O75360 (PROP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein prophet of Pit-1
Short name=PROP-1

Alternative name(s):
Pituitary-specific homeodomain factor

Gene names

Name:

PROP1

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	226 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Disease mutation Dwarfism
Domain	Homeobox
Ligand	DNA-binding
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	blood vessel development Inferred from electronic annotation. Source: Compara canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara cell migration Inferred from electronic annotation. Source: Compara central nervous system development Traceable author statement Ref.2. Source: ProtInc dorsal/ventral pattern formation Inferred from electronic annotation. Source: Compara hypophysis morphogenesis Inferred from electronic annotation. Source: Compara hypothalamus cell differentiation Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara somatotropin secreting cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	transcription factor complex Inferred from electronic annotation. Source: Compara
Molecular_function	chromatin binding Inferred from electronic annotation. Source: Compara 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 226	226	Homeobox protein prophet of Pit-1		PRO_0000049271
Regions
	DNA binding	69 – 128	60	Homeobox
Natural variations
	Natural variant	20	1	N → S. Ref.1 Ref.2 Ref.4 Corresponds to variant rs7445271 [ dbSNP | Ensembl ].		VAR_054972
	Natural variant	73	1	R → 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 variant	73	1	R → H in CPHD2; familial. Ref.7		VAR_012746
	Natural variant	88	1	F → S in CPHD2; impairs binding of the mutated protein to DNA target sequences. Ref.6		VAR_063235
	Natural variant	99	1	R → 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 variant	117	1	F → I in CPHD2; familial. Ref.2		VAR_003769
	Natural variant	120	1	R → C in CPHD2; familial. Ref.2 Ref.5		VAR_003770
	Natural variant	125	1	R → W in CPHD2. Ref.10		VAR_054973
	Natural variant	142	1	A → T. Corresponds to variant rs1800197 [ dbSNP | Ensembl ].		VAR_014531

Sequences

	Sequence		Length	Mass (Da)
	O75360 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: CE6D59B3D295A86D	FASTA	226	24,984
	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

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

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.
IPI	IPI00025308.
RefSeq	NP_006252.3. NM_006261.4.
UniGene	Hs.158301.
3D structure databases
ProteinModelPortal	O75360.
SMR	O75360. Positions 71-128.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000311290.
PTM databases
PhosphoSite	O75360.
Proteomic databases
PaxDb	O75360.
PRIDE	O75360.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308304; ENSP00000311290; ENSG00000175325.
GeneID	5626.
KEGG	hsa:5626.
UCSC	uc003mif.1. human.
Organism-specific databases
CTD	5626.
GeneCards	GC05M177419.
HGNC	HGNC:9455. PROP1.
MIM	262600. phenotype. 601538. gene.
neXtProt	NX_O75360.
Orphanet	95494. Combined pituitary hormone deficiencies, genetic forms. 226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function. 90695. Panhypopituitarism.
PharmGKB	PA33808.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG293463.
HOGENOM	HOG000115706.
HOVERGEN	HBG053691.
InParanoid	O75360.
KO	K09327.
OMA	TCFPHPY.
OrthoDB	EOG4BZN3X.
PhylomeDB	O75360.
Gene expression databases
Bgee	O75360.
CleanEx	HS_PROP1.
Genevestigator	O75360.
GermOnline	ENSG00000175325. Homo sapiens.
Family and domain databases
Gene3D	1.10.10.60. 1 hit.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR000047. HTH_motif. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. [Graphical view]
PRINTS	PR00031. HTHREPRESSR.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	5626.
NextBio	21868.
SOURCE	Search...

Entry information

Entry name

PROP1_HUMAN

Accession

Primary (citable) accession number: O75360

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	November 2, 2010
Last modified:	May 1, 2013
This is version 114 of the entry and version 2 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.