PTHR_BOVIN
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 03-AUG-2022, entry version 127.
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.ENSBTAP00000040744; -.
DR PaxDb; P58073; -.
DR PRIDE; P58073; -.
DR Ensembl; ENSBTAT00000008581; ENSBTAP00000008581; ENSBTAG00000006538.
DR Ensembl; ENSBTAT00000043154; ENSBTAP00000040744; ENSBTAG00000006538.
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; MFAKLFQ; -.
DR OrthoDB; 1359745at2759; -.
DR TreeFam; TF332953; -.
DR Reactome; R-BTA-373080; Class B/2 (Secretin family receptors).
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000006538; Expressed in diaphragm and 85 other 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; 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 /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
