Reviewed, UniProtKB/Swiss-Prot P42580 (NKX12_MOUSE)

Names and origin

Protein names

Recommended name:
    NK1 transcription factor-related protein 2
Alternative name(s):
    Homeobox protein SAX-1
    NKX-1.1

Gene names

Name:	Nkx1-2
Synonyms:	Nkx1.1, Sax1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	305 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	May function in cell specification, particularly in the CNS.
Subunit structure	Interacts with HIPK1, HIPK2, and HIPK3. Ref.4
Subcellular location	Nucleus Probable.
Tissue specificity	Expression detected in adult brain, testis and spleen. In the testis, expressed in the germ cells of the seminiferous epithelium, in elongating spermatids and in spermatozoa. Expressed throughout the brain with highest levels in regions of the cerebral cortex, hippocampus, diencephalon, pons, medulla and cerebellum. In the embryo, expressed in the developing posterior central nervous system. First seen in the ectoderm lateral to the primitive streak, later it encompasses the neural plate. Starting at day 9.5 pc, expressed in distinct areas of spinal cord, hindbrain, midbrain and forebrain. Ref.1 Ref.2
Developmental stage	In the embryo, expressed at highest levels at day 10 with levels decreasing during further development. Ref.2
Post-translational modification	Phosphorylated by HIPK2 in vitro. Ref.4
Sequence similarities	Belongs to the NK-1 homeobox family. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: InterPro
Cellular component	nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Ref.4 Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro transcription factor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P42580-1)

Also known as: E4.29;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P42580-2)

Also known as: E4.27;

The sequence of this isoform differs from the canonical sequence as follows:
     129-151: AEGLPASPGSPGSPRPRRRRAES → EPSPAAPSQGARALPSLTSSWWP
     152-305: Missing.

Isoform 3 (identifier: P42580-3)

Also known as: T5.17;

The sequence of this isoform differs from the canonical sequence as follows:
     44-165: Missing.

Isoform 4 (identifier: P42580-4)

Also known as: T5.18;

The sequence of this isoform differs from the canonical sequence as follows:
     1-148: Missing.
     149-165: AESSCAKPRRARTAFTY → MTSIDQAPDKSETLLTL

Isoform 5 (identifier: P42580-5)

Also known as: T8.7;

The sequence of this isoform differs from the canonical sequence as follows:
     53-83: Missing.

Isoform 6 (identifier: P42580-6)

Also known as: T5.1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-114: MLAWQDVGAK...ERWQGVHEGS → FQFAAGELWP...SCPPAGASRC

