SRGN_MOUSE
ID SRGN_MOUSE Reviewed; 152 AA.
AC P13609; Q3TZD4; Q8C2U2;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Serglycin;
DE AltName: Full=Mastocytoma proteoglycan core protein;
DE AltName: Full=Secretory granule proteoglycan core protein;
DE AltName: Full=gp600;
DE Flags: Precursor;
GN Name=Srgn; Synonyms=Prg, Prg1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2532501; DOI=10.1042/bj2630105;
RA Kjellen L., Pettersson L., Lillhager P., Steen M.L., Pettersson U.,
RA Lehtonen P., Karlsson T., Ruoslahti E., Hellman L.;
RT "Primary structure of a mouse mastocytoma proteoglycan core protein.";
RL Biochem. J. 263:105-113(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2777804; DOI=10.1016/s0021-9258(19)84764-6;
RA Avraham S., Austen K.F., Nicodemus C.F., Gartner M.C., Stevens R.L.;
RT "Cloning and characterization of the mouse gene that encodes the peptide
RT core of secretory granule proteoglycans and expression of this gene in
RT transfected rat-1 fibroblasts.";
RL J. Biol. Chem. 264:16719-16726(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2726751; DOI=10.1073/pnas.86.10.3763;
RA Avraham S., Stevens R.L., Nicodemus C.F., Gartner M.C., Austen K.F.,
RA Weis J.H.;
RT "Molecular cloning of a cDNA that encodes the peptide core of a mouse mast
RT cell secretory granule proteoglycan and comparison with the analogous rat
RT and human cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:3763-3767(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2121613; DOI=10.1016/0378-1119(90)90230-o;
RA Angerth T., Huang R., Aveskogh M., Pettersson I., Kjellen L., Hellman L.;
RT "Cloning and structural analysis of a gene encoding a mouse mastocytoma
RT proteoglycan core protein; analysis of its evolutionary relation to three
RT cross hybridizing regions in the mouse genome.";
RL Gene 93:235-240(1990).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION.
RX PubMed=8502243; DOI=10.1016/0161-5890(93)90146-3;
RA Elliott J.F., Miller C.L., Pohajdak B., Talbot D., Helgason C.D.,
RA Bleackley R.C., Paetkau V.;
RT "Induction of a proteoglycan core protein mRNA in mouse T lymphocytes.";
RL Mol. Immunol. 30:749-754(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, Inner ear, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Czech II; TISSUE=Mammary gland;
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 [8]
RP PROTEIN SEQUENCE OF 86-101, INTERACTION WITH CD44, AND GLYCOSYLATION.
RX PubMed=7535771; DOI=10.1074/jbc.270.13.7437;
RA Toyama-Sorimachi N., Sorimachi H., Tobita Y., Kitamura F., Yagita H.,
RA Suzuki K., Miyasaka M.;
RT "A novel ligand for CD44 is serglycin, a hematopoietic cell lineage-
RT specific proteoglycan. Possible involvement in lymphoid cell adherence and
RT activation.";
RL J. Biol. Chem. 270:7437-7444(1995).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15231821; DOI=10.1074/jbc.m405856200;
RA Abrink M., Grujic M., Pejler G.;
RT "Serglycin is essential for maturation of mast cell secretory granule.";
RL J. Biol. Chem. 279:40897-40905(2004).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16046402; DOI=10.1074/jbc.m501708200;
RA Grujic M., Braga T., Lukinius A., Eloranta M.-L., Knight S.D., Pejler G.,
RA Abrink M.;
RT "Serglycin-deficient cytotoxic T lymphocytes display defective secretory
RT granule maturation and granzyme B storage.";
RL J. Biol. Chem. 280:33411-33418(2005).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17081126; DOI=10.1515/bc.2006.189;
RA Lundequist A., Abrink M., Pejler G.;
RT "Mast cell-dependent activation of pro matrix metalloprotease 2: a role for
RT serglycin proteoglycan-dependent mast cell proteases.";
RL Biol. Chem. 387:1513-1519(2006).
RN [12]
RP FUNCTION, GLYCOSYLATION, AND DISRUPTION PHENOTYPE.
RX PubMed=17010166; DOI=10.1111/j.1742-4658.2006.05489.x;
RA Henningsson F., Hergeth S., Cortelius R., Abrink M., Pejler G.;
RT "A role for serglycin proteoglycan in granular retention and processing of
RT mast cell secretory granule components.";
RL FEBS J. 273:4901-4912(2006).
RN [13]
RP FUNCTION.
RX PubMed=16807245; DOI=10.1074/jbc.m512889200;
RA Zernichow L., Abrink M., Hallgren J., Grujic M., Pejler G., Kolset S.O.;
RT "Serglycin is the major secreted proteoglycan in macrophages and has a role
RT in the regulation of macrophage tumor necrosis factor-alpha secretion in
RT response to lipopolysaccharide.";
RL J. Biol. Chem. 281:26792-26801(2006).
