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PR01444

Identifier
LATROPHILIN  [View Relations]  [View Alignment]  
Accession
PR01444
No. of Motifs
4
Creation Date
29-NOV-2000  (UPDATE 19-OCT-2009)
Title
Latrophilin receptor signature
Database References
PRINTS; PR90007 7TM; PR90006 GPCRCLAN; PR00249 GPCRSECRETIN

PFAM; PF02354 Latrophilin
INTERPRO; IPR003334
MIM; 607018
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. JUPPNER, 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. MATSUSHITA, H., LELIANOVA, V.G. AND USHKARYOV, Y.A.
The latrophilin family: multiply spliced G protein-coupled receptors with
differential tissue distribution.
FEBS LETT. 443 348-352 (1999).

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.
 
Latrophilins are a family of secretin-like GPCRs that can be subdivided
into 3 subtypes: LPH1, LPH2 and LPH3. LPH1 is a brain-specific calcium
independent receptor of alpha-latrotoxin (LTX), a neurotoxin. It is the
affinity of this form of the receptor for LTX that gives the family its
name. LPH2 and LPH3, whilst sharing extensive sequence similarity to LPH1,
do not bind LTX. LPH2 is distributed throughout most tissues, whereas LPH3
is also brain-specific [6]. The endogenous ligand(s) for these receptors are
at present unknown. Binding of LTX to LPH1 stimulates exocytosis and the
subsequent release of large amounts of neurotransmitters from neuronal and
endocrine cells. The latrophilins possess up to 7 sites of alternative
splicing; the resulting number of possible splice variants leads to a highly
variable family of proteins.
 
LATROPHILIN is a 4-element fingerprint that provides a signature for the
latrophilin receptors. The fingerprint was derived from an initial alignment
of 3 sequences: the motifs were drawn from conserved regions spanning
virtually the full alignment length, focusing on those areas of the
alignment that characterise the latrophilin receptors but distinguish them
from the rest of the secretin-like superfamily - motifs 1 and 2 reside in
the N-terminal domain; motif 3 spans the first cytoplasmic loop; and motif 4
lies in the C-terminal domain. Two iterations on SPTR57_40f were required to
reach convergence, at which point a true set comprising 26 sequences was
identified. Three partial matches were also found (Q4RZU0_TETNG, 
B6MUJ8_BRAFL and Q69HN9_CIOIN), all of which are family members that fail
to match the full complement of motifs.
Summary Information
  26 codes involving  4 elements
0 codes involving 3 elements
3 codes involving 2 elements
Composite Feature Index
426262626
30000
23210
1234
True Positives
A6NE11_HUMAN  A8MW65_HUMAN  B1ALT8_HUMAN  B1ALT9_HUMAN  
B1ALU0_HUMAN B1ALU1_HUMAN B1ALU2_HUMAN B1ALU3_HUMAN
B1ALU4_HUMAN B1ALU5_HUMAN LPHN1_MOUSE LPHN3_HUMAN
LPHN3_MOUSE O88917 O88923 O94910
O95490 O97802 O97803 O97804
O97806 O97808 O97817 O97827
O97831 Q9Z173
True Positive Partials
Codes involving 2 elements
B6MUJ8_BRAFL Q4RZU0_TETNG Q69HN9_CIOIN
Sequence Titles
A6NE11_HUMAN Putative uncharacterized protein LPHN2 - Homo sapiens (Human). 
A8MW65_HUMAN Putative uncharacterized protein LPHN2 - Homo sapiens (Human).
B1ALT8_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALT9_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALU0_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALU1_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALU2_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALU3_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALU4_HUMAN Latrophilin 2 - Homo sapiens (Human).
B1ALU5_HUMAN Latrophilin 2 - Homo sapiens (Human).
LPHN1_MOUSE Latrophilin-1 - Mus musculus (Mouse).
LPHN3_HUMAN Latrophilin-3 - Homo sapiens (Human).
LPHN3_MOUSE Latrophilin-3 - Mus musculus (Mouse).
O88917 CALCIUM-INDEPENDENT ALPHA-LATROTOXIN RECEPTOR 1 PRECURSOR (LATROPHILIN 1) (LRP1) (CIRL) (CL1) (LPH1) - Rattus norvegicus (Rat).
O88923 CALCIUM-INDEPENDENT ALPHA-LATROTOXIN RECEPTOR 2 PRECURSOR (LATROPHILIN 2) (LRP2) (CIRL) (CL2) (LPH2) - Rattus norvegicus (Rat).
O94910 KIAA0821 PROTEIN - Homo sapiens (Human).
O95490 LATROPHILIN-2 - Homo sapiens (Human).
O97802 LATROPHILIN 2 SPLICE VARIANT BAAAE - Bos taurus (Bovine).
O97803 LATROPHILIN 2 SPLICE VARIANT BAAAF - Bos taurus (Bovine).
O97804 LATROPHILIN 2 SPLICE VARIANT BAABE - Bos taurus (Bovine).
O97806 LATROPHILIN 2 SPLICE VARIANT BABAE - Bos taurus (Bovine).
O97808 LATROPHILIN 2 SPLICE VARIANT BABBE - Bos taurus (Bovine).
O97817 LATROPHILIN 2 SPLICE VARIANT BBBBF - Bos taurus (Bovine).
O97827 LATROPHILIN 3 SPLICE VARIANT BBBF - Bos taurus (Bovine).
O97831 LATROPHILIN-1 - Bos taurus (Bovine).
Q9Z173 CALCIUM-INDEPENDENT ALPHA-LATROTOXIN RECEPTOR HOMOLOG 3 - Rattus norvegicus (Rat).

