and granulin-4 are resistant to ELANE (PubMed:12526812,
CC       PubMed:28743268). Cleaved by CTSL in lysosome thus regulating the
CC       maturation and turnover of progranulin within the lysosome
CC       (PubMed:28743268). {ECO:0000269|PubMed:12526812,
CC       ECO:0000269|PubMed:28743268}.
CC   -!- DISEASE: Ubiquitin-positive frontotemporal dementia (UP-FTD)
CC       [MIM:607485]: Frontotemporal dementia (FTD) is the second most common
CC       cause of dementia in people under the age of 65 years. It is an
CC       autosomal dominant neurodegenerative disease.
CC       {ECO:0000269|PubMed:16862116, ECO:0000269|PubMed:16983685,
CC       ECO:0000269|PubMed:18183624}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Ceroid lipofuscinosis, neuronal, 11 (CLN11) [MIM:614706]: A
CC       form of neuronal ceroid lipofuscinosis characterized by rapidly
CC       progressive visual loss due to retinal dystrophy, seizures, cerebellar
CC       ataxia, and cerebellar atrophy. Cognitive decline may also occur.
CC       Neuronal ceroid lipofuscinoses are progressive neurodegenerative,
CC       lysosomal storage diseases characterized by intracellular accumulation
CC       of autofluorescent liposomal material. {ECO:0000269|PubMed:22608501}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- SIMILARITY: Belongs to the granulin family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/40757/GRN";
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DR   EMBL; X62320; CAA44196.1; -; mRNA.
DR   EMBL; AF055008; AAC09359.1; -; mRNA.
DR   EMBL; M75161; AAA58617.1; -; mRNA.
DR   EMBL; AY124489; AAM94026.1; -; mRNA.
DR   EMBL; BT006844; AAP35490.1; -; mRNA.
DR   EMBL; AK023348; BAB14535.1; -; mRNA.
DR   EMBL; AK222522; BAD96242.1; -; mRNA.
DR   EMBL; CH471178; EAW51599.1; -; Genomic_DNA.
DR   EMBL; CH471178; EAW51600.1; -; Genomic_DNA.
DR   EMBL; BC000324; AAH00324.1; -; mRNA.
DR   EMBL; BC010577; AAH10577.1; -; mRNA.
DR   CCDS; CCDS11483.1; -. [P28799-1]
DR   PIR; JC1284; GYHU.
DR   RefSeq; NP_002078.1; NM_002087.3. [P28799-1]
DR   RefSeq; XP_005257310.1; XM_005257253.1.
DR   PDB; 1G26; NMR; -; A=281-311.
DR   PDB; 2JYE; NMR; -; A=281-337.
DR   PDB; 2JYT; NMR; -; A=364-417.
DR   PDB; 2JYU; NMR; -; A=364-417.
DR   PDB; 2JYV; NMR; -; A=123-179.
DR   PDB; 6NUG; NMR; -; A=284-307.
DR   PDBsum; 1G26; -.
DR   PDBsum; 2JYE; -.
DR   PDBsum; 2JYT; -.
DR   PDBsum; 2JYU; -.
DR   PDBsum; 2JYV; -.
DR   PDBsum; 6NUG; -.
DR   AlphaFoldDB; P28799; -.
DR   SMR; P28799; -.
DR   BioGRID; 109153; 234.
DR   CORUM; P28799; -.
DR   DIP; DIP-41742N; -.
DR   IntAct; P28799; 424.
DR   MINT; P28799; -.
DR   STRING; 9606.ENSP00000053867; -.
DR   GlyConnect; 1290; 5 N-Linked glycans (1 site), 3 O-Linked glycans (1 site).
DR   GlyCosmos; P28799; 6 sites, 5 glycans.
DR   GlyGen; P28799; 9 sites, 5 N-linked glycans (1 site), 5 O-linked glycans (3 sites).
DR   iPTMnet; P28799; -.
DR   MetOSite; P28799; -.
DR   PhosphoSitePlus; P28799; -.
DR   SwissPalm; P28799; -.
DR   BioMuta; GRN; -.
DR   DMDM; 77416865; -.
DR   EPD; P28799; -.
DR   jPOST; P28799; -.
DR   MassIVE; P28799; -.
DR   MaxQB; P28799; -.
DR   PaxDb; 9606-ENSP00000053867; -.
DR   PeptideAtlas; P28799; -.
DR   ProteomicsDB; 54499; -. [P28799-1]
DR   ProteomicsDB; 54500; -. [P28799-2]
DR   ProteomicsDB; 81234; -.
DR   Pumba; P28799; -.