RN [14]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17147513; DOI=10.1042/bj20061257;
RA Braga T., Grujic M., Lukinius A., Hellman L., Abrink M., Pejler G.;
RT "Serglycin proteoglycan is required for secretory granule integrity in
RT mucosal mast cells.";
RL Biochem. J. 403:49-57(2007).
RN [15]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17272511; DOI=10.1182/blood-2006-02-001719;
RA Niemann C.U., Abrink M., Pejler G., Fischer R.L., Christensen E.I.,
RA Knight S.D., Borregaard N.;
RT "Neutrophil elastase depends on serglycin proteoglycan for localization in
RT granules.";
RL Blood 109:4478-4486(2007).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Plays a role in formation of mast cell secretory granules and
CC mediates storage of various compounds in secretory vesicles. Required
CC for storage of some proteases in both connective tissue and mucosal
CC mast cells and for storage of granzyme B in T-lymphocytes. Plays a role
CC in localizing neutrophil elastase in azurophil granules of neutrophils.
CC Mediates processing of MMP2. Plays a role in cytotoxic cell granule-
CC mediated apoptosis by forming a complex with granzyme B which is
CC delivered to cells by perforin to induce apoptosis. Regulates the
CC secretion of TNF-alpha and may also regulate protease secretion.
CC Inhibits bone mineralization. {ECO:0000269|PubMed:15231821,
CC ECO:0000269|PubMed:16046402, ECO:0000269|PubMed:16807245,
CC ECO:0000269|PubMed:17010166, ECO:0000269|PubMed:17081126,
CC ECO:0000269|PubMed:17147513, ECO:0000269|PubMed:17272511}.
CC -!- SUBUNIT: Binds to activated CD44 and to GZMB.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule
CC {ECO:0000269|PubMed:16046402}. Cytolytic granule
CC {ECO:0000250|UniProtKB:P10124}. Secreted, extracellular space
CC {ECO:0000269|PubMed:16046402}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P10124}. Note=Found in mast cell granules and in
CC cytoplasmic granules of cytolytic T-lymphocytes from where it is
CC secreted upon cell activation (PubMed:16046402). Secreted
CC constitutively by endothelial cells and macrophages. Located to Golgi
CC apparatus during neutrophil differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P10124, ECO:0000269|PubMed:16046402}.
CC -!- INDUCTION: By phorbol myristate acetate in T-lymphocytes. This
CC induction is not inhibited by cyclosporine.
CC {ECO:0000269|PubMed:8502243}.
CC -!- PTM: O-glycosylated; contains chondroitin sulfate and heparan sulfate.
CC {ECO:0000269|PubMed:17010166, ECO:0000269|PubMed:7535771}.
CC -!- DISRUPTION PHENOTYPE: Mice develop normally and are fertile but display
CC mast cell granule and T-lymphocyte secretory granule defects. Granules
CC are more amorphous than in the wild-type and show a less defined dense
CC core formation. There is a lack of mast cell-specific protease activity
CC although mRNAs for a variety of proteases are detected and storage of
CC granzyme B is affected in T-lymphocytes. Neutrophil granules display a
CC lack of neutrophil elastase and processing of MMP2 is abrogated.
CC Macrophages show no major morphological defects.
CC {ECO:0000269|PubMed:15231821, ECO:0000269|PubMed:17010166,
CC ECO:0000269|PubMed:17081126, ECO:0000269|PubMed:17147513,
CC ECO:0000269|PubMed:17272511}.
CC -!- SIMILARITY: Belongs to the serglycin family. {ECO:0000305}.
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DR EMBL; X16133; CAA34259.1; -; mRNA.
DR EMBL; M27393; AAA39965.1; -; Genomic_DNA.
DR EMBL; M27391; AAA39965.1; JOINED; Genomic_DNA.
DR EMBL; M27392; AAA39965.1; JOINED; Genomic_DNA.
DR EMBL; J04549; AAA40111.1; -; mRNA.
DR EMBL; M33499; AAA39900.1; -; Genomic_DNA.
DR EMBL; M34603; AAA39991.1; -; mRNA.
DR EMBL; AK087960; BAC40059.1; -; mRNA.
DR EMBL; AK151357; BAE30332.1; -; mRNA.
DR EMBL; AK157945; BAE34275.1; -; mRNA.
DR EMBL; BC037076; AAH37076.1; -; mRNA.
DR CCDS; CCDS23889.1; -.
DR PIR; JQ0791; JQ0791.
DR RefSeq; NP_035287.1; NM_011157.2.
DR RefSeq; XP_006513438.1; XM_006513375.2.
DR RefSeq; XP_006513439.1; XM_006513376.3.
DR RefSeq; XP_006513440.1; XM_006513377.3.
DR AlphaFoldDB; P13609; -.
DR BioGRID; 202359; 1.
DR IntAct; P13609; 1.
