PTH4_DANRE
ID PTH4_DANRE Reviewed; 121 AA.
AC A0A1L2F565; A0A286YAB1;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Parathyroid hormone 4 {ECO:0000305|PubMed:28148780};
DE Flags: Precursor;
GN Name=pth4 {ECO:0000303|PubMed:28148780};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000312|EMBL:ANW35450.1};
RN [1] {ECO:0000312|EMBL:ANW35450.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=28148780; DOI=10.1096/fj.201600815r;
RA Suarez-Bregua P., Torres-Nunez E., Saxena A., Guerreiro P., Braasch I.,
RA Prober D.A., Moran P., Cerda-Reverter J.M., Du S.J., Adrio F., Power D.M.,
RA Canario A.V., Postlethwait J.H., Bronner M.E., Canestro C., Rotllant J.;
RT "Pth4, an ancient parathyroid hormone lost in eutherian mammals, reveals a
RT new brain-to-bone signaling pathway.";
RL FASEB J. 31:569-583(2017).
RN [2] {ECO:0000312|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000312|Proteomes:UP000000437};
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Neuroendocrine peptide which is produced by a subset of
CC neurons in the hypothalamus. Activates the G-protein coupled receptors
CC pth1ra, pth1rb and pth2r with similar affinity. Receptor binding
CC stimulates intracellular cAMP production. Plays a role in bone
CC mineralization by regulating expression of factors involved in
CC phosphate homeostasis. Important for embryonic bone development.
CC {ECO:0000269|PubMed:28148780}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:28148780}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in a bilateral cluster of
CC neurons in the dorsal region of the periventricular hypothalamus. Their
CC axons project through the midbrain and hindbrain and down the spinal
CC cord. {ECO:0000269|PubMed:28148780}.
CC -!- DEVELOPMENTAL STAGE: Detected at 0-3 hours post-fertilization (hpf),
CC probably due to inheritance of maternal transcripts. Expression then
CC declines, and increases again from 12 hpf onwards. Detected in the
CC developing hypothalamus from 24 hpf. At 3 days post-fertilization
CC (dpf), found in two subsets of neurons in the lateral hypothalamus.
CC {ECO:0000269|PubMed:28148780}.
CC -!- INDUCTION: Up-regulated by runx2a. {ECO:0000269|PubMed:28148780}.
CC -!- SIMILARITY: Belongs to the parathyroid hormone family. {ECO:0000305}.
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DR EMBL; KT182088; ANW35450.1; -; mRNA.
DR EMBL; CU856139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; A0A1L2F565; -.
DR Ensembl; ENSDART00000179067; ENSDARP00000144118; ENSDARG00000106914.
DR ZFIN; ZDB-GENE-180611-1; pth4.
DR GeneTree; ENSGT00390000004933; -.
DR PRO; PR:A0A1L2F565; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 22.
DR Bgee; ENSDARG00000106914; Expressed in dorsal periventricular hypothalamus and 6 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005179; F:hormone activity; IBA:GO_Central.
DR GO; GO:0051428; F:peptide hormone receptor binding; IBA:GO_Central.
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:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0002076; P:osteoblast development; IBA:GO_Central.
DR GO; GO:0030500; P:regulation of bone mineralization; IMP:ZFIN.
DR GO; GO:0032330; P:regulation of chondrocyte differentiation; IBA:GO_Central.
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.
PE 2: Evidence at transcript level;
KW Cleavage on pair of basic residues; Hormone; Neuropeptide;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..29
FT /evidence="ECO:0000305"
FT /id="PRO_0000443086"
FT PEPTIDE 32..121
FT /note="Parathyroid hormone 4"
FT /evidence="ECO:0000305"
FT /id="PRO_0000443087"
FT REGION 77..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 121 AA; 13799 MW; 55747D88CEFA8B35 CRC64;
MLKMQRSQQR VALMMLMVVA AVHCQESESR RAVTEHQLMH DRGRSIQSLK RLIWLSSAIE
GLHTAQARTL EPDSRWRSRG AQLYSQPGRE ESSGGQKRAL ETLLSDLYRA HLTFGLGEPE
K
