P28069 (PIT1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	291 AA.
Sequence status	Complete.
Protein existence	Evidence 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 adrenocorticotrophic 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Inferred from electronic annotation. Source: Compara cell fate specification Inferred from electronic annotation. Source: Compara determination of adult lifespan Inferred from electronic annotation. Source: Compara 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: Compara nuclear transport Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of inositol trisphosphate biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of multicellular organism growth Inferred from electronic annotation. Source: Compara regulation of insulin-like growth factor receptor signaling pathway Inferred from electronic annotation. Source: Compara somatotropin secreting cell development Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA nucleus Inferred from direct assay. Source: HPA
Molecular_function	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: Compara RNA polymerase II transcription coactivator activity Inferred from direct assay PubMed 9685346. Source: BHF-UCL chromatin binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding transcription factor activity Inferred from direct assay PubMed 9482665. Source: BHF-UCL transcription corepressor activity Inferred from electronic annotation. Source: Compara
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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 291	291	Pituitary-specific positive transcription factor 1		PRO_0000100697
Regions
	Domain	124 – 198	75	POU-specific
	DNA binding	214 – 273	60	Homeobox
Natural variations
	Alternative sequence	47	1	T → TVPSILSLIQTPKCLCTHFS VTTLGNT in isoform A.		VSP_002314
	Natural variant	4	1	Q → R. Ref.11 Corresponds to variant rs1051612 [ dbSNP | Ensembl ].		VAR_003776
	Natural variant	19	1	A → V. Corresponds to variant rs35182189 [ dbSNP | Ensembl ].		VAR_049361
	Natural variant	24	1	P → L in CPHD1. Ref.8		VAR_003777
	Natural variant	135	1	F → C in CPHD1. Ref.12		VAR_010574
	Natural variant	143	1	R → Q in CPHD1. Ref.8		VAR_003778
	Natural variant	158	1	A → P in CPHD1. Ref.10		VAR_003779
	Natural variant	172	1	R → 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 variant	174	1	E → G in CPHD1. Ref.13		VAR_010575
	Natural variant	179	1	S → 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 variant	193	1	W → R in CPHD1. Ref.15		VAR_015260
	Natural variant	227	1	D → Y. Ref.11 Corresponds to variant rs1131815 [ dbSNP | Ensembl ].		VAR_003780
	Natural variant	230	1	E → 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 variant	239	1	P → S in CPHD1; loss of function. Ref.14		VAR_010576
	Natural variant	271	1	R → W in CPHD1. Ref.7 Ref.8 Ref.9 Ref.16		VAR_003781

Sequences

	Sequence		Length	Mass (Da)
	Isoform B (Pit-1B) (GHF-1) [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 0866777E3E425873	FASTA	291	32,912
	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
	Isoform A (Pit-1A) (GHF-2) [UniParc]. Checksum: 3982D139208D46FD	FASTA	317	35,669
	10 20 30 40 50 60 MSCQAFTSAD TFIPLNSDAS ATLPLIMHHS AAECLPVSNH ATNVMSTVPS ILSLIQTPKC 70 80 90 100 110 120 LCTHFSVTTL GNTATGLHYS VPSCHYGNQP STYGVMAGSL TPCLYKFPDH TLSHGFPPIH 130 140 150 160 170 180 QPLLAEDPTA ADFKQELRRK SKLVEEPIDM DSPEIRELEK FANEFKVRRI KLGYTQTNVG 190 200 210 220 230 240 EALAAVHGSE FSQTTICRFE NLQLSFKNAC KLKAILSKWL EEAEQVGALY NEKVGANERK 250 260 270 280 290 300 RKRRTTISIA AKDALERHFG EQNKPSSQEI MRMAEELNLE KEVVRVWFCN RRQREKRVKT 310 SLNQSLFSIS KEHLECR

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.

Web resources

GeneReviews

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.
IPI	IPI00000794. IPI00216420.
PIR	S18718.
RefSeq	NP_000297.1. NM_000306.2. NP_001116229.1. NM_001122757.1.
UniGene	Hs.591654.
3D structure databases
ProteinModelPortal	P28069.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1521664.
STRING	9606.ENSP00000342931.
PTM databases
PhosphoSite	P28069.
Polymorphism databases
DMDM	123408.
Proteomic databases
PaxDb	P28069.
PRIDE	P28069.
Protocols and materials databases
DNASU	5449.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000344265; ENSP00000342931; ENSG00000064835. ENST00000350375; ENSP00000263781; ENSG00000064835.
GeneID	5449.
KEGG	hsa:5449.
UCSC	uc003dqq.1. human. uc010hoj.1. human.
Organism-specific databases
CTD	5449.
GeneCards	GC03M087307.
HGNC	HGNC:9210. POU1F1.
HPA	HPA041646.
MIM	173110. gene. 613038. phenotype.
neXtProt	NX_P28069.
Orphanet	95494. Combined pituitary hormone deficiencies, genetic forms. 226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
PharmGKB	PA33534.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG241031.
HOGENOM	HOG000116302.
HOVERGEN	HBG053120.
KO	K09363.
OMA	ATNVMST.
Gene expression databases
ArrayExpress	P28069.
Bgee	P28069.
CleanEx	HS_POU1F1.
Genevestigator	P28069.
GermOnline	ENSG00000064835. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit. 1.10.260.40. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR010982. Lambda_DNA-bd_dom. IPR015586. Pit_1. IPR013847. POU. IPR000327. POU_specific. [Graphical view]
PANTHER	PTHR11636:SF17. PTHR11636:SF17. 1 hit.
Pfam	PF00046. Homeobox. 1 hit. PF00157. Pou. 1 hit. [Graphical view]
PRINTS	PR00028. POUDOMAIN.
SMART	SM00389. HOX. 1 hit. SM00352. POU. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit. SSF47413. Lambda_like_DNA. 1 hit.
PROSITE	PS00027. 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]
ProtoNet	Search...
Other
GenomeRNAi	5449.
NextBio	21089.
SOURCE	Search...

Entry information

Entry name

PIT1_HUMAN

Accession

Primary (citable) accession number: P28069
Secondary accession number(s): O75757 , Q15132, Q15133, Q9UD34, Q9UEL3

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	May 29, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

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.