SCG3_HUMAN
ID SCG3_HUMAN Reviewed; 468 AA.
AC Q8WXD2; A8K2B0; B3KQP6; B4DK99; F5H3R8; Q96C83; Q96GE8; Q9Y6G7;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 13-APR-2004, sequence version 3.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Secretogranin-3;
DE AltName: Full=Secretogranin III;
DE Short=SgIII;
DE Flags: Precursor;
GN Name=SCG3; ORFNames=UNQ2502/PRO5990;
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] (ISOFORM 1).
RC TISSUE=Pituitary;
RA Song H., Peng Y., Huang Q., Dai M., Mao Y., Zhang Q., Mao M., Fu G.,
RA Luo M., Chen J., Hu R.;
RT "Human secretogranin III mRNA, complete cds.";
RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12098761;
RA Rong Y.P., Liu F., Zeng L.C., Ma W.J., Wei D.Z., Han Z.G.;
RT "Cloning and characterization of a novel human secretory protein:
RT secretogranin III.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao 34:411-417(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Retinoblastoma, and Thalamus;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [6]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ALA-167.
RC TISSUE=Brain, 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 [8]
RP POLYMORPHISM.
RX PubMed=17200173; DOI=10.1210/jc.2006-1808;
RA Tanabe A., Yanagiya T., Iida A., Saito S., Sekine A., Takahashi A.,
RA Nakamura T., Tsunoda T., Kamohara S., Nakata Y., Kotani K., Komatsu R.,
RA Itoh N., Mineo I., Wada J., Funahashi T., Miyazaki S., Tokunaga K.,
RA Hamaguchi K., Shimada T., Tanaka K., Yamada K., Hanafusa T., Oikawa S.,
RA Yoshimatsu H., Sakata T., Matsuzawa Y., Kamatani N., Nakamura Y., Hotta K.;
RT "Functional single-nucleotide polymorphisms in the secretogranin III (SCG3)
RT gene that form secretory granules with appetite-related neuropeptides are
RT associated with obesity.";
RL J. Clin. Endocrinol. Metab. 92:1145-1154(2007).
RN [9]
RP INTERACTION WITH SCG2, AND FUNCTION.
RX PubMed=19357184; DOI=10.1677/joe-08-0531;
RA Hotta K., Hosaka M., Tanabe A., Takeuchi T.;
RT "Secretogranin II binds to secretogranin III and forms secretory granules
RT with orexin, neuropeptide Y, and POMC.";
RL J. Endocrinol. 202:111-121(2009).
RN [10]
RP GLYCOSYLATION AT THR-216; THR-231 AND SER-359, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=23234360; DOI=10.1021/pr300963h;
RA Halim A., Ruetschi U., Larson G., Nilsson J.;
RT "LC-MS/MS characterization of O-glycosylation sites and glycan structures
RT of human cerebrospinal fluid glycoproteins.";
RL J. Proteome Res. 12:573-584(2013).
RN [11]
RP FUNCTION.
RX PubMed=29154827; DOI=10.1016/j.bbrc.2017.11.080;
RA Tang F., Pacheco M.T.F., Chen P., Liang D., Li W.;
RT "Secretogranin III promotes angiogenesis through MEK/ERK signaling
RT pathway.";
RL Biochem. Biophys. Res. Commun. 495:781-786(2018).
CC -!- FUNCTION: Member of the granin protein family that regulates the
CC biogenesis of secretory granules (PubMed:19357184). Acts as a sorting
CC receptor for intragranular proteins including chromogranin A/CHGA (By
CC similarity). May also play a role in angiogenesis. Promotes endothelial
CC proliferation, migration and tube formation through MEK/ERK signaling
CC pathway (PubMed:29154827). {ECO:0000250|UniProtKB:P47868,
CC ECO:0000269|PubMed:19357184, ECO:0000269|PubMed:29154827}.
CC -!- SUBUNIT: Interacts with CHGA (PubMed:19357184) (By similarity).
CC Interacts with secretogranin II/SCG2 (PubMed:19357184). Interacts (via
CC C-terminus) with CPE (By similarity). {ECO:0000250|UniProtKB:P47867,
CC ECO:0000269|PubMed:19357184}.
