PITX2

Functionⁱ

Controls cell proliferation in a tissue-specific manner and is involved in morphogenesis. During embryonic development, exerts a role in the expansion of muscle progenitors. May play a role in the proper localization of asymmetric organs such as the heart and stomach. Isoform PTX2C is involved in left-right asymmetry the developing embryo (By similarity).By similarity

Regions

Feature key	Position(s)	DescriptionActions	Graphical view	Length
DNA bindingⁱ	85 – 144	HomeoboxPROSITE-ProRule annotationAdd BLAST		60

GO - Molecular functionⁱ

DNA-binding transcription factor activity
Source: UniProtKB
Inferred from direct assayⁱ
- "Identification of a dominant negative homeodomain mutation in Rieger syndrome."
  Saadi I., Semina E.V., Amendt B.A., Harris D.J., Murphy K.P., Murray J.C., Russo A.F.
  J Biol Chem 276:23034-23041(2001) [PubMed] [Europe PMC] [Abstract]
DNA-binding transcription factor activity, RNA polymerase II-specific
Source: BHF-UCL
Inferred from direct assayⁱ
- "The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities."
  Amendt B.A., Sutherland L.B., Semina E.V., Russo A.F.
  J Biol Chem 273:20066-20072(1998) [PubMed] [Europe PMC] [Abstract]
DNA-binding transcription repressor activity, RNA polymerase II-specific
Source: BHF-UCL
Inferred from direct assayⁱ
- "Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis."
  Berry F.B., Lines M.A., Oas J.M., Footz T., Underhill D.A., Gage P.J., Walter M.A.
  Hum. Mol. Genet. 15:905-919(2006) [PubMed] [Europe PMC] [Abstract]
identical protein binding
Source: IntAct
Inferred from physical interactionⁱ
- "Dominant negative dimerization of a mutant homeodomain protein in Axenfeld-Rieger syndrome."
  Saadi I., Kuburas A., Engle J.J., Russo A.F.
  Mol Cell Biol 23:1968-1982(2003) [PubMed] [Europe PMC] [Abstract]
phosphoprotein binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- "Proteomic and genomic analysis of PITX2 interacting and regulating networks."
  Huang Y., Huang K., Boskovic G., Dementieva Y., Denvir J., Primerano D.A., Zhu G.Z.
  FEBS Lett 583:638-642(2009) [PubMed] [Europe PMC] [Abstract]
protein homodimerization activity
Source: BHF-UCL
Inferred from physical interactionⁱ
- "Proteomic and genomic analysis of PITX2 interacting and regulating networks."
  Huang Y., Huang K., Boskovic G., Dementieva Y., Denvir J., Primerano D.A., Zhu G.Z.
  FEBS Lett 583:638-642(2009) [PubMed] [Europe PMC] [Abstract]
- "Dominant negative dimerization of a mutant homeodomain protein in Axenfeld-Rieger syndrome."
  Saadi I., Kuburas A., Engle J.J., Russo A.F.
  Mol Cell Biol 23:1968-1982(2003) [PubMed] [Europe PMC] [Abstract]
ribonucleoprotein complex binding
Source: BHF-UCL
Inferred by curatorⁱ
- "Proteomic and genomic analysis of PITX2 interacting and regulating networks."
  Huang Y., Huang K., Boskovic G., Dementieva Y., Denvir J., Primerano D.A., Zhu G.Z.
  FEBS Lett 583:638-642(2009) [PubMed] [Europe PMC] [Abstract]
RNA polymerase II activating transcription factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- "The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities."
  Amendt B.A., Sutherland L.B., Semina E.V., Russo A.F.
  J Biol Chem 273:20066-20072(1998) [PubMed] [Europe PMC] [Abstract]
- "Dominant negative dimerization of a mutant homeodomain protein in Axenfeld-Rieger syndrome."
  Saadi I., Kuburas A., Engle J.J., Russo A.F.
  Mol Cell Biol 23:1968-1982(2003) [PubMed] [Europe PMC] [Abstract]
RNA polymerase II cis-regulatory region sequence-specific DNA binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
RNA polymerase II transcription factor binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- "Cell-specific activation of the atrial natriuretic factor promoter by PITX2 and MEF2A."
  Toro R., Saadi I., Kuburas A., Nemer M., Russo A.F.
  J Biol Chem 279:52087-52094(2004) [PubMed] [Europe PMC] [Abstract]
- "Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis."
  Berry F.B., Lines M.A., Oas J.M., Footz T., Underhill D.A., Gage P.J., Walter M.A.
  Hum. Mol. Genet. 15:905-919(2006) [PubMed] [Europe PMC] [Abstract]
sequence-specific DNA binding
Source: GO_Central
Inferred from biological aspect of ancestorⁱ
- "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
  Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
  Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
sequence-specific double-stranded DNA binding
Source: ARUK-UCL
Inferred from direct assayⁱ
- "Impact of cytosine methylation on DNA binding specificities of human transcription factors."
  Yin Y., Morgunova E., Jolma A., Kaasinen E., Sahu B., Khund-Sayeed S., Das P.K., Kivioja T., Dave K., Zhong F., Nitta K.R., Taipale M., Popov A., Ginno P.A., Domcke S., Yan J., Schubeler D., Vinson C., Taipale J.
  Science 356:0-0(2017) [PubMed] [Europe PMC] [Abstract]
transcription factor binding
Source: UniProtKB
Inferred from physical interactionⁱ
- "Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis."
  Berry F.B., Lines M.A., Oas J.M., Footz T., Underhill D.A., Gage P.J., Walter M.A.
  Hum. Mol. Genet. 15:905-919(2006) [PubMed] [Europe PMC] [Abstract]
transcription regulatory region sequence-specific DNA binding
Source: BHF-UCL
Inferred from direct assayⁱ
- "The molecular basis of Rieger syndrome. Analysis of Pitx2 homeodomain protein activities."
  Amendt B.A., Sutherland L.B., Semina E.V., Russo A.F.
  J Biol Chem 273:20066-20072(1998) [PubMed] [Europe PMC] [Abstract]
- "Dominant negative dimerization of a mutant homeodomain protein in Axenfeld-Rieger syndrome."
  Saadi I., Kuburas A., Engle J.J., Russo A.F.
  Mol Cell Biol 23:1968-1982(2003) [PubMed] [Europe PMC] [Abstract]