DR STRING; 10090.ENSMUSP00000125622; -.
DR GlyGen; P13609; 8 sites.
DR EPD; P13609; -.
DR MaxQB; P13609; -.
DR PaxDb; P13609; -.
DR PRIDE; P13609; -.
DR ProteomicsDB; 257068; -.
DR Antibodypedia; 609; 238 antibodies from 25 providers.
DR DNASU; 19073; -.
DR Ensembl; ENSMUST00000020271; ENSMUSP00000020271; ENSMUSG00000020077.
DR Ensembl; ENSMUST00000160987; ENSMUSP00000125622; ENSMUSG00000020077.
DR Ensembl; ENSMUST00000162161; ENSMUSP00000125533; ENSMUSG00000020077.
DR GeneID; 19073; -.
DR KEGG; mmu:19073; -.
DR UCSC; uc007fhi.1; mouse.
DR CTD; 5552; -.
DR MGI; MGI:97756; Srgn.
DR VEuPathDB; HostDB:ENSMUSG00000020077; -.
DR eggNOG; ENOG502S72N; Eukaryota.
DR GeneTree; ENSGT00390000000885; -.
DR HOGENOM; CLU_142594_0_0_1; -.
DR InParanoid; P13609; -.
DR OMA; ANCIDEK; -.
DR OrthoDB; 1340705at2759; -.
DR PhylomeDB; P13609; -.
DR TreeFam; TF336310; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 19073; 1 hit in 71 CRISPR screens.
DR ChiTaRS; Srgn; mouse.
DR PRO; PR:P13609; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P13609; protein.
DR Bgee; ENSMUSG00000020077; Expressed in gastrula and 245 other tissues.
DR ExpressionAtlas; P13609; baseline and differential.
DR Genevisible; P13609; MM.
DR GO; GO:0044194; C:cytolytic granule; IEA:UniProtKB-SubCell.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; ISO:MGI.
DR GO; GO:0042629; C:mast cell granule; IDA:UniProtKB.
DR GO; GO:0099091; C:postsynaptic specialization, intracellular component; IDA:SynGO.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:0030141; C:secretory granule; IBA:GO_Central.
DR GO; GO:0042588; C:zymogen granule; ISO:MGI.
DR GO; GO:0005518; F:collagen binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0031214; P:biomineral tissue development; IEA:UniProtKB-KW.
DR GO; GO:0140507; P:granzyme-mediated programmed cell death signaling pathway; ISS:UniProtKB.
DR GO; GO:0033382; P:maintenance of granzyme B location in T cell secretory granule; IMP:UniProtKB.
DR GO; GO:0033373; P:maintenance of protease location in mast cell secretory granule; IMP:UniProtKB.
DR GO; GO:0033364; P:mast cell secretory granule organization; IMP:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IDA:SynGO.
DR GO; GO:0030502; P:negative regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:UniProtKB.
DR GO; GO:0016485; P:protein processing; IDA:UniProtKB.
DR GO; GO:0099175; P:regulation of postsynapse organization; IDA:SynGO.
DR GO; GO:0033363; P:secretory granule organization; IBA:GO_Central.
DR GO; GO:0033371; P:T cell secretory granule organization; IMP:UniProtKB.
DR InterPro; IPR007455; Serglycin.
DR Pfam; PF04360; Serglycin; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Biomineralization; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Golgi apparatus; Lysosome; Proteoglycan; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT PROPEP 26..74
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000290036"
FT CHAIN 75..152
FT /note="Serglycin"
FT /id="PRO_0000026680"
FT REPEAT 89..90
FT /note="1"
FT REPEAT 91..92
FT /note="2"
FT REPEAT 93..94
FT /note="3"
FT REPEAT 95..96
FT /note="4"
FT REPEAT 97..98
FT /note="5"
FT REPEAT 99..100
FT /note="6"
FT REPEAT 101..102
FT /note="7"
FT REPEAT 103..104
FT /note="8"
FT REPEAT 105..106
FT /note="9"
FT REPEAT 107..108
FT /note="10"
FT REGION 66..115
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 89..108
FT /note="10 X 2 AA tandem repeats of G-S"
FT COMPBIAS 85..107
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 92
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 94
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000250"
FT CARBOHYD 98
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 100
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 102
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 106
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="O-linked (Xyl...) (glycosaminoglycan) serine"
FT /evidence="ECO:0000255"
FT DISULFID 38..47
FT /evidence="ECO:0000255"
SQ SEQUENCE 152 AA; 16711 MW; DCEC9829BA31036F CRC64;
MQVPVGSRLV LALAFVLVWG SSVQGYPARR ARYQWVRCKP NGFFANCIEE KGPQFDLIDE
SNNIGPPMNN PVLMEGPSKD FISNYDDYGS GSGSGSGSGS GSGSGSGSGF LGDMEWEYQP
TDESNIVYFN YKPFDRILTE QNQDQPEDDF II