DR   TopDownProteomics; P28799-2; -. [P28799-2]
DR   TopDownProteomics; P28799-3; -. [P28799-3]
DR   Antibodypedia; 1406; 721 antibodies from 38 providers.
DR   DNASU; 2896; -.
DR   Ensembl; ENST00000053867.8; ENSP00000053867.2; ENSG00000030582.19. [P28799-1]
DR   GeneID; 2896; -.
DR   KEGG; hsa:2896; -.
DR   MANE-Select; ENST00000053867.8; ENSP00000053867.2; NM_002087.4; NP_002078.1.
DR   UCSC; uc002igp.2; human. [P28799-1]
DR   AGR; HGNC:4601; -.
DR   CTD; 2896; -.
DR   DisGeNET; 2896; -.
DR   GeneCards; GRN; -.
DR   GeneReviews; GRN; -.
DR   HGNC; HGNC:4601; GRN.
DR   HPA; ENSG00000030582; Low tissue specificity.
DR   MalaCards; GRN; -.
DR   MIM; 138945; gene.
DR   MIM; 607485; phenotype.
DR   MIM; 614706; phenotype.
DR   neXtProt; NX_P28799; -.
DR   OpenTargets; ENSG00000030582; -.
DR   Orphanet; 79262; Adult neuronal ceroid lipofuscinosis.
DR   Orphanet; 275864; Behavioral variant of frontotemporal dementia.
DR   Orphanet; 168486; Congenital neuronal ceroid lipofuscinosis.
DR   Orphanet; 79263; Infantile neuronal ceroid lipofuscinosis.
DR   Orphanet; 79264; Juvenile neuronal ceroid lipofuscinosis.
DR   Orphanet; 168491; Late infantile neuronal ceroid lipofuscinosis.
DR   Orphanet; 100070; Progressive non-fluent aphasia.
DR   Orphanet; 100069; Semantic dementia.
DR   PharmGKB; PA28998; -.
DR   VEuPathDB; HostDB:ENSG00000030582; -.
DR   eggNOG; KOG4296; Eukaryota.
DR   GeneTree; ENSGT00470000042293; -.
DR   HOGENOM; CLU_026274_0_0_1; -.
DR   InParanoid; P28799; -.
DR   OMA; QTCCKLA; -.
DR   OrthoDB; 11342at2759; -.
DR   PhylomeDB; P28799; -.
DR   TreeFam; TF319678; -.
DR   PathwayCommons; P28799; -.
DR   Reactome; R-HSA-6798695; Neutrophil degranulation.
DR   SignaLink; P28799; -.
DR   SIGNOR; P28799; -.
DR   BioGRID-ORCS; 2896; 18 hits in 1158 CRISPR screens.
DR   ChiTaRS; GRN; human.
DR   EvolutionaryTrace; P28799; -.
DR   GeneWiki; Granulin; -.
DR   GenomeRNAi; 2896; -.
DR   Pharos; P28799; Tbio.
DR   PRO; PR:P28799; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P28799; Protein.
DR   Bgee; ENSG00000030582; Expressed in monocyte and 210 other cell types or tissues.
DR   ExpressionAtlas; P28799; baseline and differential.
DR   GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005768; C:endosome; IDA:HPA.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IDA:ARUK-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR   GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR   GO; GO:0005764; C:lysosome; IDA:HPA.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR   GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR   GO; GO:0008083; F:growth factor activity; TAS:ProtInc.
DR   GO; GO:0051087; F:protein-folding chaperone binding; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0002265; P:astrocyte activation involved in immune response; ISS:UniProtKB.
DR   GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB.
DR   GO; GO:0007041; P:lysosomal transport; IMP:UniProtKB.
DR   GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR   GO; GO:0002282; P:microglial cell activation involved in immune response; ISS:UniProtKB.
DR   GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:UniProtKB.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:UniProtKB.
DR   GO; GO:1902564; P:negative regulation of neutrophil activation; IDA:UniProtKB.
DR   GO; GO:0060266; P:negative regulation of respiratory burst involved in inflammatory response; IDA:UniProtKB.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR   GO; GO:1905247; P:positive regulation of aspartic-type peptidase activity; IMP:UniProtKB.
DR   GO; GO:0048680; P:positive regulation of axon regeneration; ISS:UniProtKB.
DR   GO; GO:0030335; P:positive regulation of cell migration; IMP:ARUK-UCL.
DR   GO; GO:1900426; P:positive regulation of defense response to bacterium; ISS:UniProtKB.
DR   GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR   GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB.
DR   GO; GO:0106016; P:positive regulation of inflammatory response to wounding; ISS:UniProtKB.
