IN35_HUMAN
ID IN35_HUMAN Reviewed; 286 AA.
AC P80217; C9JGX1; Q92984; Q99537; Q9BV98;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 5.
DT 03-AUG-2022, entry version 168.
DE RecName: Full=Interferon-induced 35 kDa protein {ECO:0000303|PubMed:8954125};
DE Short=IFP 35 {ECO:0000303|PubMed:29038465, ECO:0000303|PubMed:8954125};
DE Short=Ifi-35 {ECO:0000303|PubMed:26342464, ECO:0000303|PubMed:29350881};
GN Name=IFI35 {ECO:0000312|HGNC:HGNC:5399};
GN Synonyms=IFP35 {ECO:0000303|PubMed:29038465};
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 (ISOFORM 1), HOMODIMERIZATION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND INDUCTION BY IFN-GAMMA.
RX PubMed=8288566; DOI=10.1016/s0021-9258(17)42225-3;
RA Bange F.-C., Vogel U., Flohr T., Kiekenbeck M., Denecke B., Boettger E.C.;
RT "IFP 35 is an interferon-induced leucine zipper protein that undergoes
RT interferon-regulated cellular redistribution.";
RL J. Biol. Chem. 269:1091-1098(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT VAL-128 (ISOFORM 2), AND
RP INTERACTION WITH BATF.
RX PubMed=8954125; DOI=10.1006/bbrc.1996.1799;
RA Wang X., Johansen L.M., Tae H.-J., Taparowsky E.J.;
RT "IFP 35 forms complexes with B-ATF, a member of the AP1 family of
RT transcription factors.";
RL Biochem. Biophys. Res. Commun. 229:316-322(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT VAL-128
RP (ISOFORM 2).
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-283 (ISOFORM 1), AND VARIANT
RP VAL-126.
RX PubMed=8938427; DOI=10.1101/gr.6.11.1029;
RA Smith T.M., Lee M.K., Szabo C.I., Jerome N., McEuen M., Taylor M., Hood L.,
RA King M.-C.;
RT "Complete genomic sequence and analysis of 117 kb of human DNA containing
RT the gene BRCA1.";
RL Genome Res. 6:1029-1049(1996).
RN [6]
RP PROTEIN SEQUENCE OF 2-18.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP FUNCTION, INDUCTION BY IFN-ALPHA, SUBCELLULAR LOCATION, INTERACTION WITH
RP NMI, AND PHOSPHORYLATION.
RX PubMed=10779520; DOI=10.1074/jbc.m003177200;
RA Zhou X., Liao J., Meyerdierks A., Feng L., Naumovski L., Bottger E.C.,
RA Omary M.B.;
RT "Interferon-alpha induces nmi-IFP35 heterodimeric complex formation that is
RT affected by the phosphorylation of IFP35.";
RL J. Biol. Chem. 275:21364-21371(2000).
RN [8]
RP FUNCTION, HOMODIMERIZATION, INTERACTION WITH NMI, INDUCTION BY IFN-ALPHA,
RP AND SUBCELLULAR LOCATION.
RX PubMed=10950963; DOI=10.1074/jbc.m006975200;
RA Chen J., Shpall R.L., Meyerdierks A., Hagemeier M., Boettger E.C.,
RA Naumovski L.;
RT "Interferon-inducible Myc/STAT-interacting protein Nmi associates with IFP
RT 35 into a high molecular mass complex and inhibits proteasome-mediated
RT degradation of IFP 35.";
RL J. Biol. Chem. 275:36278-36284(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 FUNCTION, INTERACTION WITH NMI AND TRIM21, AND SUBCELLULAR LOCATION.
RX PubMed=26342464; DOI=10.1016/j.virol.2015.08.013;
RA Das A., Dinh P.X., Pattnaik A.K.;
RT "Trim21 regulates Nmi-IFI35 complex-mediated inhibition of innate antiviral
RT response.";
RL Virology 485:383-392(2015).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29038465; DOI=10.1038/s41467-017-00930-9;
RA Xiahou Z., Wang X., Shen J., Zhu X., Xu F., Hu R., Guo D., Li H., Tian Y.,
RA Liu Y., Liang H.;
RT "NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and
RT injury.";
RL Nat. Commun. 8:950-950(2017).
