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P28069 (PIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Pituitary-specific positive transcription factor 1

Short name=PIT-1
Alternative name(s):
Growth hormone factor 1
Short name=GHF-1
Gene names
Name:POU1F1
Synonyms:GHF1, PIT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length291 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Activates growth hormone and prolactin genes. Specifically binds to the consensus sequence 5'-TAAAT-3'.

Subcellular location

Nucleus.

Involvement in disease

Pituitary hormone deficiency, combined, 1 (CPHD1) [MIM:613038]: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD1 is characterized by pleiotropic deficiencies of growth hormone, prolactin and thyroid-stimulating hormone, while the production of adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone are preserved. In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen. Some cases present with severe mental retardation along with short stature.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17

Sequence similarities

Belongs to the POU transcription factor family. Class-1 subfamily.

Contains 1 homeobox DNA-binding domain.

Contains 1 POU-specific domain.

Sequence caution

The sequence CAA54440.2 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Dwarfism
   DomainHomeobox
   LigandDNA-binding
   Molecular functionActivator
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell differentiation

Inferred from electronic annotation. Source: Ensembl

cell fate specification

Inferred from electronic annotation. Source: Ensembl

determination of adult lifespan

Inferred from electronic annotation. Source: Ensembl

negative regulation of cell proliferation

Traceable author statement PubMed 9392392. Source: ProtInc

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

nuclear transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of inositol trisphosphate biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of multicellular organism growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 9685346. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 9482665. Source: BHF-UCL

regulation of insulin-like growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

somatotropin secreting cell development

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Traceable author statement Ref.6. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

   Molecular_functionRNA polymerase II activating transcription factor binding

Inferred from physical interaction PubMed 12612071PubMed 9685346. Source: BHF-UCL

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription coactivator activity

Inferred from direct assay PubMed 9685346. Source: BHF-UCL

chromatin binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 9482665. Source: BHF-UCL

transcription corepressor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform B (identifier: P28069-1)

Also known as: Pit-1B; GHF-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 A (identifier: P28069-2)

Also known as: Pit-1A; GHF-2;

The sequence of this isoform differs from the canonical sequence as follows:
     47-47: T → TVPSILSLIQTPKCLCTHFSVTTLGNT
Note: Altered in its ability to trans-activate compared to isoform B.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 291291Pituitary-specific positive transcription factor 1
PRO_0000100697

Regions

Domain124 – 19875POU-specific
DNA binding214 – 27360Homeobox

Natural variations

Alternative sequence471T → TVPSILSLIQTPKCLCTHFS VTTLGNT in isoform A.
VSP_002314
Natural variant41Q → R. Ref.11
Corresponds to variant rs1051612 [ dbSNP | Ensembl ].
VAR_003776
Natural variant191A → V.
Corresponds to variant rs35182189 [ dbSNP | Ensembl ].
VAR_049361
Natural variant241P → L in CPHD1. Ref.8
VAR_003777
Natural variant1351F → C in CPHD1. Ref.12
VAR_010574
Natural variant1431R → Q in CPHD1. Ref.8
VAR_003778
Natural variant1581A → P in CPHD1. Ref.10
VAR_003779
Natural variant1721R → Q in CPHD1; associated with severe impairment of transactivation; has a greatly reduced DNA-binding affinity as the wild-type protein. Ref.16
VAR_063425
Natural variant1741E → G in CPHD1. Ref.13
VAR_010575
Natural variant1791S → R in CPHD1; transactivation capacity of this mutant is markedly decreased on the GH1, PRL, TSHB and POU1F1 genes; abolishes the functional interaction of POU1F1 on the PRL promoter with the coactivator CREBBP but not with the transcription factor LHX3; displays normal nuclear accumulation but a markedly decreased binding to a DNA response element. Ref.17
VAR_063426
Natural variant1931W → R in CPHD1. Ref.15
VAR_015260
Natural variant2271D → Y. Ref.11
Corresponds to variant rs1131815 [ dbSNP | Ensembl ].
VAR_003780
Natural variant2301E → K in CPHD1; associated with less severe impairment of transactivation; has a similar DNA-binding affinity as the wild-type protein. Ref.16
VAR_063427
Natural variant2391P → S in CPHD1; loss of function. Ref.14
VAR_010576
Natural variant2711R → W in CPHD1. Ref.7 Ref.8 Ref.9 Ref.16
VAR_003781

Sequences

Sequence LengthMass (Da)Tools
Isoform B (Pit-1B) (GHF-1) [UniParc].