Complete GO annotation on QuickGO ...

GO - Biological processⁱ

Complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Developmental protein, DNA-binding

Molecular function

Developmental protein, DNA-binding

Enzyme and pathway databases

PathwayCommonsⁱ	Q99697
Reactomeⁱ	R-HSA-8866906, TFAP2 (AP-2) family regulates transcription of other transcription factors
SignaLinkⁱ	Q99697
SIGNORⁱ	Q99697

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Pituitary homeobox 2Curated Alternative name(s): ALL1-responsive protein ARP1 Homeobox protein PITX2 Paired-like homeodomain transcription factor 2 RIEG bicoid-related homeobox transcription factor Solurshin
Gene namesⁱ	Name:PITX2Imported Synonyms:ARP1, RGS, RIEG, RIEG1
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 4

Organism-specific databases

Human Gene Nomenclature Database More...HGNCⁱ	HGNC:9005, PITX2
MIMⁱ	601542, gene
neXtProtⁱ	NX_Q99697
VEuPathDBⁱ	HostDB:ENSG00000164093.15

Keywords - Cellular componentⁱ

Nucleus

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Axenfeld-Rieger syndrome 1 (RIEG1)5 Publications

The disease is caused by variants affecting the gene represented in this entry.

Disease descriptionAn autosomal dominant disorder of morphogenesis that results in abnormal development of the anterior segment of the eye, and results in blindness from glaucoma in approximately 50% of affected individuals. Additional features include aniridia, maxillary hypoplasia, hypodontia, anal stenosis, redundant periumbilical skin.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_003763	100	L → Q in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893857Ensembl.	1
Natural variantⁱVAR_058735	110	P → L in RIEG1. 2 PublicationsCorresponds to variant dbSNP:rs1057519484Ensembl.	1
Natural variantⁱVAR_058736	110	P → R in RIEG1. 1 Publication	1
Natural variantⁱVAR_003764	114	T → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893858Ensembl.	1
Natural variantⁱVAR_035028	128 – 134	Missing in RIEG1; more than 100-fold reduction in DNA binding activity as well as no detectable transactivation activity.	7
Natural variantⁱVAR_035029	129	V → L in RIEG1; more than 200% increase in transactivation activity. 1 PublicationCorresponds to variant dbSNP:rs121909249Ensembl.	1
Natural variantⁱVAR_058737	134	K → E in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs387906810Ensembl.	1
Natural variantⁱVAR_058738	136	R → C in RIEG1. 2 Publications	1
Natural variantⁱVAR_003766	137	R → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893859Ensembl.	1
Natural variantⁱVAR_058739	151	L → V in RIEG1. 1 Publication	1
Natural variantⁱVAR_058740	154	N → T in RIEG1. 1 Publication	1

Anterior segment dysgenesis 4 (ASGD4)4 Publications

The disease is caused by variants affecting the gene represented in this entry.

