GILT_HUMAN
ID GILT_HUMAN Reviewed; 250 AA.
AC P13284; Q76MF9; Q8NEI4; Q8WU77; Q9UL08;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 05-APR-2011, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Gamma-interferon-inducible lysosomal thiol reductase;
DE EC=1.8.-.- {ECO:0000269|PubMed:10639150, ECO:0000269|PubMed:10852914};
DE AltName: Full=Gamma-interferon-inducible protein IP-30;
DE AltName: Full=Legumaturain;
DE Flags: Precursor;
GN Name=IFI30; Synonyms=GILT, IP30;
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], INDUCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=3136170; DOI=10.1016/s0021-9258(18)37889-x;
RA Luster A.D., Weinshank R.L., Feinman R., Ravetch J.V.;
RT "Molecular and biochemical characterization of a novel gamma-interferon-
RT inducible protein.";
RL J. Biol. Chem. 263:12036-12043(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, IDENTIFICATION BY MASS SPECTROMETRY, PROTEIN
RP SEQUENCE OF N-TERMINUS, GLYCOSYLATION, AND MUTAGENESIS OF CYS-72 AND
RP CYS-75.
RX PubMed=10639150; DOI=10.1073/pnas.97.2.745;
RA Arunachalam B., Phan U.T., Geuze H.J., Cresswell P.;
RT "Enzymatic reduction of disulfide bonds in lysosomes: characterization of a
RT gamma-interferon-inducible lysosomal thiol reductase (GILT).";
RL Proc. Natl. Acad. Sci. U.S.A. 97:745-750(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Arahira M., Fukazawa C.;
RT "A novel Asn-bond specific endoproteolytic enzyme from Human.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
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].
RC TISSUE=Skin;
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 SUBUNIT, CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-72 AND CYS-75, AND
RP GLYCOSYLATION.
RX PubMed=10852914; DOI=10.1074/jbc.m003459200;
RA Phan U.T., Arunachalam B., Cresswell P.;
RT "Gamma-interferon-inducible lysosomal thiol reductase (GILT). Maturation,
RT activity, and mechanism of action.";
RL J. Biol. Chem. 275:25907-25914(2000).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
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 [11]
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).
CC -!- FUNCTION: Lysosomal thiol reductase that can reduce protein disulfide
CC bonds. May facilitate the complete unfolding of proteins destined for
CC lysosomal degradation. Plays an important role in antigen processing.
CC Facilitates the generation of MHC class II-restricted epitodes from
CC disulfide bond-containing antigen by the endocytic reduction of
CC disulfide bonds (By similarity). Facilitates also MHC class I-
CC restricted recognition of exogenous antigens containing disulfide bonds
CC by CD8+ T-cells or crosspresentation (By similarity). {ECO:0000250}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1200 uM for F(ab')2 fragment when denatured
CC {ECO:0000269|PubMed:10639150};
CC KM=10 uM for F(ab')2 fragment {ECO:0000269|PubMed:10639150};
CC Note=Kinetic parameters shown are for mature enzyme.;
CC pH dependence:
CC Optimum pH is 4-5. {ECO:0000269|PubMed:10639150};
CC -!- SUBUNIT: Dimer; disulfide-linked. {ECO:0000269|PubMed:10852914,
CC ECO:0000269|PubMed:3136170}.
CC -!- INTERACTION:
CC P13284; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-2868897, EBI-739863;
CC P13284; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-2868897, EBI-945833;
CC P13284; P22735: TGM1; NbExp=3; IntAct=EBI-2868897, EBI-2562368;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10639150,
CC ECO:0000269|PubMed:3136170}. Lysosome {ECO:0000269|PubMed:10639150,
CC ECO:0000269|PubMed:3136170}.
CC -!- INDUCTION: Expressed constitutively in antigen-presenting cells and
CC induced by IFN-gamma in other cell types. {ECO:0000269|PubMed:3136170}.
CC -!- PTM: N-glycosylated. Sugar chains contain mannose-6-phosphate.
CC {ECO:0000269|PubMed:10639150, ECO:0000269|PubMed:10852914}.
CC -!- PTM: Synthesized as a 35 kDa precursor which is then processed into the
CC mature 30 kDa form via cleavage of N-terminal and C-terminal
CC propeptides. Processing of the precursor is mediated by multiple
CC lysosomal proteases.
CC -!- MISCELLANEOUS: Both precursor form and mature form have thiol reductase
CC activity.
CC -!- SIMILARITY: Belongs to the GILT family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA36105.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAA36105.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAA36105.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. N-terminal sequence identical to a region of chromosome 11.; Evidence={ECO:0000305};
CC Sequence=AAF04618.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA. N-terminal sequence identical to a region of chromosome 11.; Evidence={ECO:0000305};
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DR EMBL; J03909; AAA36105.1; ALT_SEQ; mRNA.
DR EMBL; AF097362; AAF04618.1; ALT_SEQ; mRNA.
DR EMBL; AB049659; BAC98466.1; -; mRNA.
DR EMBL; AC007192; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093080; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC068499; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471106; EAW84662.1; -; Genomic_DNA.
DR EMBL; BC021136; AAH21136.1; -; mRNA.
DR EMBL; BC031020; AAH31020.1; -; mRNA.
DR CCDS; CCDS46015.1; -.
DR PIR; A43708; A43708.
DR RefSeq; NP_006323.2; NM_006332.4.
DR AlphaFoldDB; P13284; -.
DR SMR; P13284; -.
DR BioGRID; 115704; 77.
DR IntAct; P13284; 31.
