GRN_HUMAN
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 03-AUG-2022, entry version 227.
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 GBA 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 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 GBA; this interaction prevents aggregation of GBA-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 GBA and prevents GBA 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; Q8N865: C7orf31; NbExp=3; IntAct=EBI-747754, EBI-10174456;
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; A0A0A0MR69: CCDC88C; NbExp=3; IntAct=EBI-747754, EBI-12954453;
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: MYLPF; 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; 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; 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; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-747754, EBI-358545;
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; Q8TAB7: 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 GBA 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="http://atlasgeneticsoncology.org/Genes/GRNID40757ch17q21.html";
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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. [P28799-1]
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; 216.
DR CORUM; P28799; -.
DR DIP; DIP-41742N; -.
DR IntAct; P28799; 422.
DR MINT; P28799; -.
DR STRING; 9606.ENSP00000053867; -.
DR GlyConnect; 1290; 5 N-Linked glycans (1 site), 3 O-Linked glycans (1 site).
DR GlyGen; P28799; 8 sites, 5 N-linked glycans (1 site), 4 O-linked glycans (2 sites).
DR iPTMnet; P28799; -.
DR MetOSite; P28799; -.
DR PhosphoSitePlus; P28799; -.
DR BioMuta; GRN; -.
DR DMDM; 77416865; -.
DR EPD; P28799; -.
DR jPOST; P28799; -.
DR MassIVE; P28799; -.
DR MaxQB; P28799; -.
DR PaxDb; P28799; -.
DR PeptideAtlas; P28799; -.
DR PRIDE; P28799; -.
DR ProteomicsDB; 54499; -. [P28799-1]
DR ProteomicsDB; 54500; -. [P28799-2]
DR ProteomicsDB; 81234; -.
DR TopDownProteomics; P28799-2; -. [P28799-2]
DR TopDownProteomics; P28799-3; -. [P28799-3]
DR Antibodypedia; 1406; 668 antibodies from 38 providers.
DR DNASU; 2896; -.
DR Ensembl; ENST00000053867.8; ENSP00000053867.2; ENSG00000030582.18. [P28799-1]
DR Ensembl; ENST00000639447.1; ENSP00000492014.1; ENSG00000030582.18. [P28799-2]
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 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; 275864; Behavioral variant of frontotemporal dementia.
DR Orphanet; 314629; CLN11 disease.
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; CCPYSSA; -.
DR OrthoDB; 162721at2759; -.
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 1078 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 208 other tissues.
DR ExpressionAtlas; P28799; baseline and differential.
DR Genevisible; P28799; HS.
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:UniProtKB.
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:0051087; F:chaperone binding; IDA:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; TAS:ProtInc.
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; -; 7.
DR InterPro; IPR000118; Granulin.
DR InterPro; IPR039036; Granulin_fam.
DR InterPro; IPR037277; Granulin_sf.
DR PANTHER; PTHR12274; PTHR12274; 1.
DR Pfam; PF00396; Granulin; 7.
DR SMART; SM00277; GRAN; 7.
DR PROSITE; PS00799; GRANULINS; 7.
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
