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Protein

Homeobox protein Nkx-2.1

Gene

Nkx2-1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi161 – 22060HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • circadian rhythm Source: UniProtKB
  • development of primary female sexual characteristics 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 from RNA polymerase II promoter Source: NTNU_SB
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3866. Nkx2-1.

Subcellular locationi

  • Nucleus By similarity

GO - Cellular componenti

  • nucleoplasm Source: UniProtKB
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 372372Homeobox protein Nkx-2.1PRO_0000049345Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei255 – 2551PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated on serine residues by STK3/MST2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP23441.

PTM databases

iPTMnetiP23441.
PhosphoSiteiP23441.

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

WithEntry#Exp.IntActNotes
Pax8P519745EBI-1223127,EBI-1223113
Wwtr1Q9EPK53EBI-1223127,EBI-1211920From a different organism.

Protein-protein interaction databases

IntActiP23441. 2 interactions.
MINTiMINT-125247.
STRINGi10116.ENSRNOP00000011453.

Structurei

Secondary structure

1
372
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi162 – 1643Combined sources
Helixi170 – 18213Combined sources
Beta strandi183 – 1853Combined sources
Helixi188 – 19811Combined sources
Helixi202 – 21817Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FTTNMR-A161-227[»]
DisProtiDP00071.
ProteinModelPortaliP23441.
SMRiP23441. Positions 161-227.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23441.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi234 – 24411Poly-GlyAdd
BLAST
Compositional biasi247 – 2548Poly-Gln
Compositional biasi295 – 30410Poly-Ala

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0842. Eukaryota.
ENOG410XR21. LUCA.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP23441.
PhylomeDBiP23441.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

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.

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1FTTNMR-A161-227[»]
DisProtiDP00071.
ProteinModelPortaliP23441.
SMRiP23441. Positions 161-227.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP23441. 2 interactions.
MINTiMINT-125247.
STRINGi10116.ENSRNOP00000011453.

PTM databases

iPTMnetiP23441.
PhosphoSiteiP23441.

Proteomic databases

PaxDbiP23441.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:3866. rat.

Organism-specific databases

RGDi3866. Nkx2-1.

Phylogenomic databases

eggNOGiKOG0842. Eukaryota.
ENOG410XR21. LUCA.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP23441.
PhylomeDBiP23441.

Miscellaneous databases

EvolutionaryTraceiP23441.
PROiP23441.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNKX21_RAT
AccessioniPrimary (citable) accession number: P23441
Secondary accession number(s): O08630, O70121
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: July 6, 2016
This is version 140 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.