emboss-test 6.4.0-2 / usr / share / EMBOSS / test / data / prosite.doc

{PDOC00000}
{BEGIN}
**********************************
*** PROSITE documentation file ***
**********************************

Release  : 16.0 of July 1999

Copyright: Amos Bairoch
           Swiss Institute of Bioinformatics (SIB)
           CMU
           University of Geneva
           1, Rue Michel Servet, 1211 Geneva 4
           Switzerland

Email    : bairoch@medecine.unige.ch
Telephone: +41-22-702 54 77
Fax      : +41-22-702 55 02

Acknowledgements:

 - To  all those mentioned in this document  who  have reviewed the entry(ies)
   for which they are listed as experts. With specific thanks to Rein Aasland,
   Mark Boguski,  Peer  Bork,  Josh  Cherry,  Andre Chollet, Frank Kolakowski,
   David Landsman, Bernard Henrissat,  Eugene Koonin,  Steve Henikoff,  Manuel
   Peitsch and Jonathan Reizer.
 - Brigitte  Boeckmann  is  the author of the PDOC00691, PDOC00703, PDOC00829,
   PDOC00796, PDOC00798,    PDOC00799,    PDOC00906,   PDOC00907,   PDOC00908,
   PDOC00912, PDOC00913,    PDOC00924,    PDOC00928,   PDOC00929,   PDOC00955,
   PDOC00961, PDOC00966, PDOC00988 and PDOC50020 entries.
 - Philipp Bucher is the author of the PDOC50001 and PDOC50002 entries.
 - Kay  Hofmann  is  the  author of  the  PDOC50003, PDOC50006,  PDOC50007 and
   PDOC50017 entries.
 - Keith Robison is the author of the PDOC00830 and PDOC00861 entries.
 - Chantal Hulo is the author of the PDOC00987 entry.
 - Vivienne Baillie Gerritsen for undertaking the major task of correcting the
   grammar and style of this document.

   ------------------------------------------------------------------------
   PROSITE is copyright.   It  is  produced  by  the  Swiss  Institute   of
   Bioinformatics (SIB). There are no restrictions on its use by non-profit
   institutions as long as its  content is in no way modified. Usage by and
   for commercial  entities requires a license agreement.   For information
   about the licensing scheme  see: http://www.isb-sib.ch/announce/ or send
   an email to license@isb-sib.ch.
   ------------------------------------------------------------------------
{END}
{PDOC00210}
{PS00237; G_PROTEIN_RECEPTOR}
{BEGIN}
*****************************************
* G-protein coupled receptors signature *
*****************************************

G-protein coupled receptors [1 to 4,E1,E2] (also called R7G) are  an extensive
group of  hormones,  neurotransmitters,  odorants  and  light  receptors which
transduce extracellular  signals   by  interaction  with  guanine  nucleotide-
binding (G) proteins. The receptors that are currently known to belong to this
family are listed below.

 - 5-hydroxytryptamine (serotonin) 1A to 1F, 2A to 2C, 4, 5A, 5B, 6 and 7 [5].
 - Acetylcholine, muscarinic-type, M1 to M5.
 - Adenosine A1, A2A, A2B and A3 [6].
 - Adrenergic alpha-1A to -1C; alpha-2A to -2D;  beta-1 to -3 [7].
 - Angiotensin II types I and II.
 - Bombesin subtypes 3 and 4.
 - Bradykinin B1 and B2.
 - c3a and C5a anaphylatoxin.
 - Cannabinoid CB1 and CB2.
 - Chemokines C-C CC-CKR-1 to CC-CKR-8.
 - Chemokines C-X-C CXC-CKR-1 to CXC-CKR-4.
 - Cholecystokinin-A and cholecystokinin-B/gastrin.
 - Dopamine D1 to D5 [8].
 - Endothelin ET-a and ET-b [9].
 - fMet-Leu-Phe (fMLP) (N-formyl peptide).
 - Follicle stimulating hormone (FSH-R) [10].
 - Galanin.
 - Gastrin-releasing peptide (GRP-R).
 - Gonadotropin-releasing hormone (GNRH-R).
 - Histamine H1 and H2 (gastric receptor I).
 - Lutropin-choriogonadotropic hormone (LSH-R) [10].
 - Melanocortin MC1R to MC5R.
 - Melatonin.
 - Neuromedin B (NMB-R).
 - Neuromedin K (NK-3R).
 - Neuropeptide Y types 1 to 6.
 - Neurotensin (NT-R).
 - Octopamine (tyramine), from insects.
 - Odorants [11].
 - Opioids delta-, kappa- and mu-types [12].
 - Oxytocin (OT-R).
 - Platelet activating factor (PAF-R).
 - Prostacyclin.
 - Prostaglandin D2.
 - Prostaglandin E2, EP1 to EP4 subtypes.
 - Prostaglandin F2.
 - Purinoreceptors (ATP) [13].
 - Somatostatin types 1 to 5.
 - Substance-K (NK-2R).
 - Substance-P (NK-1R).
 - Thrombin.
 - Thromboxane A2.
 - Thyrotropin (TSH-R) [10].
 - Thyrotropin releasing factor (TRH-R).
 - Vasopressin V1a, V1b and V2.
 - Visual pigments (opsins and rhodopsin) [14].