B6MUJ8_BRAFL Putative uncharacterized protein - Branchiostoma floridae (Florida lancelet) (Amphioxus).
Q4RZU0_TETNG Chromosome 18 SCAF14786, whole genome shotgun sequence - Tetraodon nigroviridis (Green puffer).
Q69HN9_CIOIN Lectomedin 1 alpha-like - Ciona intestinalis (Transparent sea squirt).
Scan History
SPTR57_40f 2  300  NSINGLE    
Initial Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
CYLPDAFKIMTQRCNNRTQC O95490 84 84 -
CYLPDAYKIMSQRCNNRTQC O97827 146 146 -
CYLPDAFKIMSQRCNNRTQC O97831 83 83 -

Motif 2 width=23
Element Seqn Id St Int Rpt
FFNKERTRNIVKFDLRTRIKSGE O95490 220 116 -
FFNKERTRNIVKFDLRTRIKSGE O97827 287 121 -
FYNKERTRNIVKYDLRTRIKSGE O97831 224 121 -

Motif 3 width=16
Element Seqn Id St Int Rpt
GLQSDRNTIHKNLCIN O95490 874 631 -
GLQSDRNTIHKNLCIS O97827 972 662 -
GLQTDRNTIHKNLCIN O97831 886 639 -

Motif 4 width=13
Element Seqn Id St Int Rpt
QKKVRKEYGKCFR O95490 1088 198 -
QKKVRKEYGKCLR O97827 1195 207 -
QKKVHKEYSKCLR O97831 1100 198 -
Final Motifs
Motif 1  width=20
Element Seqn Id St Int Rpt
CYLPDAFKIMTQRCNNRTQC A6NE11_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC O95490 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALU5_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALU4_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALU3_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALU2_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALU1_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALU0_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALT9_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC B1ALT8_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC A8MW65_HUMAN 84 84 -
CYLPDAFKIMTQRCNNRTQC O97817 84 84 -
CYLPDAFKIMTQRCNNRTQC O97808 84 84 -
CYLPDAFKIMTQRCNNRTQC O97806 84 84 -
CYLPDAFKIMTQRCNNRTQC O97804 84 84 -
CYLPDAFKIMTQRCNNRTQC O97803 84 84 -
CYLPDAFKIMTQRCNNRTQC O97802 84 84 -
CYLPDAFKIMTQRCNNRTQC O88923 84 84 -
CYLPDAYKIMSQRCNNRTQC O97827 146 146 -
CYLPDAYKIMSQRCNNRTQC Q9Z173 146 146 -
CYLPDAYKIMSQRCNNRTQC LPHN3_MOUSE 146 146 -
CYLPDAYKIMSQRCNNRTQC LPHN3_HUMAN 78 78 -
CYLPDAFKIMSQRCNNRTQC O97831 83 83 -
CYLPDAFKIMSQRCNNRTQC O88917 83 83 -
CYLPDAFKIMSQRCNNRTQC LPHN1_MOUSE 83 83 -
CYLPDAFKIMSQRCNNRTQC O94910 83 83 -

Motif 2 width=23
Element Seqn Id St Int Rpt
FFNKERTRNIVKFDLRTRIKSGE A6NE11_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE O95490 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALU5_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALU4_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALU3_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALU2_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALU1_HUMAN 224 120 -
FFNKERTRNIVKFDLRTRIKSGE B1ALU0_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALT9_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE B1ALT8_HUMAN 220 116 -
FFNKERTRNIVKFDLRTRIKSGE A8MW65_HUMAN 220 116 -
FFNKERTRNIVKYDLRTRIKSGE O97817 224 120 -
FFNKERTRNIVKYDLRTRIKSGE O97808 224 120 -
FFNKERTRNIVKYDLRTRIKSGE O97806 224 120 -
FFNKERTRNIVKYDLRTRIKSGE O97804 224 120 -
FFNKERTRNIVKYDLRTRIKSGE O97803 224 120 -
FFNKERTRNIVKYDLRTRIKSGE O97802 224 120 -
FFNKERTRNIVKFDLRTRIKSGE O88923 224 120 -
FFNKERTRNIVKFDLRTRIKSGE O97827 287 121 -
FFNKERTRNIVKFDLRTRIKSGE Q9Z173 287 121 -
FFNKERTRNIVKFDLRTRIKSGE LPHN3_MOUSE 287 121 -
FFNKERTRNIVKFDLRTRIKSGE LPHN3_HUMAN 219 121 -
FYNKERTRNIVKYDLRTRIKSGE O97831 224 121 -
FYNKERTRNIVKYDLRTRIKSGE O88917 224 121 -
FYNKERTRNIVKYDLRTRIKSGE LPHN1_MOUSE 219 116 -
FYNKERTRNIVKYDLRTRIKSGE O94910 224 121 -

