PTHR_MOUSE
ID PTHR_MOUSE Reviewed; 175 AA.
AC P22858;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 150.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2249778; DOI=10.1016/0378-1119(90)90362-u;
RA Mangin M., Ikeda K., Broadus A.E.;
RT "Structure of the mouse gene encoding parathyroid hormone-related
RT peptide.";
RL Gene 95:195-202(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [3]
RP FUNCTION.
RX PubMed=17301089; DOI=10.1242/dev.000182;
RA Hens J.R., Dann P., Zhang J.P., Harris S., Robinson G.W., Wysolmerski J.;
RT "BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic
RT mammary development and to inhibit hair follicle induction.";
RL Development 134:1221-1230(2007).
RN [4]
RP FUNCTION.
RX PubMed=20501677; DOI=10.1210/en.2009-1494;
RA Guo J., Liu M., Yang D., Bouxsein M.L., Thomas C.C., Schipani E.,
RA Bringhurst F.R., Kronenberg H.M.;
RT "Phospholipase C signaling via the parathyroid hormone (PTH)/PTH-related
RT peptide receptor is essential for normal bone responses to PTH.";
RL Endocrinology 151:3502-3513(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.
CC {ECO:0000269|PubMed:17301089, ECO:0000269|PubMed:20501677}.
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; M60057; AAA63639.1; -; Genomic_DNA.
DR EMBL; M60058; AAA63639.1; JOINED; Genomic_DNA.
DR EMBL; M60056; AAA63639.1; JOINED; Genomic_DNA.
DR EMBL; BC058187; AAH58187.1; -; mRNA.
DR CCDS; CCDS39717.1; -.
DR PIR; JN0103; JN0103.
DR AlphaFoldDB; P22858; -.
DR BMRB; P22858; -.
DR SMR; P22858; -.
DR STRING; 10090.ENSMUSP00000051433; -.
DR iPTMnet; P22858; -.
DR PhosphoSitePlus; P22858; -.
DR PaxDb; P22858; -.
DR PRIDE; P22858; -.
DR MGI; MGI:97800; Pthlh.
DR eggNOG; ENOG502S3J9; Eukaryota.
DR InParanoid; P22858; -.
DR PhylomeDB; P22858; -.
DR Reactome; R-MMU-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-MMU-418555; G alpha (s) signalling events.
DR PRO; PR:P22858; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P22858; protein.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; TAS:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
DR GO; GO:0005179; F:hormone activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0055074; P:calcium ion homeostasis; TAS:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IMP:MGI.
DR GO; GO:0001958; P:endochondral ossification; IMP:MGI.
DR GO; GO:0007492; P:endoderm development; IDA:MGI.
DR GO; GO:0048286; P:lung alveolus development; IMP:MGI.
DR GO; GO:0060487; P:lung epithelial cell differentiation; IMP:MGI.
DR GO; GO:0010960; P:magnesium ion homeostasis; TAS:MGI.
DR GO; GO:0060649; P:mammary gland bud elongation; IMP:MGI.
DR GO; GO:0061182; P:negative regulation of chondrocyte development; ISO:MGI.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IDA:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0060659; P:nipple sheath formation; IMP:MGI.
DR GO; GO:0002076; P:osteoblast development; IMP:MGI.
DR GO; GO:0055062; P:phosphate ion homeostasis; TAS:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0016485; P:protein processing; IDA:MGI.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IBA:GO_Central.
DR GO; GO:0010468; P:regulation of gene expression; ISO:MGI.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0043129; P:surfactant homeostasis; IMP:MGI.
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_0000023229"
FT CHAIN 37..175
FT /note="Parathyroid hormone-related protein"
FT /id="PRO_0000023230"
FT PEPTIDE 143..173
FT /note="Osteostatin"
FT /evidence="ECO:0000250"
FT /id="PRO_0000023231"
FT REGION 57..68
FT /note="Important for receptor binding"
FT /evidence="ECO:0000250"
FT REGION 74..175
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"
SQ SEQUENCE 175 AA; 20100 MW; 6D27CFCC31900B45 CRC64;
MLRRLVQQWS VLVFLLSYSV PSRGRSVEGL GRRLKRAVSE HQLLHDKGKS IQDLRRRFFL
HHLIAEIHTA EIRATSEVSP NSKPAPNTKN HPVRFGSDDE GRYLTQETNK VETYKEQPLK
TPGKKKKGKP GKRREQEKKK RRTRSAWPST AASGLLEDPL PHTSRTSLEP SLRTH
