MDFIC_HUMAN
ID MDFIC_HUMAN Reviewed; 246 AA.
AC Q9P1T7; Q9P1T6;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=MyoD family inhibitor domain-containing protein;
DE AltName: Full=I-mfa domain-containing protein;
DE Short=hIC;
GN Name=MDFIC {ECO:0000312|HGNC:HGNC:28870};
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] {ECO:0000305, ECO:0000312|EMBL:AAF36998.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=T-cell {ECO:0000269|PubMed:10671520};
RX PubMed=10671520; DOI=10.1074/jbc.275.7.4848;
RA Thebault S., Gachon F., Lemasson I., Devaux C., Mesnard J.-M.;
RT "Molecular cloning of a novel human I-mfa domain-containing protein that
RT differently regulates human T-cell leukemia virus type I and HIV-1
RT expression.";
RL J. Biol. Chem. 275:4848-4857(2000).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAP33842.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH HIV-1
RP TAT (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION.
RC TISSUE=Leukocyte {ECO:0000269|PubMed:16260749};
RX PubMed=16260749; DOI=10.1073/pnas.0503519102;
RA Gautier V.W., Sheehy N., Duffy M., Hashimoto K., Hall W.W.;
RT "Direct interaction of the human I-mfa domain-containing protein, HIC, with
RT HIV-1 Tat results in cytoplasmic sequestration and control of Tat
RT activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:16362-16367(2005).
RN [3] {ECO:0000305}
RP SUBCELLULAR LOCATION, DOMAIN, AND NUCLEOLAR LOCALIZATION SIGNAL.
RX PubMed=11139147; DOI=10.1078/0171-9335-00111;
RA Thebault S., Basbous J., Gay B., Devaux C., Mesnard J.-M.;
RT "Sequence requirement for the nucleolar localization of human I-mfa domain-
RT containing protein (HIC p40).";
RL Eur. J. Cell Biol. 79:834-838(2000).
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH AXIN1 AND LEF1.
RX PubMed=12192039; DOI=10.1128/mcb.22.18.6393-6405.2002;
RA Kusano S., Raab-Traub N.;
RT "I-mfa domain proteins interact with Axin and affect its regulation of the
RT Wnt and c-Jun N-terminal kinase signaling pathways.";
RL Mol. Cell. Biol. 22:6393-6405(2002).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CCNT1 AND HIV-1 TAT (MICROBIAL INFECTION), AND
RP SUBCELLULAR LOCATION.
RX PubMed=12944466; DOI=10.1128/mcb.23.18.6373-6384.2003;
RA Young T.M., Wang Q., Pe'ery T., Mathews M.B.;
RT "The human I-mfa domain-containing protein, HIC, interacts with cyclin T1
RT and modulates P-TEFb-dependent transcription.";
RL Mol. Cell. Biol. 23:6373-6384(2003).
RN [6]
RP FUNCTION, AND INTERACTION WITH HIV-1 TAT AND HIV-1 REV (MICROBIAL
RP INFECTION).
RX DOI=10.1186/1742-4690-3-S1-S106;
RA Gu L., Gautier V., Sheehy N., Tsuji T., Hayakawa H., Hall W.;
RT "The human I-mfa domain containing protein, HIC, interacts with HIV-1 Tat
RT and Rev and sequesters them in the cytoplasm.";
RL Retrovirology 3:S106-S106(2006).
RN [7]
RP INTERACTION WITH CCNT2.
RX PubMed=17289077; DOI=10.1016/j.jmb.2007.01.020;
RA Wang Q., Young T.M., Mathews M.B., Pe'ery T.;
RT "Developmental regulators containing the I-mfa domain interact with T
RT cyclins and Tat and modulate transcription.";
RL J. Mol. Biol. 367:630-646(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-140, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-128; SER-140 AND SER-143, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
CC -!- FUNCTION: Acts as a transcriptional activator or repressor. Inhibits
CC the transcriptional activation of Zic family proteins ZIC1, ZIC2 and
CC ZIC3. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the
CC cytoplasm. Modulates the expression from both cellular and viral
CC promoters. Down-regulates Tat-dependent transcription of the human
CC immunodeficiency virus type 1 (HIV-1) LTR by interacting with HIV-1 Tat
CC and Rev and impairing their nuclear import, probably by rendering the
CC NLS domains inaccessible to importin-beta. Also stimulates activation
CC of human T-cell leukemia virus type I (HTLV-I) LTR. Binds to the axin
CC complex, resulting in an increase in the level of free beta-catenin.
