IFIX_HUMAN
ID IFIX_HUMAN Reviewed; 492 AA.
AC Q6K0P9; Q5T3W6; Q6K0P6; Q6K0P7; Q6K0P8; Q8WW65;
DT 20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Pyrin and HIN domain-containing protein 1;
DE AltName: Full=Interferon-inducible protein X;
GN Name=PYHIN1; Synonyms=IFIX;
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] (ISOFORMS 1; 2; 3; 4 AND 5), SUBCELLULAR
RP LOCATION, INDUCTION BY IFN, AND TISSUE SPECIFICITY.
RX PubMed=15122330; DOI=10.1038/sj.onc.1207592;
RA Ding Y., Wang L., Su L.-K., Frey J.A., Shao R., Hunt K.K., Yan D.-H.;
RT "Antitumor activity of IFIX, a novel interferon-inducible HIN-200 gene, in
RT breast cancer.";
RL Oncogene 23:4556-4566(2004).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 3 AND 6).
RC TISSUE=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 [5]
RP FUNCTION, AND INTERACTION WITH MDM2.
RX PubMed=16479015; DOI=10.1128/mcb.26.5.1979-1996.2006;
RA Ding Y., Lee J.-F., Lu H., Lee M.-H., Yan D.-H.;
RT "Interferon-inducible protein IFIXalpha1 functions as a negative regulator
RT of HDM2.";
RL Mol. Cell. Biol. 26:1979-1996(2006).
RN [6]
RP FUNCTION.
RX PubMed=18247378; DOI=10.1002/mc.20423;
RA Yamaguchi H., Ding Y., Lee J.-F., Zhang M., Pal A., Bornmann W., Yan D.-H.,
RA Hung M.-C.;
RT "Interferon-inducible protein IFIXalpha inhibits cell invasion by
RT upregulating the metastasis suppressor maspin.";
RL Mol. Carcinog. 47:739-743(2008).
CC -!- FUNCTION: Major mediator of the tumor suppressor activity of IFN in
CC breast cancer cells. Promotes ubiquitination and subsequent degradation
CC of MDM2, which leads to p53/TP53 stabilization. Promotes ubiquitination
CC and subsequent degradation of HDAC1, which in turn enhances maspin
CC expression, and impairs invasive activity of cancer cells.
CC {ECO:0000269|PubMed:16479015, ECO:0000269|PubMed:18247378}.
CC -!- SUBUNIT: Interacts with MDM2. {ECO:0000269|PubMed:16479015}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Nucleus, nucleoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 5]: Nucleus. Nucleus speckle.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1; Synonyms=alpha1;
CC IsoId=Q6K0P9-1; Sequence=Displayed;
CC Name=2; Synonyms=alpha2;
CC IsoId=Q6K0P9-2; Sequence=VSP_033657;
CC Name=3; Synonyms=beta1;
CC IsoId=Q6K0P9-3; Sequence=VSP_033660;
CC Name=4; Synonyms=beta2;
CC IsoId=Q6K0P9-4; Sequence=VSP_033657, VSP_033660;
CC Name=5; Synonyms=gamma1;
CC IsoId=Q6K0P9-5; Sequence=VSP_033658, VSP_033659;
CC Name=6; Synonyms=gamma2;
CC IsoId=Q6K0P9-6; Sequence=VSP_033657, VSP_033658, VSP_033659;
CC -!- TISSUE SPECIFICITY: Expressed in spleen, lymph node and peripheral
CC blood leukocytes, and at lower levels in thymus, bone marrow and fetal
CC liver. Down-regulated in breast tumors. {ECO:0000269|PubMed:15122330}.
CC -!- INDUCTION: By IFN-alphas and IFNG/IFN-gamma in hematopoietic cancer
CC cells. {ECO:0000269|PubMed:15122330}.
CC -!- DOMAIN: The HIN-200 domain mediates interaction with MDM2.
CC -!- SIMILARITY: Belongs to the HIN-200 family. {ECO:0000305}.
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DR EMBL; AY185344; AAO67506.1; -; mRNA.
DR EMBL; AY185345; AAO67507.1; -; mRNA.
DR EMBL; AY185346; AAO67508.1; -; mRNA.
