ZN683_HUMAN
ID ZN683_HUMAN Reviewed; 524 AA.
AC Q8IZ20; Q5T141; Q5T146; Q5T147; Q5T149; Q8NEN4;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Tissue-resident T-cell transcription regulator protein ZNF683 {ECO:0000305};
DE AltName: Full=Homolog of Blimp-1 in T-cell {ECO:0000250|UniProtKB:I7HJS4};
DE Short=Hobit {ECO:0000250|UniProtKB:I7HJS4};
DE AltName: Full=Zinc finger protein 683 {ECO:0000312|HGNC:HGNC:28495};
GN Name=ZNF683 {ECO:0000312|HGNC:HGNC:28495};
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 [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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ASN-204.
RC TISSUE=Testis;
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 [3]
RP TISSUE SPECIFICITY (MICROBIAL INFECTION), AND INDUCTION (MICROBIAL
RP INFECTION).
RX PubMed=20921622; DOI=10.1172/jci42758;
RA Hertoghs K.M., Moerland P.D., van Stijn A., Remmerswaal E.B., Yong S.L.,
RA van de Berg P.J., van Ham S.M., Baas F., ten Berge I.J., van Lier R.A.;
RT "Molecular profiling of cytomegalovirus-induced human CD8+ T cell
RT differentiation.";
RL J. Clin. Invest. 120:4077-4090(2010).
RN [4]
RP FUNCTION (ISOFORM 1), LACK OF FUNCTION (ISOFORM 2), DNA-BINDING (ISOFORMS 1
RP AND 2), DOMAIN, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND TISSUE
RP SPECIFICITY (ISOFORMS 1 AND 2).
RX PubMed=26179882; DOI=10.1002/eji.201545650;
RA Vieira Braga F.A., Hertoghs K.M., Kragten N.A., Doody G.M., Barnes N.A.,
RA Remmerswaal E.B., Hsiao C.C., Moerland P.D., Wouters D., Derks I.A.,
RA van Stijn A., Demkes M., Hamann J., Eldering E., Nolte M.A., Tooze R.M.,
RA ten Berge I.J., van Gisbergen K.P., van Lier R.A.;
RT "Blimp-1 homolog Hobit identifies effector-type lymphocytes in humans.";
RL Eur. J. Immunol. 45:2945-2958(2015).
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. Plays a role in the development,
CC retention and long-term establishment of adaptive and innate tissue-
CC resident lymphocyte T cell types in non-lymphoid organs, such as the
CC skin and gut, but also in other nonbarrier tissues like liver and
CC kidney, and therefore may provide immediate immunological protection
CC against reactivating infections or viral reinfection. Also plays a role
CC in the differentiation of both thymic and peripheral NKT cells.
CC Negatively regulates the accumulation of interferon-gamma (IFN-gamma)
CC in NKT cells at steady state or after antigenic stimulation. Positively
CC regulates granzyme B production in NKT cells after innate stimulation.
CC Associates with the transcriptional repressor PRDM1/BLIMP1 to chromatin
CC at gene promoter regions. {ECO:0000250|UniProtKB:I7HJS4}.
CC -!- FUNCTION: [Isoform 1]: Lacks transcriptional repressor activity. Binds
CC to DNA within promoter regions of the transcriptional repressor
CC PRDM1/BLIMP1 target sites. Unable to regulate interferon-gamma (IFN-
CC gamma) production in cytomegalovirus (CMV)-infected effector CD8(+) T-
CC cells. {ECO:0000269|PubMed:26179882}.
CC -!- FUNCTION: [Isoform 2]: Transcriptional repressor that binds to DNA
CC within promoter regions of the transcriptional repressor PRDM1/BLIMP1
CC target sites. Regulates interferon-gamma (IFN-gamma) production in
CC cytomegalovirus (CMV)-infected effector CD8(+) T cells.
CC {ECO:0000269|PubMed:26179882}.