RN [12]
RP FUNCTION, AND DOMAIN.
RX PubMed=29350881; DOI=10.1111/apha.13037;
RA Jian D., Wang W., Zhou X., Jia Z., Wang J., Yang M., Zhao W., Jiang Z.,
RA Hu X., Zhu J.;
RT "Interferon-induced protein 35 inhibits endothelial cell proliferation,
RT migration and re-endothelialization of injured arteries by inhibiting the
RT nuclear factor-kappa B pathway.";
RL Acta Physiol. 223:e13037-e13037(2018).
CC -!- FUNCTION: Acts as a signaling pathway regulator involved in innate
CC immune system response (PubMed:26342464, PubMed:29038465,
CC PubMed:29350881). In response to interferon IFN-alpha, associates in a
CC complex with signaling pathway regulator NMI to regulate immune
CC response; the complex formation prevents proteasome-mediated
CC degradation of IFI35 and correlates with IFI35 dephosphorylation
CC (PubMed:10779520, PubMed:10950963). In complex with NMI, inhibits
CC virus-triggered type I interferon/IFN-beta production
CC (PubMed:26342464). In complex with NMI, negatively regulates nuclear
CC factor NF-kappa-B signaling by inhibiting the nuclear translocation,
CC activation and transcription of the NF-kappa-B subunit p65/RELA,
CC resulting in the inhibition of endothelial cell proliferation,
CC migration and re-endothelialization of injured arteries
CC (PubMed:29350881). Beside its role as an intracellular signaling
CC pathway regulator, also functions extracellularly as damage-associated
CC molecular patterns (DAMPs) to promote inflammation when actively
CC released by macrophage to the extracellular space during cell injury
CC and pathogen invasion (PubMed:29038465). Macrophage-secreted IFI35
CC activates NF-kappa-B signaling in adjacent macrophages through Toll-
CC like receptor 4/TLR4 activation, thereby inducing NF-kappa-B
CC translocation from the cytoplasm into the nucleus which promotes the
CC release of pro-inflammatory cytokines (PubMed:29038465).
CC {ECO:0000269|PubMed:10779520, ECO:0000269|PubMed:10950963,
CC ECO:0000269|PubMed:26342464, ECO:0000269|PubMed:29038465,
CC ECO:0000269|PubMed:29350881}.
CC -!- SUBUNIT: Homodimer (PubMed:8288566, PubMed:10950963). Also interacts
CC with BATF (PubMed:8954125). Interacts with TRIM21 (PubMed:26342464).
CC Interacts with NMI; the interaction is direct and is facilitated by
CC TRIM21 (PubMed:10779520, PubMed:10950963, PubMed:26342464).
CC {ECO:0000269|PubMed:10779520, ECO:0000269|PubMed:10950963,
CC ECO:0000269|PubMed:26342464, ECO:0000269|PubMed:8288566,
CC ECO:0000269|PubMed:8954125}.
CC -!- INTERACTION:
CC P80217; Q6UXB4: CLEC4G; NbExp=4; IntAct=EBI-2115067, EBI-2114729;
CC P80217-2; P54253: ATXN1; NbExp=3; IntAct=EBI-12823003, EBI-930964;
CC P80217-2; P46379-2: BAG6; NbExp=3; IntAct=EBI-12823003, EBI-10988864;
CC P80217-2; O75934: BCAS2; NbExp=3; IntAct=EBI-12823003, EBI-1050106;
CC P80217-2; O43739-2: CYTH3; NbExp=3; IntAct=EBI-12823003, EBI-11974015;
CC P80217-2; O75190-2: DNAJB6; NbExp=3; IntAct=EBI-12823003, EBI-12593112;
CC P80217-2; O14645: DNALI1; NbExp=3; IntAct=EBI-12823003, EBI-395638;
CC P80217-2; A0A0C4DGQ7: EML2; NbExp=3; IntAct=EBI-12823003, EBI-12112376;
CC P80217-2; Q14192: FHL2; NbExp=5; IntAct=EBI-12823003, EBI-701903;
CC P80217-2; P21333-2: FLNA; NbExp=3; IntAct=EBI-12823003, EBI-9641086;
CC P80217-2; O14901: KLF11; NbExp=3; IntAct=EBI-12823003, EBI-948266;
CC P80217-2; P31153: MAT2A; NbExp=3; IntAct=EBI-12823003, EBI-1050743;
CC P80217-2; Q13287: NMI; NbExp=4; IntAct=EBI-12823003, EBI-372942;
CC P80217-2; Q9BVL2: NUP58; NbExp=3; IntAct=EBI-12823003, EBI-2811583;
CC P80217-2; Q8N2W9: PIAS4; NbExp=3; IntAct=EBI-12823003, EBI-473160;
CC P80217-2; P37840: SNCA; NbExp=3; IntAct=EBI-12823003, EBI-985879;
CC P80217-2; P00441: SOD1; NbExp=3; IntAct=EBI-12823003, EBI-990792;
CC P80217-2; Q13148: TARDBP; NbExp=6; IntAct=EBI-12823003, EBI-372899;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10779520,
CC ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:8288566}. Nucleus
CC {ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:26342464,
CC ECO:0000269|PubMed:8288566}. Secreted {ECO:0000269|PubMed:29038465}.
