PTHR_HUMAN
ID PTHR_HUMAN Reviewed; 177 AA.
AC P12272; Q15251; Q6FH74;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Parathyroid hormone-related protein;
DE Short=PTH-rP;
DE Short=PTHrP;
DE AltName: Full=Parathyroid hormone-like protein;
DE Short=PLP;
DE Contains:
DE RecName: Full=PTHrP[1-36];
DE Contains:
DE RecName: Full=PTHrP[38-94];
DE Contains:
DE RecName: Full=Osteostatin;
DE AltName: Full=PTHrP[107-139];
DE Flags: Precursor;
GN Name=PTHLH; Synonyms=PTHRP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3616618; DOI=10.1126/science.3616618;
RA Suva L.J., Winslow G.A., Wettenhall R.E.H., Hammonds R.G., Moseley J.M.,
RA Diefenbach-Jagger H., Rodda C.P., Kemp B.E., Rodriguez H., Chen E.Y.,
RA Hudson P.J., Martin T.J., Wood W.I.;
RT "A parathyroid hormone-related protein implicated in malignant
RT hypercalcemia: cloning and expression.";
RL Science 237:893-896(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2829195; DOI=10.1073/pnas.85.2.597;
RA Mangin M., Webb A.C., Dreyer B.E., Posillico J.T., Ikeda K., Weir E.C.,
RA Stewart A.F., Bander N.H., Milstone L., Barton D.E., Francke U.,
RA Broadus A.E.;
RT "Identification of a cDNA encoding a parathyroid hormone-like peptide from
RT a human tumor associated with humoral hypercalcemia of malignancy.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:597-601(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2708388; DOI=10.1016/s0021-9258(18)83294-x;
RA Yasuda T., Banville D., Hendy G.N., Goltzman D.;
RT "Characterization of the human parathyroid hormone-like peptide gene.
RT Functional and evolutionary aspects.";
RL J. Biol. Chem. 264:7720-7725(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=3290897; DOI=10.1073/pnas.85.13.4605;
RA Thiede M.A., Strewler G.J., Nissenson R.A., Rosenblatt M., Rodan G.A.;
RT "Human renal carcinoma expresses two messages encoding a parathyroid
RT hormone-like peptide: evidence for the alternative splicing of a single-
RT copy gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:4605-4609(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE OF 1-33.
RC TISSUE=Liver;
RX PubMed=2744490; DOI=10.1016/0378-1119(89)90363-6;
RA Suva L.J., Mather K.A., Gillespie M.T., Webb G.C., Ng K.W., Winslow G.A.,
RA Wood W.I., Martin T.J., Hudson P.J.;
RT "Structure of the 5' flanking region of the gene encoding human
RT parathyroid-hormone-related protein (PTHrP).";
RL Gene 77:95-105(1989).
RN [9]
RP PROTEIN SEQUENCE OF 37-52.
RX PubMed=2885845; DOI=10.1073/pnas.84.14.5048;
RA Moseley J.M., Kubota M., Diefenbach-Jagger H., Wettenhall R.E.H.,
RA Kemp B.E., Suva L.J., Rodda C.P., Ebeling P.R., Hudson P.J., Zajac J.D.,
RA Martin T.J.;
RT "Parathyroid hormone-related protein purified from a human lung cancer cell
RT line.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:5048-5052(1987).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORM 3).
RX PubMed=2928340; DOI=10.1073/pnas.86.7.2408;
RA Mangin M., Ikeda K., Dreyer B.E., Broadus A.E.;
RT "Isolation and characterization of the human parathyroid hormone-like
RT peptide gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2408-2412(1989).
RN [11]
RP CHARACTERIZATION OF OSTEOSTATIN ACTIVITY.
RX PubMed=1915066; DOI=10.1210/endo-129-4-1762;
RA Fenton A.J., Kemp B.E., Kent G.N., Moseley J.M., Zheng M.H., Rowe D.J.,
RA Britto J.M., Martin T.J., Nicholson G.C.;
RT "A carboxyl-terminal peptide from the parathyroid hormone-related protein
RT inhibits bone resorption by osteoclasts.";
RL Endocrinology 129:1762-1768(1991).
RN [12]
RP CHARACTERIZATION OF OSTEOSTATIN ACTIVITY.
RX PubMed=1954916; DOI=10.1210/endo-129-6-3424;
RA Fenton A.J., Kemp B.E., Hammonds R.G., Mitchelhill K., Moseley J.M.,
RA Martin T.J., Nicholson G.C.;
RT "A potent inhibitor of osteoclastic bone resorption within a highly
RT conserved pentapeptide region of parathyroid hormone-related protein;
RT PTHrP107-111.";
RL Endocrinology 129:3424-3426(1991).