Disease descriptionA form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis. ASGD4 is an autosomal dominant disease.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_003765	115	R → H in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs104893861Ensembl.	1
Natural variantⁱVAR_003762	130	R → W in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs121909248Ensembl.	1
Isoform PTX2A (identifier: Q99697-3)
Natural variantⁱVAR_082833	58	F → L in ASGD4. 1 Publication	1

Ring dermoid of cornea (RDC)2 Publications

The disease is caused by variants affecting the gene represented in this entry.

Disease descriptionAn ocular disorder characterized by bilateral annular limbal dermoids (growths with a skin-like structure) with corneal and conjunctival extension.

Related information in OMIM

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Natural variantⁱVAR_035027	108	R → H in RDC; results in 25% loss of transactivation activity. 2 PublicationsCorresponds to variant dbSNP:rs104893862Ensembl.		1

Keywords - Diseaseⁱ

Disease variant, Peters anomaly

Organism-specific databases

DisGeNET More...DisGeNETⁱ	5308
MalaCards human disease database More...MalaCardsⁱ	PITX2
MIMⁱ	137600, phenotype 180500, phenotype 180550, phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000164093
Orphanetⁱ	98978, Axenfeld anomaly 782, Axenfeld-Rieger syndrome 334, Familial atrial fibrillation 708, Peters anomaly 91483, Rieger anomaly 91481, Ring dermoid of cornea
PharmGKBⁱ	PA33339

Miscellaneous databases

Pharosⁱ	Q99697, Tbio

Pharosⁱ

Q99697, Tbio

Genetic variation databases

BioMutaⁱ	PITX2
DMDMⁱ	6174907

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
ChainⁱPRO_0000049223	1 – 317	Pituitary homeobox 2Add BLAST		317

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Modified residueⁱ	90	Phosphothreonine; by PKB/AKT2By similarity		1

Post-translational modificationⁱ

Phosphorylation at Thr-90 impairs its association with the CCND1 mRNA-stabilizing complex thus shortening the half-life of CCND1.By similarity

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

jPOSTⁱ	Q99697
MassIVEⁱ	Q99697
MaxQB - The MaxQuant DataBase More...MaxQBⁱ	Q99697
PaxDbⁱ	Q99697
PeptideAtlas More...PeptideAtlasⁱ	Q99697
PRIDEⁱ	Q99697
ProteomicsDBⁱ	78403 [Q99697-1] 78404 [Q99697-2] 78405 [Q99697-3]

PTM databases

iPTMnetⁱ	Q99697
PhosphoSitePlusⁱ	Q99697

Expressionⁱ

Gene expression databases

Bgeeⁱ	ENSG00000164093, Expressed in placenta and 148 other tissues
ExpressionAtlasⁱ	Q99697, baseline and differential
Genevisibleⁱ	Q99697, HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	ENSG00000164093, Tissue enhanced (placenta, retina, skeletal muscle)

HPAⁱ

ENSG00000164093, Tissue enhanced (placenta, retina, skeletal muscle)

Interactionⁱ

Subunit structureⁱ

Interacts with PITX2.

1 Publication

Binary interactionsⁱ

Hide details

Q99697

With	#Exp.	IntAct
CTNNB1 [P35222]	2	EBI-1175211,EBI-491549
YBX1 [P67809]	3	EBI-1175211,EBI-354065
Hoxa1 [P09022] from Mus musculus.	3	EBI-1175211,EBI-3957603

Isoform PTX2C [Q99697-2]