Last modified August 1, 1992. Version 1.
Checksum: 0866777E3E425873

FASTA29132,912
        10         20         30         40         50         60 
MSCQAFTSAD TFIPLNSDAS ATLPLIMHHS AAECLPVSNH ATNVMSTATG LHYSVPSCHY 

        70         80         90        100        110        120 
GNQPSTYGVM AGSLTPCLYK FPDHTLSHGF PPIHQPLLAE DPTAADFKQE LRRKSKLVEE 

       130        140        150        160        170        180 
PIDMDSPEIR ELEKFANEFK VRRIKLGYTQ TNVGEALAAV HGSEFSQTTI CRFENLQLSF 

       190        200        210        220        230        240 
KNACKLKAIL SKWLEEAEQV GALYNEKVGA NERKRKRRTT ISIAAKDALE RHFGEQNKPS 

       250        260        270        280        290 
SQEIMRMAEE LNLEKEVVRV WFCNRRQREK RVKTSLNQSL FSISKEHLEC R 

« Hide

Isoform A (Pit-1A) (GHF-2) [UniParc].

Checksum: 3982D139208D46FD
Show »

FASTA31735,669

References

[1]"Cloning of the human cDNA for transcription factor Pit-1."
Lew A.M., Elsholtz H.P.
Nucleic Acids Res. 19:6329-6329(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B).
Tissue: Pituitary anterior lobe.
[2]"Nucleotide sequence of the complementary DNA for human Pit-1/GHF-1."
Tatsumi K.I., Notomi T., Amino N., Miyai K.
Biochim. Biophys. Acta 1129:231-234(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM B).
[3]"The structure and the chromosomal location of the human PIT1 gene."
Tatsumi K., Notomi T., Irie Y., Endo Y., Onogi S., Amino N., Miyai K.
Submitted (AUG-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM A).
[4]"A novel pituitary transcription factor is produced by alternative splicing of the human GHF-1/PIT-1 gene."
Delhase M., Vila V., Hooghe-Peters E.L., Castrillo J.-L.
Gene 155:273-275(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-71, ALTERNATIVE SPLICING (ISOFORM A).
Tissue: Placenta.
[5]Delhase M.
Submitted (DEC-2010) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[6]"Characterization of the gene encoding human pituitary-specific transcription factor, Pit-1."
Ohta K., Nobukuni Y., Mitsubuchi H., Ohta T., Tohma T., Jinno Y., Endo F., Matsuda I.
Gene 122:387-388(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-47.
[7]"A 'hot spot' in the Pit-1 gene responsible for combined pituitary hormone deficiency: clinical and molecular correlates."
Cohen L.E., Wondisford F.E., Salvatoni A., Maghnie M., Brucker-Davis F., Weintraub B.D., Radovick S.
J. Clin. Endocrinol. Metab. 80:679-684(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 214-273, VARIANT CPHD1 TRP-271.
[8]"Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency."
Ohta K., Nobukuni Y., Mitsubuchi H., Fujimoto S., Matsuo N., Inagaki H., Endo F., Matsuda I.
Biochem. Biophys. Res. Commun. 189:851-855(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CPHD1 LEU-24; GLN-143 AND TRP-271.
[9]"A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency."
Radovick S., Nations M., Du Y., Berg L.A., Weintraub B.D., Wondisford F.E.
Science 257:1115-1118(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 TRP-271.
[10]"Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia."
Pfaeffle R.W., DiMattia G.E., Parks J.S., Brown M.R., Wit J.M., Jansen M., van der Nat H., van den Brande J.L., Rosenfeld M.G., Ingraham H.A.
Science 257:1118-1121(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 PRO-158.
[11]"Cloning of a human GHF-1/Pit-1 cDNA variant."
Pernasetti F.M., Wera S., Belayew A., Martial J.A.
Nucleic Acids Res. 21:3584-3584(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-4 AND TYR-227.
Tissue: Pituitary.
[12]"A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency."
Pellegrini-Bouiller I., Belicar P., Barlier A., Gunz G., Charvet J.P., Jaquet P., Brue T., Vialettes B., Enjalbert A.
J. Clin. Endocrinol. Metab. 81:2790-2796(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 CYS-135.
[13]"Central hypothyroidism reveals compound heterozygous mutations in the Pit-1 gene."
Brown M.R., Parks J.S., Adess M.E., Rich B.H., Rosenthal I.M., Voss T.C., VanderHeyden T.C., Hurley D.L.
Horm. Res. 49:98-102(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 GLY-174.
[14]"Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency."
Pernasetti F.M., Milner R.D.G., Al-Ashwal A.A.Z., de Zegher F., Chavez V.M., Muller M., Martial J.A.
J. Clin. Endocrinol. Metab. 83:2079-2083(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 SER-239.
[15]"Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the PIT1/POU1F1 gene."
Hendriks-Stegeman B.I., Augustijn K.D., Bakker B., Holthuizen P., van der Vliet P.C., Jansen M.
J. Clin. Endocrinol. Metab. 86:1545-1550(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 ARG-193.
[16]"Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency."
Turton J.P.G., Reynaud R., Mehta A., Torpiano J., Saveanu A., Woods K.S., Tiulpakov A., Zdravkovic V., Hamilton J., Attard-Montalto S., Parascandalo R., Vella C., Clayton P.E., Shalet S., Barton J., Brue T., Dattani M.T.
J. Clin. Endocrinol. Metab. 90:4762-4770(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CPHD1 GLN-172; LYS-230 AND TRP-271, CHARACTERIZATION OF VARIANTS CPHD1 GLN-172 AND LYS-230.
[17]"Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency."
Miyata I., Vallette-Kasic S., Saveanu A., Takeuchi M., Yoshikawa H., Tajima A., Tojo K., Reynaud R., Gueydan M., Enjalbert A., Tajima N., Eto Y., Brue T.
J. Clin. Endocrinol. Metab. 91:4981-4987(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD1 ARG-179, CHARACTERIZATION OF VARIANT CPHD1 ARG-179.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L18781 mRNA. Translation: AAA60093.1.
X62429 mRNA. Translation: CAA44295.1.
D10216 mRNA. Translation: BAA01068.1.
X72215 mRNA. Translation: CAA51017.1.
D12892 Genomic DNA. Translation: BAA02291.1.
X77223, X77224 Genomic DNA. Translation: CAA54440.2. Sequence problems.
X77223, X77224 Genomic DNA. Translation: CAA54441.1.
D11333 Genomic DNA. Translation: BAA34536.1.
CCDSCCDS2919.1. [P28069-1]
CCDS46873.1. [P28069-2]
PIRS18718.
RefSeqNP_000297.1. NM_000306.3. [P28069-1]
NP_001116229.1. NM_001122757.2. [P28069-2]
UniGeneHs.591654.