Note: Incomplete sequence.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 305	305	NK1 transcription factor-related protein 2		PRO_0000049290
Regions
	DNA binding	156 – 215	60	Homeobox
	Compositional bias	88 – 96	9	Poly-Glu
	Compositional bias	143 – 148	6	Poly-Arg
	Compositional bias	239 – 242	4	Poly-Gly
Natural variations
	Alternative sequence	1 – 148	148	Missing in isoform 4.		VSP_002281
	Alternative sequence	1 – 114	114	MLAWQ…VHEGS → FQFAAGELWPNHCRRQRLSA SSPDPSTAGLGPAGGGHVGM AGRRGQGGPLSPQDLLLCLG HLGSAKIHASCPPAGASRC in isoform 6.		VSP_002280
	Alternative sequence	44 – 165	122	Missing in isoform 3.		VSP_002284
	Alternative sequence	53 – 83	31	Missing in isoform 5.		VSP_002283
	Alternative sequence	129 – 151	23	AEGLP…RRAES → EPSPAAPSQGARALPSLTSS WWP in isoform 2.		VSP_002285
	Alternative sequence	149 – 165	17	AESSC…TAFTY → MTSIDQAPDKSETLLTL in isoform 4.		VSP_002282
	Alternative sequence	152 – 305	154	Missing in isoform 2.		VSP_002286
Experimental info
	Sequence conflict	216	1	P → S in AAF43673. Ref.2
	Sequence conflict	216	1	P → S in AAF43677. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (E4.29) [UniParc]. Last modified November 1, 1995. Version 1. Checksum: E02E09A40453FF1B	FASTA	305	32,013
	10 20 30 40 50 60 MLAWQDVGAK AAPSHHKISF SVLDILDPQK FTRAALPPVR LAALEAKKSL EEVEAGQDAC 70 80 90 100 110 120 SGNPIGSQET PDAVGRGIDP GSPVEGSEAE EEEEAEDAGR AHQPERWQGV HEGSPEARAV 130 140 150 160 170 180 AVGTEESGAE GLPASPGSPG SPRPRRRRAE SSCAKPRRAR TAFTYEQLVA LENKFRATRY 190 200 210 220 230 240 LSVCERLNLA LSLSLTETQV KIWFQNRRTK WKKQNPGADG AVQAGGGAPQ PGTPGAVAGG 250 260 270 280 290 300 GGSATGSSPG PPVPGALPYQ TFPTYPATNV LFPAASFPLT TAANGSPFTP FLGPSYLTPF YAPHL
	Isoform 2 (E4.27). Checksum: ECC2434E4C68B6DF	FASTA	151	15,808
	10 20 30 40 50 60 MLAWQDVGAK AAPSHHKISF SVLDILDPQK FTRAALPPVR LAALEAKKSL EEVEAGQDAC 70 80 90 100 110 120 SGNPIGSQET PDAVGRGIDP GSPVEGSEAE EEEEAEDAGR AHQPERWQGV HEGSPEARAV 130 140 150 AVGTEESGEP SPAAPSQGAR ALPSLTSSWW P
	Isoform 3 (T5.17). Checksum: A5CDE25BB20DFE1F	FASTA	183	19,268
	10 20 30 40 50 60 MLAWQDVGAK AAPSHHKISF SVLDILDPQK FTRAALPPVR LAAEQLVALE NKFRATRYLS 70 80 90 100 110 120 VCERLNLALS LSLTETQVKI WFQNRRTKWK KQNPGADGAV QAGGGAPQPG TPGAVAGGGG 130 140 150 160 170 180 SATGSSPGPP VPGALPYQTF PTYPATNVLF PAASFPLTTA ANGSPFTPFL GPSYLTPFYA PHL
	Isoform 4 (T5.18). Checksum: EB6EC49E7982C7AD	FASTA	157	16,463
	10 20 30 40 50 60 MTSIDQAPDK SETLLTLEQL VALENKFRAT RYLSVCERLN LALSLSLTET QVKIWFQNRR 70 80 90 100 110 120 TKWKKQNPGA DGAVQAGGGA PQPGTPGAVA GGGGSATGSS PGPPVPGALP YQTFPTYPAT 130 140 150 NVLFPAASFP LTTAANGSPF TPFLGPSYLT PFYAPHL
	Isoform 5 (T8.7). Checksum: 97342B35C20A1818	FASTA	274	29,049
	10 20 30 40 50 60 MLAWQDVGAK AAPSHHKISF SVLDILDPQK FTRAALPPVR LAALEAKKSL EEVEGSEAEE 70 80 90 100 110 120 EEEAEDAGRA HQPERWQGVH EGSPEARAVA VGTEESGAEG LPASPGSPGS PRPRRRRAES 130 140 150 160 170 180 SCAKPRRART AFTYEQLVAL ENKFRATRYL SVCERLNLAL SLSLTETQVK IWFQNRRTKW 190 200 210 220 230 240 KKQNPGADGA VQAGGGAPQP GTPGAVAGGG GSATGSSPGP PVPGALPYQT FPTYPATNVL 250 260 270 FPAASFPLTT AANGSPFTPF LGPSYLTPFY APHL
	Isoform 6 (T5.1). Checksum: 8126345CB7EB04D2	FASTA	270	27,891
	10 20 30 40 50 60 FQFAAGELWP NHCRRQRLSA SSPDPSTAGL GPAGGGHVGM AGRRGQGGPL SPQDLLLCLG 70 80 90 100 110 120 HLGSAKIHAS CPPAGASRCP EARAVAVGTE ESGAEGLPAS PGSPGSPRPR RRRAESSCAK 130 140 150 160 170 180 PRRARTAFTY EQLVALENKF RATRYLSVCE RLNLALSLSL TETQVKIWFQ NRRTKWKKQN 190 200 210 220 230 240 PGADGAVQAG GGAPQPGTPG AVAGGGGSAT GSSPGPPVPG ALPYQTFPTY PATNVLFPAA 250 260 270 SFPLTTAANG SPFTPFLGPS YLTPFYAPHL