With	#Exp.	IntAct
ANKRD10 - isoform 2 [Q9NXR5-2]	3	EBI-12138495,EBI-12102070
ATN1 [Q86V38]	3	EBI-12138495,EBI-11954292
CYSRT1 [A8MQ03]	3	EBI-12138495,EBI-3867333
DAZAP2 [Q15038]	3	EBI-12138495,EBI-724310
DDIT4L [Q96D03]	3	EBI-12138495,EBI-742054
DYNLT1 [P63172]	3	EBI-12138495,EBI-1176455
HEY1 [Q9Y5J3]	3	EBI-12138495,EBI-7231130
HOXA1 [P49639]	3	EBI-12138495,EBI-740785
KRT34 [O76011]	3	EBI-12138495,EBI-1047093
KRTAP15-1 [Q3LI76]	3	EBI-12138495,EBI-11992140
KRTAP19-5 [Q3LI72]	3	EBI-12138495,EBI-1048945
KRTAP19-7 [Q3SYF9]	3	EBI-12138495,EBI-10241353
KRTAP3-3 [Q9BYR6]	3	EBI-12138495,EBI-3957694
KRTAP6-1 [Q3LI64]	3	EBI-12138495,EBI-12111050
KRTAP7-1 [Q8IUC3]	3	EBI-12138495,EBI-18394498
OIP5 [O43482]	3	EBI-12138495,EBI-536879
PFDN5 [Q99471]	3	EBI-12138495,EBI-357275
POU2AF1 [Q16633]	3	EBI-12138495,EBI-943588
PSMB4 [P28070]	3	EBI-12138495,EBI-603350
RBPMS - isoform C [Q93062-3]	3	EBI-12138495,EBI-740343
SMUG1 - isoform 2 [Q53HV7-2]	3	EBI-12138495,EBI-12275818
TBX22 [Q9Y458]	3	EBI-12138495,EBI-6427217
TEX37 [Q96LM6]	3	EBI-12138495,EBI-743976
TINAGL1 [Q9GZM7]	3	EBI-12138495,EBI-715869
TLE5 - isoform 2 [Q08117-2]	3	EBI-12138495,EBI-11741437
TRAF1 [Q13077]	3	EBI-12138495,EBI-359224
TRIB3 [Q96RU7]	3	EBI-12138495,EBI-492476
UFSP1 [Q6NVU6]	3	EBI-12138495,EBI-12068150
VGLL3 - isoform 2 [A8MV65-2]	3	EBI-12138495,EBI-11957216
WWOX - isoform 5 [Q9NZC7-5]	3	EBI-12138495,EBI-12040603

PITX2 - isoform PTX2A [Q99697-3]

With	#Exp.	IntAct
FOXC1 [Q12948]	6	EBI-1175243,EBI-1175253
MEF2A [Q02078]	2	EBI-1175243,EBI-2656305
itself	5	EBI-1175243,EBI-1175243
Pou1f1 [P10037] from Rattus norvegicus.	2	EBI-1175243,EBI-9825525

GO - Molecular functionⁱ

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGRIDⁱ	111325, 51 interactors
CORUMⁱ	Q99697
IntActⁱ	Q99697, 52 interactors
Molecular INTeraction database More...MINTⁱ	Q99697
STRINGⁱ	9606.ENSP00000304169

Miscellaneous databases

RNActⁱ	Q99697, protein

RNActⁱ

Q99697, protein

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	86 – 88	Combined sources	3
Beta strandⁱ	90 – 92	Combined sources	3
Helixⁱ	94 – 106	Combined sources	13
Helixⁱ	112 – 122	Combined sources	11
Helixⁱ	126 – 141	Combined sources	16

Show more details

3D structure databases

SMRⁱ	Q99697
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	Q99697

EvolutionaryTraceⁱ

Q99697

Family & Domainsⁱ

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	279 – 292	OARPROSITE-ProRule annotationAdd BLAST		14
Motifⁱ	285 – 289	Nuclear localization signalSequence analysis		5

Sequence similaritiesⁱ

Belongs to the paired homeobox family. Bicoid subfamily.Curated

Keywords - Domainⁱ

Homeobox

Phylogenomic databases

eggNOGⁱ	KOG0486, Eukaryota
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00940000162789
HOGENOMⁱ	CLU_030301_0_0_1
InParanoidⁱ	Q99697
OMAⁱ	YEDMYPS
Database of Orthologous Groups More...OrthoDBⁱ	1432356at2759
PhylomeDBⁱ	Q99697
TreeFamⁱ	TF351940

Family and domain databases

Conserved Domains Database More...CDDⁱ	cd00086, homeodomain, 1 hit
InterProⁱ	View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR016233, Homeobox_Pitx/unc30 IPR003654, OAR_dom
Pfam protein domain database More...Pfamⁱ	View protein in Pfam PF00046, Homeodomain, 1 hit PF03826, OAR, 1 hit
PIRSFⁱ	PIRSF000563, Homeobox_protein_Pitx/Unc30, 1 hit
SMARTⁱ	View protein in SMART SM00389, HOX, 1 hit
SUPFAMⁱ	SSF46689, SSF46689, 1 hit
PROSITEⁱ	View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit PS50803, OAR, 1 hit

Sequences (3+)ⁱ

Sequence statusⁱ: Complete.

