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Protein

Pituitary homeobox 2

Gene

PITX2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi85 – 144HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • chromatin DNA binding Source: Ensembl
  • DNA binding transcription factor activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • phosphoprotein binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • ribonucleoprotein complex binding Source: BHF-UCL
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: Ensembl
  • RNA polymerase II transcription coactivator activity Source: BHF-UCL
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: Ensembl
  • transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • transcriptional repressor activity, RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB
  • transcription regulatory region sequence-specific DNA binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, DNA-binding

Enzyme and pathway databases

ReactomeiR-HSA-8866906 TFAP2 (AP-2) family regulates transcription of other transcription factors
SignaLinkiQ99697
SIGNORiQ99697

Names & Taxonomyi

Protein namesi
Recommended name:
Pituitary homeobox 2
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:PITX2
Synonyms:ARP1, RGS, RIEG, RIEG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000164093.15
HGNCiHGNC:9005 PITX2
MIMi601542 gene
neXtProtiNX_Q99697

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

Pathology & Biotechi

Involvement in diseasei

Axenfeld-Rieger syndrome 1 (RIEG1)5 Publications
The disease is caused by mutations 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.
See also OMIM:180500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003763100L → Q in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893857Ensembl.1
Natural variantiVAR_058735110P → L in RIEG1. 2 PublicationsCorresponds to variant dbSNP:rs1057519484Ensembl.1
Natural variantiVAR_058736110P → R in RIEG1. 1 Publication1
Natural variantiVAR_003764114T → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893858Ensembl.1
Natural variantiVAR_035028128 – 134Missing in RIEG1; more than 100-fold reduction in DNA binding activity as well as no detectable transactivation activity. 7
Natural variantiVAR_035029129V → L in RIEG1; more than 200% increase in transactivation activity. 1 PublicationCorresponds to variant dbSNP:rs121909249Ensembl.1
Natural variantiVAR_058737134K → E in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs387906810Ensembl.1
Natural variantiVAR_058738136R → C in RIEG1. 2 Publications1
Natural variantiVAR_003766137R → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893859Ensembl.1
Natural variantiVAR_058739151L → V in RIEG1. 1 Publication1
Natural variantiVAR_058740154N → T in RIEG1. 1 Publication1
Anterior segment dysgenesis 4 (ASGD4)4 Publications
The disease is caused by mutations 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.
See also OMIM:137600
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003765115R → H in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs104893861EnsemblClinVar.1
Natural variantiVAR_003762130R → W in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs121909248Ensembl.1
Isoform PTX2A (identifier: Q99697-3)
Natural varianti58F → L in ASGD4. 1 Publication1
Ring dermoid of cornea (RDC)2 Publications
The disease is caused by mutations 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.
See also OMIM:180550
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035027108R → H in RDC; results in 25% loss of transactivation activity. 2 PublicationsCorresponds to variant dbSNP:rs104893862Ensembl.1

Keywords - Diseasei

Disease mutation, Peters anomaly

Organism-specific databases

DisGeNETi5308
GeneReviewsiPITX2
MalaCardsiPITX2
MIMi137600 phenotype
180500 phenotype
180550 phenotype
OpenTargetsiENSG00000164093
Orphaneti98978 Axenfeld anomaly
782 Axenfeld-Rieger syndrome
334 Familial atrial fibrillation
708 Peters anomaly
91483 Rieger anomaly
91481 Ring dermoid of cornea
PharmGKBiPA33339

Polymorphism and mutation databases

BioMutaiPITX2
DMDMi6174907

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000492231 – 317Pituitary homeobox 2Add BLAST317

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei90Phosphothreonine; by PKB/AKT2By similarity1

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

MaxQBiQ99697
PaxDbiQ99697
PeptideAtlasiQ99697
PRIDEiQ99697

PTM databases

iPTMnetiQ99697
PhosphoSitePlusiQ99697

Expressioni

Gene expression databases

BgeeiENSG00000164093
CleanExiHS_PITX2
ExpressionAtlasiQ99697 baseline and differential
GenevisibleiQ99697 HS

Organism-specific databases

HPAiHPA050074
HPA062728

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • phosphoprotein binding Source: BHF-UCL
  • protein homodimerization activity Source: BHF-UCL
  • RNA polymerase II activating transcription factor binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111325, 18 interactors
CORUMiQ99697
IntActiQ99697, 42 interactors
MINTiQ99697
STRINGi9606.ENSP00000304169

Structurei

Secondary structure

1317
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi86 – 88Combined sources3
Beta strandi90 – 92Combined sources3
Helixi94 – 106Combined sources13
Helixi112 – 122Combined sources11
Helixi126 – 141Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2L7FNMR-P85-144[»]
2L7MNMR-P85-144[»]
2LKXNMR-A85-144[»]
ProteinModelPortaliQ99697
SMRiQ99697
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99697

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi279 – 292OARPROSITE-ProRule annotationAdd BLAST14
Motifi285 – 289Nuclear localization signalSequence analysis5

