| IED ID | IndEnz0002006916 |
| Enzyme Type ID | protease006916 |
| Protein Name |
Progranulin PGRN Acrogranin Epithelin precursor Glycoprotein of 88 Kda GP88 Glycoprotein 88 Granulin precursor PC cell-derived growth factor PCDGF Proepithelin PEPI Cleaved into: Paragranulin; Granulin-1 Granulin G ; Granulin-2 Granulin F ; Granulin-3 Epithelin-2 Granulin B ; Granulin-4 Epithelin-1 Granulin A ; Granulin-5 Granulin C ; Granulin-6 Granulin D ; Granulin-7 Granulin E |
| Gene Name | GRN |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MWTLVSWVALTAGLVAGTRCPDGQFCPVACCLDPGGASYSCCRPLLDKWPTTLSRHLGGPCQVDAHCSAGHSCIFTVSGTSSCCPFPEAVACGDGHHCCPRGFHCSADGRSCFQRSGNNSVGAIQCPDSQFECPDFSTCCVMVDGSWGCCPMPQASCCEDRVHCCPHGAFCDLVHTRCITPTGTHPLAKKLPAQRTNRAVALSSSVMCPDARSRCPDGSTCCELPSGKYGCCPMPNATCCSDHLHCCPQDTVCDLIQSKCLSKENATTDLLTKLPAHTVGDVKCDMEVSCPDGYTCCRLQSGAWGCCPFTQAVCCEDHIHCCPAGFTCDTQKGTCEQGPHQVPWMEKAPAHLSLPDPQALKRDVPCDNVSSCPSSDTCCQLTSGEWGCCPIPEAVCCSDHQHCCPQGYTCVAEGQCQRGSEIVAGLEKMPARRASLSHPRDIGCDQHTSCPVGQTCCPSLGGSWACCQLPHAVCCEDRQHCCPAGYTCNVKARSCEKEVVSAQPATFLARSPHVGVKDVECGEGHFCHDNQTCCRDNRQGWACCPYRQGVCCADRRHCCPAGFRCAARGTKCLRREAPRWDAPLRDPALRQLL |
| Enzyme Length | 593 |
| Uniprot Accession Number | P28799 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation (PubMed:28541286, PubMed:28073925, PubMed:18378771, PubMed:28453791, PubMed:12526812). Regulates protein trafficking to lysosomes and, also the activity of lysosomal enzymes (PubMed:28453791, PubMed:28541286). Facilitates also the acidification of lysosomes, causing degradation of mature CTSD by CTSB (PubMed:28073925). In addition, functions as wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures (By similarity). Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases (PubMed:12526812). Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity (PubMed:18378771). {ECO:0000250|UniProtKB:P28798, ECO:0000269|PubMed:12526812, ECO:0000269|PubMed:18378771, ECO:0000269|PubMed:28073925, ECO:0000269|PubMed:28453791, ECO:0000269|PubMed:28541286}.; FUNCTION: [Granulin-4]: Promotes proliferation of the epithelial cell line A431 in culture.; FUNCTION: [Granulin-3]: Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8. {ECO:0000269|PubMed:12526812}.; FUNCTION: [Granulin-7]: Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity. {ECO:0000269|PubMed:28453791}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Alternative sequence (3); Beta strand (13); Chain (1); Disulfide bond (12); Glycosylation (5); Natural variant (14); Peptide (8); Sequence conflict (10); Signal peptide (1); Turn (4) |
| Keywords | 3D-structure;Alternative splicing;Cytokine;Direct protein sequencing;Disulfide bond;Glycoprotein;Lysosome;Neurodegeneration;Neuronal ceroid lipofuscinosis;Reference proteome;Repeat;Secreted;Signal |
| Interact With | Q6UY14-3; Q9UIJ7; Q9NYG5; D3DTF8; Q8N6T3; Q8N6T3-3; Q9Y575-3; Q96DX5-3; Q6XD76; Q96FT7-4; P46379-2; Q16611; Q8IXM2; Q14457; Q96LC9; Q9GZL8; Q8WUW1; Q9Y297; Q32Q52; Q8TAB5; Q6P5X5; Q6P5X5-2; Q53FE4; Q8N865; Q9BRJ6; O00555; Q96NX5; O75808; Q8N5R6; A0A0A0MR69; P50750-2; O14646-2; Q9Y3D0; Q99967; Q9Y240; Q96DZ5; Q16740; Q9BT09; Q6PJW8-3; Q9UNS2; Q9UGL9; Q02930-3; Q49AN0; P01040; P07339; P42830; Q8TB03; P00167; A8MQ03; Q16643; Q5TAQ9-2; Q9P1A6-3; Q07687; Q9NQL9; P49184; Q16610; O75530-2; O60841; Q6UXG2-3; Q8TE68-3; Q9H6S3; O15540; Q9UNN5; Q6SJ93; Q96AQ9; Q5TZK3; Q5HYJ3-3; Q17RN3; Q8IZU1; Q9NW38; Q53R41; Q8NFZ0; Q9UBX5; P15976-2; P23769-2; Q9NXC2; P10075; O76003; Q9Y223-2; Q9HBQ8; Q7Z602; Q9Y4H4; O75409; Q6NXT2; P68431; A8K0U2; Q03014; P49639; P09017; P22692; Q14005-2; Q9NXX0; Q9UNL4; Q8IXL9; Q9Y6F6-3; Q86U28; Q14145; Q12756; Q9UIH9; P57682; Q9Y2M5; O76011; Q07627; Q9BYS1; P60409; P60410; Q8IUC1; P59990; Q52LG2; Q3SY46; Q3LI76; Q3SYF9; Q6PEX3; P26371; Q3LI64; Q3LI66; Q8IUC2; Q14847-2; O95447; Q5T7P2; Q5T7P3; Q5T752; Q5T753; Q5TA79; O14633; Q5TA82; Q5T5A8; Q5T5B0; Q5TA78; Q9UPM6; Q68G74; A2RU56; Q96JB6; Q14693; Q6Q4G3-4; Q9UDY8-2; Q9GZQ8; Q99683; P61244-4; O95243-2; Q6FHY5; P41218; Q86VF5-3; Q9Y2R5; O43196-4; Q8IXL7-2; Q96A32; Q9NPC7; O15069; Q99608; Q9P032; Q12986; Q8N5V2; Q9UBE8; Q96AM0; Q6IAD4; Q14995; Q7Z417; O43482; Q96FW1; P32242; Q15077; P07237; O75781-2; Q9NR21-5; Q86SE9-2; O15534; Q96FX8; Q96LB9; Q9BWX1; A2BDE7; O75925; Q9BZM1; Q58EX7-2; Q9Y342; Q8TBJ4; Q9H1D9; Q12837; P09565; P54646; O43741; P11908; P07602; P40306; P28062-2; Q8TBK9; Q8WUK0; Q14671; Q7Z7K5; P47897; Q96PK6; Q96PM5-4; Q8TCX5; Q9ULX5; Q8WVD3; Q9UBS8; Q9H0X6; P62244; Q66K80; Q8N488; Q969E2; P34741; P60896; Q9NTN9-3; Q14141; Q13530; O43765; Q9NUL5-3; O60902-3; O15198-2; P49901; Q9HCE7-2; Q96DI7; Q99523; A0A024R4B0; Q6RVD6; P20155; Q7Z698; O43597; Q9C004; Q6PJ21; Q9UNE7; Q8NBJ7; Q17RD7-3; Q5VWN6; P17735; Q86VP1; P62380; Q8IYN2; Q13569; P28347-2; Q8NA77; O60830; Q04724; Q08117-2; Q8N0U2; Q53NU3; Q71RG4-4; P19438; P20333; Q9UPQ4-2; Q9BVS5; Q96Q11-3; Q9Y3Q8; O14817; A0A024RCB9; Q99614; Q5W5X9-3; Q5VYS8-5; Q9BRU9; Q6EMK4; P45880; Q8NEZ2; Q8NEZ2-2; P58304; Q9GZS3; Q9NZC7-5; Q8IY57-5; O95070; P25490; O43167-2; Q9NTW7; Q15776; Q15973; P52744; Q9UJW8-4; Q16600; Q8WUU4; Q8N895; Q8N0Y2-2; Q96MN9-2; Q6ZNH5; Q96C55; Q68EA5; Q7Z3I7; Q96I27-2; Q96N77-2; Q9BS34; Q9H7X3; Q5TEC3; Q6NX45; Q3KP31; Q16670; O15535; A0A384ME25; Q7L8T7; Q7Z783; P09022; D3DTF8; Q9UII2; Q8TAB7; P50750-2; Q02930-3; P80370; O14531; Q92997; O15540; Q96AQ9; Q5HYJ3-3; Q8N7T0; P49639; Q5TA79; Q8IXL7-2; Q14995; P09565; Q14671; Q7Z7K5; Q969E2; P34741; Q9NTG7; O95416; A0A024R4B0; Q7Z699; P17735; Q8TDR4; Q71RG4-4; Q9Y2B4; P25490; Q9C0A1; Q9UJW8-4; Q8N895; A0A087WZY1; Q7L8T7; P07339; P07339; P07339; P07339; P07339; P07339; P07339 |
| Induction | INDUCTION: Increased in response to lysosome alkalization. {ECO:0000269|PubMed:28073925}. |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21092856, ECO:0000269|PubMed:26370502}. Lysosome {ECO:0000269|PubMed:21092856, ECO:0000269|PubMed:26370502, ECO:0000269|PubMed:28073925, ECO:0000269|PubMed:28541286, ECO:0000269|PubMed:28743268}. Note=Endocytosed by SORT1 and delivred to lysosomes (PubMed:21092856, PubMed:28073925). Targeted to lysosome by PSAP via M6PR and LRP1, in both biosynthetic and endocytic pathways (PubMed:26370502, PubMed:28073925). Co-localized with GBA in the intracellular trafficking compartments until to lysosome (By similarity). {ECO:0000250|UniProtKB:P28798, ECO:0000269|PubMed:21092856, ECO:0000269|PubMed:26370502, ECO:0000269|PubMed:28073925}. |
| Modified Residue | |
| Post Translational Modification | PTM: Cleaved by ELANE; proteolysis is blocked by SLPI and is concentration- and time-dependent and induces CXCL8/IL-8 production; granulin-3 and granulin-4 are resistant to ELANE (PubMed:12526812, PubMed:28743268). Cleaved by CTSL in lysosome thus regulating the maturation and turnover of progranulin within the lysosome (PubMed:28743268). {ECO:0000269|PubMed:12526812, ECO:0000269|PubMed:28743268}. |
| Signal Peptide | SIGNAL 1..17; /evidence=ECO:0000255 |
| Structure 3D | NMR spectroscopy (6) |
| Cross Reference PDB | 1G26; 2JYE; 2JYT; 2JYU; 2JYV; 6NUG; |
| Mapped Pubmed ID | 12900424; 15231748; 16189514; 16713569; 16983677; 17110338; 17371905; 17446270; 18654987; 18752597; 18985028; 19343720; 19618231; 19847305; 19940479; 20061636; 20711500; 21078624; 21516116; 21596751; 21988832; 22014111; 23088713; 23455922; 24070898; 25416956; 26005049; 27258413; 27760429; 8692836; |
| Motif | |
| Gene Encoded By | |
| Mass | 63,544 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |