ID   TIP39_HUMAN             Reviewed;         100 AA.
AC   Q96A98; Q96DJ4;
DT   07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 119.
DE   RecName: Full=Tuberoinfundibular peptide of 39 residues;
DE            Short=TIP39;
DE   AltName: Full=Parathyroid hormone 2;
DE   Flags: Precursor;
GN   Name=PTH2; Synonyms=TIP39, TIPF39;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH PTH2R.
RC   TISSUE=Brain;
RX   PubMed=12098667; DOI=10.1677/joe.0.1740095;
RA   Hansen I.A., Jakob O., Wortmann S., Arzberger T., Allolio B., Blind E.;
RT   "Characterization of the human and mouse genes encoding the
RT   tuberoinfundibular peptide of 39 residues, a ligand of the parathyroid
RT   hormone receptor family.";
RL   J. Endocrinol. 174:95-102(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=11818570; DOI=10.1073/pnas.042416199;
RA   Dobolyi A., Ueda H., Uchida H., Palkovits M., Usdin T.B.;
RT   "Anatomical and physiological evidence for involvement of
RT   tuberoinfundibular peptide of 39 residues in nociception.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:1651-1656(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=12559132; DOI=10.1016/s0028-3908(02)00335-0;
RA   Della Penna K., Kinose F., Sun H., Koblan K.S., Wang H.;
RT   "Tuberoinfundibular peptide of 39 residues (TIP39): molecular structure and
RT   activity for parathyroid hormone 2 receptor.";
RL   Neuropharmacology 44:141-153(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-85, FUNCTION, AND INTERACTION WITH PTH2R.
RC   TISSUE=Brain;
RX   PubMed=11861531; DOI=10.1210/endo.143.3.8698;
RA   John M.R., Arai M., Rubin D.A., Jonsson K.B., Jueppner H.;
RT   "Identification and characterization of the murine and human gene encoding
RT   the tuberoinfundibular peptide of 39 residues.";
RL   Endocrinology 143:1047-1057(2002).
RN   [6]
RP   FUNCTION.
RX   PubMed=12754053; DOI=10.1016/s0014-2999(03)01673-x;
RA   Misiano P., Scott B.B., Scheideler M.A., Garnier M.;
RT   "PTH2 receptor-mediated inhibitory effect of parathyroid hormone and TIP39
RT   on cell proliferation.";
RL   Eur. J. Pharmacol. 468:159-166(2003).
RN   [7]
RP   FUNCTION.
RX   PubMed=14988434; DOI=10.1210/me.2003-0487;
RA   Bisello A., Manen D., Pierroz D.D., Usdin T.B., Rizzoli R., Ferrari S.L.;
RT   "Agonist-specific regulation of parathyroid hormone (PTH) receptor type 2
RT   activity: structural and functional analysis of PTH- and tuberoinfundibular
RT   peptide (TIP) 39-stimulated desensitization and internalization.";
RL   Mol. Endocrinol. 18:1486-1498(2004).
CC   -!- FUNCTION: Plays a role as a potent and selective agonist of PTH2R
CC       resulting in adenyl cyclase activation and intracellular calcium levels
CC       elevation. Induces protein kinase C beta activation, recruitment of
CC       beta-arrestin and PTH2R internalization. May inhibit cell proliferation
CC       via its action on PTH2R activation. Neuropeptide which may also have a
CC       role in spermatogenesis. May activate nociceptors and nociceptive
CC       circuits. {ECO:0000269|PubMed:11861531, ECO:0000269|PubMed:12559132,
CC       ECO:0000269|PubMed:12754053, ECO:0000269|PubMed:14988434}.
CC   -!- SUBUNIT: Ligand of high affinity for the PTH2 receptor (PTH2R).
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Highly expressed in fetal and adult brain,
CC       cerebellum and trachea. Weakly expressed in spinal cord, fetal liver,
CC       kidney and heart. {ECO:0000269|PubMed:12098667}.
CC   -!- SIMILARITY: Belongs to the parathyroid hormone family. {ECO:0000305}.
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DR   EMBL; AY037555; AAK68689.1; -; mRNA.
DR   EMBL; BC093995; AAH93995.1; -; mRNA.
DR   EMBL; BC093997; AAH93997.1; -; mRNA.
