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P78337 (PITX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pituitary homeobox 1
Alternative name(s):
Hindlimb-expressed homeobox protein backfoot
Homeobox protein PITX1
Paired-like homeodomain transcription factor 1
Gene names
Name:PITX1
Synonyms:BFT, PTX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length314 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb.

Subcellular location

Nucleus.

Involvement in disease

Clubfoot, congenital, with or without deficiency of long bones and/or mirror-image polydactyly (CCF) [MIM:119800]: A congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities. Clubfoot may occur in isolation or as part of a syndrome. Some patients present tibial hemimelia, bilateral patellar hypoplasia, and preaxial mirror-image polydactyly.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.12

Liebenberg syndrome (LBNBG) [MIM:186550]: An upper limb-malformation syndrome characterized by the combination of dysplastic elbow joints and the fusion of wrist bones with consequent radial deviation.
Note: The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving the PITX1 locus results in LBNBG. Translocation t(5;18)(q31.1;q12.3). Additionally, two chromosome 5 deletions located 5'of PITX1 have been found in LBNBG patients. These structural variations cause altered expression of PITX1 in the forelimb via the activation of ectopic enhancers (Ref.9). Ref.9

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
Developmental protein
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processanatomical structure morphogenesis

Traceable author statement Ref.1. Source: ProtInc

branchiomeric skeletal muscle development

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from electronic annotation. Source: Ensembl

embryonic hindlimb morphogenesis

Inferred from electronic annotation. Source: Ensembl

myoblast fate commitment

Inferred from electronic annotation. Source: Ensembl

pituitary gland development

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleolus

Inferred from direct assay. Source: HPA

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionRNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 314314Pituitary homeobox 1
PRO_0000049218

Regions

DNA binding89 – 14860Homeobox
Region147 – 279133Interacts with PIT-1 By similarity
Motif280 – 29314OAR
Motif286 – 2905Nuclear localization signal Potential
Compositional bias19 – 246Poly-Pro

Amino acid modifications

Modified residue11N-acetylmethionine Ref.11
Modified residue461Phosphoserine Ref.7
Modified residue481Phosphoserine Ref.7

Natural variations

Natural variant1301E → K in CCF; reduces the ability to transactivate a luciferase reporter gene; suppresses wild-type activity in a dose-dependent manner. Ref.12
VAR_058113
Natural variant2991G → A. Ref.3 Ref.4 Ref.6
Corresponds to variant rs479632 [ dbSNP | Ensembl ].
VAR_049586

Experimental info

Sequence conflict171L → F in AAC51126. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P78337 [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: F0DFE45E14508A43

FASTA31434,128
        10         20         30         40         50         60 
MDAFKGGMSL ERLPEGLRPP PPPPHDMGPA FHLARPADPR EPLENSASES SDTELPEKER 

        70         80         90        100        110        120 
GGEPKGPEDS GAGGTGCGGA DDPAKKKKQR RQRTHFTSQQ LQELEATFQR NRYPDMSMRE 

       130        140        150        160        170        180 
EIAVWTNLTE PRVRVWFKNR RAKWRKRERN QQLDLCKGGY VPQFSGLVQP YEDVYAAGYS 

       190        200        210        220        230        240 
YNNWAAKSLA PAPLSTKSFT FFNSMSPLSS QSMFSAPSSI SSMTMPSSMG PGAVPGMPNS 

       250        260        270        280        290        300 
GLNNINNLTG SSLNSAMSPG ACPYGTPASP YSVYRDTCNS SLASLRLKSK QHSSFGYGGL 