3D structure databases

ProteinModelPortalP28069.
SMRP28069. Positions 129-273.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111445. 13 interactions.
MINTMINT-1521664.
STRING9606.ENSP00000342931.

PTM databases

PhosphoSiteP28069.

Polymorphism databases

DMDM123408.

Proteomic databases

PaxDbP28069.
PRIDEP28069.

Protocols and materials databases

DNASU5449.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000344265; ENSP00000342931; ENSG00000064835. [P28069-2]
ENST00000350375; ENSP00000263781; ENSG00000064835. [P28069-1]
GeneID5449.
KEGGhsa:5449.
UCSCuc003dqq.1. human. [P28069-1]
uc010hoj.1. human. [P28069-2]

Organism-specific databases

CTD5449.
GeneCardsGC03M087307.
HGNCHGNC:9210. POU1F1.
HPAHPA041646.
MIM173110. gene.
613038. phenotype.
neXtProtNX_P28069.
Orphanet95494. Combined pituitary hormone deficiencies, genetic forms.
226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
PharmGKBPA33534.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG241031.
HOGENOMHOG000116302.
HOVERGENHBG053120.
KOK09363.
OMATATGLHY.
OrthoDBEOG7DJSMG.
PhylomeDBP28069.
TreeFamTF316413.

Gene expression databases

ArrayExpressP28069.
BgeeP28069.
CleanExHS_POU1F1.
GenevestigatorP28069.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
1.10.260.40. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR010982. Lambda_DNA-bd_dom.
IPR015586. Pit_1.
IPR013847. POU.
IPR000327. POU_specific.
[Graphical view]
PANTHERPTHR11636:SF82. PTHR11636:SF82. 1 hit.
PfamPF00046. Homeobox. 1 hit.
PF00157. Pou. 1 hit.
[Graphical view]
PRINTSPR00028. POUDOMAIN.
SMARTSM00389. HOX. 1 hit.
SM00352. POU. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
SSF47413. SSF47413. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS00035. POU_1. 1 hit.
PS00465. POU_2. 1 hit.
PS51179. POU_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPituitary-specific_positive_transcription_factor_1.
GenomeRNAi5449.
NextBio21089.
PROP28069.
SOURCESearch...

Entry information

Entry namePIT1_HUMAN
AccessionPrimary (citable) accession number: P28069
Secondary accession number(s): O75757 expand/collapse secondary AC list , Q15132, Q15133, Q9UD34, Q9UEL3
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: July 9, 2014
This is version 149 of the entry and version 1 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 3

Human chromosome 3: entries, gene names and cross-references to MIM