 - Proto-oncogene mas.
 - A number of orphan receptors (whose ligand is not known) from  mammals  and
   birds.
 - Caenorhabditis  elegans  putative    receptors  C06G4.5, C38C10.1, C43C3.2,
   T27D1.3 and ZC84.4.
 - Three putative receptors encoded  in  the  genome of cytomegalovirus: US27,
   US28, and UL33.
 - ECRF3, a putative receptor encoded in the genome of herpesvirus saimiri.

The  structure of all  these receptors is  thought  to be identical. They have
seven hydrophobic regions,  each  of which most probably  spans  the membrane.
The N-terminus is located on the  extracellular  side of the  membrane  and is
often  glycosylated,  while  the  C-terminus  is  cytoplasmic   and  generally
phosphorylated.  Three extracellular loops  alternate with three intracellular
loops to link the seven transmembrane regions.  Most,  but  not  all  of these
receptors, lack a signal peptide. The most conserved parts  of  these proteins
are the transmembrane regions and the first two cytoplasmic loops. A conserved
acidic-Arg-aromatic triplet is  present  in  the N-terminal  extremity  of the
second cytoplasmic loop [15] and could be implicated in the interaction with G
proteins.

To detect this widespread family of  proteins we have developed a pattern that
contains the conserved triplet and that also spans the major part of the third
transmembrane helix.

-Consensus pattern: [GSTALIVMFYWC]-[GSTANCPDE]-{EDPKRH}-x(2)-[LIVMNQGA]-x(2)-
                    [LIVMFT]-[GSTANC]-[LIVMFYWSTAC]-[DENH]-R-[FYWCSH]-x(2)-
                    [LIVM]
-Sequences known to belong to this class detected by the pattern: the majority
 of receptors. About 5% are not detected.
-Other sequence(s) detected in SWISS-PROT: 50.

-Expert(s) to contact by email:
           Attwood T.K.; attwood@bsm.bioc.ucl.ac.uk
           Kolakowski L.F. Jr.; kolakowski@uthsca.edu

-Last update: July 1998 / Text revised.

[ 1] Strosberg A.D.
     Eur. J. Biochem. 196:1-10(1991).
[ 2] Kerlavage A.R.
     Curr. Opin. Struct. Biol. 1:394-401(1991).
[ 3] Probst W.C., Snyder L.A., Schuster D.I., Brosius J., Sealfon S.C.
     DNA Cell Biol. 11:1-20(1992).
[ 4] Savarese T.M., Fraser C.M.
     Biochem. J. 283:1-9(1992).
[ 5] Branchek T.
     Curr. Biol. 3:315-317(1993).
[ 6] Stiles G.L.
     J. Biol. Chem. 267:6451-6454(1992).
[ 7] Friell T., Kobilka B.K., Lefkowitz R.J., Caron M.G.
     Trends Neurosci. 11:321-324(1988).
[ 8] Stevens C.F.
     Curr. Biol. 1:20-22(1991).
[ 9] Sakurai T., Yanagisawa M., Masaki T.
     Trends Pharmacol. Sci. 13:103-107(1992).
[10] Salesse R., Remy J.J., Levin J.M., Jallal B., Garnier J.
     Biochimie 73:109-120(1991).
[11] Lancet D., Ben-Arie N.
     Curr. Biol. 3:668-674(1993).
[12] Uhl G.R., Childers S., Pasternak G.
     Trends Neurosci. 17:89-93(1994).
[13] Barnard E.A., Burnstock G., Webb T.E.
     Trends Pharmacol. Sci. 15:67-70(1994).
[14] Applebury M.L., Hargrave P.A.
     Vision Res. 26:1881-1895(1986).
[15] Attwood T.K., Eliopoulos E.E., Findlay J.B.C.
     Gene 98:153-159(1991).
{END}
{PDOC00559}
{PS00649; G_PROTEIN_RECEP_F2_1}
{PS00650; G_PROTEIN_RECEP_F2_2}
{BEGIN}
***************************************************
* G-protein coupled receptors family 2 signatures *
***************************************************