CC Note=Cytoplasmic IFI35 localizes in punctate granular structures
CC (PubMed:10950963). Nuclear localization increased is stimulated by IFN-
CC alpha (PubMed:8288566, PubMed:10950963). Extracelullar following
CC secretion by macrophage (PubMed:29038465).
CC {ECO:0000269|PubMed:10950963, ECO:0000269|PubMed:29038465,
CC ECO:0000269|PubMed:8288566}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P80217-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P80217-2; Sequence=VSP_003569;
CC -!- TISSUE SPECIFICITY: Expressed in a wide range of cell types, including
CC fibroblasts, macrophages, and epithelial cells.
CC {ECO:0000269|PubMed:29038465, ECO:0000269|PubMed:8288566}.
CC -!- INDUCTION: Up-regulated by interferons IFN-alpha and IFN-gamma.
CC {ECO:0000269|PubMed:10779520, ECO:0000269|PubMed:10950963,
CC ECO:0000269|PubMed:8288566}.
CC -!- DOMAIN: The NID domain 1 is involved in the negative regulation of
CC p65/RELA transcription and the negative regulation of NF-kappa-B
CC pathway activation. {ECO:0000269|PubMed:29350881}.
CC -!- PTM: Phosphorylated. Dephosphorylation correlates with the formation of
CC a complex with NMI. {ECO:0000269|PubMed:10779520}.
CC -!- MISCELLANEOUS: [Isoform 2]: Due to a polymorphism at the 3'-splice
CC acceptor site of intron 4. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the NMI family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB61703.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR EMBL; U72882; AAB61703.1; ALT_SEQ; mRNA.
DR EMBL; AC055866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001356; AAH01356.1; -; mRNA.
DR EMBL; L78833; AAC37597.1; -; Genomic_DNA.
DR CCDS; CCDS11450.1; -. [P80217-2]
DR CCDS; CCDS82134.1; -. [P80217-1]
DR PIR; JC5262; JC5262.
DR RefSeq; NP_001317159.1; NM_001330230.1. [P80217-1]
DR RefSeq; NP_005524.2; NM_005533.4. [P80217-2]
DR AlphaFoldDB; P80217; -.
DR BioGRID; 109656; 28.
DR CORUM; P80217; -.
DR IntAct; P80217; 23.
DR MINT; P80217; -.
DR STRING; 9606.ENSP00000395590; -.
DR GlyGen; P80217; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P80217; -.
DR PhosphoSitePlus; P80217; -.
DR BioMuta; IFI35; -.
DR DMDM; 311033494; -.
DR EPD; P80217; -.
DR jPOST; P80217; -.
DR MassIVE; P80217; -.
DR MaxQB; P80217; -.
DR PaxDb; P80217; -.
DR PeptideAtlas; P80217; -.
DR PRIDE; P80217; -.
DR ProteomicsDB; 57673; -. [P80217-1]
DR ProteomicsDB; 57674; -. [P80217-2]
DR Antibodypedia; 29492; 340 antibodies from 25 providers.
DR DNASU; 3430; -.
DR Ensembl; ENST00000415816.7; ENSP00000394579.3; ENSG00000068079.8. [P80217-1]
DR Ensembl; ENST00000438323.2; ENSP00000395590.2; ENSG00000068079.8. [P80217-2]
DR GeneID; 3430; -.