CC -!- INTERACTION:
CC Q8WXD2; O00560: SDCBP; NbExp=3; IntAct=EBI-12162999, EBI-727004;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000250|UniProtKB:P47868}. Cytoplasmic vesicle, secretory vesicle
CC membrane {ECO:0000250|UniProtKB:P47868}; Peripheral membrane protein
CC {ECO:0000250}. Secreted {ECO:0000269|PubMed:12098761}. Note=Associated
CC with the secretory granule membrane through direct binding to
CC cholesterol-enriched lipid rafts. {ECO:0000250|UniProtKB:P47868}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8WXD2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8WXD2-2; Sequence=VSP_042876;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver and
CC skeletal muscle. {ECO:0000269|PubMed:12098761}.
CC -!- PTM: O-glycosylated. {ECO:0000269|PubMed:23234360}.
CC -!- POLYMORPHISM: Polymorphisms in the 5'-flanking region and in intron 1
CC may have an effect on transcriptional activity and be associated with
CC an increase in subcutaneous, but not visceral, fat area. Hence, may
CC influence the risk of obesity.
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DR EMBL; AF078851; AAD44483.1; -; mRNA.
DR EMBL; AF453583; AAL67431.1; -; mRNA.
DR EMBL; AY359093; AAQ89451.1; -; mRNA.
DR EMBL; AK075314; BAG52108.1; -; mRNA.
DR EMBL; AK290175; BAF82864.1; -; mRNA.
DR EMBL; AK296466; BAG59111.1; -; mRNA.
DR EMBL; AC020892; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471082; EAW77426.1; -; Genomic_DNA.
DR EMBL; BC009511; AAH09511.2; -; mRNA.
DR EMBL; BC014539; AAH14539.1; -; mRNA.
DR CCDS; CCDS10142.1; -. [Q8WXD2-1]
DR CCDS; CCDS53947.1; -. [Q8WXD2-2]
DR RefSeq; NP_001158729.1; NM_001165257.1. [Q8WXD2-2]
DR RefSeq; NP_037375.2; NM_013243.3. [Q8WXD2-1]
DR AlphaFoldDB; Q8WXD2; -.
DR BioGRID; 118874; 10.
DR DIP; DIP-29451N; -.
DR IntAct; Q8WXD2; 8.
DR STRING; 9606.ENSP00000220478; -.
DR GlyConnect; 732; 13 N-Linked glycans (1 site), 1 O-Linked glycan (3 sites).
DR GlyGen; Q8WXD2; 5 sites, 14 N-linked glycans (2 sites), 2 O-linked glycans (3 sites).
DR iPTMnet; Q8WXD2; -.
DR PhosphoSitePlus; Q8WXD2; -.
DR BioMuta; SCG3; -.
DR DMDM; 46397796; -.
DR EPD; Q8WXD2; -.
DR jPOST; Q8WXD2; -.
DR MassIVE; Q8WXD2; -.
DR PaxDb; Q8WXD2; -.
DR PeptideAtlas; Q8WXD2; -.
DR PRIDE; Q8WXD2; -.
DR ProteomicsDB; 75012; -. [Q8WXD2-1]
DR ProteomicsDB; 75013; -. [Q8WXD2-2]
DR Antibodypedia; 1520; 284 antibodies from 31 providers.
DR DNASU; 29106; -.
DR Ensembl; ENST00000220478.8; ENSP00000220478.3; ENSG00000104112.9. [Q8WXD2-1]
DR Ensembl; ENST00000542355.6; ENSP00000445205.2; ENSG00000104112.9. [Q8WXD2-2]
DR GeneID; 29106; -.
DR KEGG; hsa:29106; -.
DR MANE-Select; ENST00000220478.8; ENSP00000220478.3; NM_013243.4; NP_037375.2.
DR UCSC; uc002abh.4; human. [Q8WXD2-1]
DR CTD; 29106; -.
DR DisGeNET; 29106; -.
DR GeneCards; SCG3; -.
DR HGNC; HGNC:13707; SCG3.
DR HPA; ENSG00000104112; Tissue enhanced (brain, pituitary gland, retina).