A number of peptide hormones bind to  G-protein coupled  receptors that, while
structurally similar to the majority of G-protein coupled receptors (R7G) (see
the relevant entry <PDOC00210>),  do not show any  similarity  at the level of
their sequence,  thus  representing  a  new family whose current known members
[1,2] are listed below:

 - Calcitonin receptor.
 - Calcitonin gene-related peptide receptor.
 - Corticotropin releasing factor receptor types 1 and 2.
 - Gastric inhibitory polypeptide receptor.
 - Glucagon receptor.
 - Glucagon-like peptide 1 receptor.
 - Growth hormone-releasing hormone receptor.
 - Parathyroid hormone / parathyroid hormone-related peptide types 1 and 2.
 - Pituitary adenylate cyclase activating polypeptide receptor.
 - Secretin receptor.
 - Vasoactive intestinal peptide receptor types 1 and 2.
 - Insects diuretic hormone receptor.

In addition to the above characterized receptors, this family also includes:

 - Caenorhabditis elegans putative receptor C13B9.4.
 - Caenorhabditis elegans putative receptor ZK643.3.
 - Human  leucocyte  antigen  CD97, a protein that contains, in its N-terminal
   section, 3 EGF-like domains (see <PDOC00021>).
 - Human cell surface glycoprotein EMR1,  a protein  that  contains, in its N-
   terminal section, 6 EGF-like domains (see <PDOC00021>).
 - Mouse  cell  surface glycoprotein F4/80, a protein that contains, in its N-
   terminal section, 7 EGF-like domains (see <PDOC00021>).

All the  characterized receptors are coupled to G-proteins which activate both
adenylyl cyclase and the phosphatidylinositol-calcium pathway.

Like classical R7G they  seem  to  contain seven transmembrane regions.  Their
N-terminus is probably located on the extracellular side of the  membrane  and
potentially glycosylated, while their C-terminus is probably cytoplasmic.  But
apart from these topological similarities they do share any region of sequence
similarity and are therefore probably not evolutionary related.

Every receptor  gene  in this family is encoded on multiple exons, and several
of these  genes  are  alternatively  spliced  to  yield  functionally distinct
products.

The N-terminal extracellular domain of these receptors contains five conserved
cysteines  residues  which  could  be  involved in  disulfide  bonds;  we have
developed a pattern in the region that spans the first three cysteines.

One of the most highly conserved regions spans the C-terminal part of the last
transmembrane  region and the  beginning of the adjacent intracellular region.
We have used this region as a second signature pattern.

-Consensus pattern: C-x(3)-[FYWLIV]-D-x(3,4)-C-[FW]-x(2)-[STAGV]-x(8,9)-C-[PF]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for CD97, EMR1 and F4/80.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Consensus pattern: Q-G-[LMFCA]-[LIVMFT]-[LIV]-x-[LIVFST]-[LIF]-[VFYH]-C-
                    [LFY]-x-N-x(2)-V
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Expert(s) to contact by email:
           Kolakowski L.F. Jr.; kolakowski@uthsca.edu

-Last update: July 1998 / Patterns and text revised.

