ID   PTHR_BOVIN              Reviewed;         177 AA.
AC   P58073; A6QPN9; Q8HYS1;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   24-JAN-2024, entry version 134.
DE   RecName: Full=Parathyroid hormone-related protein;
DE            Short=PTH-rP;
DE            Short=PTHrP;
DE   Contains:
DE     RecName: Full=Osteostatin;
DE   Flags: Precursor;
GN   Name=PTHLH;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=9584841; DOI=10.1677/jme.0.0200271;
RA   Wojcik S.F., Schanbacher F.L., McCauley L.K., Zhou H., Kartsogiannis V.,
RA   Capen C.C., Rosol T.J.;
RT   "Cloning of bovine parathyroid hormone-related protein (PTHrP) cDNA and
RT   expression of PTHrP mRNA in the bovine mammary gland.";
RL   J. Mol. Endocrinol. 20:271-280(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Holstein-Friesian; TISSUE=Mammary gland;
RA   Onda K., Inaba M., Ono K.;
RT   "Molecular cloning of bovine parathyroid hormone-related protein cDNA.";
RL   Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal spinal cord;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
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).
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   -!- TISSUE SPECIFICITY: Expressed in the mammary gland.
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; AB097837; BAC44840.1; -; mRNA.
DR   EMBL; BC149411; AAI49412.1; -; mRNA.
DR   RefSeq; NP_777178.1; NM_174753.1.
DR   RefSeq; XP_005206971.1; XM_005206914.3.
DR   AlphaFoldDB; P58073; -.
DR   BMRB; P58073; -.
DR   SMR; P58073; -.
DR   STRING; 9913.ENSBTAP00000008581; -.
DR   PaxDb; 9913-ENSBTAP00000040744; -.
DR   Ensembl; ENSBTAT00000008581.5; ENSBTAP00000008581.4; ENSBTAG00000006538.6.
DR   Ensembl; ENSBTAT00000043154.4; ENSBTAP00000040744.3; ENSBTAG00000006538.6.
DR   GeneID; 286767; -.
DR   KEGG; bta:286767; -.
DR   CTD; 5744; -.
DR   VEuPathDB; HostDB:ENSBTAG00000006538; -.
DR   VGNC; VGNC:33517; PTHLH.
DR   eggNOG; ENOG502S3J9; Eukaryota.
DR   GeneTree; ENSGT00390000004933; -.
DR   HOGENOM; CLU_095189_0_0_1; -.
DR   InParanoid; P58073; -.
DR   OMA; LQRWFFA; -.
DR   TreeFam; TF332953; -.
DR   Reactome; R-BTA-373080; Class B/2 (Secretin family receptors).
DR   Reactome; R-BTA-418555; G alpha (s) signalling events.
DR   Proteomes; UP000009136; Chromosome 5.
DR   Bgee; ENSBTAG00000006538; Expressed in diaphragm and 85 other cell types or tissues.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR   GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR   GO; GO:0005179; F:hormone activity; IBA:GO_Central.
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; IBA:GO_Central.
DR   GO; GO:0030282; P:bone mineralization; IEA:InterPro.
DR   GO; GO:0061182; P:negative regulation of chondrocyte development; IEA:Ensembl.
DR   GO; GO:0002076; P:osteoblast development; IBA:GO_Central.
DR   GO; GO:0032330; P:regulation of chondrocyte differentiation; IBA:GO_Central.
DR   GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR   GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR   InterPro; IPR003626; PTH-rel.
DR   InterPro; IPR001415; PTH/PTH-rel.
DR   PANTHER; PTHR17223; PARATHYROID HORMONE-RELATED; 1.
DR   PANTHER; PTHR17223:SF0; PARATHYROID HORMONE-RELATED PROTEIN; 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                   /evidence="ECO:0000250"
FT                   /id="PRO_0000023217"
FT   CHAIN           37..177
FT                   /note="Parathyroid hormone-related protein"
FT                   /id="PRO_0000023218"
FT   PEPTIDE         143..175
FT                   /note="Osteostatin"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000023219"
FT   REGION          57..68
FT                   /note="Important for receptor binding"
FT                   /evidence="ECO:0000250"
FT   REGION          74..149
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   CONFLICT        26
FT                   /note="S -> L (in Ref. 2; BAC44840)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   177 AA;  20408 MW;  6A5B48ECB219EF08 CRC64;
     MLWRLVQQWS VAVFLLSYSV PSCGRSVEEL GRRLKRAVSE HQLLHDKGKS IQDLRRRFFL
     HHLIAEIHTA EIRATSEVSP NSKPAPNTKN HPVRFGSDDE GKYLTQETNK VETYKEQPLK
     TPGKKKKSKP GKRKEQEKKK RRTRSAWLTS YVAGTGLEED YLSDISATSL ELNSRRH
//