DR   GO; GO:1905673; P:positive regulation of lysosome organization; IDA:UniProtKB.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR   GO; GO:1903334; P:positive regulation of protein folding; ISS:UniProtKB.
DR   GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR   GO; GO:0050727; P:regulation of inflammatory response; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR   Gene3D; 2.10.25.160; Granulin; 7.
DR   InterPro; IPR000118; Granulin.
DR   InterPro; IPR039036; Granulin_fam.
DR   InterPro; IPR037277; Granulin_sf.
DR   PANTHER; PTHR12274; GRANULIN; 1.
DR   PANTHER; PTHR12274:SF3; PROGRANULIN; 1.
DR   Pfam; PF00396; Granulin; 7.
DR   SMART; SM00277; GRAN; 7.
DR   SUPFAM; SSF57277; Granulin repeat; 6.
DR   PROSITE; PS00799; GRANULINS; 7.
DR   Genevisible; P28799; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Cytokine; Direct protein sequencing;
KW   Disulfide bond; Glycoprotein; Lysosome; Neurodegeneration;
KW   Neuronal ceroid lipofuscinosis; Reference proteome; Repeat; Secreted;
KW   Signal.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..593
FT                   /note="Progranulin"
FT                   /id="PRO_0000012693"
FT   PEPTIDE         18..?47
FT                   /note="Paragranulin"
FT                   /id="PRO_0000012694"
FT   PEPTIDE         ?58..?113
FT                   /note="Granulin-1"
FT                   /id="PRO_0000012695"
FT   PEPTIDE         123..179
FT                   /note="Granulin-2"
FT                   /id="PRO_0000012696"
FT   PEPTIDE         206..261
FT                   /note="Granulin-3"
FT                   /id="PRO_0000012697"
FT   PEPTIDE         281..336
FT                   /note="Granulin-4"
FT                   /id="PRO_0000012698"
FT   PEPTIDE         364..417
FT                   /note="Granulin-5"
FT                   /id="PRO_0000012699"
FT   PEPTIDE         442..?496
FT                   /note="Granulin-6"
FT                   /id="PRO_0000012700"
FT   PEPTIDE         ?518..?573
FT                   /note="Granulin-7"
FT                   /id="PRO_0000012701"
FT   CARBOHYD        118
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:20188224"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        265
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218,
FT                   ECO:0000269|PubMed:20188224"
FT   CARBOHYD        368
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:20188224"
FT   CARBOHYD        530
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:20188224"
FT   DISULFID        126..139
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        133..149
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        284..296
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        290..306
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        297..314
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        307..321
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        315..328
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        322..335
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        366..378
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        372..388
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        397..410
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   DISULFID        404..416
FT                   /evidence="ECO:0000269|PubMed:18359860"
FT   VAR_SEQ         1..71
FT                   /note="MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRPLLDKWPTT
FT                   LSRHLGGPCQVDAHCSAGH -> MAITAAHGASTAVQTGDPASKDQVTTPWVPSSALIV
FT                   SSNARTSPRAVLWSMAPGGAAPCPRLPAVKTGCTA (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_053472"
FT   VAR_SEQ         72..251
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_053473"
FT   VAR_SEQ         377..531
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6"
FT                   /id="VSP_001837"
FT   VARIANT         9
FT                   /note="A -> D (in UP-FTD; no significant difference in the
FT                   total mRNA between cases and controls; although the mutant
FT                   protein is expressed it is not secreted and appears to be
FT                   trapped within an intracellular compartment;
FT                   dbSNP:rs63751243)"
FT                   /evidence="ECO:0000269|PubMed:16983685,
FT                   ECO:0000269|PubMed:18183624"
FT                   /id="VAR_044451"
FT   VARIANT         19
FT                   /note="R -> W (in dbSNP:rs63750723)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064625"
FT   VARIANT         55
FT                   /note="R -> W (in dbSNP:rs1555610922)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064626"
FT   VARIANT         69
FT                   /note="A -> T (in dbSNP:rs199944486)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064627"
