MAFF (gene)

MAFF
Identifiers
Aliases	MAFF, U-MAF, hMafF, MAF bZIP transcription factor F
External IDs	MGI: 96910 HomoloGene: 7825 GeneCards: MAFF
Gene ontology Molecular function • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • transcription factor activity, sequence-specific DNA binding • sequence-specific DNA binding • DNA binding Cellular component • mitochondrion • nucleus • nucleoplasm Biological process • regulation of transcription from RNA polymerase II promoter • skeletal muscle cell differentiation • regulation of epidermal cell differentiation • blood coagulation • in utero embryonic development • regulation of transcription, DNA-templated • transcription from RNA polymerase II promoter • parturition • transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23764	17133
Ensembl	ENSG00000185022	ENSMUSG00000042622
UniProt	Q9ULX9	O54791
RefSeq (mRNA)	NM_152878 NM_001161572 NM_001161573 NM_001161574 NM_012323	NM_010755 NM_001304830 NM_001304831 NM_001304832
RefSeq (protein)	NP_001155044.1 NP_001155045.1 NP_001155046.1 NP_036455.1	NP_001291759.1 NP_034885.1
Location (UCSC)	Chr 22: 38.2 – 38.22 Mb	Chr 15: 79.35 – 79.36 Mb
PubMed search	[1]	[2]
Wikidata

Structures of the Maf family proteins.

Transcription factor MafF is a bZip Maf transcription factor protein that in humans is encoded by the MAFF gene.^[3][4]

MafF is one of the small Maf proteins, which are basic region and basic leucine zipper (bZIP)-type transcription factors. The HUGO Gene Nomenclature Committee-approved gene name of MAFF is “v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog F”.

Discovery

MafF was first cloned and identified in chicken in 1993 as a member of the small Maf (sMaf) genes.^[3] MAFF has been identified in many vertebrates, including humans.^[4] There are three functionally redundant sMaf proteins in vertebrates, MafF, MafG, and MafK.

Structure

MafF has a bZIP structure that consists of a basic region for DNA binding and a leucine zipper structure for dimer formation.^[3] Similar to other sMafs, MafF lacks any canonical transcriptional activation domains.^[3]

Expression

MAFF is broadly but differentially expressed in various tissues. MAFF expression was detected in all 16 tissues examined by the human BodyMap Project, but relatively abundant in adipose, colon, lung, prostate and skeletal muscle tissues.^[5] Human MAFF gene is induced by proinflammatory cytokines, interleukin 1 beta and tumor necrosis factor in myometrial cells.^[6]

Function

Because of sequence similarity, no functional differences have been observed among the sMafs in terms of their bZIP structures. sMafs form homodimers by themselves and heterodimers with other specific bZIP transcription factors, such as CNC (cap 'n' collar) proteins [p45 NF-E2 (NFE2), Nrf1 (NFE2L1), Nrf2 (NFE2L2), and Nrf3 (NFE2L3)]^{[7][8][9][10]} and Bach proteins (BACH1 and BACH2).^[11]

Target genes

sMafs regulate different target genes depending on their partners. For instance, the p45-NF-E2-sMaf heterodimer regulate genes responsible for platelet production.^[7][12][13] Nrf2-sMaf heterodimer regulates a battery of cytoprotective genes, such as antioxidant/xenobiotic metabolizing enzyme genes.^[9][14] The Bach1-sMaf heterodimer regulates the heme oxygenase-1 gene.^[11] In particular, it has been reported that MafF regulates the oxytocin receptor gene.^[15] The contribution of individual sMafs to the transcriptional regulation of their target genes has not yet been well examined.

Disease linkage

Loss of sMafs results in disease-like phenotypes as summarized in table below. Mice lacking MafF are seemingly healthy under laboratory conditions.^[16] However, mice lacking MafG exhibit mild neuronal phenotype and mild thrombocytopenia,^[17] mice lacking Mafg and one allele of Mafk (Mafg^−/−::Mafk^+/−) exhibit progressive neuronal degeneration, thrombocytopenia and cataract,^[18][19] and mice lacking MafG and MafK (Mafg^−/−::Mafk^−/−) exhibit more severe neuronal degeneration and die in the perinatal stage.^[20] Mice lacking MafF, MafG and MafK are embryonic lethal, demonstrating that MafF is indispensable for embryonic development.^[21] Embryonic fibroblasts that are derived from Maff^−/−::Mafg^-/−::Mafk^−/− mice fail to activate Nrf2-dependent cytoprotective genes in response to stress.^[14]

In addition, accumulating evidence suggests that as partners of CNC and Bach proteins, sMafs are involved in the onset and progression of various human diseases, including neurodegeneration, arteriosclerosis and cancer.