       310 
QGPASGLNAC QYNS 

« Hide

References

« Hide 'large scale' references
[1]"Backfoot, a novel homeobox gene, maps to human chromosome 5 (BFT) and mouse chromosome 13 (Bft)."
Shang J., Li X., Ring H.Z., Clayton D.A., Francke U.
Genomics 40:108-113(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Human and murine PTX1/Ptx1 gene maps to the region for Treacher Collins syndrome."
Crawford M.J., Lanctot C., Tremblay J.J., Jenkins N.A., Gilbert D.J., Copeland N.G., Beatty B., Drouin J.
Mamm. Genome 8:841-845(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-299.
Tissue: Embryo.
[4]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ALA-299.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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], VARIANT ALA-299.
Tissue: Pancreas and Placenta.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46 AND SER-48, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus."
Spielmann M., Brancati F., Krawitz P.M., Robinson P.N., Ibrahim D.M., Franke M., Hecht J., Lohan S., Dathe K., Nardone A.M., Ferrari P., Landi A., Wittler L., Timmermann B., Chan D., Mennen U., Klopocki E., Mundlos S.
Am. J. Hum. Genet. 91:629-635(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN LBNBG.
[10]"Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly."
Klopocki E., Kahler C., Foulds N., Shah H., Joseph B., Vogel H., Luttgen S., Bald R., Besoke R., Held K., Mundlos S., Kurth I.
Eur. J. Hum. Genet. 20:705-708(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CCF.
[11]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Asymmetric lower-limb malformations in individuals with homeobox PITX1 gene mutation."
Gurnett C.A., Alaee F., Kruse L.M., Desruisseau D.M., Hecht J.T., Wise C.A., Bowcock A.M., Dobbs M.B.
Am. J. Hum. Genet. 83:616-622(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CCF LYS-130, CHARACTERIZATION OF VARIANT CCF LYS-130.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U70370 mRNA. Translation: AAC51126.1.
AF009650, AF009648, AF009649 Genomic DNA. Translation: AAB65251.1.
AK290635 mRNA. Translation: BAF83324.1.
AC004764 Genomic DNA. Translation: AAC17733.1.
AC008406 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW62226.1.
CH471062 Genomic DNA. Translation: EAW62227.1.
BC009412 mRNA. Translation: AAH09412.1.
BC003685 mRNA. Translation: AAH03685.1.
CCDSCCDS4182.1.
RefSeqNP_002644.4. NM_002653.4.
UniGeneHs.84136.

3D structure databases

ProteinModelPortalP78337.
SMRP78337. Positions 89-148.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111324. 9 interactions.
IntActP78337. 3 interactions.
MINTMINT-260914.
STRING9606.ENSP00000265340.

PTM databases

PhosphoSiteP78337.

Polymorphism databases

DMDM108935922.

Proteomic databases

MaxQBP78337.
PaxDbP78337.
PeptideAtlasP78337.
PRIDEP78337.

Protocols and materials databases

DNASU5307.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000265340; ENSP00000265340; ENSG00000069011.
ENST00000506438; ENSP00000427542; ENSG00000069011.
GeneID5307.
KEGGhsa:5307.
UCSCuc010jea.3. human.

Organism-specific databases

CTD5307.
GeneCardsGC05M134363.
H-InvDBHIX0005190.
HGNCHGNC:9004. PITX1.
HPAHPA008743.
MIM119800. phenotype.
186550. phenotype.
602149. gene.
neXtProtNX_P78337.
Orphanet1275. Brachydactyly - elbow wrist dysplasia.
293144. Familial clubfoot due to 5q31 microdeletion.
293150. Familial clubfoot due to PITX1 point mutation.
PharmGKBPA33338.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG249113.
HOGENOMHOG000273886.
HOVERGENHBG068770.
InParanoidP78337.
KOK09356.
OMACKNSYLP.
PhylomeDBP78337.
TreeFamTF351940.

Gene expression databases

ArrayExpressP78337.
BgeeP78337.
CleanExHS_PITX1.
GenevestigatorP78337.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR016233. Homeobox_Pitx/unc30.
IPR009057. Homeodomain-like.
IPR003654. OAR_dom.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF03826. OAR. 1 hit.
[Graphical view]
PIRSFPIRSF000563. Homeobox_protein_Pitx/Unc30. 1 hit.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS50803. OAR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPITX1. human.
GeneWikiPITX1.
GenomeRNAi5307.
NextBio20514.
PROP78337.
SOURCESearch...

Entry information

Entry namePITX1_HUMAN
AccessionPrimary (citable) accession number: P78337
Secondary accession number(s): A8K3M0 expand/collapse secondary AC list , D3DQB0, O14677, O60425, Q9BTI5
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 139 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM