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PR00393

Identifier
PTRHORMONER  [View Relations]  [View Alignment]  
Accession
PR00393
No. of Motifs
6
Creation Date
15-APR-1995  (UPDATE 07-JUN-1999)
Title
Parathyroid hormone receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN

INTERPRO; IPR002170
GCRDB; GCR_0206
Literature References
1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.   
PROTEIN ENG. 7(2) 195-203 (1994).
 
2. ISHIHARA T., NAKAMURA S., KAZIRO, Y., TAKAHASHI, T., TAKAHASHI, K.
AND NAGATA, S.  
Molecular cloning and expression of a cDNA encoding the secretin receptor.
EMBO J. 10 1635-1641 (1991).
 
3. LIN, H.Y., HARRIS, T.L., FLANNERY, M.S., ARUFFO, A., KAJI, E.H.,
GORN, A., KOLAKOWSKI, L.F., LODISH, H.F. AND GOLDRING, S.R.
Expression cloning of adenylate cyclase-coupled calcitonin receptor.
SCIENCE 254 1022-1024 (1991). 
 
4. JUEPPNER, H., ABOU-SAMRA, A.-B., FREEMAN, M., KONG, X.F.,
SCHIPANI, E., RICHARDS, J., KOLALOWSKI, L.F., HOCK, J., POTTS, J.T.,
KRONENBERG, H.M. AND SEGRE, G.E.
A G protein linked receptor for parathyroid hormone and parathyroid
hormone-related peptide.
SCIENCE 254 1024-1026 (1991).
 
5. ISHIHARA, T., SHIGEMOTO, R., MORI, K., TAKAHASHI, K. AND NAGATA, S.
Functional expression and tissue distribution of a novel receptor for
vasoactive intestinal polypeptide.
NEURON 8(4) 811-819 (1992).
 
6. WATSON, S. AND ARKINSTALL, S.
Parathyroid hormone (PTH).
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.231-233.

Documentation
G protein-coupled receptors (GPCRs) constitute a vast protein family that   
encompasses a wide range of functions (including various autocrine, para-   
crine and endocrine processes). They show considerable diversity at the   
sequence level, on the basis of which they can be separated into distinct   
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,   
but between which there is no statistically significant similarity in   
sequence [1]. The currently known clan members include the rhodopsin-like   
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating   
pheromone receptors, and the metabotropic glutamate receptor family.       
 
The secretin-like GPCRs include secretin [2], calcitonin [3], parathyroid   
hormone/parathyroid hormone-related peptides [4] and vasoactive intestinal
peptide [5], all of which activate adenylyl cyclase and the phosphatidyl-   
inositol-calcium pathway. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, in a manner
reminiscent of the rhodopsins and other receptors believed to interact with
G proteins. However, while a similar 3D framework has been proposed to
account for this, there is no significant sequence identity between these
families: the secretin-like receptors thus bear their own unique `7TM'
signature.      
 
Parathyroid hormone (PTH) is involved in calcium homeostasis within the
body in combination with calcitonin and vitamin D [6]. PTH is released in
response to hypocalcaemia and stimulates a rise in blood calcium; the
converse is true for calcitonin. The principle targets for PTH are bone
and kidney. Antagonists at the PTH receptor are of potential clinical use
in the treatment of hyperparathyroidism and short-term hypercalcaemic
states. In addition to its presence in bone and kidney, the receptor is
found in lower levels in blood vessels, where it mediates vasodilation.
The principle second messenger pathway is activation of adenylyl cyclase
through Gs. In addition, PTH stimulates phosphoinositide metabolism on
the expressed receptor.
 
PTRHORMONER is a 6-element fingerprint that provides a signature for the
parathyroid hormone/parathyroid related peptide receptors. The fingerprint
was derived from an initial alignment of 4 sequences: the motifs were
drawn from conserved sections within either loop or TM regions, focusing
on those areas of the alignment that characterise the parathyroid hormone
receptors but distinguish them from the rest of the secretin-like family -
motifs 1 and 2 were drawn from the N-terminal region leading into the first
TM domain; motif 3 lies in the loop region preceding the third TM domain;
motif 4 spans the loop region leading into the seventh TM region; and 
motifs 5 and 6 were drawn from the C-terminus. Two iterations on OWL25.2
were required to reach convergence, at which point a true set comprising
7 sequences was identified.
 
An update on SPTR37_9f identified a true set of 5 sequences.
Summary Information
5 codes involving  6 elements
0 codes involving 5 elements
0 codes involving 4 elements
0 codes involving 3 elements
0 codes involving 2 elements
Composite Feature Index
6555555
5000000
4000000
3000000
2000000
123456
True Positives
PTRR_DIDMA    PTRR_HUMAN    PTRR_MOUSE    PTRR_PIG      
PTRR_RAT
Sequence Titles
PTRR_DIDMA  PARATHYROID HORMONE/PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR PRECURSOR (PTH/PTHR RECEPTOR) - DIDELPHIS MARSUPIALIS VIRGINIANA (NORTH AMERICAN OPOSSUM). 
PTRR_HUMAN PARATHYROID HORMONE/PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR PRECURSOR (PTH/PTHR RECEPTOR) - HOMO SAPIENS (HUMAN).
PTRR_MOUSE PARATHYROID HORMONE/PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR PRECURSOR (PTH/PTHR RECEPTOR) - MUS MUSCULUS (MOUSE).
PTRR_PIG PARATHYROID HORMONE/PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR PRECURSOR (PTH/PTHR RECEPTOR) - SUS SCROFA (PIG).
PTRR_RAT PARATHYROID HORMONE/PARATHYROID HORMONE-RELATED PEPTIDE RECEPTOR PRECURSOR (PTH/PTHR RECEPTOR) - RATTUS NORVEGICUS (RAT).
Scan History
OWL25_2    2  50   NSINGLE    
SPTR37_9f 2 6 NSINGLE
Initial Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
SRSAKTKKEKPAEKLYPQAEESRE PTRR_DIDMA 70 70 -
SRSAKTKKEKPAEKLYSQAEESRE OPOPTHR 70 70 -
STSGKPRKDKASGKLYPESEEDKE PTRR_HUMAN 73 73 -
STSGKPRKEKASGKFYPESKENKD PTRR_RAT 73 73 -

Motif 2 width=15
Element Seqn Id St Int Rpt
NETREREVFDRLGMI PTRR_DIDMA 173 79 -
NETREREVFDRLGMI PTRR_HUMAN 176 79 -
NETREREVFDRLGMI OPOPTHR 173 79 -
NETREREVFDRLGMI PTRR_RAT 176 79 -

Motif 3 width=13
Element Seqn Id St Int Rpt
DEAERLTEEELRA PTRR_HUMAN 251 60 -
DEIERITEEELRA OPOPTHR 248 60 -
DEAERLTEEELHI PTRR_RAT 251 60 -
DEIERITEEELRA PTRR_DIDMA 248 60 -

Motif 4 width=14
Element Seqn Id St Int Rpt
YTEVSGTLWQIQMH PTRR_RAT 429 165 -
YTEVSGILWQVQMH OPOPTHR 423 162 -
YTEVSGILWQVQMH PTRR_DIDMA 423 162 -
YTEVSGTLWQVQMH PTRR_HUMAN 429 165 -

Motif 5 width=21
Element Seqn Id St Int Rpt
TLALDFKRKARSGSSTYSYGP OPOPTHR 472 35 -
TLALDFKRKARSGSSSYSYGP PTRR_HUMAN 478 35 -
TLALDFKRKARSGSSSYSYGP PTRR_RAT 478 35 -
TLALDFKRKARSGSSTYSYGP PTRR_DIDMA 472 35 -

Motif 6 width=19
Element Seqn Id St Int Rpt
TNVGPRAGLSLPLSPRLPP PTRR_RAT 506 7 -
TNVGPRGGLALSLSPRLAP PTRR_DIDMA 500 7 -
TNVGPRVGLGLPLSPRLLP PTRR_HUMAN 506 7 -
TNVGPRGGLALSLSPRLAP OPOPTHR 500 7 -
Final Motifs
Motif 1  width=24
Element Seqn Id St Int Rpt
STSGKPRKDKASGKLYPESEEDKE PTRR_HUMAN 73 73 -
STSGKPRKEKAPGKFYPESKENKD PTRR_MOUSE 73 73 -
STSGKPRKEKASGKFYPESKENKD PTRR_RAT 73 73 -
PTSGKPRKEKASGKLYPESGEDTG PTRR_PIG 73 73 -
SRSAKTKKEKPAEKLYPQAEESRE PTRR_DIDMA 70 70 -

Motif 2 width=15
Element Seqn Id St Int Rpt
NETREREVFDRLGMI PTRR_HUMAN 176 79 -
NETREREVFDRLGMI PTRR_MOUSE 176 79 -
NETREREVFDRLGMI PTRR_RAT 176 79 -
NETREREVFDRLGMI PTRR_PIG 172 75 -
NETREREVFDRLGMI PTRR_DIDMA 173 79 -

Motif 3 width=13
Element Seqn Id St Int Rpt
DEAERLTEEELRA PTRR_HUMAN 251 60 -
DEAERLTEEELHI PTRR_MOUSE 251 60 -
DEAERLTEEELHI PTRR_RAT 251 60 -
DEAERLTEEELRA PTRR_PIG 247 60 -
DEIERITEEELRA PTRR_DIDMA 248 60 -

Motif 4 width=14
Element Seqn Id St Int Rpt
YTEVSGTLWQVQMH PTRR_HUMAN 429 165 -
YTEVSGTLWQIQMH PTRR_MOUSE 429 165 -
YTEVSGTLWQIQMH PTRR_RAT 429 165 -
YTEVSGTLWQVQMH PTRR_PIG 424 164 -
YTEVSGILWQVQMH PTRR_DIDMA 423 162 -

Motif 5 width=21
Element Seqn Id St Int Rpt
TLALDFKRKARSGSSSYSYGP PTRR_HUMAN 478 35 -
TLALDFKRKARSGSSSYSYGP PTRR_MOUSE 478 35 -
TLALDFKRKARSGSSSYSYGP PTRR_RAT 478 35 -
TLALDFKRKARSGSSSYSYGP PTRR_PIG 473 35 -
TLALDFKRKARSGSSTYSYGP PTRR_DIDMA 472 35 -

Motif 6 width=19
Element Seqn Id St Int Rpt
TNVGPRVGLGLPLSPRLLP PTRR_HUMAN 506 7 -
TNVGPRAGLSLPLSPRLLP PTRR_MOUSE 506 7 -
TNVGPRAGLSLPLSPRLPP PTRR_RAT 506 7 -
TNVGPRTGLGLPLSPRLLP PTRR_PIG 501 7 -
TNVGPRGGLALSLSPRLAP PTRR_DIDMA 500 7 -