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    PTHLH parathyroid hormone-like hormone [ Homo sapiens ]

    Gene ID: 5744, updated on 11-May-2012
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    Summary

    Official Symbol
    PTHLHprovided by HGNC
    Official Full Name
    parathyroid hormone-like hormoneprovided by HGNC
    Primary source
    HGNC:9607
    See related
    Ensembl:ENSG00000087494; HPRD:01348; MIM:168470; Vega:OTTHUMG00000169221
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HHM; PLP; BDE2; PTHR; PTHRP; MGC14611
    Summary
    The protein encoded by this gene is a member of the parathyroid hormone family. This hormone regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. This hormone is involved in lactation possibly by regulating the mobilization and transfer of calcium to the milk. The receptor of this hormone, PTHR1, is responsible for most cases of humoral hypercalcemia of malignancy. Four alternatively spliced transcript variants encoding two distinct isoforms have been observed. There is also evidence for alternative translation initiation from non-AUG (CUG and GUG) start sites, in-frame and downstream of the initiator AUG codon, to give rise to nuclear forms of this hormone. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    12p12.1-p11.2
    Sequence :
    Chromosome: 12; NC_000012.11 (28111017..28124916, complement)
    See PTHLH in Epigenomics, MapViewer

    Chromosome 12 - NC_000012.11Genomic Context describing neighboring genes Neighboring gene MANSC domain containing 4 Neighboring gene kelch domain containing 5 Neighboring gene intraflagellar transport 57 homolog (Chlamydomonas) pseudogene Neighboring gene uncharacterized LOC729291

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target. Li J, et al. J Clin Invest, 2011 Dec. PMID 22056386.
    2. PTHrP(1-34)-mediated repression of the PHEX gene in osteoblastic cells involves the transcriptional repressor E4BP4. Pellicelli M, et al. J Cell Physiol, 2012 Jun. PMID 21826652.
    3. Methylation of specific CpG sites in the P2 promoter of parathyroid hormone-related protein determines the invasive potential of breast cancer cell lines. Tost J, et al. Epigenetics, 2011 Aug. PMID 21775817.
    4. Parathyroid hormone-related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy. Ortega A, et al. J Cell Physiol, 2012 May. PMID 21732369.
    5. 1,25-Dihydroxyvitamin D(3) regulates PTHrP expression via transcriptional, post-transcriptional and post-translational pathways. Bhatia V, et al. Mol Cell Endocrinol, 2011 Aug 6. PMID 21664243.

    See all (146) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. PTHrP(1-34)-mediated repression of the PHEX gene in osteoblastic cells involves the transcriptional repressor E4BP4.
      Title: PTHrP(1-34)-mediated repression of the PHEX gene in osteoblastic cells involves the transcriptional repressor E4BP4.
    2. Data show that PTHrP is upregulated in the kidney of patients with diabetic nephropathy.
      Title: Parathyroid hormone-related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy.
    3. Methylation of the PTHrP P2 is a potential marker of breast cancer progression and might be used to evaluate the metastatic potential of breast tumors.
      Title: Methylation of specific CpG sites in the P2 promoter of parathyroid hormone-related protein determines the invasive potential of breast cancer cell lines.
    4. PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts, indicating PTHrP's importance for metastatic spread.
      Title: PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target.
    5. Regulation of PTHrP levels is dependent on VDR expression by the cells, in that suppressing VDR expression with siRNA inhibits the 1,25D-mediated downregulation of PTHrP expression.
      Title: 1,25-Dihydroxyvitamin D(3) regulates PTHrP expression via transcriptional, post-transcriptional and post-translational pathways.
    6. Calcium activated CaR results in MAPK-mediated stimulation of parathyroid hormone-related protein production in human lung squamous cell carcinoma lines.
      Title: The calcium-sensing receptor is necessary for the rapid development of hypercalcemia in human lung squamous cell carcinoma.
    7. findings indicate that PTHrP plays an autocrine/paracrine neoplastic role in GCT by allowing the proliferating stromal cells to evade apoptosis, possibly through non-traditional caspase-independent pathways
      Title: PTHrP induces autocrine/paracrine proliferation of bone tumor cells through inhibition of apoptosis.
    8. this study established that steroid hormones negatively regulate PTHrP expression.
      Title: Negative regulation of parathyroid hormone-related protein expression by steroid hormones.
    9. PTHrP stimulates prostate cancer cell growth and upregulates aldo-keto reductase 1C3
      Title: PTHrP stimulates prostate cancer cell growth and upregulates aldo-keto reductase 1C3.
    10. PTHLH has a low signal expression in human gastric enterochromaffin-like cells. Serum gastrin levels correlate with PTHLH RNA levels in gastric mucosa.
      Title: The expression of PTHLH in human gastric mucosa enterochromaffin-like cells.
    Submit: New GeneRIF Correction See all (98)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Brachydactyly, type E2