Motif 3 width=16
Element Seqn Id St Int Rpt
GLQSDRNTIHKNLCIN A6NE11_HUMAN 861 618 -
GLQSDRNTIHKNLCIN O95490 874 631 -
GLQSDRNTIHKNLCIN B1ALU5_HUMAN 861 618 -
GLQSDRNTIHKNLCIN B1ALU4_HUMAN 874 631 -
GLQSDRNTIHKNLCIN B1ALU3_HUMAN 874 631 -
GLQSDRNTIHKNLCIN B1ALU2_HUMAN 874 631 -
GLQSDRNTIHKNLCIN B1ALU1_HUMAN 799 552 -
GLQSDRNTIHKNLCIN B1ALU0_HUMAN 861 618 -
GLQSDRNTIHKNLCIN B1ALT9_HUMAN 861 618 -
GLQSDRNTIHKNLCIN B1ALT8_HUMAN 861 618 -
GLQSDRNTIHKNLCIN A8MW65_HUMAN 861 618 -
GLQSDRNTIHKNLCIN O97817 878 631 -
GLQSDRNTIHKNLCIN O97808 812 565 -
GLQSDRNTIHKNLCIN O97806 812 565 -
GLQSDRNTIHKNLCIN O97804 799 552 -
GLQSDRNTIHKNLCIN O97803 799 552 -
GLQSDRNTIHKNLCIN O97802 799 552 -
GLQSDRNTIHKNLCIN O88923 878 631 -
GLQSDRNTIHKNLCIS O97827 972 662 -
GLQSDRNTIHKNLCIS Q9Z173 971 661 -
GLQSDRNTIHKNLCIS LPHN3_MOUSE 972 662 -
GLQSDRNTIHKNLCIS LPHN3_HUMAN 891 649 -
GLQTDRNTIHKNLCIN O97831 886 639 -
GLQTDRNTIHKNLCIN O88917 886 639 -
GLQTDRNTIHKNLCIN LPHN1_MOUSE 881 639 -
GLQTDRNTIHKNLCIN O94910 887 640 -

Motif 4 width=13
Element Seqn Id St Int Rpt
QKKVRKEYGKCFR A6NE11_HUMAN 1075 198 -
QKKVRKEYGKCFR O95490 1088 198 -
QKKVRKEYGKCFR B1ALU5_HUMAN 1090 213 -
QKKVRKEYGKCFR B1ALU4_HUMAN 1103 213 -
QKKVRKEYGKCFR B1ALU3_HUMAN 1103 213 -
QKKVRKEYGKCFR B1ALU2_HUMAN 1088 198 -
QKKVRKEYGKCFR B1ALU1_HUMAN 1013 198 -
QKKVRKEYGKCFR B1ALU0_HUMAN 1075 198 -
QKKVRKEYGKCFR B1ALT9_HUMAN 1075 198 -
QKKVRKEYGKCFR B1ALT8_HUMAN 1075 198 -
QKKVRKEYGKCFR A8MW65_HUMAN 1075 198 -
QKKVRKEYGKCFR O97817 1107 213 -
QKKVRKEYGKCFR O97808 1041 213 -
QKKVRKEYGKCFR O97806 1026 198 -
QKKVRKEYGKCFR O97804 1028 213 -
QKKVRKEYGKCFR O97803 1013 198 -
QKKVRKEYGKCFR O97802 1013 198 -
QKKVRKEYAKCFR O88923 1116 222 -
QKKVRKEYGKCLR O97827 1195 207 -
QKKVRKEYGKCLR Q9Z173 1194 207 -
QKKVRKEYGKCLR LPHN3_MOUSE 1195 207 -
QKKVRKEYGKCLR LPHN3_HUMAN 1105 198 -
QKKVHKEYSKCLR O97831 1100 198 -
QKKVHKEYSKCLR O88917 1100 198 -
QKKVHKEYSKCLR LPHN1_MOUSE 1095 198 -
QKKVHKEYSKCLR O94910 1101 198 -