DR KEGG; hsa:3430; -.
DR MANE-Select; ENST00000415816.7; ENSP00000394579.3; NM_001330230.2; NP_001317159.1.
DR UCSC; uc021txx.2; human. [P80217-1]
DR CTD; 3430; -.
DR DisGeNET; 3430; -.
DR GeneCards; IFI35; -.
DR HGNC; HGNC:5399; IFI35.
DR HPA; ENSG00000068079; Low tissue specificity.
DR MIM; 600735; gene.
DR neXtProt; NX_P80217; -.
DR OpenTargets; ENSG00000068079; -.
DR PharmGKB; PA29645; -.
DR VEuPathDB; HostDB:ENSG00000068079; -.
DR eggNOG; ENOG502QUNN; Eukaryota.
DR GeneTree; ENSGT00530000063686; -.
DR HOGENOM; CLU_047262_1_1_1; -.
DR InParanoid; P80217; -.
DR OMA; YMSGKIQ; -.
DR OrthoDB; 1133123at2759; -.
DR PhylomeDB; P80217; -.
DR TreeFam; TF332752; -.
DR PathwayCommons; P80217; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; P80217; -.
DR BioGRID-ORCS; 3430; 18 hits in 1086 CRISPR screens.
DR ChiTaRS; IFI35; human.
DR GeneWiki; IFI35; -.
DR GenomeRNAi; 3430; -.
DR Pharos; P80217; Tbio.
DR PRO; PR:P80217; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P80217; protein.
DR Bgee; ENSG00000068079; Expressed in granulocyte and 155 other tissues.
DR Genevisible; P80217; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:1901223; P:negative regulation of NIK/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0045089; P:positive regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR Gene3D; 3.30.70.330; -; 2.
DR InterPro; IPR034460; IFP35.
DR InterPro; IPR009909; Nmi/IFP35_dom.
DR InterPro; IPR009938; Nmi/IFP35_N.
DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf.
DR PANTHER; PTHR15225:SF1; PTHR15225:SF1; 1.
DR Pfam; PF07334; IFP_35_N; 1.
DR Pfam; PF07292; NID; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Direct protein sequencing; Immunity;
KW Innate immunity; Nucleus; Phosphoprotein; Reference proteome; Secreted.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801"
FT CHAIN 2..286
FT /note="Interferon-induced 35 kDa protein"
FT /id="PRO_0000159704"
FT DOMAIN 81..170
FT /note="NID 1"
FT /evidence="ECO:0000303|PubMed:29350881"
FT DOMAIN 183..266
FT /note="NID 2"
FT /evidence="ECO:0000303|PubMed:29350881"
FT REGION 5..26
FT /note="Leucine-zipper"
FT VAR_SEQ 126
FT /note="M -> VMM (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8954125"
FT /id="VSP_003569"
FT VARIANT 126
FT /note="M -> V (in dbSNP:rs588703)"
FT /evidence="ECO:0000269|PubMed:8938427"
FT /id="VAR_063758"
FT CONFLICT 264..286
FT /note="EVEALTVVPQGQQGLAVFTSESG -> GRGPDSRTPRTAGPSSLHL (in
FT Ref. 1; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT VARIANT P80217-2:128
FT /note="M -> V (in dbSNP:rs588703)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:8954125"
FT /id="VAR_082872"
SQ SEQUENCE 286 AA; 31546 MW; 3FCAB26E97317508 CRC64;
MSAPLDAALH ALQEEQARLK MRLWDLQQLR KELGDSPKDK VPFSVPKIPL VFRGHTQQDP
EVPKSLVSNL RIHCPLLAGS ALITFDDPKV AEQVLQQKEH TINMEECRLR VQVQPLELPM
VTTIQMSSQL SGRRVLVTGF PASLRLSEEE LLDKLEIFFG KTRNGGGDVD VRELLPGSVM
LGFARDGVAQ RLCQIGQFTV PLGGQQVPLR VSPYVNGEIQ KAEIRSQPVP RSVLVLNIPD
ILDGPELHDV LEIHFQKPTR GGGEVEALTV VPQGQQGLAV FTSESG