RN [13]
RP CHARACTERIZATION OF OSTEOSTATIN ACTIVITY.
RX PubMed=9144344; DOI=10.1359/jbmr.1997.12.5.778;
RA Martinez M.E., Garcia-Ocana A., Sanchez M., Medina S., del Campo T.,
RA Valin A., Sanchez-Cabezudo M.J., Esbrit P.;
RT "C-terminal parathyroid hormone-related protein inhibits proliferation and
RT differentiation of human osteoblast-like cells.";
RL J. Bone Miner. Res. 12:778-785(1997).
RN [14]
RP CHARACTERIZATION OF OSTEOSTATIN ACTIVITY.
RX PubMed=9048639; DOI=10.1210/endo.138.3.4990;
RA Cornish J., Callon K.E., Nicholson G.C., Reid I.R.;
RT "Parathyroid hormone-related protein-(107-139) inhibits bone resorption in
RT vivo.";
RL Endocrinology 138:1299-1304(1997).
RN [15]
RP NUCLEOCYTOPLASMIC SHUTTLING.
RX PubMed=12852260; DOI=10.1016/s0083-6729(03)01010-0;
RA Jans D.A., Thomas R.J., Gillespie M.T.;
RT "Parathyroid hormone-related protein (PTHrP): a nucleocytoplasmic shuttling
RT protein with distinct paracrine and intracrine roles.";
RL Vitam. Horm. 66:345-384(2003).
RN [16]
RP NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=11401507; DOI=10.1006/bbrc.2001.4607;
RA Lam M.H., Hu W., Xiao C.Y., Gillespie M.T., Jans D.A.;
RT "Molecular dissection of the importin beta1-recognized nuclear targeting
RT signal of parathyroid hormone-related protein.";
RL Biochem. Biophys. Res. Commun. 282:629-634(2001).
RN [17]
RP REVIEW.
RX PubMed=12538599; DOI=10.1210/en.2002-220818;
RA Fiaschi-Taesch N.M., Stewart A.F.;
RT "Minireview: parathyroid hormone-related protein as an intracrine factor
RT -- trafficking mechanisms and functional consequences.";
RL Endocrinology 144:407-411(2003).
RN [18]
RP FUNCTION.
RX PubMed=20637541; DOI=10.1016/j.canlet.2010.06.009;
RA Mula R.V., Bhatia V., Falzon M.;
RT "PTHrP promotes colon cancer cell migration and invasion in an integrin
RT alpha6beta4-dependent manner through activation of Rac1.";
RL Cancer Lett. 298:119-127(2010).
RN [19]
RP STRUCTURE BY NMR OF 37-70.
RX PubMed=10050767; DOI=10.1016/s0014-5793(98)01658-5;
RA Weidler M., Marx U.C., Seidel G., Schafer W., Hoffmann E., Esswein A.,
RA Rosch P.;
RT "The structure of human parathyroid hormone-related protein(1-34) in near-
RT physiological solution.";
RL FEBS Lett. 444:239-244(1999).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 103-130.
RX PubMed=12504010; DOI=10.1016/s1097-2765(02)00727-x;
RA Cingolani G., Bednenko J., Gillespie M.T., Gerace L.;
RT "Molecular basis for the recognition of a nonclassical nuclear localization
RT signal by importin beta.";
RL Mol. Cell 10:1345-1353(2002).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 48-70 IN COMPLEX WITH PTH1R,
RP INTERACTION WITH PTH1R, AND MUTAGENESIS OF ARG-57; PHE-59; LEU-60; LEU-63;
RP ILE-64 AND HIS-68.
RX PubMed=19674967; DOI=10.1074/jbc.m109.022905;
RA Pioszak A.A., Parker N.R., Gardella T.J., Xu H.E.;
RT "Structural basis for parathyroid hormone-related protein binding to the
RT parathyroid hormone receptor and design of conformation-selective
RT peptides.";
RL J. Biol. Chem. 284:28382-28391(2009).
RN [22]
RP VARIANT [LARGE SCALE ANALYSIS] THR-169.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [23]
RP VARIANTS BDE2 PRO-44 AND PRO-60.