See also

• MAF (gene)

References

Further reading

External links

• MAFF protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook MafF

  Transcription factors and intracellular receptors
  (1) Basic domains (1.1) Basic leucine zipper (bZIP) Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA HLF MAF B F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1 (1.2) Basic helix-loop-helix (bHLH) ATOH1 AhR AHRR ARNT ASCL1 BHLH 2 3 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND 1 2 HES 5 6 HEY 1 2 L HES1 HIF 1A 3A ID 1 2 3 4 LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins 1 2 3 NeuroD 1 2 NPAS 1 2 3 OLIG 1 2 Pho4 Scleraxis SIM 1 2 TAL 1 2 Twist USF1 (1.3) bHLH-ZIP AP-4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP 1 2 (1.4) NF-1 NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4) (1.5) RF-X RFX 1 2 3 4 5 6 ANK (1.6) Basic helix-span-helix (bHSH) AP-2 α β γ δ ε
  (2) Zinc finger DNA-binding domains (2.1) Nuclear receptor (Cys4) subfamily 1 Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR subfamily 2 COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX subfamily 3 Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ subfamily 4 NUR NGFIB NOR1 NURR1 subfamily 5 LRH-1 SF1 subfamily 6 GCNF subfamily 0 DAX1 SHP (2.2) Other Cys4 GATA 1 2 3 4 5 6 MTA 1 2 3 TRPS1 (2.3) Cys2His2 General transcription factors TFIIA TFIIB TFIID TFIIE 1 2 TFIIF 1 2 TFIIH 1 2 4 2I 3A 3C1 3C2 ATBF1 BCL 6 11A 11B CTCF E4F1 EGR 1 2 3 4 ERV3 GFI1 GLI-Krüppel family 1 2 3 REST S1 S2 YY1 HIC 1 2 HIVEP 1 2 3 IKZF 1 2 3 ILF 2 3 KLF 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 17 MTF1 MYT1 OSR1 PRDM9 SALL 1 2 3 4 SP 1 2 4 7 8 TSHZ3 WT1 Zbtb7 7A 7B ZBTB 11 16 17 20 32 33 40 zinc finger 3 7 9 10 19 22 24 33B 34 35 41 43 44 51 74 143 146 148 165 202 217 219 238 239 259 267 268 281 295 300 318 330 346 350 365 366 384 423 451 452 471 593 638 644 649 655 (2.4) Cys6 HIVEP1 (2.5) Alternating composition AIRE DIDO1 GRLF1 ING 1 2 4 JARID 1A 1B 1C 1D 2 JMJD1B (2.6) WRKY WRKY
  (3) Helix-turn-helix domains (3.1) Homeodomain ARX CDX 1 2 CRX CUTL1 DBX 1 2 DLX 3 4 5 EMX 1 2 EN 1 2 FHL 1 2 3 HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 1 2 3 4 5 6 MKX LMX 1A 1B MEIS 1 2 MEOX2 MNX1 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 6-1 6-2 NOBOX PBX 1 2 3 PHF 1 3 6 8 10 16 17 20 21A PHOX 2A 2B PITX 1 2 3 POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 OTX 1 2 PDX1 SATB2 SHOX2 SIX 1 2 3 4 5 VAX1 ZEB 1 2 (3.2) Paired box PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 RAX (3.3) Fork head / winged helix E2F 1 2 3 4 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4 (3.4) Heat shock factors HSF 1 2 4 (3.5) Tryptophan clusters ELF 2 4 5 EGF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2 (3.6) TEA domain transcriptional enhancer factor 1 2 3 4
  (4) β-Scaffold factors with minor groove contacts (4.1) Rel homology region NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5 (4.2) STAT STAT 1 2 3 4 5 6 (4.3) p53 p53 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF TP63 (4.4) MADS box Mef2 A B C D SRF (4.6) TATA-binding proteins TBP TBPL1 (4.7) High-mobility group BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B LEF1 SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF 3 4 TOX 1 2 3 4 (4.9) Grainyhead TFCP2 (4.10) Cold-shock domain CSDA YBX1 (4.11) Runt CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1
  (0) Other transcription factors (0.2) HMGI(Y) HMGA 1 2 HBP1 (0.3) Pocket domain Rb RBL1 RBL2 (0.5) AP-2/EREBP-related factors Apetala 2 EREBP B3 (0.6) Miscellaneous ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma
  see also transcription factor/coregulator deficiencies