ID   PTHR_RABIT              Reviewed;         177 AA.
AC   Q9GLC7;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   25-MAY-2022, entry version 91.
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; Synonyms=PTHRP;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   McCaughern-Carucci J.F., Mitnick M., Emanuel J.R., Dworetzky S.I.;
RT   "Cloning and expression of rabbit parathyroid hormone-related protein.";
RL   Submitted (AUG-2000) 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   -!- 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; AF300703; AAG13414.1; -; mRNA.
DR   RefSeq; NP_001076122.1; NM_001082653.1.
DR   AlphaFoldDB; Q9GLC7; -.
DR   SMR; Q9GLC7; -.
DR   STRING; 9986.ENSOCUP00000011922; -.
DR   GeneID; 100009357; -.
DR   KEGG; ocu:100009357; -.
DR   CTD; 5744; -.
DR   eggNOG; ENOG502S3J9; Eukaryota.
DR   InParanoid; Q9GLC7; -.
DR   OrthoDB; 1359745at2759; -.
DR   Proteomes; UP000001811; 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; IEA:UniProtKB-SubCell.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0051428; F:peptide hormone receptor binding; ISS:UniProtKB.
DR   GO; GO:0030282; P:bone mineralization; IEA:InterPro.
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_0000023232"
FT   CHAIN           37..177
FT                   /note="Parathyroid hormone-related protein"
FT                   /id="PRO_0000023233"
FT   PEPTIDE         143..175
FT                   /note="Osteostatin"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000023234"
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"
SQ   SEQUENCE   177 AA;  20005 MW;  E2D9F4327657B919 CRC64;
     MLRRLVQQWS VAVFLLSYSV PSCGRSVEGP GRRLKRAVSE HQLLHDKGKS IQDLRRRFFL
     HHLIAEIHTA EIRATSEVSP NSKPAANTKN HAVRFGSDDE GRYLTQETNK VEPYKEQPLK
     TPGKKKKGKP GKRKEQEKKK RRTRSAWPLS AGAGSGLAGD HLSDISEPEP ELDSRRH