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O75360 (PROP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 121. 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·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein prophet of Pit-1

Short name=PROP-1
Alternative name(s):
Pituitary-specific homeodomain factor
Gene names
Name:PROP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length226 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.

Subcellular location

Nucleus By similarity.

Tissue specificity

Expressed specifically in embryonic pituitary.

Involvement in disease

Pituitary hormone deficiency, combined, 2 (CPHD2) [MIM:262600]: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD2 is characterized by pleiotropic deficiencies of growth hormone, thyroid-stimulating hormone, follicle-stimulating hormone, luteinizing hormone, prolactin and adrenocorticotropic hormone.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.2 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the paired homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Dwarfism
   DomainHomeobox
   LigandDNA-binding
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processblood vessel development

Inferred from electronic annotation. Source: Ensembl

canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from electronic annotation. Source: Ensembl

central nervous system development

Traceable author statement Ref.2. Source: ProtInc

dorsal/ventral pattern formation

Inferred from electronic annotation. Source: Ensembl

hypophysis morphogenesis

Inferred from electronic annotation. Source: Ensembl

hypothalamus cell differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

somatotropin secreting cell differentiation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentnucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionchromatin binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: InterPro

transcription regulatory region sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

AESQ081174EBI-9027467,EBI-717810

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 226226Homeobox protein prophet of Pit-1
PRO_0000049271

Regions

DNA binding69 – 12860Homeobox

Natural variations

Natural variant201N → S. Ref.1 Ref.2 Ref.4
Corresponds to variant rs7445271 [ dbSNP | Ensembl ].
VAR_054972
Natural variant731R → C in CPHD2; familial; no detectable DNA binding observed with the mutant protein in electromobility shift assays; whereas in vitro translated PROP1 and the mutant proteins were similar in their expression and electrophoretic properties. Ref.1 Ref.7 Ref.9
VAR_003768
Natural variant731R → H in CPHD2; familial. Ref.7
VAR_012746
Natural variant881F → S in CPHD2; impairs binding of the mutated protein to DNA target sequences. Ref.6
VAR_063235
Natural variant991R → Q in CPHD2; displays a significant decrease in DNA binding on a paired-box response element (PRDQ9) and trans-activation of a luciferase reporter gene. Ref.8
VAR_063236
Natural variant1171F → I in CPHD2; familial. Ref.2
VAR_003769
Natural variant1201R → C in CPHD2; familial. Ref.2 Ref.5
VAR_003770
Natural variant1251R → W in CPHD2. Ref.10
VAR_054973
Natural variant1421A → T.
Corresponds to variant rs1800197 [ dbSNP | Ensembl ].
VAR_014531

Sequences

Sequence LengthMass (Da)Tools
O75360 [UniParc].

Last modified November 2, 2010. Version 2.
Checksum: CE6D59B3D295A86D

FASTA22624,984
        10         20         30         40         50         60 
MEAERRRQAE KPKKGRVGSN LLPERHPATG TPTTTVDSSA PPCRRLPGAG GGRSRFSPQG 

        70         80         90        100        110        120 
GQRGRPHSRR RHRTTFSPVQ LEQLESAFGR NQYPDIWARE SLARDTGLSE ARIQVWFQNR 

       130        140        150        160        170        180 
RAKQRKQERS LLQPLAHLSP AAFSSFLPES TACPYSYAAP PPPVTCFPHP YSHALPSQPS 

       190        200        210        220 
TGGAFALSHQ SEDWYPTLHP APAGHLPCPP PPPMLPLSLE PSKSWN 

« Hide

References

« Hide 'large scale' references
[1]"Human Prop-1: cloning, mapping, genomic structure. Mutations in familial combined pituitary hormone deficiency."
Duquesnoy P., Roy A., Dastot F., Ghali I., Teinturier C., Netchine I., Cacheux V., Hafez M., Salah N., Chaussain J.-L., Goossens M., Bougneres P., Amselem S.
FEBS Lett. 437:216-220(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANTS SER-20 AND CPHD CYS-73.
[2]"Mutations in PROP1 cause familial combined pituitary hormone deficiency."
Wu W., Cogan J.D., Pfaeffle R.W., Dasen J.S., Frisch H., O'Connell S.M., Flynn S.E., Brown M.R., Mullis P.E., Parks J.S., Phillips J.A. III, Rosenfeld M.G.
Nat. Genet. 18:147-149(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-20; CPHD2 ILE-117 AND CYS-120.
[3]"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].
[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], VARIANT SER-20.
[5]"Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C)."
Fluck C., Deladoey J., Rutishauser K., Eble A., Marti U., Wu W., Mullis P.E.
J. Clin. Endocrinol. Metab. 83:3727-3734(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD2 CYS-120.
[6]"Combined pituitary hormone deficiency caused by a novel mutation of a highly conserved residue (F88S) in the homeodomain of PROP-1."
Osorio M.G., Kopp P., Marui S., Latronico A.C., Mendonca B.B., Arnhold I.J.
J. Clin. Endocrinol. Metab. 85:2779-2785(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD2 SER-88, CHARACTERIZATION OF VARIANT CPHD2 SER-88.
[7]"PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency."
Vallette-Kasic S., Barlier A., Teinturier C., Diaz A., Manavela M., Berthezene F., Bouchard P., Chaussain J.-L., Brauner R., Pellegrini-Bouiller I., Jaquet P., Enjalbert A., Brue T.
J. Clin. Endocrinol. Metab. 86:4529-4535(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CPHD2 CYS-73 AND HIS-73.
[8]"Familial combined pituitary hormone deficiency due to a novel mutation R99Q in the hot spot region of Prophet of Pit-1 presenting as constitutional growth delay."
Vieira T.C., Dias da Silva M.R., Cerutti J.M., Brunner E., Borges M., Arnaldi L.T., Kopp P., Abucham J.
J. Clin. Endocrinol. Metab. 88:38-44(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD2 GLN-99.
[9]"A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies."
Reynaud R., Chadli-Chaieb M., Vallette-Kasic S., Barlier A., Sarles J., Pellegrini-Bouiller I., Enjalbert A., Chaieb L., Brue T.
J. Clin. Endocrinol. Metab. 89:5779-5786(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD2 CYS-73, CHARACTERIZATION OF VARIANT CPHD2 CYS-73.
[10]"Molecular analysis of novel PROP1 mutations associated with combined pituitary hormone deficiency (CPHD)."
Kelberman D., Turton J.P., Woods K.S., Mehta A., Al-Khawari M., Greening J., Swift P.G., Otonkoski T., Rhodes S.J., Dattani M.T.
Clin. Endocrinol. (Oxf.) 70:96-103(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD2 TRP-125.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF076214 Genomic DNA. Translation: AAC77453.1.
AF076215 mRNA. Translation: AAC77454.1.
AF041141, AF041139, AF041140 Genomic DNA. Translation: AAC27900.1.
AC136940 Genomic DNA. No translation available.
BC069076 mRNA. Translation: AAH69076.1.
RefSeqNP_006252.3. NM_006261.4.
UniGeneHs.158301.

3D structure databases

ProteinModelPortalO75360.
SMRO75360. Positions 71-128.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111610. 2 interactions.
IntActO75360. 9 interactions.
STRING9606.ENSP00000311290.

PTM databases

PhosphoSiteO75360.

Proteomic databases

PaxDbO75360.
PRIDEO75360.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000308304; ENSP00000311290; ENSG00000175325.
GeneID5626.
KEGGhsa:5626.
UCSCuc003mif.1. human.

Organism-specific databases

CTD5626.
GeneCardsGC05M177419.
HGNCHGNC:9455. PROP1.
MIM262600. phenotype.
601538. gene.
neXtProtNX_O75360.
Orphanet95494. Combined pituitary hormone deficiencies, genetic forms.
226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
90695. Panhypopituitarism.
PharmGKBPA33808.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG293463.
HOGENOMHOG000115706.
HOVERGENHBG053691.
InParanoidO75360.
KOK09327.
OMATCFPHPY.
OrthoDBEOG7P8P9G.
PhylomeDBO75360.
TreeFamTF315976.

Gene expression databases

BgeeO75360.
CleanExHS_PROP1.
GenevestigatorO75360.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR000047. HTH_motif.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00031. HTHREPRESSR.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPROP1.
GenomeRNAi5626.
NextBio21868.
PROO75360.
SOURCESearch...

Entry information

Entry namePROP1_HUMAN
AccessionPrimary (citable) accession number: O75360
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: November 2, 2010
Last modified: March 19, 2014
This is version 121 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