CC Affects axin regulation of the WNT and JNK signaling pathways.
CC {ECO:0000269|PubMed:10671520, ECO:0000269|PubMed:12192039,
CC ECO:0000269|PubMed:12944466, ECO:0000269|PubMed:16260749,
CC ECO:0000269|Ref.6}.
CC -!- SUBUNIT: Interacts with HAND1; leading to sequester HAND1 into the
CC nucleolus and prevent its activity. Interacts with ZIC2 (By
CC similarity). The C-terminus interacts with AXIN1, the histidine-rich
CC region of CCNT1/cyclin-T and weakly with LEF1 (PubMed:12192039).
CC Interacts with CCNT2 (PubMed:17289077). {ECO:0000250|UniProtKB:Q8BX65,
CC ECO:0000269|PubMed:12192039, ECO:0000269|PubMed:17289077}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via C-terminus) with HIV-1
CC Tat and Rev. {ECO:0000269|PubMed:12944466, ECO:0000269|PubMed:16260749,
CC ECO:0000269|Ref.6}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus. Note=Also shows
CC a granular distribution in the cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm
CC {ECO:0000269|PubMed:10671520, ECO:0000269|PubMed:11139147,
CC ECO:0000269|PubMed:12944466, ECO:0000269|PubMed:16260749}. Note=Weak
CC expression in the nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=2 {ECO:0000269|PubMed:10671520, ECO:0000269|PubMed:16260749};
CC Synonyms=p32 {ECO:0000269|PubMed:10671520};
CC IsoId=Q9P1T7-2; Sequence=Displayed;
CC Name=1 {ECO:0000269|PubMed:10671520}; Synonyms=p40
CC {ECO:0000269|PubMed:10671520};
CC IsoId=Q9P1T7-1; Sequence=VSP_037970;
CC -!- TISSUE SPECIFICITY: Expressed in lymphoid organs (spleen, thymus,
CC peripheral blood leukocytes) as well as prostate, uterus and small
CC intestine. {ECO:0000269|PubMed:10671520}.
CC -!- DOMAIN: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for
CC transcription activation (By similarity). The cysteine-rich C-terminus
CC is involved in its granular distribution in the cytoplasm.
CC {ECO:0000250, ECO:0000269|PubMed:11139147}.
CC -!- MISCELLANEOUS: [Isoform 2]: Major isoform.
CC -!- MISCELLANEOUS: [Isoform 1]: Minor isoform. Initiates from a GTG codon.
CC Contains a Nucleolar localization signal at positions 45-63.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the MDFI family. {ECO:0000255}.
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DR EMBL; AF054589; AAF36998.1; -; mRNA.
DR EMBL; AF054589; AAF36999.1; -; mRNA.
DR EMBL; AY196485; AAP33842.1; -; mRNA.
DR CCDS; CCDS34737.1; -. [Q9P1T7-1]
DR CCDS; CCDS55155.1; -. [Q9P1T7-2]
DR RefSeq; NP_001159817.1; NM_001166345.1. [Q9P1T7-2]
DR RefSeq; NP_951038.1; NM_199072.4. [Q9P1T7-1]
DR AlphaFoldDB; Q9P1T7; -.
DR BioGRID; 119002; 16.
DR IntAct; Q9P1T7; 11.
DR STRING; 9606.ENSP00000484656; -.
DR iPTMnet; Q9P1T7; -.
DR PhosphoSitePlus; Q9P1T7; -.
DR SwissPalm; Q9P1T7; -.
DR BioMuta; MDFIC; -.
DR DMDM; 257051035; -.
DR EPD; Q9P1T7; -.
DR jPOST; Q9P1T7; -.