FT   VARIANT         119
FT                   /note="Missing (in dbSNP:rs758168578)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064628"
FT   VARIANT         120
FT                   /note="S -> Y (in dbSNP:rs63750043)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064629"
FT   VARIANT         182
FT                   /note="T -> M (in dbSNP:rs63750479)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064630"
FT   VARIANT         221
FT                   /note="C -> S (in dbSNP:rs758322775)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064631"
FT   VARIANT         275
FT                   /note="P -> L (in dbSNP:rs529849967)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064632"
FT   VARIANT         376
FT                   /note="D -> N (in dbSNP:rs143030899)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064633"
FT   VARIANT         398
FT                   /note="S -> L (in dbSNP:rs148213321)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064634"
FT   VARIANT         433
FT                   /note="R -> Q (in dbSNP:rs114248177)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064635"
FT   VARIANT         515
FT                   /note="G -> A (in dbSNP:rs25647)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_014830"
FT   VARIANT         564
FT                   /note="R -> H (in dbSNP:rs971443926)"
FT                   /evidence="ECO:0000269|PubMed:20020531"
FT                   /id="VAR_064636"
FT   CONFLICT        219
FT                   /note="S -> H (in Ref. 12; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        290
FT                   /note="C -> S (in Ref. 13; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        386
FT                   /note="W -> H (in Ref. 12; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        407
FT                   /note="G -> R (in Ref. 3; AAA58617)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        428
FT                   /note="K -> E (in Ref. 8; BAD96242)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        434
FT                   /note="A -> G (in Ref. 3; AAA58617)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        454
FT                   /note="Q -> G (in Ref. 3; AAA58617)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        460
FT                   /note="L -> Q (in Ref. 3; AAA58617)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        547
FT                   /note="R -> A (in Ref. 3; AAA58617)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        567
FT                   /note="A -> R (in Ref. 3; AAA58617)"
FT                   /evidence="ECO:0000305"
FT   STRAND          137..141
FT                   /evidence="ECO:0007829|PDB:2JYV"
FT   STRAND          143..145
FT                   /evidence="ECO:0007829|PDB:2JYV"
FT   STRAND          147..151
FT                   /evidence="ECO:0007829|PDB:2JYV"
FT   STRAND          282..285
FT                   /evidence="ECO:0007829|PDB:1G26"
FT   STRAND          288..290
FT                   /evidence="ECO:0007829|PDB:1G26"
FT   STRAND          294..298
FT                   /evidence="ECO:0007829|PDB:1G26"
FT   STRAND          304..308
FT                   /evidence="ECO:0007829|PDB:1G26"
FT   STRAND          315..319
FT                   /evidence="ECO:0007829|PDB:2JYE"
FT   TURN            330..333
FT                   /evidence="ECO:0007829|PDB:2JYE"
FT   TURN            367..369
FT                   /evidence="ECO:0007829|PDB:2JYU"
FT   STRAND          377..380
FT                   /evidence="ECO:0007829|PDB:2JYT"
FT   STRAND          382..384
FT                   /evidence="ECO:0007829|PDB:2JYT"
FT   STRAND          386..389
FT                   /evidence="ECO:0007829|PDB:2JYT"
FT   TURN            399..402
FT                   /evidence="ECO:0007829|PDB:2JYU"
FT   STRAND          409..411
FT                   /evidence="ECO:0007829|PDB:2JYT"
FT   TURN            412..414
FT                   /evidence="ECO:0007829|PDB:2JYT"
FT   STRAND          415..417
FT                   /evidence="ECO:0007829|PDB:2JYT"
SQ   SEQUENCE   593 AA;  63544 MW;  4E5947F1B4EDE619 CRC64;
     MWTLVSWVAL TAGLVAGTRC PDGQFCPVAC CLDPGGASYS CCRPLLDKWP TTLSRHLGGP
     CQVDAHCSAG HSCIFTVSGT SSCCPFPEAV ACGDGHHCCP RGFHCSADGR SCFQRSGNNS
     VGAIQCPDSQ FECPDFSTCC VMVDGSWGCC PMPQASCCED RVHCCPHGAF CDLVHTRCIT
     PTGTHPLAKK LPAQRTNRAV ALSSSVMCPD ARSRCPDGST CCELPSGKYG CCPMPNATCC
     SDHLHCCPQD TVCDLIQSKC LSKENATTDL LTKLPAHTVG DVKCDMEVSC PDGYTCCRLQ
     SGAWGCCPFT QAVCCEDHIH CCPAGFTCDT QKGTCEQGPH QVPWMEKAPA HLSLPDPQAL
     KRDVPCDNVS SCPSSDTCCQ LTSGEWGCCP IPEAVCCSDH QHCCPQGYTC VAEGQCQRGS
     EIVAGLEKMP ARRASLSHPR DIGCDQHTSC PVGQTCCPSL GGSWACCQLP HAVCCEDRQH
     CCPAGYTCNV KARSCEKEVV SAQPATFLAR SPHVGVKDVE CGEGHFCHDN QTCCRDNRQG
     WACCPYRQGV CCADRRHCCP AGFRCAARGT KCLRREAPRW DAPLRDPALR QLL
//