    Humoral hypercalcemia of malignancy

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    P12272 P49407 ARRB1    HPRD  PubMed  
    P12272 P24941 CDK2    HPRD  PubMed  
    P12272 P05231 IL6    HPRD  PubMed  
    P12272 P07288 KLK3    HPRD  PubMed  
    P12272 Q14974 KPNB1    HPRD  PubMed  
    P12272 Q03431 PTH1R    HPRD  PubMed  
    BioGRID:111716 BioGRID:106901 ARRB1    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:111716 BioGRID:110035 KPNB1    BioGRID  PubMed Co-crystal Structure; Reconstituted Complex 
    BioGRID:111716 BioGRID:111362 PLK1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:111716 BioGRID:111717 PTH1R    BioGRID  PubMed Reconstituted Complex 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Class B/2 (Secretin family receptors), organism-specific biosystem (from REACTOME)
      Class B/2 (Secretin family receptors), organism-specific biosystemThis family is known as Family B (secretin-receptor family, family 2) G-protein-coupled receptors. Family B GPCRs include secretin, calcitonin, parathyroid hormone/parathyroid hormone-related peptide...
    • Endochondral Ossification, organism-specific biosystem (from WikiPathways)
      Endochondral Ossification, organism-specific biosystem
      Endochondral Ossification
    • G alpha (s) signalling events, organism-specific biosystem (from REACTOME)
      G alpha (s) signalling events, organism-specific biosystemThe general function of the G alpha (s) subunit (Gs) is to activate adenylate cyclase, which in turn produces cAMP, leading to the activation of cAMP-dependent protein kinases (often referred to col...
    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
      GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
    • GPCR ligand binding, organism-specific biosystem (from REACTOME)
      GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by GPCR, organism-specific biosystem (from REACTOME)
      Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...
    • Signaling events mediated by the Hedgehog family, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by the Hedgehog family, organism-specific biosystem
      Signaling events mediated by the Hedgehog family

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    hormone activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    peptide hormone receptor binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    activation of adenylate cyclase activity by G-protein signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cAMP metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cell-cell signaling TAS
    Traceable Author Statement
    more info
    		 PubMed 
    endochondral ossification IEA
    Inferred from Electronic Annotation
    more info
    		  
    endoderm development IEA
    Inferred from Electronic Annotation
    more info
    		  
    epidermis development TAS
    Traceable Author Statement
    more info
    		 PubMed 
    epithelial cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    female pregnancy TAS
    Traceable Author Statement
    more info
    		 PubMed 
    lung alveolus development IEA
    Inferred from Electronic Annotation
    more info
    		  
    mammary gland bud elongation IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    negative regulation of chondrocyte differentiation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of sequence-specific DNA binding transcription factor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    nipple sheath formation IEA
    Inferred from Electronic Annotation
    more info
    		  
    osteoblast development IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of cAMP biosynthetic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein processing IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    skeletal system development IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    surfactant homeostasis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
    		  
    extracellular space TAS
    Traceable Author Statement
    more info
    		 PubMed 
    intracellular IEA
    Inferred from Electronic Annotation
    more info
    		  
    NOT nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
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    General protein information

    Preferred Names
    parathyroid hormone-related protein
    Names
    parathyroid hormone-related protein
    PTH-rP
    osteostatin
    PTH-related protein
    parathyroid hormone-like related protein
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_023197.1 RefSeqGene

