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ZN683_MOUSE
ID   ZN683_MOUSE             Reviewed;         458 AA.
AC   I7HJS4;
DT   05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2012, sequence version 1.
DT   03-AUG-2022, entry version 62.
DE   RecName: Full=Tissue-resident T-cell transcription regulator protein ZNF683 {ECO:0000305};
DE   AltName: Full=Homolog of Blimp-1 in T-cell {ECO:0000303|PubMed:22885984};
DE            Short=Hobit {ECO:0000303|PubMed:22885984};
DE   AltName: Full=Zinc finger protein 683 {ECO:0000312|MGI:MGI:3650254};
GN   Name=Znf683 {ECO:0000312|MGI:MGI:3650254}; Synonyms=Gm13060, Zfp683;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J {ECO:0000312|Ensembl:ENSMUSP00000101508,
RC   ECO:0000312|Proteomes:UP000000589};
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=22885984; DOI=10.1038/ni.2393;
RA   van Gisbergen K.P., Kragten N.A., Hertoghs K.M., Wensveen F.M., Jonjic S.,
RA   Hamann J., Nolte M.A., van Lier R.A.;
RT   "Mouse Hobit is a homolog of the transcriptional repressor Blimp-1 that
RT   regulates NKT cell effector differentiation.";
RL   Nat. Immunol. 13:864-871(2012).
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INDUCTION
RP   (MICROBIAL INFECTION).
RX   PubMed=27102484; DOI=10.1126/science.aad2035;
RA   Mackay L.K., Minnich M., Kragten N.A., Liao Y., Nota B., Seillet C.,
RA   Zaid A., Man K., Preston S., Freestone D., Braun A., Wynne-Jones E.,
RA   Behr F.M., Stark R., Pellicci D.G., Godfrey D.I., Belz G.T., Pellegrini M.,
RA   Gebhardt T., Busslinger M., Shi W., Carbone F.R., van Lier R.A.,
RA   Kallies A., van Gisbergen K.P.;
RT   "Hobit and Blimp1 instruct a universal transcriptional program of tissue
RT   residency in lymphocytes.";
RL   Science 352:459-463(2016).
CC   -!- FUNCTION: Transcription factor that mediates a transcriptional program
CC       in various innate and adaptive immune tissue-resident lymphocyte T-cell
CC       types such as tissue-resident memory T (Trm), natural killer (trNK) and
CC       natural killer T (NKT) cells and negatively regulates gene expression
CC       of proteins that promote the egress of tissue-resident T-cell
CC       populations from non-lymphoid organs (PubMed:22885984,
CC       PubMed:27102484). Plays a role in the development, retention and long-
CC       term establishment of adaptive and innate tissue-resident lymphocyte T-
CC       cell types in non-lymphoid organs, such as the skin and gut, but also
CC       in other nonbarrier tissues like liver and kidney, and therefore may
CC       provide immediate immunological protection against reactivating
CC       infections or viral reinfection (PubMed:22885984, PubMed:27102484).
CC       Also plays a role in the differentiation of both thymic and peripheral
CC       NKT cells (PubMed:22885984). Negatively regulates the accumulation of
CC       interferon-gamma (IFN-gamma) in NKT cells at steady state or after
CC       antigenic stimulation (PubMed:22885984). Positively regulates granzyme
CC       B production in NKT cells after innate stimulation (PubMed:22885984).
CC       Associates with the transcriptional repressor PRDM1/BLIMP1 to chromatin
CC       at gene promoter regions (PubMed:27102484).
CC       {ECO:0000269|PubMed:22885984, ECO:0000269|PubMed:27102484}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in tissue-resident memory T (Trm) cell
CC       population in non-lymphoid organs, such as skin and gut
CC       (PubMed:27102484). Expressed in innate lymphocytes, including tissue-
CC       resident natural killer (trNK) and natural killer T (NKT) cells in
CC       thymus, spleen and liver (PubMed:22885984, PubMed:27102484).
CC       {ECO:0000269|PubMed:22885984, ECO:0000269|PubMed:27102484}.
CC   -!- INDUCTION: Up-regulated by interleukin IL15 in a TBX21/T-bet-dependent
CC       manner in tissue-resident memory T (Trm) cell population
CC       (PubMed:27102484). Up-regulated during the differentiation of natural
CC       killer T (NKT) cells (PubMed:22885984). Down-regulated in NKT cells
CC       after antigenic stimulation (PubMed:22885984).
CC       {ECO:0000269|PubMed:22885984, ECO:0000269|PubMed:27102484}.
CC   -!- INDUCTION: (Microbial infection) Up-regulated in response to Herpes
CC       simplex virus (HSV) infection in skin CD8(+) tissue-resident memory T
CC       (Trm) cells, but not in spleen. {ECO:0000269|PubMed:27102484}.
CC   -!- INDUCTION: (Microbial infection) Up-regulated in response to
CC       choriomeningitis virus (LCMV) infection in gut CD8(+) tissue-resident
CC       memory T (Trm) cells. {ECO:0000269|PubMed:27102484}.
