IFI6_HUMAN
ID IFI6_HUMAN Reviewed; 130 AA.
AC P09912; Q13141; Q13142; Q5VVR2; Q5VVR3; Q6IE95; Q969M8;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2002, sequence version 2.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Interferon alpha-inducible protein 6 {ECO:0000305};
DE AltName: Full=Interferon-induced protein 6-16 {ECO:0000303|PubMed:14728724};
DE Short=Ifi-6-16 {ECO:0000303|PubMed:14728724};
GN Name=IFI6 {ECO:0000312|HGNC:HGNC:4054};
GN Synonyms=G1P3 {ECO:0000303|PubMed:15685448};
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 A).
RX PubMed=3017706; DOI=10.1002/j.1460-2075.1986.tb04402.x;
RA Kelly J.M., Porter A.C.G., Chernajovsky Y., Gilbert C.S., Stark G.R.,
RA Kerr I.M.;
RT "Characterization of a human gene inducible by alpha- and beta-interferons
RT and its expression in mouse cells.";
RL EMBO J. 5:1601-1606(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS A; B AND C).
RC TISSUE=Placenta;
RX PubMed=7596809; DOI=10.1093/nar/23.11.1854;
RA Turri M.G., Cuin K.A., Porter A.C.G.;
RT "Characterisation of a novel minisatellite that provides multiple splice
RT donor sites in an interferon-induced transcript.";
RL Nucleic Acids Res. 23:1854-1861(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC TISSUE=Cerebellum;
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=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC TISSUE=Placenta, and 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 INDUCTION BY INTERFERON.
RX PubMed=14728724; DOI=10.1186/1471-2164-5-8;
RA Parker N., Porter A.C.G.;
RT "Identification of a novel gene family that includes the interferon-
RT inducible human genes 6-16 and ISG12.";
RL BMC Genomics 5:8-8(2004).
RN [9]
RP FUNCTION, INTERACTION WITH CIB1, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=15685448; DOI=10.1007/s00262-004-0645-2;
RA Tahara E. Jr., Tahara H., Kanno M., Naka K., Takeda Y., Matsuzaki T.,
RA Yamazaki R., Ishihara H., Yasui W., Barrett J.C., Ide T., Tahara E.;
RT "G1P3, an interferon inducible gene 6-16, is expressed in gastric cancers
RT and inhibits mitochondrial-mediated apoptosis in gastric cancer cell line
RT TMK-1 cell.";
RL Cancer Immunol. Immunother. 54:729-740(2005).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION BY INTERFERON.
RX PubMed=17823654; DOI=10.1172/jci31122;
RA Cheriyath V., Glaser K.B., Waring J.F., Baz R., Hussein M.A., Borden E.C.;
RT "G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis
RT in human myeloma cells.";
RL J. Clin. Invest. 117:3107-3117(2007).
RN [11]
RP FUNCTION, AND INDUCTION.
RX PubMed=26244642; DOI=10.1371/journal.pone.0132743;
RA Qi Y., Li Y., Zhang Y., Zhang L., Wang Z., Zhang X., Gui L., Huang J.;
RT "IFI6 Inhibits Apoptosis via Mitochondrial-Dependent Pathway in Dengue
RT Virus 2 Infected Vascular Endothelial Cells.";
RL PLoS ONE 10:E0132743-E0132743(2015).
RN [12]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25757571; DOI=10.1038/srep09012;
RA Meyer K., Kwon Y.C., Liu S., Hagedorn C.H., Ray R.B., Ray R.;
RT "Interferon-alpha inducible protein 6 impairs EGFR activation by CD81 and
RT inhibits hepatitis C virus infection.";
RL Sci. Rep. 5:9012-9012(2015).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27673746; DOI=10.1111/boc.201600034;
RA Gytz H., Hansen M.F., Skovbjerg S., Kristensen A.C., Hoerlyck S.,
RA Jensen M.B., Fredborg M., Markert L.D., McMillan N.A., Christensen E.I.,
RA Martensen P.M.;
RT "Apoptotic properties of the type 1 interferon induced family of human
RT mitochondrial membrane ISG12 proteins.";
RL Biol. Cell 109:94-112(2017).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=29899394; DOI=10.1038/s41416-018-0137-3;
RA Cheriyath V., Kaur J., Davenport A., Khalel A., Chowdhury N., Gaddipati L.;
RT "G1P3 (IFI6), a mitochondrial localised antiapoptotic protein, promotes
RT metastatic potential of breast cancer cells through mtROS.";
RL Br. J. Cancer 119:52-64(2018).