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show all Align All

Isoform PTX2B (identifier: Q99697-1) [UniParc]FASTA Add to basket

Also known as: ARP1B

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

« Hide

        10         20         30         40         50
METNCRKLVS ACVQLGVQPA AVECLFSKDS EIKKVEFTDS PESRKEAASS 
        60         70         80         90        100
KFFPRQHPGA NEKDKSQQGK NEDVGAEDPS KKKRQRRQRT HFTSQQLQEL 
       110        120        130        140        150
EATFQRNRYP DMSTREEIAV WTNLTEARVR VWFKNRRAKW RKRERNQQAE 
       160        170        180        190        200
LCKNGFGPQF NGLMQPYDDM YPGYSYNNWA AKGLTSASLS TKSFPFFNSM 
       210        220        230        240        250
NVNPLSSQSM FSPPNSISSM SMSSSMVPSA VTGVPGSSLN SLNNLNNLSS 
       260        270        280        290        300
PSLNSAVPTP ACPYAPPTPP YVYRDTCNSS LASLRLKAKQ HSSFGYASVQ 
       310 
NPASNLSACQ YAVDRPV

Length:317

Mass (Da):35,370

Last modified:July 15, 1999 - v2

Checksum:ⁱ00853AFDBA4433CB

GO

Isoform PTX2C (identifier: Q99697-2) [UniParc]FASTA Add to basket

Also known as: ARP1C

The sequence of this isoform differs from the canonical sequence as follows:
1-61: METNCRKLVS...FFPRQHPGAN → MNCMKGPLHL...ISDTSSPEAA

« Hide

        10         20         30         40         50
MNCMKGPLHL EHRAAGTKLS AVSSSSCHHP QPLAMASVLA PGQPRSLDSS 
        60         70         80         90        100
KHRLEVHTIS DTSSPEAAEK DKSQQGKNED VGAEDPSKKK RQRRQRTHFT 
       110        120        130        140        150
SQQLQELEAT FQRNRYPDMS TREEIAVWTN LTEARVRVWF KNRRAKWRKR 
       160        170        180        190        200
ERNQQAELCK NGFGPQFNGL MQPYDDMYPG YSYNNWAAKG LTSASLSTKS 
       210        220        230        240        250
FPFFNSMNVN PLSSQSMFSP PNSISSMSMS SSMVPSAVTG VPGSSLNSLN 
       260        270        280        290        300
NLNNLSSPSL NSAVPTPACP YAPPTPPYVY RDTCNSSLAS LRLKAKQHSS 
       310        320 
FGYASVQNPA SNLSACQYAV DRPV

Show »

Length:324

Mass (Da):35,796

Checksum:ⁱ7379DD12E1B0013C

GO

Isoform PTX2A (identifier: Q99697-3) [UniParc]FASTA Add to basket

Also known as: ARP1A

The sequence of this isoform differs from the canonical sequence as follows:
16-61: Missing.

« Hide

        10         20         30         40         50
METNCRKLVS ACVQLEKDKS QQGKNEDVGA EDPSKKKRQR RQRTHFTSQQ 
        60         70         80         90        100
LQELEATFQR NRYPDMSTRE EIAVWTNLTE ARVRVWFKNR RAKWRKRERN 
       110        120        130        140        150
QQAELCKNGF GPQFNGLMQP YDDMYPGYSY NNWAAKGLTS ASLSTKSFPF 
       160        170        180        190        200
FNSMNVNPLS SQSMFSPPNS ISSMSMSSSM VPSAVTGVPG SSLNSLNNLN 
       210        220        230        240        250
NLSSPSLNSA VPTPACPYAP PTPPYVYRDT CNSSLASLRL KAKQHSSFGY 
       260        270 
ASVQNPASNL SACQYAVDRP V

Show »

