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Protein

Homeobox protein Nkx-2.1

Gene

Nkx2-1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis. Forms a regulatory loop with GRHL2 that coordinates lung epithelial cell morphogenesis and differentiation (By similarity). Activates the transcription of GNRHR and plays a role in enhancing the circadian oscillation of its gene expression. Represses the transcription of the circadian transcriptional repressor NR1D1 (PubMed:22356123).By similarity1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi161 – 220HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • core promoter binding Source: CAFA
  • DNA binding Source: RGD
  • DNA binding transcription factor activity Source: MGI
  • intronic transcription regulatory region sequence-specific DNA binding Source: UniProtKB
  • protein homodimerization activity Source: CAFA
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: NTNU_SB
  • sequence-specific DNA binding Source: RGD
  • TBP-class protein binding Source: CAFA
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: NTNU_SB

GO - Biological processi

  • cellular response to leptin stimulus Source: RGD
  • circadian rhythm Source: UniProtKB
  • development of primary female sexual characteristics Source: RGD
  • embryonic lung development Source: RGD
  • feeding behavior Source: RGD
  • hyperosmotic salinity response Source: RGD
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of circadian rhythm Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • regulation of blood volume by renin-angiotensin Source: RGD
  • regulation of transcription, DNA-templated Source: RGD
  • response to ethanol Source: RGD
  • response to lipopolysaccharide Source: RGD

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein Nkx-2.1
Alternative name(s):
Thyroid nuclear factor 1
Thyroid transcription factor 1
Short name:
TTF-1
Gene namesi
Name:Nkx2-1Imported
Synonyms:Nkx-2.1, Titf1, Ttf-1, Ttf1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3866 Nkx2-1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000493451 – 372Homeobox protein Nkx-2.1Add BLAST372

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei255PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on serine residues by STK3/MST2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP23441
PRIDEiP23441

PTM databases

iPTMnetiP23441
PhosphoSitePlusiP23441

Expressioni

Tissue specificityi

Thyroid, lung and CNS. Expressed in restricted regions of the developing brain within the diencephalon, in parts of the hypothalamus and neurohypophysis, and in the telencephalon.

Inductioni

Expression oscillates in a diurnal and melatonin-dependent fashion in the preoptic area (POA) region in the hypothalamus, with maximal expression attained during the dark phase of the light/dark cycle.1 Publication

Interactioni

Subunit structurei

Interacts with WWTR1.By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein homodimerization activity Source: CAFA
  • TBP-class protein binding Source: CAFA

Protein-protein interaction databases

IntActiP23441, 2 interactors
MINTiP23441
STRINGi10116.ENSRNOP00000011453

Structurei

Secondary structure

1372
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi162 – 164Combined sources3
Helixi170 – 182Combined sources13
Beta strandi183 – 185Combined sources3
Helixi188 – 198Combined sources11
Helixi202 – 218Combined sources17

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1FTTNMR-A161-227[»]
DisProtiDP00071
ProteinModelPortaliP23441
SMRiP23441
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23441

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi234 – 244Poly-GlyAdd BLAST11
Compositional biasi247 – 254Poly-Gln8
Compositional biasi295 – 304Poly-Ala10

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0842 Eukaryota
ENOG410XR21 LUCA
HOGENOMiHOG000231923
HOVERGENiHBG006689
InParanoidiP23441
PhylomeDBiP23441

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR020479 Homeobox_metazoa
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PRINTSiPR00024 HOMEOBOX
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit

Sequencei

Sequence statusi: Complete.

P23441-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSMSPKHTTP FSVSDILSPL EESYKKVGME GGGLGAPLAA YRQGQAAPPA
60 70 80 90 100
AAMQQHAVGH HGAVTAAYHM TAAGVPQLSH SAVGGYCNGN LGNMSELPPY
110 120 130 140 150
QDTMRNSASG PGWYGANPDP RFPAISRFMG PASGMNMSGM GGLGSLGDVS
160 170 180 190 200
KNMAPLPSAP RRKRRVLFSQ AQVYELERRF KQQKYLSAPE REHLASMIHL
210 220 230 240 250
TPTQVKIWFQ NHRYKMKRQA KDKAAQQQLQ QDSGGGGGGG GGAGCPQQQQ
260 270 280 290 300
AQQQSPRRVA VPVLVKDGKP CQAGAPAPGA ASLQGHAQQQ AQQQAQAAQA
310 320 330 340 350
AAAAISVGSG GAGLGAHPGH QPGSAGQSPD LAHHAASPAA LQGQVSSLSH
360 370
LNSSGSDYGA MSCSTLLYGR TW
Length:372
Mass (Da):38,554
Last modified:November 1, 1991 - v1
Checksum:i8694421DA25D4135
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53858 mRNA Translation: CAA37851.1
D38035 Genomic DNA Translation: BAA07231.1 Sequence problems.
PIRiS12002
UniGeneiRn.34265

Genome annotation databases

UCSCiRGD:3866 rat

Similar proteinsi

Entry informationi

Entry nameiNKX21_RAT
AccessioniPrimary (citable) accession number: P23441
Secondary accession number(s): O08630, O70121
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: May 23, 2018
This is version 151 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health