CC -!- FUNCTION: Plays a role in apoptosis, negatively regulating the
CC intrinsinc apoptotic signaling pathway and TNFSF10-induced apoptosis
CC (PubMed:15685448, PubMed:17823654, PubMed:26244642). However, it has
CC also been shown to have a pro-apoptotic activity (PubMed:27673746). Has
CC an antiviral activity towards hepatitis C virus/HCV by inhibiting the
CC EGFR signaling pathway, which activation is required for entry of the
CC virus into cells (PubMed:25757571). {ECO:0000269|PubMed:15685448,
CC ECO:0000269|PubMed:17823654, ECO:0000269|PubMed:25757571,
CC ECO:0000269|PubMed:26244642, ECO:0000269|PubMed:27673746}.
CC -!- SUBUNIT: Interacts with CIB1; the interaction is direct.
CC {ECO:0000269|PubMed:15685448}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000269|PubMed:15685448, ECO:0000269|PubMed:17823654,
CC ECO:0000269|PubMed:25757571, ECO:0000269|PubMed:27673746,
CC ECO:0000269|PubMed:29899394}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=A;
CC IsoId=P09912-1; Sequence=Displayed;
CC Name=B;
CC IsoId=P09912-2; Sequence=VSP_001502;
CC Name=C;
CC IsoId=P09912-3; Sequence=VSP_001503;
CC -!- INDUCTION: Up-regulated by type-I interferon (PubMed:14728724,
CC PubMed:17823654). Up-regulated upon Dengue virus type 2/DENV2 infection
CC (at protein level) (PubMed:26244642). {ECO:0000269|PubMed:14728724,
CC ECO:0000269|PubMed:17823654, ECO:0000269|PubMed:26244642}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:15685448}.
CC -!- SIMILARITY: Belongs to the IFI6/IFI27 family. {ECO:0000305}.
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DR EMBL; X02492; CAA26322.1; -; mRNA.
DR EMBL; U22970; AAC50159.1; -; Genomic_DNA.
DR EMBL; U22970; AAC50160.1; -; Genomic_DNA.
DR EMBL; U22970; AAC50161.1; -; Genomic_DNA.
DR EMBL; BT006850; AAP35496.1; -; mRNA.
DR EMBL; AK314488; BAG37089.1; -; mRNA.
DR EMBL; AL445490; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07744.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07745.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07746.1; -; Genomic_DNA.
DR EMBL; BC011601; AAH11601.1; -; mRNA.
DR EMBL; BC015603; AAH15603.1; -; mRNA.
DR EMBL; BN000257; CAE12275.1; -; mRNA.
DR CCDS; CCDS306.1; -. [P09912-1]
DR CCDS; CCDS307.1; -. [P09912-2]
DR CCDS; CCDS308.1; -. [P09912-3]
DR PIR; A26316; A26316.
DR RefSeq; NP_002029.3; NM_002038.3. [P09912-1]
DR RefSeq; NP_075010.1; NM_022872.2. [P09912-2]
DR RefSeq; NP_075011.1; NM_022873.2. [P09912-3]
DR AlphaFoldDB; P09912; -.
DR BioGRID; 108812; 49.
DR STRING; 9606.ENSP00000342513; -.
DR iPTMnet; P09912; -.
DR PhosphoSitePlus; P09912; -.
DR BioMuta; IFI6; -.
DR DMDM; 20178294; -.
DR MassIVE; P09912; -.
DR MaxQB; P09912; -.
DR PeptideAtlas; P09912; -.
DR PRIDE; P09912; -.
