MAFA_MOUSE
ID MAFA_MOUSE Reviewed; 359 AA.
AC Q8CF90;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Transcription factor MafA;
DE AltName: Full=Pancreatic beta-cell-specific transcriptional activator;
DE AltName: Full=V-maf musculoaponeurotic fibrosarcoma oncogene homolog A;
GN Name=Mafa;
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 [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND INDUCTION BY GLUCOSE.
RX PubMed=12368292; DOI=10.1074/jbc.m206796200;
RA Kataoka K., Han S.I., Shioda S., Hirai M., Nishizawa M., Handa H.;
RT "MafA is a glucose-regulated and pancreatic beta-cell-specific
RT transcriptional activator for the insulin gene.";
RL J. Biol. Chem. 277:49903-49910(2002).
RN [2]
RP PROTEIN SEQUENCE OF 34-40; 293-303 AND 327-352, FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, TYROSINE PHOSPHORYLATION, AND MASS
RP SPECTROMETRY.
RX PubMed=12917329; DOI=10.1128/mcb.23.17.6049-6062.2003;
RA Matsuoka T.A., Zhao L., Artner I., Jarrett H.W., Friedman D., Means A.,
RA Stein R.;
RT "Members of the large Maf transcription family regulate insulin gene
RT transcription in islet beta cells.";
RL Mol. Cell. Biol. 23:6049-6062(2003).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=14680841; DOI=10.1016/j.bbrc.2003.10.196;
RA Kajihara M., Sone H., Amemiya M., Katoh Y., Isogai M., Shimano H.,
RA Yamada N., Takahashi S.;
RT "Mouse MafA, homologue of zebrafish somite Maf 1, contributes to the
RT specific transcriptional activity through the insulin promoter.";
RL Biochem. Biophys. Res. Commun. 312:831-842(2003).
RN [4]
RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=14973194; DOI=10.1073/pnas.0306233101;
RA Matsuoka T.A., Artner I., Henderson E., Means A., Sander M., Stein R.;
RT "The MafA transcription factor appears to be responsible for tissue-
RT specific expression of insulin.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:2930-2933(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH NEUROD1 AND PDX1.
RX PubMed=15665000; DOI=10.1074/jbc.m409475200;
RA Zhao L., Guo M., Matsuoka T.A., Hagman D.K., Parazzoli S.D., Poitout V.,
RA Stein R.;
RT "The islet beta cell-enriched MafA activator is a key regulator of insulin
RT gene transcription.";
RL J. Biol. Chem. 280:11887-11894(2005).
RN [6]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=15923615; DOI=10.1128/mcb.25.12.4969-4976.2005;
RA Zhang C., Moriguchi T., Kajihara M., Esaki R., Harada A., Shimohata H.,
RA Oishi H., Hamada M., Morito N., Hasegawa K., Kudo T., Engel J.D.,
RA Yamamoto M., Takahashi S.;
RT "MafA is a key regulator of glucose-stimulated insulin secretion.";
RL Mol. Cell. Biol. 25:4969-4976(2005).
CC -!- FUNCTION: Transcriptional factor that activates insulin gene expression
CC (PubMed:12368292, PubMed:15665000). Acts synergistically with
CC NEUROD1/BETA2 and PDX1 (PubMed:15665000). Binds the insulin enhancer
CC C1/RIPE3b element (PubMed:12917329, PubMed:14680841, PubMed:14973194,
CC PubMed:15665000). Binds to consensus TRE-type MARE 5'-TGCTGACTCAGCA-3'
CC DNA sequence (By similarity). {ECO:0000250|UniProtKB:Q8NHW3,
CC ECO:0000269|PubMed:12368292, ECO:0000269|PubMed:12917329,
CC ECO:0000269|PubMed:14680841, ECO:0000269|PubMed:14973194,
CC ECO:0000269|PubMed:15665000}.
CC -!- SUBUNIT: Forms homodimers (By similarity). Interacts with NEUROD1 and
CC PDX1 (PubMed:15665000). May interact with MAFB, FOS, JUN and PCAF (By
CC similarity). {ECO:0000250|UniProtKB:O57342,
CC ECO:0000250|UniProtKB:Q8NHW3, ECO:0000269|PubMed:15665000}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12368292,
CC ECO:0000269|PubMed:12917329, ECO:0000269|PubMed:14973194}.
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, spleen, pancreas and
CC kidney (PubMed:12368292, PubMed:14680841). In the pancreas, expressed
CC in the insulin-producing beta-cells of the islets of Langerhans (at
CC protein level) (PubMed:12917329, PubMed:15923615). Also expressed in
CC the eye (PubMed:12368292, PubMed:15923615).
CC {ECO:0000269|PubMed:12368292, ECO:0000269|PubMed:12917329,
CC ECO:0000269|PubMed:14680841, ECO:0000269|PubMed:15923615}.
CC -!- DEVELOPMENTAL STAGE: In the developing pancreas, expressed exclusively
CC in the insulin-positive cells from 13.5 dpc onward and never in the
CC glucagon-expressing cells (at protein level) (PubMed:14973194). At
CC 12.5dpc, at the mRNA level, detected in each formed somite, in myotomal
CC cells. Also detected in the head neural tube, liver cells and, at low
CC levels, in some mesenchyme-like cells (PubMed:14680841).