CC -!- INTERACTION:
CC Q8IZ20; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-12005952, EBI-3867333;
CC Q8IZ20; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-12005952, EBI-11962084;
CC Q8IZ20; P86480: PRR20D; NbExp=3; IntAct=EBI-12005952, EBI-12754095;
CC Q8IZ20; Q9BQY4: RHOXF2; NbExp=3; IntAct=EBI-12005952, EBI-372094;
CC Q8IZ20; Q9Y3S2: ZNF330; NbExp=3; IntAct=EBI-12005952, EBI-373456;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Extra large, XL {ECO:0000303|PubMed:26179882};
CC IsoId=Q8IZ20-1; Sequence=Displayed;
CC Name=2; Synonyms=Large, L {ECO:0000303|PubMed:26179882};
CC IsoId=Q8IZ20-2; Sequence=VSP_018167;
CC -!- TISSUE SPECIFICITY: Expressed in terminally differentiated effector
CC CD8(+) T-cells, but not in naive and central memory cells
CC (PubMed:26179882). Expressed in terminally differentiated natural
CC killer (NK) cells and natural killer (NKT) T-cells (at protein level)
CC (PubMed:26179882). Expressed strongly in effector-type CD8(+) T-cells
CC and weakly in naive and memory CD8(+) T-cells (PubMed:26179882).
CC Expressed in terminally differentiated natural killer (NK) cells
CC (PubMed:26179882). Isoform 2 is strongly expressed in effector CD8(+) T
CC and natural killer (NK) cells (PubMed:26179882). Isoform 1 is expressed
CC in effector CD8(+) T and natural killer (NK) cells (PubMed:26179882).
CC {ECO:0000269|PubMed:26179882}.
CC -!- TISSUE SPECIFICITY: (Microbial infection) Expressed in cytomegalovirus
CC (CMV)-infected effector CD8(+) T-cells (at protein level)
CC (PubMed:20921622). {ECO:0000269|PubMed:20921622}.
CC -!- INDUCTION: (Microbial infection) Up-regulated by cytomegalovirus (CMV)
CC infection in long-lived effector CD8(+) T-cells (PubMed:20921622).
CC {ECO:0000269|PubMed:20921622}.
CC -!- DOMAIN: The C2H2-type zinc finger are necessary for DNA-binding
CC (PubMed:26179882). {ECO:0000269|PubMed:26179882}.
CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH28731.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAH29505.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AL451139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC028731; AAH28731.2; ALT_INIT; mRNA.
DR EMBL; BC029505; AAH29505.1; ALT_INIT; mRNA.
DR CCDS; CCDS279.2; -. [Q8IZ20-2]
DR CCDS; CCDS76126.1; -. [Q8IZ20-1]
DR RefSeq; NP_001108231.1; NM_001114759.2. [Q8IZ20-2]
DR RefSeq; NP_001294854.1; NM_001307925.1. [Q8IZ20-1]
DR RefSeq; NP_775845.2; NM_173574.3. [Q8IZ20-2]
DR RefSeq; XP_005245887.1; XM_005245830.3. [Q8IZ20-1]
DR RefSeq; XP_005245889.1; XM_005245832.3. [Q8IZ20-1]
DR RefSeq; XP_011539500.1; XM_011541198.2. [Q8IZ20-1]
DR AlphaFoldDB; Q8IZ20; -.
DR SMR; Q8IZ20; -.
DR BioGRID; 129197; 9.
DR IntAct; Q8IZ20; 7.
DR STRING; 9606.ENSP00000344095; -.
DR iPTMnet; Q8IZ20; -.
DR PhosphoSitePlus; Q8IZ20; -.
DR BioMuta; ZNF683; -.
DR DMDM; 205371859; -.
DR MassIVE; Q8IZ20; -.
DR PaxDb; Q8IZ20; -.
DR PeptideAtlas; Q8IZ20; -.
DR PRIDE; Q8IZ20; -.
DR ProteomicsDB; 71269; -. [Q8IZ20-1]
DR ProteomicsDB; 71270; -. [Q8IZ20-2]
DR Antibodypedia; 16076; 55 antibodies from 17 providers.
DR DNASU; 257101; -.
DR Ensembl; ENST00000349618.8; ENSP00000344095.3; ENSG00000176083.18. [Q8IZ20-2]
DR Ensembl; ENST00000403843.5; ENSP00000384782.1; ENSG00000176083.18. [Q8IZ20-1]
DR Ensembl; ENST00000436292.5; ENSP00000388792.1; ENSG00000176083.18. [Q8IZ20-1]
DR GeneID; 257101; -.
DR KEGG; hsa:257101; -.
DR MANE-Select; ENST00000349618.8; ENSP00000344095.3; NM_001114759.3; NP_001108231.1. [Q8IZ20-2]
DR UCSC; uc001bmg.2; human. [Q8IZ20-1]
DR CTD; 257101; -.
