P63015 (PAX6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Paired box protein Pax-6

Alternative name(s):
Oculorhombin

Gene names

Name:	Pax6
Synonyms:	Pax-6, Sey

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	422 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells. Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains By similarity. Ref.8
Subunit structure	Interacts with MAF and MAFB. Interacts with TRIM11; this interaction leads to ubiquitination and proteasomal degradation, as well as inhibition of transactivation, possibly in part by preventing PAX6 binding to consensus DNA sequences. Ref.9 Ref.10
Subcellular location	Nucleus.
Developmental stage	Expressed in the developing eye, nose, brain and pancreas. At 9 dpc, expressed in the telencephalon, diencephalon, neural tube, optic vesicle and pancreas. Throughout development, expression continues in the dorsal and ventral pancreas. Expressed during cortical neurogenesis from 11 to 18 dpc. High levels in the early radial glial progenitors from 11 to 14 dpc and gradually decrease thereafter (at protein level). During corticogenesis, the protein level declines faster than that of the mRNA, due to proteasomal degradation. In newborn animals, becomes restricted to endocrine cells of the islets of Langerhans. Ref.10
Post-translational modification	Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal degradation. Ref.10
Involvement in disease	Defects in Pax6 are the cause of a condition known as small eye (Sey) which results in the complete lack of eyes and nasal primordia.
Sequence similarities	Belongs to the paired homeobox family. Contains 1 homeobox DNA-binding domain. Contains 1 paired domain.
Sequence caution	The sequence AAA40109.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Differentiation Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Domain	Homeobox Paired box
Ligand	DNA-binding
Molecular function	Developmental protein
PTM	Ubl conjugation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	astrocyte differentiation Inferred from mutant phenotype PubMed 19258013. Source: MGI axon guidance Inferred from mutant phenotype PubMed 11967891PubMed 14586016. Source: MGI blood vessel development Inferred from electronic annotation. Source: Compara cell fate determination Inferred from mutant phenotype PubMed 12756174. Source: MGI cerebral cortex regionalization Inferred from mutant phenotype PubMed 12764040. Source: MGI commitment of neuronal cell to specific neuron type in forebrain Inferred from mutant phenotype PubMed 11124115. Source: MGI cornea development in camera-type eye Inferred from electronic annotation. Source: Compara dorsal/ventral axis specification Inferred from mutant phenotype PubMed 10588713. Source: MGI embryonic camera-type eye morphogenesis Inferred from genetic interaction PubMed 18653562. Source: MGI eye photoreceptor cell development Inferred from mutant phenotype PubMed 12648492. Source: MGI forebrain anterior/posterior pattern specification Inferred from mutant phenotype PubMed 9169845. Source: MGI forebrain dorsal/ventral pattern formation Inferred from mutant phenotype PubMed 11050125PubMed 11124115. Source: MGI forebrain-midbrain boundary formation Inferred from mutant phenotype PubMed 9169845. Source: MGI glucose homeostasis Inferred from electronic annotation. Source: Compara hindbrain development Inferred from electronic annotation. Source: Compara iris morphogenesis Inferred from electronic annotation. Source: Compara keratinocyte differentiation Inferred from mutant phenotype PubMed 16080917. Source: MGI lacrimal gland development Inferred from mutant phenotype PubMed 10821755. Source: MGI lens development in camera-type eye Inferred from mutant phenotype PubMed 6877261. Source: MGI negative regulation of epithelial cell proliferation Inferred from mutant phenotype PubMed 16080917. Source: MGI negative regulation of neuron differentiation Inferred from genetic interaction PubMed 16950124. Source: MGI neuron migration Inferred from mutant phenotype PubMed 15758185. Source: MGI oligodendrocyte cell fate specification Inferred from mutant phenotype PubMed 9828088. Source: MGI pancreatic A cell development Inferred from mutant phenotype PubMed 20592023. Source: BHF-UCL pituitary gland development Inferred from mutant phenotype PubMed 10588713. Source: MGI positive regulation of cell fate specification Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell differentiation Inferred from mutant phenotype PubMed 16080917. Source: MGI positive regulation of neuroblast proliferation Inferred from mutant phenotype PubMed 18287938. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 16407227. Source: BHF-UCL protein localization to organelle Inferred from mutant phenotype PubMed 16024294. Source: MGI regulation of cell migration Inferred from mutant phenotype PubMed 10409504. Source: MGI regulation of timing of cell differentiation Inferred from mutant phenotype PubMed 9828088. Source: MGI regulation of transcription from RNA polymerase II promoter involved in somatic motor neuron fate commitment Inferred from mutant phenotype PubMed 9230312. Source: MGI regulation of transcription from RNA polymerase II promoter involved in spinal cord motor neuron fate specification Inferred from mutant phenotype PubMed 9230312. Source: MGI regulation of transcription from RNA polymerase II promoter involved in ventral spinal cord interneuron specification Inferred from mutant phenotype PubMed 9230312. Source: MGI response to wounding Inferred from electronic annotation. Source: Compara salivary gland morphogenesis Inferred from mutant phenotype PubMed 11731698. Source: MGI signal transduction involved in regulation of gene expression Inferred from direct assay PubMed 18462699. Source: MGI smoothened signaling pathway Inferred from direct assay PubMed 18590716. Source: MGI
Cellular_component	cytoplasm Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from direct assay PubMed 20592023. Source: BHF-UCL transcription factor complex Traceable author statement PubMed 10197584. Source: MGI
Molecular_function	AT DNA binding Inferred from electronic annotation. Source: Compara R-SMAD binding Inferred from direct assay PubMed 17251190. Source: BHF-UCL RNA polymerase II core promoter sequence-specific DNA binding Inferred from direct assay PubMed 16407227PubMed 20592023. Source: BHF-UCL co-SMAD binding Inferred from direct assay PubMed 17251190. Source: BHF-UCL double-stranded DNA binding Inferred from electronic annotation. Source: Compara histone acetyltransferase binding Inferred from direct assay PubMed 16407227. Source: BHF-UCL sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from direct assay PubMed 16407227PubMed 20592023. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P63015-1)