DR ProteomicsDB; 52273; -. [P09912-1]
DR ProteomicsDB; 52274; -. [P09912-2]
DR ProteomicsDB; 52275; -. [P09912-3]
DR Antibodypedia; 1278; 155 antibodies from 23 providers.
DR DNASU; 2537; -.
DR Ensembl; ENST00000339145.8; ENSP00000342513.4; ENSG00000126709.16. [P09912-3]
DR Ensembl; ENST00000361157.11; ENSP00000354736.6; ENSG00000126709.16. [P09912-1]
DR Ensembl; ENST00000362020.4; ENSP00000355152.4; ENSG00000126709.16. [P09912-2]
DR Ensembl; ENST00000679644.1; ENSP00000505325.1; ENSG00000126709.16. [P09912-1]
DR GeneID; 2537; -.
DR KEGG; hsa:2537; -.
DR MANE-Select; ENST00000361157.11; ENSP00000354736.6; NM_002038.4; NP_002029.3.
DR UCSC; uc001bon.2; human. [P09912-1]
DR CTD; 2537; -.
DR DisGeNET; 2537; -.
DR GeneCards; IFI6; -.
DR HGNC; HGNC:4054; IFI6.
DR HPA; ENSG00000126709; Low tissue specificity.
DR MIM; 147572; gene.
DR neXtProt; NX_P09912; -.
DR OpenTargets; ENSG00000126709; -.
DR PharmGKB; PA28466; -.
DR VEuPathDB; HostDB:ENSG00000126709; -.
DR eggNOG; ENOG502SCCP; Eukaryota.
DR GeneTree; ENSGT00940000163178; -.
DR HOGENOM; CLU_119109_0_0_1; -.
DR InParanoid; P09912; -.
DR OMA; FWKALTY; -.
DR OrthoDB; 1593440at2759; -.
DR PhylomeDB; P09912; -.
DR TreeFam; TF340510; -.
DR PathwayCommons; P09912; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; P09912; -.
DR BioGRID-ORCS; 2537; 11 hits in 1077 CRISPR screens.
DR ChiTaRS; IFI6; human.
DR GeneWiki; IFI6; -.
DR GenomeRNAi; 2537; -.
DR Pharos; P09912; Tbio.
DR PRO; PR:P09912; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P09912; protein.
DR Bgee; ENSG00000126709; Expressed in adenohypophysis and 170 other tissues.
DR ExpressionAtlas; P09912; baseline and differential.
DR Genevisible; P09912; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005743; C:mitochondrial inner membrane; IDA:UniProtKB.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0097190; P:apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0098586; P:cellular response to virus; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:HGNC-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IMP:BHF-UCL.
DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; IMP:HGNC-UCL.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:0042058; P:regulation of epidermal growth factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IMP:HGNC-UCL.
DR Gene3D; 6.10.110.10; -; 1.
DR InterPro; IPR009311; IFI6/IFI27-like.
DR InterPro; IPR038213; IFI6/IFI27-like_sf.
DR PANTHER; PTHR16932; PTHR16932; 1.
DR Pfam; PF06140; Ifi-6-16; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Antiviral defense; Apoptosis; Immunity;
KW Innate immunity; Membrane; Mitochondrion; Mitochondrion inner membrane;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..130
FT /note="Interferon alpha-inducible protein 6"
FT /id="PRO_0000008741"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 75..95
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 99..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 24
FT /note="G -> GENAG (in isoform B)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_001502"
FT VAR_SEQ 24
FT /note="G -> GENAGKDAG (in isoform C)"
FT /evidence="ECO:0000305"
FT /id="VSP_001503"
FT CONFLICT 8
FT /note="L -> V (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="G -> R (in Ref. 1 and 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 130 AA; 12927 MW; B1C2992A59203B38 CRC64;
MRQKAVSLFL CYLLLFTCSG VEAGKKKCSE SSDSGSGFWK ALTFMAVGGG LAVAGLPALG
FTGAGIAANS VAASLMSWSA ILNGGGVPAG GLVATLQSLG AGGSSVVIGN IGALMGYATH
KYLDSEEDEE