DR   EMBL; AY048588; AAL06597.1; -; mRNA.
DR   CCDS; CCDS12763.1; -.
DR   RefSeq; NP_848544.1; NM_178449.3.
DR   PDB; 7F16; EM; 2.80 A; P=62-100.
DR   PDBsum; 7F16; -.
DR   AlphaFoldDB; Q96A98; -.
DR   EMDB; EMD-31405; -.
DR   SMR; Q96A98; -.
DR   BioGRID; 125223; 8.
DR   IntAct; Q96A98; 1.
DR   STRING; 9606.ENSP00000270631; -.
DR   iPTMnet; Q96A98; -.
DR   PhosphoSitePlus; Q96A98; -.
DR   BioMuta; PTH2; -.
DR   PaxDb; 9606-ENSP00000270631; -.
DR   PeptideAtlas; Q96A98; -.
DR   ProteomicsDB; 75938; -.
DR   Antibodypedia; 31997; 72 antibodies from 13 providers.
DR   DNASU; 113091; -.
DR   Ensembl; ENST00000270631.2; ENSP00000270631.1; ENSG00000142538.2.
DR   GeneID; 113091; -.
DR   KEGG; hsa:113091; -.
DR   MANE-Select; ENST00000270631.2; ENSP00000270631.1; NM_178449.4; NP_848544.1.
DR   UCSC; uc002pnn.1; human.
DR   AGR; HGNC:30828; -.
DR   CTD; 113091; -.
DR   DisGeNET; 113091; -.
DR   GeneCards; PTH2; -.
DR   HGNC; HGNC:30828; PTH2.
DR   HPA; ENSG00000142538; Tissue enhanced (brain).
DR   MIM; 608386; gene.
DR   neXtProt; NX_Q96A98; -.
DR   OpenTargets; ENSG00000142538; -.
DR   PharmGKB; PA162400324; -.
DR   VEuPathDB; HostDB:ENSG00000142538; -.
DR   eggNOG; ENOG502S3PJ; Eukaryota.
DR   GeneTree; ENSGT00410000026259; -.
DR   HOGENOM; CLU_2319483_0_0_1; -.
DR   InParanoid; Q96A98; -.
DR   OMA; LVSWGHR; -.
DR   OrthoDB; 5230686at2759; -.
DR   PhylomeDB; Q96A98; -.
DR   TreeFam; TF353520; -.
DR   PathwayCommons; Q96A98; -.
DR   Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR   Reactome; R-HSA-418555; G alpha (s) signalling events.
DR   SignaLink; Q96A98; -.
DR   SIGNOR; Q96A98; -.
DR   BioGRID-ORCS; 113091; 16 hits in 1133 CRISPR screens.
DR   GeneWiki; TIP39; -.
DR   GenomeRNAi; 113091; -.
DR   Pharos; Q96A98; Tdark.
DR   PRO; PR:Q96A98; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   RNAct; Q96A98; Protein.
DR   Bgee; ENSG00000142538; Expressed in secondary oocyte and 48 other cell types or tissues.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0007218; P:neuropeptide signaling pathway; IEA:UniProtKB-KW.
DR   InterPro; IPR029396; TIP39.
DR   PANTHER; PTHR28585; TUBEROINFUNDIBULAR PEPTIDE OF 39 RESIDUES; 1.
DR   PANTHER; PTHR28585:SF1; TUBEROINFUNDIBULAR PEPTIDE OF 39 RESIDUES; 1.
DR   Pfam; PF14980; TIP39; 1.
DR   Genevisible; Q96A98; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cleavage on pair of basic residues; Neuropeptide;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..30
FT                   /evidence="ECO:0000255"
FT   PROPEP          31..59
FT                   /id="PRO_0000045942"
FT   PEPTIDE         62..100
FT                   /note="Tuberoinfundibular peptide of 39 residues"
FT                   /id="PRO_0000045943"
FT   HELIX           66..94
FT                   /evidence="ECO:0007829|PDB:7F16"
SQ   SEQUENCE   100 AA;  11202 MW;  7F0F1A273829E8F6 CRC64;
     METRQVSRSP RVRLLLLLLL LLVVPWGVRT ASGVALPPVG VLSLRPPGRA WADPATPRPR
     RSLALADDAA FRERARLLAA LERRHWLNSY MHKLLVLDAP
//