RX PubMed=20170896; DOI=10.1016/j.ajhg.2010.01.023;
RA Klopocki E., Hennig B.P., Dathe K., Koll R., de Ravel T., Baten E.,
RA Blom E., Gillerot Y., Weigel J.F., Krueger G., Hiort O., Seemann P.,
RA Mundlos S.;
RT "Deletion and point mutations of PTHLH cause brachydactyly type E.";
RL Am. J. Hum. Genet. 86:434-439(2010).
CC -!- FUNCTION: Neuroendocrine peptide which is a critical regulator of
CC cellular and organ growth, development, migration, differentiation and
CC survival and of epithelial calcium ion transport. Regulates
CC endochondral bone development and epithelial-mesenchymal interactions
CC during the formation of the mammary glands and teeth. Required for
CC skeletal homeostasis. Promotes mammary mesenchyme differentiation and
CC bud outgrowth by modulating mesenchymal cell responsiveness to BMPs.
CC Up-regulates BMPR1A expression in the mammary mesenchyme and this
CC increases the sensitivity of these cells to BMPs and allows them to
CC respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling
CC in the mesenchyme, in turn, triggers epithelial outgrowth and augments
CC MSX2 expression, which causes the mammary mesenchyme to inhibit hair
CC follicle formation within the nipple sheath (By similarity). Promotes
CC colon cancer cell migration and invasion in an integrin alpha-6/beta-1-
CC dependent manner through activation of Rac1. {ECO:0000250,
CC ECO:0000269|PubMed:20637541}.
CC -!- FUNCTION: Osteostatin is a potent inhibitor of osteoclastic bone
CC resorption. {ECO:0000269|PubMed:20637541}.
CC -!- SUBUNIT: PTHrP interacts with PTH1R (via N-terminal extracellular
CC domain). {ECO:0000269|PubMed:19674967}.
CC -!- INTERACTION:
CC P12272; Q03431: PTH1R; NbExp=4; IntAct=EBI-2372758, EBI-2860297;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=P12272-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P12272-2; Sequence=VSP_004534;
CC Name=3;
CC IsoId=P12272-3; Sequence=VSP_004535;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Also expressed in the mammary gland.
CC -!- PTM: There are 3 principal secretory forms, called PTHrP[1-36],
CC PTHrP[38-94], and osteostatin (PTHrP[107-139]) arising from
CC endoproteolytic cleavage of the initial translation product. Each of
CC these secretory forms is believed to have one or more of its own
CC receptors that mediates the normal paracrine, autocrine and endocrine
CC actions.
CC -!- DISEASE: Brachydactyly E2 (BDE2) [MIM:613382]: A form of brachydactyly.
CC Brachydactyly defines a group of inherited malformations characterized
CC by shortening of the digits due to abnormal development of the
CC phalanges and/or the metacarpals. Brachydactyly type E is characterized
CC by shortening of the fingers mainly in the metacarpals and metatarsals.
CC Wide variability in the number of digits affected occurs from person to
CC person, even in the same family. Some individuals are moderately short
CC of stature. In brachydactyly type E2 variable combinations of
CC metacarpals are involved, with shortening also of the first and third
CC distal and the second and fifth middle phalanges.
CC {ECO:0000269|PubMed:20170896}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the parathyroid hormone family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PTHLHID41897ch12p11.html";
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DR EMBL; M17183; AAA60221.1; -; Genomic_DNA.
DR EMBL; X14304; CAA32480.1; -; Genomic_DNA.
DR EMBL; J03580; AAA60216.1; ALT_SEQ; mRNA.
DR EMBL; M24349; AAA60358.1; -; Genomic_DNA.
DR EMBL; M24348; AAA60358.1; JOINED; Genomic_DNA.
DR EMBL; M24350; AAA60359.1; -; Genomic_DNA.
DR EMBL; M24348; AAA60359.1; JOINED; Genomic_DNA.
DR EMBL; M24349; AAA60359.1; JOINED; Genomic_DNA.
DR EMBL; M24351; AAA60360.1; -; Genomic_DNA.
DR EMBL; M24348; AAA60360.1; JOINED; Genomic_DNA.
DR EMBL; M24349; AAA60360.1; JOINED; Genomic_DNA.
DR EMBL; CR541882; CAG46680.1; -; mRNA.
DR EMBL; CH471094; EAW96573.1; -; Genomic_DNA.
DR EMBL; BC005961; AAH05961.1; -; mRNA.
DR EMBL; J03802; AAA60218.1; -; mRNA.
DR EMBL; M34071; AAA60217.1; -; mRNA.
DR CCDS; CCDS44853.1; -. [P12272-1]
DR CCDS; CCDS8715.1; -. [P12272-2]
DR PIR; A33360; PTHU2L.
