TIP39_HUMAN
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 03-AUG-2022, entry version 113.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 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; Q96A98; -.
DR PeptideAtlas; Q96A98; -.
DR PRIDE; Q96A98; -.
DR ProteomicsDB; 75938; -.
DR Antibodypedia; 31997; 48 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 CTD; 113091; -.
DR DisGeNET; 113091; -.
DR GeneCards; PTH2; -.
DR HGNC; HGNC:30828; PTH2.
DR HPA; ENSG00000142538; Tissue enriched (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; 1601028at2759; -.
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 Reactome; R-HSA-9660821; ADORA2B mediated anti-inflammatory cytokines production.
DR SignaLink; Q96A98; -.
DR SIGNOR; Q96A98; -.
DR BioGRID-ORCS; 113091; 16 hits in 1055 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 47 other tissues.
DR Genevisible; Q96A98; HS.
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; PTHR28585; 1.
DR Pfam; PF14980; TIP39; 1.
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