Length:271

Mass (Da):30,336

Checksum:ⁱ45D2ADA6DF03FF65

GO

Computationally mapped potential isoform sequencesⁱ

There are 3 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

Entry	Entry name	Protein names	Gene names	Length	Annotation

D6RFI4	D6RFI4_HUMAN	Pituitary homeobox 2 Pituitary homeobox 2	PITX2	290	Annotation score:
D6RBG8	D6RBG8_HUMAN	Pituitary homeobox 2 Pituitary homeobox 2	PITX2	118	Annotation score:
U3KQ81	U3KQ81_HUMAN	Pituitary homeobox 2 Pituitary homeobox 2	PITX2	264	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Length
Sequence conflictⁱ	13	V → L (PubMed:8944018).Curated	1
Sequence conflictⁱ	13	V → L (Ref. 3) Curated	1
Sequence conflictⁱ	99	E → Q in AAC16257 (PubMed:8944018).Curated	1
Sequence conflictⁱ	127	A → T in BAF84280 (PubMed:14702039).Curated	1
Sequence conflictⁱ	301	N → K (PubMed:8944018).Curated	1
Sequence conflictⁱ	301	N → K (Ref. 3) Curated	1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_003763	100	L → Q in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893857Ensembl.	1
Natural variantⁱVAR_035027	108	R → H in RDC; results in 25% loss of transactivation activity. 2 PublicationsCorresponds to variant dbSNP:rs104893862Ensembl.	1
Natural variantⁱVAR_058735	110	P → L in RIEG1. 2 PublicationsCorresponds to variant dbSNP:rs1057519484Ensembl.	1
Natural variantⁱVAR_058736	110	P → R in RIEG1. 1 Publication	1
Natural variantⁱVAR_003764	114	T → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893858Ensembl.	1
Natural variantⁱVAR_003765	115	R → H in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs104893861Ensembl.	1
Natural variantⁱVAR_035028	128 – 134	Missing in RIEG1; more than 100-fold reduction in DNA binding activity as well as no detectable transactivation activity.	7
Natural variantⁱVAR_035029	129	V → L in RIEG1; more than 200% increase in transactivation activity. 1 PublicationCorresponds to variant dbSNP:rs121909249Ensembl.	1
Natural variantⁱVAR_003762	130	R → W in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs121909248Ensembl.	1
Natural variantⁱVAR_058737	134	K → E in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs387906810Ensembl.	1
Natural variantⁱVAR_058738	136	R → C in RIEG1. 2 Publications	1
Natural variantⁱVAR_003766	137	R → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893859Ensembl.	1
Natural variantⁱVAR_058739	151	L → V in RIEG1. 1 Publication	1
Natural variantⁱVAR_058740	154	N → T in RIEG1. 1 Publication	1
Isoform PTX2A (identifier: Q99697-3)
Natural variantⁱVAR_082833	58	F → L in ASGD4. 1 Publication	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_002260	1 – 61	METNC…HPGAN → MNCMKGPLHLEHRAAGTKLS AVSSSSCHHPQPLAMASVLA PGQPRSLDSSKHRLEVHTIS DTSSPEAA in isoform PTX2C. 3 PublicationsAdd BLAST		61
Alternative sequenceⁱVSP_002261	16 – 61	Missing in isoform PTX2A. 3 PublicationsAdd BLAST		46

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U69961 mRNA Translation: AAC16257.1 AF048720 mRNA Translation: AAC39716.1 AF048721 mRNA Translation: AAC39717.1 AF048722 mRNA Translation: AAC39718.1 AF238048 Genomic DNA Translation: AAK15048.1 AK127829 mRNA Translation: BAG54582.1 AK291591 mRNA Translation: BAF84280.1 AK313987 mRNA Translation: BAG36699.1 CH471057 Genomic DNA Translation: EAX06262.1 CH471057 Genomic DNA Translation: EAX06263.1 CH471057 Genomic DNA Translation: EAX06264.1 BC013998 mRNA Translation: AAH13998.1 BC106010 mRNA Translation: AAI06011.1
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS3692.1 [Q99697-1] CCDS3693.1 [Q99697-3] CCDS3694.1 [Q99697-2]
NCBI Reference Sequences More...RefSeqⁱ	NP_000316.2, NM_000325.5 [Q99697-2] NP_001191326.1, NM_001204397.1 [Q99697-1] NP_001191327.1, NM_001204398.1 [Q99697-1] NP_001191328.1, NM_001204399.1 [Q99697-3] NP_700475.1, NM_153426.2 [Q99697-1] NP_700476.1, NM_153427.2 [Q99697-3] XP_011530329.1, XM_011532027.2

Genome annotation databases

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
Q99697	Homeobox protein		PONAB		317	UniRef100_Q99697
Homeobox protein		PANTR		317
Homeobox protein		PANPA		317
Homeobox protein		GORGO		317
Pituitary homeobox 2 (Fragment)		HUMAN		290
+4
Q99697-2	Homeobox protein		PANTR		324	UniRef100_Q99697-2
Homeobox protein		PANPA		324
Homeobox protein		GORGO		324
Homeobox protein		PANTR		324
Q99697-3	Homeobox protein		PIG		271	UniRef100_Q99697-3
Homeobox protein		PONAB		271
Homeobox protein		BOBOX		271
Homeobox protein		DELLE		271
Homeobox protein		SAPAP		271
+30

