PTHR_RAT
ID PTHR_RAT Reviewed; 177 AA.
AC P13085;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 135.
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=Osteostatin;
DE Flags: Precursor;
GN Name=Pthlh; Synonyms=Pthrp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3175653; DOI=10.1126/science.3175653;
RA Thiede M.A., Rodan G.A.;
RT "Expression of a calcium-mobilizing parathyroid hormone-like peptide in
RT lactating mammary tissue.";
RL Science 242:278-280(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2747658; DOI=10.1210/mend-3-3-518;
RA Yasuda T., Banville D., Rabbani S.A., Hendy G.N., Goltzman D.;
RT "Rat parathyroid hormone-like peptide: comparison with the human homologue
RT and expression in malignant and normal tissue.";
RL Mol. Endocrinol. 3:518-525(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2342478; DOI=10.1210/mend-4-3-441;
RA Karaplis A.C., Yasuda T., Hendy G.N., Goltzman D., Banville D.;
RT "Gene-encoding parathyroid hormone-like peptide: nucleotide sequence of the
RT rat gene and comparison with the human homologue.";
RL Mol. Endocrinol. 4:441-446(1990).
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 teethRequired 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).
CC {ECO:0000250}.
CC -!- FUNCTION: Osteostatin is a potent inhibitor of osteoclastic bone
CC resorption. {ECO:0000250}.
CC -!- SUBUNIT: PTHrP interacts with PTH1R (via N-terminal extracellular
CC domain). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Secreted {ECO:0000250}.
CC -!- PTM: There are several secretory forms, including osteostatin, arising
CC from endoproteolytic cleavage of the initial translation product. Each
CC of 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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the parathyroid hormone family. {ECO:0000305}.
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DR EMBL; M21967; AAA41981.1; -; mRNA.
DR EMBL; M31603; AAA41980.1; -; mRNA.
DR EMBL; M34112; AAA41889.1; -; Genomic_DNA.
DR EMBL; M34108; AAA41889.1; JOINED; Genomic_DNA.
DR EMBL; M34111; AAA41889.1; JOINED; Genomic_DNA.
DR PIR; A34723; A30012.
DR RefSeq; NP_036768.1; NM_012636.1.
DR AlphaFoldDB; P13085; -.
DR BMRB; P13085; -.
DR SMR; P13085; -.
DR PhosphoSitePlus; P13085; -.
DR PRIDE; P13085; -.
DR GeneID; 24695; -.
DR KEGG; rno:24695; -.
DR UCSC; RGD:3441; rat.
DR CTD; 5744; -.
DR RGD; 3441; Pthlh.
DR InParanoid; P13085; -.
DR OrthoDB; 1359745at2759; -.
DR PhylomeDB; P13085; -.
DR Reactome; R-RNO-373080; Class B/2 (Secretin family receptors).
DR PRO; PR:P13085; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005179; F:hormone activity; IDA:RGD.
DR GO; GO:0051428; F:peptide hormone receptor binding; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0001958; P:endochondral ossification; ISO:RGD.
DR GO; GO:0007492; P:endoderm development; ISO:RGD.
DR GO; GO:0030855; P:epithelial cell differentiation; ISO:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0060649; P:mammary gland bud elongation; ISO:RGD.
DR GO; GO:0061182; P:negative regulation of chondrocyte development; ISO:RGD.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0060659; P:nipple sheath formation; ISO:RGD.
DR GO; GO:0002076; P:osteoblast development; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0016485; P:protein processing; ISO:RGD.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR GO; GO:0043129; P:surfactant homeostasis; ISO:RGD.
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 2: Evidence at transcript level;
KW Calcium; Cleavage on pair of basic residues; Cytoplasm; Hormone; Nucleus;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..34
FT /id="PRO_0000023235"
FT CHAIN 37..177
FT /note="Parathyroid hormone-related protein"
FT /id="PRO_0000023236"
FT PEPTIDE 143..175
FT /note="Osteostatin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000023237"
FT REGION 57..68
FT /note="Important for receptor binding"
FT /evidence="ECO:0000250"
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:0000250"
FT COMPBIAS 74..88
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 COMPBIAS 146..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 177 AA; 20204 MW; 11091EC48CA73B20 CRC64;
MLRRLVQQWS VLVFLLSYSV PSRGRSVEGL GRRLKRAVSE HQLLHDKGKS IQDLRRRFFL
HHLIAEIHTA EIRATSEVSP NSKPAPNTKN HPVRFGSDDE GRYLTQETNK VETYKEQPLK
TPGKKKKGKP GKRREQEKKK RRTRSAWPGT TGSGLLEDPQ PHTSPTSTSL EPSSRTH
