Homeobox protein Nkx-2.5

NK2 homeobox 5

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
3RKQ

Identifiers

Symbols

NKX2-5 ; CHNG5; CSX; CSX1; HLHS2; NKX2.5; NKX2E; NKX4-1; VSD3

External IDs

OMIM: 600584 MGI: 97350 HomoloGene: 3230 GeneCards: NKX2-5 Gene

Gene ontology
Molecular function	• RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding • RNA polymerase II transcription cofactor activity • transcriptional activator activity, RNA polymerase II transcription factor binding • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding • DNA binding • chromatin binding • transcription factor activity, sequence-specific DNA binding • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding • protein binding • transcription factor binding • serum response element binding • protein homodimerization activity • sequence-specific DNA binding • transcription regulatory region DNA binding • protein heterodimerization activity
Cellular component	• nucleus • transcription factor complex • cytoplasm • RNA polymerase II transcription factor complex
Biological process	• negative regulation of transcription from RNA polymerase II promoter • vasculogenesis • heart looping • heart morphogenesis • outflow tract septum morphogenesis • cardiac conduction system development • bundle of His development • Purkinje myocyte differentiation • cardiac ventricle formation • right ventricular cardiac muscle tissue morphogenesis • ventricular trabecula myocardium morphogenesis • apoptotic process involved in heart morphogenesis • septum secundum development • proepicardium development • pulmonary myocardium development • transcription from RNA polymerase II promoter • adult heart development • positive regulation of cell proliferation • negative regulation of cardiac muscle cell apoptotic process • positive regulation of transcription via serum response element binding • positive regulation of sodium ion transport • negative regulation of myotube differentiation • hemopoiesis • cell differentiation • BMP signaling pathway • thyroid gland development • embryonic heart tube development • negative regulation of apoptotic process • sarcomere organization • positive regulation of neuron differentiation • positive regulation of heart contraction • negative regulation of transcription, DNA-templated • positive regulation of transcription, DNA-templated • positive regulation of transcription from RNA polymerase II promoter • spleen development • positive regulation of cardioblast differentiation • ventricular cardiac myofibril assembly • cardiac muscle cell differentiation • cardiac muscle tissue morphogenesis • atrial cardiac muscle cell development • ventricular cardiac muscle cell development • regulation of cardiac muscle contraction • pharyngeal system development • cardiac muscle cell proliferation • regulation of cardiac muscle cell proliferation • cardiac muscle contraction • canonical Wnt signaling pathway • positive regulation of transcription initiation from RNA polymerase II promoter • heart trabecula formation • ventricular septum morphogenesis • atrial septum morphogenesis • atrioventricular node cell development • atrioventricular node cell fate commitment • embryonic heart tube left/right pattern formation • negative regulation of canonical Wnt signaling pathway • positive regulation of voltage-gated calcium channel activity • regulation of cardiac conduction
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 5:
173.23 – 173.24 Mb

Chr 17:
26.84 – 26.84 Mb

PubMed search

Homeobox protein Nkx-2.5 is a protein that in humans is encoded by the NKX2-5 gene.^[1]^[2]^[3]

Function

Homeobox-containing genes play critical roles in regulating tissue-specific gene expression essential for tissue differentiation, as well as determining the temporal and spatial patterns of development (Shiojima et al., 1995). It has been demonstrated that a Drosophila homeobox-containing gene called 'tinman' is expressed in the developing dorsal vessel and in the equivalent of the vertebrate heart. Mutations in tinman result in loss of heart formation in the embryo, suggesting that tinman is essential for Drosophila heart formation. Furthermore, abundant expression of Csx, the presumptive mouse homolog of tinman, is observed only in the heart from the time of cardiac differentiation. CSX, the human homolog of murine Csx, has a homeodomain sequence identical to that of Csx and is expressed only in the heart, again suggesting that CSX plays an important role in human heart formation.[supplied by OMIM]^[3]