DR MIM; 611796; gene.
DR neXtProt; NX_Q8WXD2; -.
DR OpenTargets; ENSG00000104112; -.
DR PharmGKB; PA34988; -.
DR VEuPathDB; HostDB:ENSG00000104112; -.
DR eggNOG; ENOG502QUJH; Eukaryota.
DR GeneTree; ENSGT00390000005488; -.
DR HOGENOM; CLU_031198_1_0_1; -.
DR InParanoid; Q8WXD2; -.
DR OMA; MEKEYEI; -.
DR OrthoDB; 692526at2759; -.
DR PhylomeDB; Q8WXD2; -.
DR TreeFam; TF331266; -.
DR PathwayCommons; Q8WXD2; -.
DR Reactome; R-HSA-114608; Platelet degranulation.
DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation.
DR SignaLink; Q8WXD2; -.
DR BioGRID-ORCS; 29106; 12 hits in 1076 CRISPR screens.
DR ChiTaRS; SCG3; human.
DR GeneWiki; SCG3; -.
DR GenomeRNAi; 29106; -.
DR Pharos; Q8WXD2; Tbio.
DR PRO; PR:Q8WXD2; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q8WXD2; protein.
DR Bgee; ENSG00000104112; Expressed in islet of Langerhans and 118 other tissues.
DR ExpressionAtlas; Q8WXD2; baseline and differential.
DR Genevisible; Q8WXD2; HS.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0030667; C:secretory granule membrane; IBA:GO_Central.
DR GO; GO:0030658; C:transport vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0033366; P:protein localization to secretory granule; IBA:GO_Central.
DR InterPro; IPR026197; SCG3.
DR PANTHER; PTHR17388; PTHR17388; 1.
DR Pfam; PF15467; SGIII; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues;
KW Cytoplasmic vesicle; Glycoprotein; Membrane; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..468
FT /note="Secretogranin-3"
FT /id="PRO_0000005461"
FT REGION 23..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 353..406
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..59
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 358..406
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 37
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47867"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P47867"
FT CARBOHYD 216
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 231
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT CARBOHYD 359
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:23234360"
FT VAR_SEQ 1..232
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042876"
FT VARIANT 125
FT /note="S -> N (in dbSNP:rs2305710)"
FT /id="VAR_013827"
FT VARIANT 167
FT /note="V -> A (in dbSNP:rs17851186)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_067273"
FT VARIANT 233
FT /note="M -> V (in dbSNP:rs35664837)"
FT /id="VAR_034484"
FT CONFLICT 79
FT /note="K -> R (in Ref. 1; AAD44483)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="D -> G (in Ref. 4; BAG52108)"
FT /evidence="ECO:0000305"
FT CONFLICT 272..274
FT /note="EEL -> RDF (in Ref. 1; AAD44483)"
FT /evidence="ECO:0000305"
FT CONFLICT 421
FT /note="K -> R (in Ref. 4; BAG59111)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 468 AA; 53005 MW; 5E6BBDDFFF3B8D82 CRC64;
MGFLGTGTWI LVLVLPIQAF PKPGGSQDKS LHNRELSAER PLNEQIAEAE EDKIKKTYPP
ENKPGQSNYS FVDNLNLLKA ITEKEKIEKE RQSIRSSPLD NKLNVEDVDS TKNRKLIDDY
DSTKSGLDHK FQDDPDGLHQ LDGTPLTAED IVHKIAARIY EENDRAVFDK IVSKLLNLGL
ITESQAHTLE DEVAEVLQKL ISKEANNYEE DPNKPTSWTE NQAGKIPEKV TPMAAIQDGL
AKGENDETVS NTLTLTNGLE RRTKTYSEDN FEELQYFPNF YALLKSIDSE KEAKEKETLI
TIMKTLIDFV KMMVKYGTIS PEEGVSYLEN LDEMIALQTK NKLEKNATDN ISKLFPAPSE
KSHEETDSTK EEAAKMEKEY GSLKDSTKDD NSNPGGKTDE PKGKTEAYLE AIRKNIEWLK
KHDKKGNKED YDLSKMRDFI NKQADAYVEK GILDKEEAEA IKRIYSSL