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 5a (identifier: P63015-2)

Also known as: Pax6-5a;

The sequence of this isoform differs from the canonical sequence as follows:
     47-47: Q → QTHADAKVQVLDNEN

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 422	422	Paired box protein Pax-6		PRO_0000050186
Regions
	Domain	4 – 130	127	Paired
	DNA binding	210 – 269	60	Homeobox
	Compositional bias	131 – 209	79	Gln/Gly-rich
	Compositional bias	279 – 422	144	Pro/Ser/Thr-rich
Natural variations
	Alternative sequence	47	1	Q → QTHADAKVQVLDNEN in isoform 5a.		VSP_011530
	Natural variant	259	1	S → P in Pax6(4Neu); defective. Ref.2
Experimental info
	Sequence conflict	18	1	G → E in BAC25729. Ref.3
	Sequence conflict	31	1	E → Q in BAC25729. Ref.3
	Sequence conflict	287	1	I → T Ref.6
	Sequence conflict	421 – 422	2	Missing Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 31, 2004. Version 1. Checksum: C33CDD2C1B13C397	FASTA	422	46,683
	10 20 30 40 50 60 MQNSHSGVNQ LGGVFVNGRP LPDSTRQKIV ELAHSGARPC DISRILQVSN GCVSKILGRY 70 80 90 100 110 120 YETGSIRPRA IGGSKPRVAT PEVVSKIAQY KRECPSIFAW EIRDRLLSEG VCTNDNIPSV 130 140 150 160 170 180 SSINRVLRNL ASEKQQMGAD GMYDKLRMLN GQTGSWGTRP GWYPGTSVPG QPTQDGCQQQ 190 200 210 220 230 240 EGGGENTNSI SSNGEDSDEA QMRLQLKRKL QRNRTSFTQE QIEALEKEFE RTHYPDVFAR 250 260 270 280 290 300 ERLAAKIDLP EARIQVWFSN RRAKWRREEK LRNQRRQASN TPSHIPISSS FSTSVYQPIP 310 320 330 340 350 360 QPTTPVSSFT SGSMLGRTDT ALTNTYSALP PMPSFTMANN LPMQPPVPSQ TSSYSCMLPT 370 380 390 400 410 420 SPSVNGRSYD TYTPPHMQTH MNSQPMGTSG TTSTGLISPG VSVPVQVPGS EPDMSQYWPR LQ
	Isoform 5a (Pax6-5a) [UniParc]. Checksum: 76CCA1E7313E2C31	FASTA	436	48,219
	10 20 30 40 50 60 MQNSHSGVNQ LGGVFVNGRP LPDSTRQKIV ELAHSGARPC DISRILQTHA DAKVQVLDNE 70 80 90 100 110 120 NVSNGCVSKI LGRYYETGSI RPRAIGGSKP RVATPEVVSK IAQYKRECPS IFAWEIRDRL 130 140 150 160 170 180 LSEGVCTNDN IPSVSSINRV LRNLASEKQQ MGADGMYDKL RMLNGQTGSW GTRPGWYPGT 190 200 210 220 230 240 SVPGQPTQDG CQQQEGGGEN TNSISSNGED SDEAQMRLQL KRKLQRNRTS FTQEQIEALE 250 260 270 280 290 300 KEFERTHYPD VFARERLAAK IDLPEARIQV WFSNRRAKWR REEKLRNQRR QASNTPSHIP 310 320 330 340 350 360 ISSSFSTSVY QPIPQPTTPV SSFTSGSMLG RTDTALTNTY SALPPMPSFT MANNLPMQPP 370 380 390 400 410 420 VPSQTSSYSC MLPTSPSVNG RSYDTYTPPH MQTHMNSQPM GTSGTTSTGL ISPGVSVPVQ 430 VPGSEPDMSQ YWPRLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Pax-6, a murine paired box gene, is expressed in the developing CNS." Walther C., Gruss P. Development 113:1435-1449(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORMS 1 AND 5A), PARTIAL PROTEIN SEQUENCE.
[2]	"Molecular characterization of Pax6(2Neu) through Pax6(10Neu): an extension of the Pax6 allelic series and the identification of two possible hypomorph alleles in the mouse Mus musculus." Favor J., Peters H., Hermann T., Schmahl W., Chatterjee B., Neuhauser-Klaus A., Sandulache R. Genetics 159:1689-1700(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 5A), VARIANT PRO-259. Strain: C3H. Tissue: Head.
[3]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6J. Tissue: Cerebellum.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5A). Strain: Czech II. Tissue: Eye and Mammary tumor.
[5]	"Pax: a murine multigene family of paired box-containing genes." Walther C., Guenet J.-L., Simon D., Deutsch U., Jostes B., Goulding M.D., Plachov D., Balling R., Gruss P. Genomics 11:424-434(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 4-131.
[6]	"Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene." Ton C.C.T., Miwa H., Saunders G.F. Genomics 13:251-256(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 45-422. Tissue: Embryo.