DR MassIVE; Q9P1T7; -.
DR MaxQB; Q9P1T7; -.
DR PaxDb; Q9P1T7; -.
DR PeptideAtlas; Q9P1T7; -.
DR PRIDE; Q9P1T7; -.
DR ProteomicsDB; 83663; -. [Q9P1T7-2]
DR ProteomicsDB; 83664; -. [Q9P1T7-1]
DR TopDownProteomics; Q9P1T7-1; -. [Q9P1T7-1]
DR Antibodypedia; 31567; 158 antibodies from 24 providers.
DR DNASU; 29969; -.
DR Ensembl; ENST00000393486.6; ENSP00000377126.1; ENSG00000135272.13. [Q9P1T7-2]
DR GeneID; 29969; -.
DR KEGG; hsa:29969; -.
DR MANE-Select; ENST00000393486.6; ENSP00000377126.1; NM_001166345.3; NP_001159817.1.
DR UCSC; uc064hfm.1; human. [Q9P1T7-2]
DR CTD; 29969; -.
DR DisGeNET; 29969; -.
DR GeneCards; MDFIC; -.
DR HGNC; HGNC:28870; MDFIC.
DR HPA; ENSG00000135272; Low tissue specificity.
DR MIM; 614511; gene.
DR neXtProt; NX_Q9P1T7; -.
DR OpenTargets; ENSG00000135272; -.
DR PharmGKB; PA142671474; -.
DR VEuPathDB; HostDB:ENSG00000135272; -.
DR eggNOG; ENOG502QSK8; Eukaryota.
DR GeneTree; ENSGT00940000158685; -.
DR HOGENOM; CLU_067479_0_1_1; -.
DR InParanoid; Q9P1T7; -.
DR OMA; NEDCCVH; -.
DR PhylomeDB; Q9P1T7; -.
DR PathwayCommons; Q9P1T7; -.
DR SignaLink; Q9P1T7; -.
DR BioGRID-ORCS; 29969; 9 hits in 1074 CRISPR screens.
DR ChiTaRS; MDFIC; human.
DR GenomeRNAi; 29969; -.
DR Pharos; Q9P1T7; Tbio.
DR PRO; PR:Q9P1T7; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9P1T7; protein.
DR Bgee; ENSG00000135272; Expressed in amniotic fluid and 195 other tissues.
DR ExpressionAtlas; Q9P1T7; baseline and differential.
DR Genevisible; Q9P1T7; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0030332; F:cyclin binding; IPI:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0030957; F:Tat protein binding; IDA:UniProtKB.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0050434; P:positive regulation of viral transcription; IDA:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; IDA:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IDA:UniProtKB.
DR InterPro; IPR026134; MDFI/MDFIC.
DR PANTHER; PTHR15304; PTHR15304; 1.
DR Pfam; PF15316; MDFI; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative initiation; Cytoplasm; Host-virus interaction;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..246
FT /note="MyoD family inhibitor domain-containing protein"
FT /id="PRO_0000280222"
FT DOMAIN 74..246
FT /note="MDFI"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 140
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MRGVRAATAAAVAATAASGLSRREAGGRAGAAAAVVRPPGRKCGRCR
FT RLANFPGRKRRRRRRKGLGATTGGCGEAVSSLHPAPHSPSSVRPAGRRARRQRRGAGSA
FT ERPM (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10671520"
FT /id="VSP_037970"
SQ SEQUENCE 246 AA; 25788 MW; B8DAAE9ADF5772A0 CRC64;
MSGAGEALAP GPVGPQRVAE AGGGQLGSTA QGKCDKDNTE KDITQATNSH FTHGEMQDQS
IWGNPSDGEL IRTQPQRLPQ LQTSAQVPSG EEIGKIKNGH TGLSNGNGIH HGAKHGSADN
RKLSAPVSQK MHRKIQSSLS VNSDISKKSK VNAVFSQKTG SSPEDCCVHC ILACLFCEFL
TLCNIVLGQA SCGICTSEAC CCCCGDEMGD DCNCPCDMDC GIMDACCESS DCLEICMECC
GICFPS