      Range
      5001..18900
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_002820.2 → NP_002811.1  parathyroid hormone-related protein isoform 2 preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' CDS and UTR, compared to variant 1. The resulting isoform (2) has a shorter C-terminus, as compared to isoform 1.
      Source sequence(s)
      BC005961, BG680355, BI963162, J03802
      Consensus CDS
      CCDS8715.1
      UniProtKB/Swiss-Prot
      P12272
      UniProtKB/TrEMBL
      Q53XY9
      Related
      ENSP00000201015, ENST00000201015
      Conserved Domains (1) summary
      cl02458
      Location:34 – 114
      Blast Score: 281
      Parathyroid; Parathyroid hormone family

    2. NM_198964.1 → NP_945315.1  parathyroid hormone-related protein isoform 2 preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, and in the 3' CDS and UTR, compared to variant 1. The resulting isoform (2) has a shorter C-terminus, as compared to isoform 1.
      Source sequence(s)
      BC005961, BG679319, BI963162, J03802
      Consensus CDS
      CCDS8715.1
      UniProtKB/Swiss-Prot
      P12272
      UniProtKB/TrEMBL
      Q53XY9
      Related
      ENSP00000379209, OTTHUMP00000240433, ENST00000395868, OTTHUMT00000402916
      Conserved Domains (1) summary
      cl02458
      Location:34 – 114
      Blast Score: 281
      Parathyroid; Parathyroid hormone family

    3. NM_198965.1 → NP_945316.1  parathyroid hormone-related protein isoform 1 preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AI569027, AI591151, AI760061, BG680355, BI752853
      Consensus CDS
      CCDS44853.1
      UniProtKB/Swiss-Prot
      P12272
      Related
      ENSP00000379213, ENST00000395872
      Conserved Domains (1) summary
      cl02458
      Location:34 – 114
      Blast Score: 278
      Parathyroid; Parathyroid hormone family

    4. NM_198966.1 → NP_945317.1  parathyroid hormone-related protein isoform 1 preproprotein

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR compared to variant 1. Both variants 1 and 4 encode the same isoform (1).
      Source sequence(s)
      AI569027, AI591151, AI760061, BG676028, BG679319
      Consensus CDS
      CCDS44853.1
      UniProtKB/Swiss-Prot
      P12272
      Related
      ENSP00000441571, OTTHUMP00000240429, ENST00000539239, OTTHUMT00000402912
      Conserved Domains (1) summary
      cl02458
      Location:34 – 114
      Blast Score: 278
      Parathyroid; Parathyroid hormone family

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000012.11 Reference GRCh37.p5 Primary Assembly

      Range
      28111017..28124916, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000144.1 Alternate HuRef

      Range
      27880337..27894279, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC008011.11 (24051..37950) None
    genomic CH471094.1 EAW96572.1
      EAW96573.1
      EAW96574.1
      EAW96575.1
      EAW96576.1
    genomic M17183.1 AAA60221.1
    genomic M24349.1 AAA60358.1
    genomic M24350.1 AAA60359.1
    genomic M24351.1 AAA60360.1
    genomic X14304.1 CAA32480.1
    mRNA AI569027.1 None
    mRNA AI591151.1 None
    mRNA AI760061.1 None
    mRNA AK313476.1 BAG36261.1
    mRNA BC005961.1 AAH05961.1
    mRNA BG676028.1 None
    mRNA BG679319.1 None
    mRNA BG680355.1 None
    mRNA BI752853.1 None
    mRNA BI963162.1 None
    mRNA BT007178.1 AAP35842.1
    mRNA CR541882.1 CAG46680.1
    mRNA J03580.1 AAA60216.1
    mRNA J03802.1 AAA60218.1
    mRNA M26958.1 AAO49791.1
    mRNA M26959.1 AAO49793.1
    mRNA M26960.1 AAN76483.1
    mRNA M34071.1 AAA60217.1
    other-genetic DQ896393.2 ABM87392.1
    other-genetic EU176428.1 ABW03879.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P12272.1 GenPept UniProtKB/Swiss-Prot:P12272
    Q53XY9 GenPept UniProtKB/TrEMBL:Q53XY9
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    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

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