Sequence similaritiesi

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0486 Eukaryota
ENOG410ZZ6J LUCA
GeneTreeiENSGT00900000140776
HOGENOMiHOG000273886
HOVERGENiHBG068770
InParanoidiQ99697
KOiK04686
OMAiPLNIDHH
OrthoDBiEOG091G0H7U
PhylomeDBiQ99697
TreeFamiTF351940

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR016233 Homeobox_Pitx/unc30
IPR003654 OAR_dom
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PF03826 OAR, 1 hit
PIRSFiPIRSF000563 Homeobox_protein_Pitx/Unc30, 1 hit
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
PS50803 OAR, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

Isoform PTX2B (identifier: Q99697-1) [UniParc]FASTAAdd to basket
Also known as: ARP1B

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.

« 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]FASTAAdd to basket
Also known as: ARP1C

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

Show »
Length:324
Mass (Da):35,796
Checksum:i7379DD12E1B0013C
GO
Isoform PTX2A (identifier: Q99697-3) [UniParc]FASTAAdd to basket
Also known as: ARP1A

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

Show »
Length:271
Mass (Da):30,336
Checksum:i45D2ADA6DF03FF65
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13V → L (PubMed:8944018).Curated1
Sequence conflicti13V → L (Ref. 3) Curated1
Sequence conflicti99E → Q in AAC16257 (PubMed:8944018).Curated1
Sequence conflicti127A → T in BAF84280 (PubMed:14702039).Curated1
Sequence conflicti301N → K (PubMed:8944018).Curated1
Sequence conflicti301N → K (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_003763100L → Q in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893857Ensembl.1
Natural variantiVAR_035027108R → H in RDC; results in 25% loss of transactivation activity. 2 PublicationsCorresponds to variant dbSNP:rs104893862Ensembl.1
Natural variantiVAR_058735110P → L in RIEG1. 2 PublicationsCorresponds to variant dbSNP:rs1057519484Ensembl.1
Natural variantiVAR_058736110P → R in RIEG1. 1 Publication1
Natural variantiVAR_003764114T → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893858Ensembl.1
Natural variantiVAR_003765115R → H in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs104893861EnsemblClinVar.1
Natural variantiVAR_035028128 – 134Missing in RIEG1; more than 100-fold reduction in DNA binding activity as well as no detectable transactivation activity. 7
Natural variantiVAR_035029129V → L in RIEG1; more than 200% increase in transactivation activity. 1 PublicationCorresponds to variant dbSNP:rs121909249Ensembl.1
Natural variantiVAR_003762130R → W in ASGD4. 1 PublicationCorresponds to variant dbSNP:rs121909248Ensembl.1
Natural variantiVAR_058737134K → E in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs387906810Ensembl.1
Natural variantiVAR_058738136R → C in RIEG1. 2 Publications1
Natural variantiVAR_003766137R → P in RIEG1. 1 PublicationCorresponds to variant dbSNP:rs104893859Ensembl.1
Natural variantiVAR_058739151L → V in RIEG1. 1 Publication1
Natural variantiVAR_058740154N → T in RIEG1. 1 Publication1
Isoform PTX2A (identifier: Q99697-3)
Natural varianti58F → L in ASGD4. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0022601 – 61METNC…HPGAN → MNCMKGPLHLEHRAAGTKLS AVSSSSCHHPQPLAMASVLA PGQPRSLDSSKHRLEVHTIS DTSSPEAA in isoform PTX2C. 3 PublicationsAdd BLAST61
Alternative sequenceiVSP_00226116 – 61Missing in isoform PTX2A. 3 PublicationsAdd BLAST46

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
CCDSiCCDS3692.1 [Q99697-1]
CCDS3693.1 [Q99697-3]
CCDS3694.1 [Q99697-2]
RefSeqiNP_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 [Q99697-3]
UniGeneiHs.643588
Hs.738484

Genome annotation databases

EnsembliENST00000306732; ENSP00000304169; ENSG00000164093 [Q99697-2]
ENST00000354925; ENSP00000347004; ENSG00000164093 [Q99697-1]
ENST00000355080; ENSP00000347192; ENSG00000164093 [Q99697-3]
ENST00000394598; ENSP00000378097; ENSG00000164093 [Q99697-1]
ENST00000613094; ENSP00000484763; ENSG00000164093 [Q99697-1]
ENST00000614423; ENSP00000481951; ENSG00000164093 [Q99697-1]
ENST00000616641; ENSP00000484909; ENSG00000164093 [Q99697-3]
GeneIDi5308
KEGGihsa:5308
UCSCiuc003iac.4 human [Q99697-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPITX2_HUMAN
AccessioniPrimary (citable) accession number: Q99697
Secondary accession number(s): A8K6C6
, B2RA02, B3KXS0, O60578, O60579, O60580, Q3KQX9, Q9BY17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1999
Last modified: May 23, 2018
This is version 193 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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