DR PIR; C33360; PTHU3L.
DR RefSeq; NP_002811.1; NM_002820.2. [P12272-2]
DR RefSeq; NP_945315.1; NM_198964.1. [P12272-2]
DR RefSeq; NP_945316.1; NM_198965.1. [P12272-1]
DR RefSeq; NP_945317.1; NM_198966.1. [P12272-1]
DR RefSeq; XP_011519076.1; XM_011520774.2. [P12272-1]
DR RefSeq; XP_011519077.1; XM_011520775.2.
DR RefSeq; XP_016875163.1; XM_017019674.1.
DR RefSeq; XP_016875164.1; XM_017019675.1. [P12272-1]
DR PDB; 1BZG; NMR; -; A=37-70.
DR PDB; 1M5N; X-ray; 2.90 A; Q=103-130.
DR PDB; 3FFD; X-ray; 2.00 A; P=37-144.
DR PDB; 3H3G; X-ray; 1.94 A; B=48-70.
DR PDBsum; 1BZG; -.
DR PDBsum; 1M5N; -.
DR PDBsum; 3FFD; -.
DR PDBsum; 3H3G; -.
DR AlphaFoldDB; P12272; -.
DR BMRB; P12272; -.
DR SMR; P12272; -.
DR BioGRID; 111716; 17.
DR IntAct; P12272; 3.
DR MINT; P12272; -.
DR STRING; 9606.ENSP00000441765; -.
DR ChEMBL; CHEMBL3712869; -.
DR GlyGen; P12272; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P12272; -.
DR PhosphoSitePlus; P12272; -.
DR BioMuta; PTHLH; -.
DR DMDM; 131542; -.
DR MassIVE; P12272; -.
DR PaxDb; P12272; -.
DR PeptideAtlas; P12272; -.
DR PRIDE; P12272; -.
DR ProteomicsDB; 52842; -. [P12272-1]
DR ProteomicsDB; 52843; -. [P12272-2]
DR ProteomicsDB; 52844; -. [P12272-3]
DR ABCD; P12272; 4 sequenced antibodies.
DR Antibodypedia; 3662; 414 antibodies from 36 providers.
DR CPTC; P12272; 2 antibodies.
DR DNASU; 5744; -.
DR Ensembl; ENST00000201015.8; ENSP00000201015.4; ENSG00000087494.16. [P12272-2]
DR Ensembl; ENST00000395868.7; ENSP00000379209.3; ENSG00000087494.16. [P12272-2]
DR Ensembl; ENST00000395872.5; ENSP00000379213.1; ENSG00000087494.16. [P12272-1]
DR Ensembl; ENST00000535992.5; ENSP00000440613.1; ENSG00000087494.16. [P12272-2]
DR Ensembl; ENST00000538310.1; ENSP00000441890.1; ENSG00000087494.16. [P12272-3]
DR Ensembl; ENST00000539239.5; ENSP00000441571.1; ENSG00000087494.16. [P12272-1]
DR Ensembl; ENST00000545234.6; ENSP00000441765.1; ENSG00000087494.16. [P12272-1]
DR GeneID; 5744; -.
DR KEGG; hsa:5744; -.
DR MANE-Select; ENST00000545234.6; ENSP00000441765.1; NM_198965.2; NP_945316.1.
DR UCSC; uc001ril.4; human. [P12272-1]
DR CTD; 5744; -.
DR DisGeNET; 5744; -.
DR GeneCards; PTHLH; -.
DR HGNC; HGNC:9607; PTHLH.
DR HPA; ENSG00000087494; Tissue enhanced (parathyroid).
DR MalaCards; PTHLH; -.
DR MIM; 168470; gene.
DR MIM; 613382; phenotype.
DR neXtProt; NX_P12272; -.
DR OpenTargets; ENSG00000087494; -.
DR Orphanet; 93387; Brachydactyly type E.
DR PharmGKB; PA33952; -.
DR VEuPathDB; HostDB:ENSG00000087494; -.
DR eggNOG; ENOG502S3J9; Eukaryota.
DR GeneTree; ENSGT00390000004933; -.
DR InParanoid; P12272; -.
DR OMA; MFAKLFQ; -.
DR PhylomeDB; P12272; -.
DR TreeFam; TF332953; -.
DR PathwayCommons; P12272; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-418555; G alpha (s) signalling events.
DR Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; P12272; -.
DR SIGNOR; P12272; -.
DR BioGRID-ORCS; 5744; 7 hits in 1080 CRISPR screens.
