NKX6-1

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NK6 homeobox 1

Identifiers

NKX6-1; NKX6.1; NKX6A

External IDs

OMIM: 602563 MGI: 1206039 HomoloGene: 4495 GeneCards: NKX6-1 Gene

Gene Ontology
Molecular function	• transcription regulatory region sequence-specific DNA binding • chromatin binding • sequence-specific DNA binding transcription factor activity
Cellular component	• nucleus • nucleolus
Biological process	• negative regulation of transcription from RNA polymerase II promoter • transcription from RNA polymerase II promoter • smoothened signaling pathway • cell proliferation • organ morphogenesis • regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification • regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification • pancreas development • endocrine pancreas development • positive regulation of insulin secretion • response to nicotine • response to drug • positive regulation of neuron differentiation • negative regulation of glial cell differentiation • positive regulation of glial cell differentiation • positive regulation of transcription from RNA polymerase II promoter • oligodendrocyte differentiation • positive regulation of sequence-specific DNA binding transcription factor activity • detection of glucose • cellular response to cytokine stimulus • cellular response to peptide hormone stimulus • type B pancreatic cell maturation • positive regulation of type B pancreatic cell development
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 4:
85.41 – 85.42 Mb

Chr 5:
101.66 – 101.67 Mb

PubMed search

Homeobox protein Nkx-6.1 is a protein that in humans is encoded by the NKX6-1 gene.^[1]^[2]

Function

In the pancreas, NKX6.1 is required for the development of beta cells and is a potent bifunctional transcription regulator that binds to AT-rich sequences within the promoter region of target genes.^[2]

References

↑ Inoue H, Rudnick A, German MS, Veile R, Donis-Keller H, Permutt MA (March 1997). "Isolation, characterization, and chromosomal mapping of the human Nkx6.1 gene (NKX6A), a new pancreatic islet homeobox gene". Genomics 40 (2): 367–70. doi:10.1006/geno.1996.4568. PMID 9119408.
↑ 2.0 2.1 "Entrez Gene: NK6 homeobox 1".

Schisler JC, Fueger PT, Babu DA, et al. (2008). "Stimulation of human and rat islet beta-cell proliferation with retention of function by the homeodomain transcription factor Nkx6.1.". Mol. Cell. Biol. 28 (10): 3465–76. doi:10.1128/MCB.01791-07. PMID 18347054.
Hori Y, Gu X, Xie X, Kim SK (2005). "Differentiation of insulin-producing cells from human neural progenitor cells.". PLoS Med. 2 (4): e103. doi:10.1371/journal.pmed.0020103. PMC 1087208. PMID 15839736.
Jørgensen MC, Vestergírd Petersen H, Ericson J, et al. (1999). "Cloning and DNA-binding properties of the rat pancreatic beta-cell-specific factor Nkx6.1.". FEBS Lett. 461 (3): 287–94. doi:10.1016/S0014-5793(99)01436-2. PMID 10567713.
Iype T, Taylor DG, Ziesmann SM, et al. (2004). "The transcriptional repressor Nkx6.1 also functions as a deoxyribonucleic acid context-dependent transcriptional activator during pancreatic beta-cell differentiation: evidence for feedback activation of the nkx6.1 gene by Nkx6.1.". Mol. Endocrinol. 18 (6): 1363–75. doi:10.1210/me.2004-0006. PMID 15056733.
Yokoi N, Kanamori M, Horikawa Y, et al. (2006). "Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects.". Diabetes 55 (8): 2379–86. doi:10.2337/db05-1203. PMID 16873704.
Zhu S, Xia HH, Yang Y, et al. (2009). "Alterations of gastric homeoprotein expression in Helicobacter pylori infection, incisural antralisation, and intestinal metaplasia.". Dig. Dis. Sci. 54 (5): 996–1002. doi:10.1007/s10620-008-0459-8. PMID 18754095.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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) · BMAL (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
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)

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NKX6-1

Function

References

Further reading