DR DisGeNET; 257101; -.
DR GeneCards; ZNF683; -.
DR HGNC; HGNC:28495; ZNF683.
DR HPA; ENSG00000176083; Tissue enriched (testis).
DR neXtProt; NX_Q8IZ20; -.
DR OpenTargets; ENSG00000176083; -.
DR PharmGKB; PA142670484; -.
DR VEuPathDB; HostDB:ENSG00000176083; -.
DR eggNOG; KOG2461; Eukaryota.
DR GeneTree; ENSGT00940000163172; -.
DR HOGENOM; CLU_040814_0_0_1; -.
DR InParanoid; Q8IZ20; -.
DR OMA; TCLAQWH; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q8IZ20; -.
DR TreeFam; TF316545; -.
DR PathwayCommons; Q8IZ20; -.
DR SignaLink; Q8IZ20; -.
DR BioGRID-ORCS; 257101; 11 hits in 1090 CRISPR screens.
DR ChiTaRS; ZNF683; human.
DR GenomeRNAi; 257101; -.
DR Pharos; Q8IZ20; Tbio.
DR PRO; PR:Q8IZ20; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q8IZ20; protein.
DR Bgee; ENSG00000176083; Expressed in sperm and 147 other tissues.
DR ExpressionAtlas; Q8IZ20; baseline and differential.
DR Genevisible; Q8IZ20; HS.
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; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:1904637; P:cellular response to ionomycin; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0033082; P:regulation of extrathymic T cell differentiation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0032823; P:regulation of natural killer cell differentiation; ISS:UniProtKB.
DR GO; GO:0032826; P:regulation of natural killer cell differentiation involved in immune response; ISS:UniProtKB.
DR GO; GO:0051136; P:regulation of NK T cell differentiation; ISS: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; IDA:UniProtKB.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 4.
DR SUPFAM; SSF57667; SSF57667; 2.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4.
PE 1: Evidence at protein level;
KW Adaptive immunity; Alternative splicing; DNA-binding;
KW Host-virus interaction; Immunity; Innate immunity; Metal-binding; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..524
FT /note="Tissue-resident T-cell transcription regulator
FT protein ZNF683"
FT /id="PRO_0000234002"
FT ZN_FING 322..344
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 350..372
FT /note="C2H2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 398..420
FT /note="C2H2-type 3; degenerate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 426..448
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 130..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 382..401
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_018167"
FT VARIANT 22
FT /note="G -> V (in dbSNP:rs35040247)"
FT /id="VAR_057442"
FT VARIANT 48
FT /note="D -> G (in dbSNP:rs10794532)"
FT /id="VAR_057443"
FT VARIANT 53
FT /note="H -> R (in dbSNP:rs10794531)"
FT /id="VAR_057444"
FT VARIANT 204
FT /note="H -> N (in dbSNP:rs17852672)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_026155"
FT VARIANT 288
FT /note="R -> L (in dbSNP:rs11247933)"
FT /id="VAR_057445"
SQ SEQUENCE 524 AA; 56905 MW; F6D800F2A8EE829A CRC64;
MKEESAAQLG CCHRPMALGG TGGSLSPSLD FQLFRGDQVF SACRPLPDMV DAHGPSCASW
LCPLPLAPGR SALLACLQDL DLNLCTPQPA PLGTDLQGLQ EDALSMKHEP PGLQASSTDD
KKFTVKYPQN KDKLGKQPER AGEGAPCPAF SSHNSSSPPP LQNRKSPSPL AFCPCPPVNS
ISKELPFLLH AFYPGYPLLL PPPHLFTYGA LPSDQCPHLL MLPQDPSYPT MAMPSLLMMV
NELGHPSARW ETLLPYPGAF QASGQALPSQ ARNPGAGAAP TDSPGLERGG MASPAKRVPL
SSQTGTAALP YPLKKKNGKI LYECNICGKS FGQLSNLKVH LRVHSGERPF QCALCQKSFT
QLAHLQKHHL VHTGERPHKC SIPWVPGRNH WKSFQAWRER EVCHKRFSSS SNLKTHLRLH
SGARPFQCSV CRSRFTQHIH LKLHHRLHAP QPCGLVHTQL PLASLACLAQ WHQGALDLMA
VASEKHMGYD IDEVKVSSTS QGKARAVSLS SAGTPLVMGQ DQNN