CC {ECO:0000269|PubMed:14680841, ECO:0000269|PubMed:14973194}.
CC -!- INDUCTION: Up-regulated by glucose in pancreatic beta-cell lines.
CC {ECO:0000269|PubMed:12368292}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:O57342}.
CC -!- PTM: Phosphorylated at tyrosines. {ECO:0000269|PubMed:12917329}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate and
CC survive until adulthood. They show a normal pancreatic morphology at
CC birth. A 12 weeks, they exhibit a reduction in the proportion of
CC Langerhans islet beta-cells and impaired glucose-stimulated insulin
CC secretion and eventually they develop diabetes mellitus.
CC {ECO:0000269|PubMed:15923615}.
CC -!- SIMILARITY: Belongs to the bZIP family. Maf subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB086961; BAC20390.1; -; Genomic_DNA.
DR CCDS; CCDS27549.1; -.
DR RefSeq; NP_919331.1; NM_194350.1.
DR AlphaFoldDB; Q8CF90; -.
DR SMR; Q8CF90; -.
DR BioGRID; 237545; 13.
DR STRING; 10090.ENSMUSP00000054226; -.
DR iPTMnet; Q8CF90; -.
DR PhosphoSitePlus; Q8CF90; -.
DR MaxQB; Q8CF90; -.
DR PaxDb; Q8CF90; -.
DR PRIDE; Q8CF90; -.
DR ProteomicsDB; 292075; -.
DR Antibodypedia; 14595; 257 antibodies from 26 providers.
DR DNASU; 378435; -.
DR Ensembl; ENSMUST00000062002; ENSMUSP00000054226; ENSMUSG00000047591.
DR GeneID; 378435; -.
DR KEGG; mmu:378435; -.
DR UCSC; uc007whe.1; mouse.
DR CTD; 389692; -.
DR MGI; MGI:2673307; Mafa.
DR VEuPathDB; HostDB:ENSMUSG00000047591; -.
DR eggNOG; KOG4196; Eukaryota.
DR GeneTree; ENSGT00940000162747; -.
DR HOGENOM; CLU_063062_0_0_1; -.
DR InParanoid; Q8CF90; -.
DR OMA; GAHHTAH; -.
DR OrthoDB; 1395389at2759; -.
DR PhylomeDB; Q8CF90; -.
DR TreeFam; TF325689; -.
DR BioGRID-ORCS; 378435; 8 hits in 75 CRISPR screens.
DR PRO; PR:Q8CF90; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8CF90; protein.
DR Bgee; ENSMUSG00000047591; Expressed in islet of Langerhans and 79 other tissues.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0030073; P:insulin secretion; ISO:MGI.
DR GO; GO:0007263; P:nitric oxide mediated signal transduction; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR004826; bZIP_Maf.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR013592; Maf_TF_N.
DR InterPro; IPR028562; MafA.
DR InterPro; IPR008917; TF_DNA-bd_sf.
DR InterPro; IPR024874; Transcription_factor_Maf_fam.
DR PANTHER; PTHR10129; PTHR10129; 1.
DR PANTHER; PTHR10129:SF30; PTHR10129:SF30; 1.
DR Pfam; PF03131; bZIP_Maf; 1.
DR Pfam; PF08383; Maf_N; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF47454; SSF47454; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
PE 1: Evidence at protein level;
KW Activator; Direct protein sequencing; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..359
FT /note="Transcription factor MafA"
FT /id="PRO_0000320275"
FT DOMAIN 260..323
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 40..105
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 172..226
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 260..285
FT /note="Basic motif"
FT REGION 288..309
FT /note="Leucine-zipper"
FT REGION 322..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 49..71
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..211
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O57342"
FT MOD_RES 49
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O57342"
FT MOD_RES 53
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O57342"
FT MOD_RES 57
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O57342"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O57342"
FT MOD_RES 65
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O57342"
FT CROSSLNK 32
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q8NHW3"
SQ SEQUENCE 359 AA; 37576 MW; B10BC396218AB8A5 CRC64;
MAAELAMGAE LPSSPLAIEY VNDFDLMKFE VKKEPPEAER FCHRLPPGSL SSTPLSTPCS
SVPSSPSFCA PSPGTGGGAG GGGSAAQAGG APGPPSGGPG TVGGASGKAV LEDLYWMSGY
QHHLNPEALN LTPEDAVEAL IGSGHHGAHH GAHHPAAAAA YEAFRGQSFA GGGGADDMGA
GHHHGAHHTA HHHHSAHHHH HHHHHHGGSG HHGGGAGHGG GGAGHHVRLE ERFSDDQLVS
MSVRELNRQL RGFSKEEVIR LKQKRRTLKN RGYAQSCRFK RVQQRHILES EKCQLQSQVE
QLKLEVGRLA KERDLYKEKY EKLAGRGGPG GAGGAGFPRE PSPAQAGPGA AKGAPDFFL