Protein	Similar proteins		Species	Score	Length	Source
Q99697	Homeobox protein		PONAB		317	UniRef90_Q99697
Homeobox protein		PANTR		317
Homeobox protein		PANPA		317
Homeobox protein		GORGO		317
Pituitary homeobox 2 (Fragment)		HUMAN		290
+49
Q99697-2	Homeobox protein		PANTR		324	UniRef90_Q99697-2
Homeobox protein		PANPA		324
Homeobox protein		GORGO		324
Homeobox protein		Aquila chrysaetos chrysaetos		405
Homeobox protein		Hirundo rustica rustica		333
+11
Q99697-3	Isoform Ptx2A of Pituitary homeobox 2		MOUSE		271	UniRef90_P97474-3
Pituitary homeobox 2		RAT		324
Homeobox protein		PAPAN		271
Homeobox protein		CERAT		271
Homeobox protein		MANLE		271
+122

Protein	Similar proteins		Species	Score	Length	Source
Q99697	Isoform Ptx2A of Pituitary homeobox 2		MOUSE		271	UniRef50_P97474-3
Pituitary homeobox 2		RAT		324
Pituitary homeobox 2		XENLA		326
Homeobox protein		PAPAN		271
Homeobox protein		CERAT		271
+280
Q99697-2	Pituitary homeobox 2		CHICK		333	UniRef50_Q99697-2
Homeobox protein		PANTR		324
Homeobox protein		PANPA		324
Homeobox protein		GORGO		324
Homeobox protein		Aquila chrysaetos chrysaetos		405
+100

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	U69961 mRNA Translation: AAC16257.1 AF048720 mRNA Translation: AAC39716.1 AF048721 mRNA Translation: AAC39717.1 AF048722 mRNA Translation: AAC39718.1 AF238048 Genomic DNA Translation: AAK15048.1 AK127829 mRNA Translation: BAG54582.1 AK291591 mRNA Translation: BAF84280.1 AK313987 mRNA Translation: BAG36699.1 CH471057 Genomic DNA Translation: EAX06262.1 CH471057 Genomic DNA Translation: EAX06263.1 CH471057 Genomic DNA Translation: EAX06264.1 BC013998 mRNA Translation: AAH13998.1 BC106010 mRNA Translation: AAI06011.1
CCDSⁱ	CCDS3692.1 [Q99697-1] CCDS3693.1 [Q99697-3] CCDS3694.1 [Q99697-2]
RefSeqⁱ	NP_000316.2, NM_000325.5 [Q99697-2] NP_001191326.1, NM_001204397.1 [Q99697-1] NP_001191327.1, NM_001204398.1 [Q99697-1] NP_001191328.1, NM_001204399.1 [Q99697-3] NP_700475.1, NM_153426.2 [Q99697-1] NP_700476.1, NM_153427.2 [Q99697-3] XP_011530329.1, XM_011532027.2

3D structure databases

Select the link destinations: Protein Data Bank Europe More...PDBeⁱ Protein Data Bank RCSB More...RCSB PDBⁱ Protein Data Bank Japan More...PDBjⁱ Links Updated	PDB entry	Method	Resolution (Å)	Chain	Positions	PDBsum
	2L7F	NMR	-	P	85-144	[»]
	2L7M	NMR	-	P	85-144	[»]
	2LKX	NMR	-	A	85-144	[»]
SMRⁱ	Q99697
ModBaseⁱ	Search...
PDBe-KBⁱ	Search...

Protein-protein interaction databases

BioGRIDⁱ	111325, 51 interactors
CORUMⁱ	Q99697
IntActⁱ	Q99697, 52 interactors
MINTⁱ	Q99697
STRINGⁱ	9606.ENSP00000304169

PTM databases

iPTMnetⁱ	Q99697
PhosphoSitePlusⁱ	Q99697

Genetic variation databases

BioMutaⁱ	PITX2
DMDMⁱ	6174907

Proteomic databases

jPOSTⁱ	Q99697
MassIVEⁱ	Q99697
MaxQBⁱ	Q99697
PaxDbⁱ	Q99697
PeptideAtlasⁱ	Q99697
PRIDEⁱ	Q99697
ProteomicsDBⁱ	78403 [Q99697-1] 78404 [Q99697-2] 78405 [Q99697-3]

Protocols and materials databases

Antibodypediaⁱ	15459, 284 antibodies
The DNASU plasmid repository More...DNASUⁱ	5308

Genome annotation databases

Ensemblⁱ	ENST00000354925; ENSP00000347004; ENSG00000164093 [Q99697-1] ENST00000355080; ENSP00000347192; ENSG00000164093 [Q99697-3] ENST00000394595; ENSP00000378095; ENSG00000164093 [Q99697-1] ENST00000613094; ENSP00000484763; ENSG00000164093 [Q99697-1] ENST00000614423; ENSP00000481951; ENSG00000164093 [Q99697-1] ENST00000616641; ENSP00000484909; ENSG00000164093 [Q99697-3] ENST00000644743; ENSP00000495061; ENSG00000164093 [Q99697-2]
GeneIDⁱ	5308
KEGGⁱ	hsa:5308
UCSCⁱ	uc003iac.4, human [Q99697-1]