Recently, postnatal roles of cardiac transcription factors have been extensively investigated. Consistent with the direct transactivation of numerous cardiac genes reactivated in response to hypertrophic stimulation, cardiac transcription factors are profoundly involved in the generation of cardiac hypertrophy or in cardioprotection from cytotoxic stress in the adult heart. Nkx-2.5 transcription factor may help myocytes endure cytotoxic stress, even though further exploration in this field is required.^[4]

Interactions

NKX2-5 has been shown to interact with GATA4^[5]^[6]^[7] and TBX5.^[5]^[8] NKX 2.5 is a transcription factor that regulates heart development in humans. NKX2.5 works along with MEF2, HAND1, and HAND2 transcription factors to direct heart looping during early heart development. NKX2.5 in vertebrates is equivalent to the ‘tinman’ gene in Drosophila and directly activates the MEF2 gene to control cardiomyocyte differentiation. NKX2.5 operates in a positive feedback loop with GATA transcription factors to regulate cardiomyocyte formation. NKX2.5 influences HAND1 and HAND2 transcription factors that control the essential asymmetrical development of the heart’s ventricles. Gene mutations of NKX2.5 lead to heart looping defects, conduction defects, and atrial septal defects in the developing heart.

References

↑ Shiojima I, Komuro I, Inazawa J, Nakahori Y, Matsushita I, Abe T, Nagai R, Yazaki Y (May 1995). "Assignment of cardiac homeobox gene CSX to human chromosome 5q34". Genomics 27 (1): 204–6. doi:10.1006/geno.1995.1027. PMID 7665173.
↑ Turbay D, Wechsler SB, Blanchard KM, Izumo S (Jan 1996). "Molecular cloning, chromosomal mapping, and characterization of the human cardiac-specific homeobox gene hCsx". Molecular Medicine 2 (1): 86–96. PMC 2230031. PMID 8900537.
1 2 "Entrez Gene: NKX2-5 NK2 transcription factor related, locus 5 (Drosophila)".
↑ Akazawa H, Komuro I (May 2003). "Roles of cardiac transcription factors in cardiac hypertrophy". Circulation Research 92 (10): 1079–88. doi:10.1161/01.RES.0000072977.86706.23. PMID 12775656.
1 2 Garg V, Kathiriya IS, Barnes R, Schluterman MK, King IN, Butler CA, Rothrock CR, Eapen RS, Hirayama-Yamada K, Joo K, Matsuoka R, Cohen JC, Srivastava D (Jul 2003). "GATA4 mutations cause human congenital heart defects and reveal an interaction with TBX5". Nature 424 (6947): 443–7. doi:10.1038/nature01827. PMID 12845333.
↑ Durocher D, Charron F, Warren R, Schwartz RJ, Nemer M (Sep 1997). "The cardiac transcription factors Nkx2-5 and GATA-4 are mutual cofactors". The EMBO Journal 16 (18): 5687–96. doi:10.1093/emboj/16.18.5687. PMC 1170200. PMID 9312027.
↑ Zhu W, Shiojima I, Hiroi Y, Zou Y, Akazawa H, Mizukami M, Toko H, Yazaki Y, Nagai R, Komuro I (Nov 2000). "Functional analyses of three Csx/Nkx-2.5 mutations that cause human congenital heart disease". The Journal of Biological Chemistry 275 (45): 35291–6. doi:10.1074/jbc.M000525200. PMID 10948187.
↑ Hiroi Y, Kudoh S, Monzen K, Ikeda Y, Yazaki Y, Nagai R, Komuro I (Jul 2001). "Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation". Nature Genetics 28 (3): 276–80. doi:10.1038/90123. PMID 11431700.

External links

NKX2-5 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

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

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

This article is issued from Wikipedia - version of the Tuesday, January 26, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.

Homeobox protein Nkx-2.5

Function

Interactions

References

Further reading

External links