DR EMBL; AY185347; AAO67509.1; -; mRNA.
DR EMBL; AL359753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW52805.1; -; Genomic_DNA.
DR EMBL; BC020822; AAH20822.1; -; mRNA.
DR EMBL; BC090944; AAH90944.1; -; mRNA.
DR EMBL; BC139741; AAI39742.1; -; mRNA.
DR CCDS; CCDS1178.1; -. [Q6K0P9-1]
DR CCDS; CCDS1179.1; -. [Q6K0P9-2]
DR CCDS; CCDS30907.1; -. [Q6K0P9-3]
DR CCDS; CCDS30908.1; -. [Q6K0P9-4]
DR RefSeq; NP_689714.2; NM_152501.4. [Q6K0P9-1]
DR RefSeq; NP_945146.1; NM_198928.4. [Q6K0P9-2]
DR RefSeq; NP_945147.1; NM_198929.4. [Q6K0P9-3]
DR RefSeq; NP_945148.1; NM_198930.3. [Q6K0P9-4]
DR RefSeq; XP_005244987.1; XM_005244930.1. [Q6K0P9-5]
DR RefSeq; XP_011507544.1; XM_011509242.2. [Q6K0P9-1]
DR AlphaFoldDB; Q6K0P9; -.
DR SMR; Q6K0P9; -.
DR BioGRID; 127225; 360.
DR IntAct; Q6K0P9; 122.
DR STRING; 9606.ENSP00000357122; -.
DR iPTMnet; Q6K0P9; -.
DR PhosphoSitePlus; Q6K0P9; -.
DR SwissPalm; Q6K0P9; -.
DR BioMuta; PYHIN1; -.
DR DMDM; 74748871; -.
DR jPOST; Q6K0P9; -.
DR MassIVE; Q6K0P9; -.
DR MaxQB; Q6K0P9; -.
DR PaxDb; Q6K0P9; -.
DR PeptideAtlas; Q6K0P9; -.
DR PRIDE; Q6K0P9; -.
DR ProteomicsDB; 66529; -. [Q6K0P9-1]
DR ProteomicsDB; 66530; -. [Q6K0P9-2]
DR ProteomicsDB; 66531; -. [Q6K0P9-3]
DR ProteomicsDB; 66532; -. [Q6K0P9-4]
DR ProteomicsDB; 66533; -. [Q6K0P9-5]
DR ProteomicsDB; 66534; -. [Q6K0P9-6]
DR Antibodypedia; 34255; 117 antibodies from 18 providers.
DR DNASU; 149628; -.
DR Ensembl; ENST00000368135.4; ENSP00000357117.4; ENSG00000163564.15. [Q6K0P9-5]
DR Ensembl; ENST00000368138.7; ENSP00000357120.3; ENSG00000163564.15. [Q6K0P9-2]
DR Ensembl; ENST00000368140.6; ENSP00000357122.1; ENSG00000163564.15. [Q6K0P9-1]
DR Ensembl; ENST00000392252.7; ENSP00000376082.3; ENSG00000163564.15. [Q6K0P9-4]
DR Ensembl; ENST00000392254.6; ENSP00000376083.2; ENSG00000163564.15. [Q6K0P9-3]
DR GeneID; 149628; -.
DR KEGG; hsa:149628; -.
DR MANE-Select; ENST00000368140.6; ENSP00000357122.1; NM_152501.5; NP_689714.2.
DR UCSC; uc001fta.5; human. [Q6K0P9-1]
DR CTD; 149628; -.
DR DisGeNET; 149628; -.
DR GeneCards; PYHIN1; -.
DR HGNC; HGNC:28894; PYHIN1.
DR HPA; ENSG00000163564; Tissue enriched (lymphoid).
DR MIM; 612677; gene.
DR neXtProt; NX_Q6K0P9; -.
DR OpenTargets; ENSG00000163564; -.
DR PharmGKB; PA134967485; -.
DR VEuPathDB; HostDB:ENSG00000163564; -.
DR eggNOG; ENOG502QTQS; Eukaryota.
DR GeneTree; ENSGT00390000013296; -.
DR HOGENOM; CLU_020123_2_0_1; -.
DR InParanoid; Q6K0P9; -.