DR EvolutionaryTrace; P12272; -.
DR GeneWiki; Parathyroid_hormone-related_protein; -.
DR GenomeRNAi; 5744; -.
DR Pharos; P12272; Tbio.
DR PRO; PR:P12272; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P12272; protein.
DR Bgee; ENSG00000087494; Expressed in periodontal ligament and 139 other tissues.
DR ExpressionAtlas; P12272; baseline and differential.
DR Genevisible; P12272; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0051428; F:peptide hormone receptor binding; IDA:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:MGI.
DR GO; GO:0030282; P:bone mineralization; IEA:InterPro.
DR GO; GO:0046058; P:cAMP metabolic process; TAS:ProtInc.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0008544; P:epidermis development; TAS:ProtInc.
DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0061182; P:negative regulation of chondrocyte development; IDA:MGI.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IDA:MGI.
DR GO; GO:0002076; P:osteoblast development; IBA:GO_Central.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:ProtInc.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:0001501; P:skeletal system development; IDA:MGI.
DR DisProt; DP00138; -.
DR IDEAL; IID00194; -.
DR InterPro; IPR003626; PTH-rel.
DR InterPro; IPR001415; PTH/PTH-rel.
DR PANTHER; PTHR17223; PTHR17223; 1.
DR Pfam; PF01279; Parathyroid; 1.
DR SMART; SM00087; PTH; 1.
DR PROSITE; PS00335; PARATHYROID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium;
KW Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing;
KW Disease variant; Hormone; Nucleus; Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..34
FT /id="PRO_0000023224"
FT CHAIN 37..177
FT /note="Parathyroid hormone-related protein"
FT /id="PRO_0000023225"
FT PEPTIDE 37..72
FT /note="PTHrP[1-36]"
FT /id="PRO_0000023226"
FT PEPTIDE 74..130
FT /note="PTHrP[38-94]"
FT /id="PRO_0000023227"
FT PEPTIDE 143..175
FT /note="Osteostatin"
FT /id="PRO_0000023228"
FT REGION 57..68
FT /note="Important for receptor binding"
FT REGION 74..177
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 108..129
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:11401507"
FT COMPBIAS 74..92
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 124..140
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 176..177
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:3290897"
FT /id="VSP_004534"
FT VAR_SEQ 176..177
FT /note="RH -> TALLWGLKKKKENNRRTHHMQLMISLFKSPLLLL (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004535"
FT VARIANT 44
FT /note="L -> P (in BDE2; dbSNP:rs267606986)"
FT /evidence="ECO:0000269|PubMed:20170896"
FT /id="VAR_063711"
FT VARIANT 60
FT /note="L -> P (in BDE2; dbSNP:rs267606985)"
FT /evidence="ECO:0000269|PubMed:20170896"
FT /id="VAR_063712"
FT VARIANT 169
FT /note="S -> T (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036433"
FT MUTAGEN 57
FT /note="R->A: Strongly reduced affinity for PTH1R."
FT /evidence="ECO:0000269|PubMed:19674967"
FT MUTAGEN 59
FT /note="F->A: Reduced affinity for PTH1R."
FT /evidence="ECO:0000269|PubMed:19674967"
FT MUTAGEN 60
FT /note="L->A,K: Strongly reduced affinity for PTH1R."
FT /evidence="ECO:0000269|PubMed:19674967"
FT MUTAGEN 63
FT /note="L->A: Reduced affinity for PTH1R."
FT /evidence="ECO:0000269|PubMed:19674967"
FT MUTAGEN 64
FT /note="I->A: Reduced affinity for PTH1R."
FT /evidence="ECO:0000269|PubMed:19674967"
FT MUTAGEN 68
FT /note="H->A: Reduced affinity for PTH1R."
FT /evidence="ECO:0000269|PubMed:19674967"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:1BZG"
FT HELIX 51..67
FT /evidence="ECO:0007829|PDB:3H3G"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:1M5N"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:1M5N"
SQ SEQUENCE 177 AA; 20194 MW; 449FDFEE954C51DB CRC64;
MQRRLVQQWS VAVFLLSYAV PSCGRSVEGL SRRLKRAVSE HQLLHDKGKS IQDLRRRFFL
HHLIAEIHTA EIRATSEVSP NSKPSPNTKN HPVRFGSDDE GRYLTQETNK VETYKEQPLK
TPGKKKKGKP GKRKEQEKKK RRTRSAWLDS GVTGSGLEGD HLSDTSTTSL ELDSRRH
