HORDB

General Information

ID: hor006400
Uniprot ID: P12272
Protein name: Osteostatin
Gene name: PTHLH
Organism: Homo sapiens (Human)
Family: Parathyroid hormone family
Source: Human
Expression: Ubiquitous. Also expressed in the mammary gland.
Disease: Diseases associated with PTHLH include Brachydactyly, Type E2 and Brachydactyly, Type E1.
Comments: NA
Taxonomy: Homo (genus), Homininae (subfamily), Hominidae (family), Hominoidea (superfamily), Catarrhini (parvorder), Simiiformes (infraorder), Haplorrhini (suborder), Primates (order), Euarchontoglires (superorder), Boreoeutheria, Eutheria, Theria, Mammalia (class), Amniota, Tetrapoda, Dipnotetrapodomorpha, Sarcopterygii (superclass), Euteleostomi, Teleostomi, Gnathostomata, Vertebrata, Craniata (subphylum), Chordata (phylum), Deuterostomia, Bilateria, Eumetazoa, Metazoa (kingdom), Opisthokonta, Eukaryota (superkingdom), cellular organisms
GO MF: GO:0005179 hormone activity; GO:0005515 protein binding; GO:0051428 peptide hormone receptor binding
GO BP: GO:0001501 skeletal system development; GO:0002076 osteoblast development; GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway; GO:0007267 cell-cell signaling; GO:0007565 female pregnancy; GO:0008284 positive regulation of cell population proliferation; GO:0008285 negative regulation of cell population proliferation; GO:0008544 epidermis development; GO:0010468 regulation of gene expression; GO:0030282 bone mineralization; GO:0032330 regulation of chondrocyte differentiation; GO:0032331 negative regulation of chondrocyte differentiation; GO:0046058 cAMP metabolic process; GO:0061182 negative regulation of chondrocyte development
GO CC: GO:0005576 extracellular region; GO:0005615 extracellular space; GO:0005634 nucleus; GO:0005654 nucleoplasm; GO:0005737 cytoplasm; GO:0005794 Golgi apparatus; GO:0005829 cytosol

Sequence Information

Sequence: TRSAWLDSGVTGSGLEGDHLSDTSTTSLELDSR
Length: 33
Propeptide: MQRRLVQQWSVAVFLLSYAVPSCGRSVEGLSRRLKRAVSEHQLLHDKGKSIQDLRRRFFLHHLIAEIHTAEIRATSEVSPNSKPSPNTKNHPVRFGSDDEGRYLTQETNKVETYKEQPLKTPGKKKKGKPGKRKEQEKKKRRTRSAWLDSGVTGSGLEGDHLSDTSTTSLELDSRRH
Signal peptide: MQRRLVQQWSVAVFLLSYAVPSCG
Modification: NA
Glycosylation: NA
Mutagenesis: NA

Activity

Function: Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Up-regulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath (By similarity). Promotes colon cancer cell migration and invasion in an integrin alpha-6/beta-1-dependent manner through activation of Rac1.
Mechanism: NA
Cross BBB: NA
Target: PTH1R
Target Unid: Q03431
IC50: NA
EC50: NA
ED50: NA
kd: NA
Half life: NA

Structure

Disulfide bond: NA
Structure ID: AF-P12272-F1(AlphaFold_DB_ID)

Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)

hor006400_AF2.pdb

hor006400_ESM.pdb

Physical Information

Mass:	402257	Formula:	C142H228N42O58
Absent amino acids:	CFIKMNPQY	Common amino acids:	S
pI:	4.04	Basic residues:	3
Polar residues:	16	Hydrophobic residues:	8
Hydrophobicity:	-60	Boman Index:	-8311
Half-Life:	7.2 hour	Half-Life Yeast:	>20 hour
Half-Life E.Coli:	>10 hour	Aliphatic Index	70.91
Instability Index:	3456.06	Extinction Coefficient cystines:	5500
Absorbance 280nm:	171.88

Literature

PubMed ID: 3616618
Title: A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression.
PubMed ID: 2829195
Title: Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy.
PubMed ID: 2708388
Title: Characterization of the human parathyroid hormone-like peptide gene. Functional and evolutionary aspects.
PubMed ID: 3290897
Title: Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene.
PubMed ID: 15489334
Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
PubMed ID: 2744490
Title: Structure of the 5' flanking region of the gene encoding human parathyroid-hormone-related protein (PTHrP).
PubMed ID: 2885845
Title: Parathyroid hormone-related protein purified from a human lung cancer cell line.
PubMed ID: 2928340
Title: Isolation and characterization of the human parathyroid hormone-like peptide gene.
PubMed ID: 1915066
Title: A carboxyl-terminal peptide from the parathyroid hormone-related protein inhibits bone resorption by osteoclasts.
PubMed ID: 1954916
Title: A potent inhibitor of osteoclastic bone resorption within a highly conserved pentapeptide region of parathyroid hormone-related protein; PTHrP[107-111].
PubMed ID: 9144344
Title: C-terminal parathyroid hormone-related protein inhibits proliferation and differentiation of human osteoblast-like cells.
PubMed ID: 9048639
Title: Parathyroid hormone-related protein-(107-139) inhibits bone resorption in vivo.
PubMed ID: 12852260
Title: Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling protein with distinct paracrine and intracrine roles.
PubMed ID: 11401507
Title: Molecular dissection of the importin beta1-recognized nuclear targeting signal of parathyroid hormone-related protein.
PubMed ID: 12538599
Title: Minireview: parathyroid hormone-related protein as an intracrine factor--trafficking mechanisms and functional consequences.
PubMed ID: 20637541
Title: PTHrP promotes colon cancer cell migration and invasion in an integrin α6β4-dependent manner through activation of Rac1.
PubMed ID: 10050767
Title: The structure of human parathyroid hormone-related protein(1-34) in near-physiological solution.
PubMed ID: 12504010
Title: Molecular basis for the recognition of a nonclassical nuclear localization signal by importin beta.
PubMed ID: 19674967
Title: Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides.
PubMed ID: 16959974
Title: The consensus coding sequences of human breast and colorectal cancers.
PubMed ID: 20170896
Title: Deletion and point mutations of PTHLH cause brachydactyly type E.