DR MINT; P13284; -.
DR STRING; 9606.ENSP00000384886; -.
DR GlyConnect; 1262; 18 N-Linked glycans (2 sites).
DR GlyGen; P13284; 5 sites, 17 N-linked glycans (2 sites).
DR iPTMnet; P13284; -.
DR PhosphoSitePlus; P13284; -.
DR BioMuta; IFI30; -.
DR DMDM; 327478582; -.
DR EPD; P13284; -.
DR jPOST; P13284; -.
DR MassIVE; P13284; -.
DR MaxQB; P13284; -.
DR PaxDb; P13284; -.
DR PeptideAtlas; P13284; -.
DR PRIDE; P13284; -.
DR ProteomicsDB; 52905; -.
DR Antibodypedia; 27932; 173 antibodies from 29 providers.
DR DNASU; 10437; -.
DR Ensembl; ENST00000407280.4; ENSP00000384886.1; ENSG00000216490.4.
DR GeneID; 10437; -.
DR KEGG; hsa:10437; -.
DR MANE-Select; ENST00000407280.4; ENSP00000384886.1; NM_006332.5; NP_006323.2.
DR UCSC; uc002nic.3; human.
DR CTD; 10437; -.
DR DisGeNET; 10437; -.
DR GeneCards; IFI30; -.
DR HGNC; HGNC:5398; IFI30.
DR HPA; ENSG00000216490; Tissue enhanced (lung, lymphoid tissue).
DR MIM; 604664; gene.
DR neXtProt; NX_P13284; -.
DR OpenTargets; ENSG00000216490; -.
DR PharmGKB; PA29644; -.
DR VEuPathDB; HostDB:ENSG00000216490; -.
DR eggNOG; KOG3160; Eukaryota.
DR GeneTree; ENSGT00390000010450; -.
DR HOGENOM; CLU_066886_0_1_1; -.
DR InParanoid; P13284; -.
DR OMA; EACVLDQ; -.
DR OrthoDB; 803513at2759; -.
DR PhylomeDB; P13284; -.
DR TreeFam; TF315141; -.
DR PathwayCommons; P13284; -.
DR Reactome; R-HSA-2132295; MHC class II antigen presentation.
DR Reactome; R-HSA-877300; Interferon gamma signaling.
DR SignaLink; P13284; -.
DR SIGNOR; P13284; -.
DR BioGRID-ORCS; 10437; 19 hits in 1082 CRISPR screens.
DR ChiTaRS; IFI30; human.
DR GeneWiki; IFI30; -.
DR GenomeRNAi; 10437; -.
DR Pharos; P13284; Tbio.
DR PRO; PR:P13284; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P13284; protein.
DR Bgee; ENSG00000216490; Expressed in monocyte and 95 other tissues.
DR ExpressionAtlas; P13284; baseline and differential.
DR Genevisible; P13284; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005576; C:extracellular region; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016667; F:oxidoreductase activity, acting on a sulfur group of donors; IMP:UniProtKB.
DR GO; GO:0016671; F:oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor; IEA:InterPro.
DR GO; GO:0042590; P:antigen processing and presentation of exogenous peptide antigen via MHC class I; ISS:UniProtKB.
DR GO; GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR InterPro; IPR004911; Interferon-induced_GILT.
DR PANTHER; PTHR13234; PTHR13234; 1.
DR Pfam; PF03227; GILT; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Lysosome; Oxidoreductase; Redox-active center; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..57
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:10639150"
FT /id="PRO_0000021328"
FT CHAIN 58..232
FT /note="Gamma-interferon-inducible lysosomal thiol
FT reductase"
FT /id="PRO_0000021329"
FT PROPEP 233..250
FT /note="Removed in mature form"
FT /evidence="ECO:0000269|PubMed:10639150"
FT /id="PRO_0000021330"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 95
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 72..75
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:10639150,
FT ECO:0000269|PubMed:10852914"
FT MUTAGEN 72
FT /note="C->S: Abolishes reducing activity, does not affect
FT dimerization. Abolishes reducing activity; when associated
FT with S-75."
FT /evidence="ECO:0000269|PubMed:10639150,
FT ECO:0000269|PubMed:10852914"
FT MUTAGEN 75
FT /note="C->S: Abolishes reducing activity, does not affect
FT dimerization. Abolishes reducing activity; when associated
FT with S-72."
FT /evidence="ECO:0000269|PubMed:10639150,
FT ECO:0000269|PubMed:10852914"
FT CONFLICT 76
FT /note="R -> Q (in Ref. 7; AAH31020)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="L -> S (in Ref. 1; AAA36105)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="H -> L (in Ref. 1; AAA36105)"
FT /evidence="ECO:0000305"
FT CONFLICT 148
FT /note="C -> WHG (in Ref. 1; AAA36105)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="T -> A (in Ref. 3; BAC98466)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 250 AA; 27964 MW; 54B4950E3788CD5A CRC64;
MTLSPLLLFL PPLLLLLDVP TAAVQASPLQ ALDFFGNGPP VNYKTGNLYL RGPLKKSNAP
LVNVTLYYEA LCGGCRAFLI RELFPTWLLV MEILNVTLVP YGNAQEQNVS GRWEFKCQHG
EEECKFNKVE ACVLDELDME LAFLTIVCME EFEDMERSLP LCLQLYAPGL SPDTIMECAM
GDRGMQLMHA NAQRTDALQP PHEYVPWVTV NGKPLEDQTQ LLTLVCQLYQ GKKPDVCPSS
TSSLRSVCFK