Organism-specific databases

CTDⁱ	5308
DisGeNETⁱ	5308
GeneCardsⁱ	PITX2
HGNCⁱ	HGNC:9005, PITX2
HPAⁱ	ENSG00000164093, Tissue enhanced (placenta, retina, skeletal muscle)
MalaCardsⁱ	PITX2
MIMⁱ	137600, phenotype 180500, phenotype 180550, phenotype 601542, gene
neXtProtⁱ	NX_Q99697
OpenTargetsⁱ	ENSG00000164093
Orphanetⁱ	98978, Axenfeld anomaly 782, Axenfeld-Rieger syndrome 334, Familial atrial fibrillation 708, Peters anomaly 91483, Rieger anomaly 91481, Ring dermoid of cornea
PharmGKBⁱ	PA33339
VEuPathDBⁱ	HostDB:ENSG00000164093.15
GenAtlas: human gene database More...GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	KOG0486, Eukaryota
GeneTreeⁱ	ENSGT00940000162789
HOGENOMⁱ	CLU_030301_0_0_1
InParanoidⁱ	Q99697
OMAⁱ	YEDMYPS
OrthoDBⁱ	1432356at2759
PhylomeDBⁱ	Q99697
TreeFamⁱ	TF351940

Enzyme and pathway databases

PathwayCommonsⁱ	Q99697
Reactomeⁱ	R-HSA-8866906, TFAP2 (AP-2) family regulates transcription of other transcription factors
SignaLinkⁱ	Q99697
SIGNORⁱ	Q99697

Miscellaneous databases

BioGRID-ORCSⁱ	5308, 2 hits in 897 CRISPR screens
ChiTaRSⁱ	PITX2, human
EvolutionaryTraceⁱ	Q99697
GeneWikiⁱ	PITX2
GenomeRNAiⁱ	5308
Pharosⁱ	Q99697, Tbio
Protein Ontology More...PROⁱ	PR:Q99697
RNActⁱ	Q99697, protein
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	ENSG00000164093, Expressed in placenta and 148 other tissues
ExpressionAtlasⁱ	Q99697, baseline and differential
Genevisibleⁱ	Q99697, HS

Family and domain databases

CDDⁱ	cd00086, homeodomain, 1 hit
InterProⁱ	View protein in InterPro IPR009057, Homeobox-like_sf IPR017970, Homeobox_CS IPR001356, Homeobox_dom IPR016233, Homeobox_Pitx/unc30 IPR003654, OAR_dom
Pfamⁱ	View protein in Pfam PF00046, Homeodomain, 1 hit PF03826, OAR, 1 hit
PIRSFⁱ	PIRSF000563, Homeobox_protein_Pitx/Unc30, 1 hit
SMARTⁱ	View protein in SMART SM00389, HOX, 1 hit
SUPFAMⁱ	SSF46689, SSF46689, 1 hit
PROSITEⁱ	View protein in PROSITE PS00027, HOMEOBOX_1, 1 hit PS50071, HOMEOBOX_2, 1 hit PS50803, OAR, 1 hit
ProtoNetⁱ	Search...
MobiDBⁱ	Search...

Entry informationⁱ

Entry nameⁱ	PITX2_HUMAN
Accessionⁱ	Q99697Primary (citable) accession number: Q99697 Secondary accession number(s): A8K6C6 Q9BY17
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
	Last sequence update:	July 15, 1999
	Last modified:	February 10, 2021
	This is version 214 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Reference proteome

Documents

Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM
Human entries with genetic variants
List of human entries with genetic variants
Human variants curated from literature reports
Index of human variants curated from literature reports
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
PDB cross-references
Index of Protein Data Bank (PDB) cross-references
SIMILARITY comments
Index of protein domains and families

Annotation systems

Supporting data

UniProtKB - Q99697 (PITX2_HUMAN)

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Pituitary homeobox 2

Select a section on the left to see content.

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Regions

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Nucleus

Nucleus

Other locations

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Keywords - Diseasei

Organism-specific databases

Miscellaneous databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

GO - Molecular functioni

Protein-protein interaction databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Motif

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Phylogenomic databases

Family and domain databases

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Genetic variation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Documents

UniProt is an ELIXIR core data resource

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Keywords - Coding sequence diversityⁱ

Cross-referencesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