DR OMA; ENEQRGM; -.
DR OrthoDB; 1304994at2759; -.
DR PhylomeDB; Q6K0P9; -.
DR TreeFam; TF337385; -.
DR PathwayCommons; Q6K0P9; -.
DR SignaLink; Q6K0P9; -.
DR SIGNOR; Q6K0P9; -.
DR BioGRID-ORCS; 149628; 1 hit in 1064 CRISPR screens.
DR ChiTaRS; PYHIN1; human.
DR GenomeRNAi; 149628; -.
DR Pharos; Q6K0P9; Tbio.
DR PRO; PR:Q6K0P9; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6K0P9; protein.
DR Bgee; ENSG00000163564; Expressed in granulocyte and 112 other tissues.
DR ExpressionAtlas; Q6K0P9; baseline and differential.
DR Genevisible; Q6K0P9; HS.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0035457; P:cellular response to interferon-alpha; IMP:UniProtKB.
DR GO; GO:0035458; P:cellular response to interferon-beta; IBA:GO_Central.
DR GO; GO:0043388; P:positive regulation of DNA binding; IDA:UniProtKB.
DR GO; GO:1902164; P:positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IDA:UniProtKB.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IBA:GO_Central.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IMP:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IMP:UniProtKB.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 2.40.50.140; -; 2.
DR InterPro; IPR004020; DAPIN.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR040205; HIN-200.
DR InterPro; IPR004021; HIN200/IF120x.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR PANTHER; PTHR12200; PTHR12200; 1.
DR Pfam; PF02760; HIN; 1.
DR Pfam; PF02758; PYRIN; 1.
DR SMART; SM01289; PYRIN; 1.
DR PROSITE; PS50824; DAPIN; 1.
DR PROSITE; PS50834; HIN_200; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell cycle; Nucleus; Reference proteome;
KW Tumor suppressor.
FT CHAIN 1..492
FT /note="Pyrin and HIN domain-containing protein 1"
FT /id="PRO_0000334524"
FT DOMAIN 1..88
FT /note="Pyrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00061"
FT DOMAIN 199..399
FT /note="HIN-200"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00106"
FT REGION 106..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 133..157
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 158..199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 89..97
FT /note="Missing (in isoform 2, isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15122330,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_033657"
FT VAR_SEQ 194..245
FT /note="SLKPLANRHATASKNIFREDPIIAMVLNATKVFKYESSENEQRRMFHATVAT
FT -> AYLMNLTLSLTAGSFLSCAVWGRDRELRNLELSATDSLSTAPIYYTPIPFAH (in
FT isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15122330,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_033658"
FT VAR_SEQ 246..492
FT /note="Missing (in isoform 5 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15122330,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_033659"
FT VAR_SEQ 454..492
FT /note="KDETHPGAQSSPANFRITSPTVAPPLSSDTSTNRHPAVP -> VTKDKDIK
FT (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15122330,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_033660"
SQ SEQUENCE 492 AA; 55065 MW; 8711AABB92477D10 CRC64;
MANNYKKIVL LKGLEVINDY HFRIVKSLLS NDLKLNPKMK EEYDKIQIAD LMEEKFPGDA
GLGKLIEFFK EIPTLGDLAE TLKREKLKVA NKIESIPVKG IIPSKKTKQK EVYPATPACT
PSNRLTAKGA EETLGPQKRK KPSEEETGTK RSKMSKEQTR PSCSAGASTS TAMGRSPPPQ
TSSSAPPNTS STESLKPLAN RHATASKNIF REDPIIAMVL NATKVFKYES SENEQRRMFH
ATVATQTQFF HVKVLNINLK RKFIKKRIII ISNYSKRNSL LEVNEASSVS EAGPDQTFEV
PKDIIRRAKK IPKINILHKQ TSGYIVYGLF MLHTKIVNRK TTIYEIQDKT GSMAVVGKGE
CHNIPCEKGD KLRLFCFRLR KRENMSKLMS EMHSFIQIQK NTNQRSHDSR SMALPQEQSQ
HPKPSEASTT LPESHLKTPQ MPPTTPSSSS FTKKDETHPG AQSSPANFRI TSPTVAPPLS
SDTSTNRHPA VP