References

[1]	"Expression of the novel murine homeobox gene Sax-1 in the developing nervous system." Schubert F.R., Fainsod A., Gruenbaum Y., Gruss P. Mech. Dev. 51:99-114(1995) [PubMed: 7669696] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Strain: C57BL/6.
[2]	"The mouse Nkx-1.2 homeobox gene: alternative RNA splicing at canonical and noncanonical splice sites." Rovescalli A.C., Cinquanta M., Ferrante J., Kozak C.A., Nirenberg M. Proc. Natl. Acad. Sci. U.S.A. 97:1982-1987(2000) [PubMed: 10681422] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM 6), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[3]	Hong S.B., Kim S.J., Noh M.J., Lee Y.M., Kim Y.S., Yoo O.J. Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 289-305. Strain: BALB/c.
[4]	"Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors." Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y. J. Biol. Chem. 273:25875-25879(1998) [PubMed: 9748262] [Abstract] Cited for: INTERACTION WITH HIPK1; HIPK2 AND HIPK3, PHOSPHORYLATION. Strain: BALB/c.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X75384 mRNA. Translation: CAA53153.1. AF222443 Genomic DNA. Translation: AAF43669.1. AF222443 Genomic DNA. Translation: AAF43670.1. AF222444 mRNA. Translation: AAF43671.1. AF222445 mRNA. Translation: AAF43672.1. AF223361 mRNA. Translation: AAF43673.1. AF223362 mRNA. Translation: AAF43674.1. AF223363 mRNA. Translation: AAF43675.1. AF223674 mRNA. Translation: AAF43676.1. AF223675 mRNA. Translation: AAF43677.1. U58137 Genomic DNA. Translation: AAB06948.1.
IPI	IPI00117489. IPI00229979. IPI00229980. IPI00229981. IPI00229982. IPI00468971.
PIR	S41860.
RefSeq	NP_033149.1.
UniGene	Mm.334281 Mm.389981
3D structure databases
HSSP	HSSP built from PDB template 1IG7 based on UniProtKB P13297.
ModBase	Search...
Genome annotation databases
Ensembl	ENSMUSG00000048528. Mus musculus. [Contig view]
GeneID	20231.
KEGG	mmu:20231.
Organism-specific databases
MGI	MGI:104806. Nkx1-2.
Phylogenomic databases
HOVERGEN	P42580.
OMA	P42580. HHKISFS.
Gene expression databases
ArrayExpress	P42580.
Bgee	P42580.
GermOnline	ENSMUSG00000048528. Mus musculus.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR012287. Homeodomain-rel. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
ProDom	PD000010. Homeobox. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00389. HOX. 1 hit. [Graphical view]
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	297865.
SOURCE	Search...

Entry information

Entry name

NKX12_MOUSE

Accession

Primary (citable) accession number: P42580
Secondary accession number(s): Q9JHF2 , Q9JKW5, Q9JKW6, Q9JKW9, Q9JKX0, Q9JKX1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	November 1, 1995
Last modified:	June 16, 2009
This is version 70 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)