[7]	"Mouse small eye results from mutations in a paired-like homeobox-containing gene." Hill R.E., Favor J., Hogan B.L.M., Ton C.C.T., Saunders G.F., Hanson I.M., Prosser J., Jordan T., Hastie N.D., van Heyningen V. Nature 354:522-525(1991) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SEY.
[8]	"Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas." St Onge L., Sosa-Pineda B., Chowdhury K., Mansouri A., Gruss P. Nature 387:406-409(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PANCREAS.
[9]	"Pax-6 and c-Maf functionally interact with the alpha-cell-specific DNA element G1 in vivo to promote glucagon gene expression." Gosmain Y., Avril I., Mamin A., Philippe J. J. Biol. Chem. 282:35024-35034(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MAF AND MAFB.
[10]	"Trim11 modulates the function of neurogenic transcription factor Pax6 through ubiquitin-proteosome system." Tuoc T.C., Stoykova A. Genes Dev. 22:1972-1986(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TRIM11, UBIQUITINATION, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X63963 mRNA. Translation: CAA45379.1. X63963 mRNA. Translation: CAA45380.1. Y19196 Genomic DNA. Translation: CAC80516.1. Y19199 Genomic DNA. Translation: CAC80519.1. AK028059 mRNA. Translation: BAC25729.1. BC011272 mRNA. Translation: AAH11272.1. BC036957 mRNA. Translation: AAH36957.1. M77842 mRNA. Translation: AAA40109.1. Different initiation.
IPI	IPI00118638. IPI00459261.
PIR	S42234.
RefSeq	NP_001231127.1. NM_001244198.1. NP_001231129.1. NM_001244200.1. NP_001231130.1. NM_001244201.1. NP_001231131.1. NM_001244202.1. NP_038655.1. NM_013627.5.
UniGene	Mm.33870. Mm.3608. Mm.487124.
3D structure databases
ProteinModelPortal	P63015.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63015. 1 interaction.
MINT	MINT-1782085.
PTM databases
PhosphoSite	P63015.
Proteomic databases
PRIDE	P63015.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000090391; ENSMUSP00000087870; ENSMUSG00000027168. ENSMUST00000090397; ENSMUSP00000087878; ENSMUSG00000027168. ENSMUST00000111082; ENSMUSP00000106711; ENSMUSG00000027168. ENSMUST00000111083; ENSMUSP00000106712; ENSMUSG00000027168. ENSMUST00000111084; ENSMUSP00000106713; ENSMUSG00000027168. ENSMUST00000111085; ENSMUSP00000106714; ENSMUSG00000027168. ENSMUST00000111086; ENSMUSP00000106715; ENSMUSG00000027168. ENSMUST00000111087; ENSMUSP00000106716; ENSMUSG00000027168. ENSMUST00000167211; ENSMUSP00000129344; ENSMUSG00000027168.
GeneID	18508.
KEGG	mmu:18508.
Organism-specific databases
CTD	5080.
MGI	MGI:97490. Pax6.
Phylogenomic databases
eggNOG	NOG326044.
GeneTree	ENSGT00680000099553.
HOVERGEN	HBG009115.
KO	K08031.
OMA	NGQTGTW.
Gene expression databases
ArrayExpress	P63015.
Bgee	P63015.
CleanEx	MM_PAX6.
Genevestigator	P63015.
GermOnline	ENSMUSG00000027168. Mus musculus.
Family and domain databases
Gene3D	1.10.10.10. 2 hits. 1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR001523. Paired_dom. IPR011991. WHTH_DNA-bd_dom. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. PF00292. PAX. 1 hit. [Graphical view]
PRINTS	PR00027. PAIREDBOX.
SMART	SM00389. HOX. 1 hit. SM00351. PAX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 2 hits.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. PS00034. PAIRED_1. 1 hit. PS51057. PAIRED_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	294236.
SOURCE	Search...

Entry information

Entry name

PAX6_MOUSE

Accession

Primary (citable) accession number: P63015
Secondary accession number(s): P32117 , P70601, Q62222, Q64037, Q8CEI5, Q8VDB5, Q921Q8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 31, 2004
Last sequence update:	August 31, 2004
Last modified:	May 1, 2013
This is version 105 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program