CC   -!- DISRUPTION PHENOTYPE: Mice show a reduction in tissue-resident memory T
CC       (Trm) cell population maintenance in the skin, gut, liver and kidney
CC       but not of splenic T-cells (PubMed:22885984, PubMed:27102484). Double
CC       knockouts for Znf683 and Prdm1/Blimp1 result in a stronger inhibition
CC       of Trm cell population maintenance (PubMed:27102484). Display an
CC       enhancement of natural killer T (NKT) cells migration preferentially to
CC       the white pulp of the spleen in response to chemotactic stimuli
CC       (PubMed:27102484). Also results in the derepressed expression of a
CC       large number of genes implicated in the egress of tissue-resident T-
CC       cells from non-lymphoide organs (PubMed:27102484).
CC       {ECO:0000269|PubMed:27102484}.
CC   -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC       family. {ECO:0000305}.
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DR   EMBL; AL670680; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; I7HJS4; -.
DR   STRING; 10090.ENSMUSP00000101508; -.
DR   iPTMnet; I7HJS4; -.
DR   PhosphoSitePlus; I7HJS4; -.
DR   PaxDb; I7HJS4; -.
DR   PeptideAtlas; I7HJS4; -.
DR   PRIDE; I7HJS4; -.
DR   Ensembl; ENSMUST00000105884; ENSMUSP00000101508; ENSMUSG00000049410.
DR   MGI; MGI:3650254; Zfp683.
DR   VEuPathDB; HostDB:ENSMUSG00000049410; -.
DR   eggNOG; KOG2461; Eukaryota.
DR   GeneTree; ENSGT00940000164781; -.
DR   HOGENOM; CLU_040814_0_0_1; -.
DR   InParanoid; I7HJS4; -.
DR   OMA; TCLAQWH; -.
DR   PhylomeDB; I7HJS4; -.
DR   TreeFam; TF316545; -.
DR   PRO; PR:I7HJS4; -.
DR   Proteomes; UP000000589; Chromosome 4.
DR   RNAct; I7HJS4; protein.
DR   Bgee; ENSMUSG00000049410; Expressed in thymus and 5 other tissues.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR   GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR   GO; GO:1904637; P:cellular response to ionomycin; ISO:MGI.
DR   GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR   GO; GO:0001779; P:natural killer cell differentiation; IMP:MGI.
DR   GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:MGI.
DR   GO; GO:0001865; P:NK T cell differentiation; IMP:MGI.
DR   GO; GO:0033082; P:regulation of extrathymic T cell differentiation; IMP:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0032823; P:regulation of natural killer cell differentiation; IMP:UniProtKB.
DR   GO; GO:0032826; P:regulation of natural killer cell differentiation involved in immune response; IMP:UniProtKB.
DR   GO; GO:0051136; P:regulation of NK T cell differentiation; IMP:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0050852; P:T cell receptor signaling pathway; ISO:MGI.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   Pfam; PF00096; zf-C2H2; 3.
DR   SMART; SM00355; ZnF_C2H2; 3.
DR   SUPFAM; SSF57667; SSF57667; 2.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3.
PE   2: Evidence at transcript level;
KW   Adaptive immunity; DNA-binding; Immunity; Innate immunity; Metal-binding;
KW   Nucleus; Reference proteome; Repeat; Transcription;
KW   Transcription regulation; Zinc; Zinc-finger.
FT   CHAIN           1..458
FT                   /note="Tissue-resident T-cell transcription regulator
FT                   protein ZNF683"
FT                   /id="PRO_0000437412"
FT   ZN_FING         301..323
FT                   /note="C2H2-type 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         329..351
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         357..379
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   REGION          84..109
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          249..275
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        249..265
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   458 AA;  50419 MW;  46CCA5D71B3FF6D3 CRC64;
     MKALDGLRES LYPSLDFQLY QDDQVCSADA SQPLADSVGA HDLAWSERMC PLPLAPAKSP
     LLACPESPDL CLCALQKTPL GRAPQDLGED ASNMRHQPPS LYKASTDSEK LTIKDSLNRE
     EMGNEPERGA YPHLPPRTSS FPDAGLDRKS LSPLTFWPWL PPTLISKEPP IHIYPIFPGY
     PLLPLPYLFT YGALPSAQHP YLFMLPPHST YPTVAGPSLL MTASGSGPRI PQEKTLLLHS
     GAFQSAGHTL HSQVESRSSR DTRTPGQAGV AAPTRRAVPG SRAGVIALPY PLKKENGKIL
     YECNVCGKNF GQLSNLKVHL RVHSGERPFQ CALCQKRFTQ LAHLQKHHLV HTGERPHQCQ
     VCHKRFSSSS NLKTHLRLHS GAKPSQCGLC PSYLTPNVYP KLHHRLRAPQ LRGLTHTHLP
     LASLTCLAQW HQGALDLVEK KMGWTVDKVS SESKGKQG
 
 
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