[ 1] Jueppner H., Abou-Samra A.-B., Freeman M., Kong X.-F., Schipani E.,
     Richards J., Kolakowski L.F. Jr., Hock J., Potts J.T. Jr.,
     Kronenberg H.M., Segre G.V.
     Science 254:1024-1026(1991).
[ 2] Hamann J., Hartmann E., Van Lier R.A.W.
     Genomics 32:144-147(1996).
{END}
{PDOC00754}
{PS00979; G_PROTEIN_RECEP_F3_1}
{PS00980; G_PROTEIN_RECEP_F3_2}
{PS00981; G_PROTEIN_RECEP_F3_3}
{BEGIN}
***************************************************
* G-protein coupled receptors family 3 signatures *
***************************************************

Glutamate and  calcium  bind  to  G-protein  coupled    receptors  that, while
structurally similar to the majority of G-protein coupled receptors (R7G) (see
the relevant entry <PDOC00210>),  do not show any  similarity  at the level of
their sequence, thus representing a new family whose current known members are
listed below:

 - The  metabotropic  glutamate  receptors  which evoke a variety of function,
   such as  long-tern  potentiation,  memory  acquisition  and learning, etc.,
   through the modulation of intracellular effectors [1,2,3].  Currently there
   are eight known  subtypes  of  metabotropic glutamate  receptors; mGluR1 to
   mGluR8. The  subtypes  mGluR1  and mGluR5 are coupled to the stimulation of
   the phosphatidylinositol-calcium  second  messenger  system  while  mGluR2,
   mGluR3, mGluR4,  mGluR6,  mGluR7  and mGluR8 are coupled to G proteins that
   inhibit adenylate cyclase activity.
 - The extracellular calcium-sensing receptor [4]  which  sense changes in the
   extracellular concentration of calcium ions.  The activity of this receptor
   is coupled  to  the  stimulation of the phosphatidylinositol-calcium second
   messenger system.
 - Caenorhabditis elegans hypothetical protein ZC506.4.

Structurally these receptors are composed of:

 a) A signal sequence;
 b) A  very  large  hydrophilic extracellular region of about 540 to 600 amino
    acid  residues. This region contains 17 conserved cysteines which could be
    involved in disulfide bonds;
 c) A region of about 250 residues that  seem  to  contain seven transmembrane
    domains;
 d) A C-terminal cytoplasmic domain of variable length (50 to 350 residues).

There are quite a number of regions of high sequence conservation both  in the
N-terminal domain  and  in the region containing the transmembrane domains. We
have selected  three  of  these  conserved  regions as signature patterns. The
first one corresponds to a highly conserved hydrophobic segment in the central
part of  the  N-terminal  extracellular  region.  The  second corresponds to a
section that contains a cluster of six cysteines in the C-terminal part of the
extracellular domain.  The  last one corresponds to the C-terminal part of the
cytoplasmic loop between the fifth and sixth transmembrane domains.

-Expert(s) to contact by email:
           Kolakowski L.F. Jr.; kolakowski@uthsca.edu

-Consensus pattern: [LV]-x-N-[LIVM](2)-x-L-F-x-I-[PA]-Q-[LIVM]-[STA]-x-
                    [STA](3)-[STAN]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Consensus pattern: C-C-[FYW]-x-C-x(2)-C-x(4)-[FYW]-x(2,4)-[DN]-x(2)-[STAH]-C-
                    x(2)-C
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Consensus pattern: F-N-E-[STA]-K-x-I-[STAG]-F-[ST]-M
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Last update: July 1998 / Patterns and text revised.

[ 1] Tanabe Y., Masu M., Ishii T., Shigemoto R., Nakanishi S.
     Neuron 8:169-179(1992).
[ 2] Okamoto N., Hori S., Akazawa C., Hayashi Y., Shigemoto R., Mizuno N.,
     Nakanishi S.
     J. Biol. Chem. 269:1231-1236(1994).
[ 3] Duvoisin R.M., Zhang C., Ramonell K.
     J. Neurosci. 15:3075-3083(1995).
[ 4] Brown E.M., Gamba G., Riccardi D., Lombardi M., Butters R., Kifor O.,
     Sun A., Hediger M.A., Lytton J., Hebert S.C.
     Nature 366:575-580(1993).
{END}
{PDOC00211}
{PS00238; OPSIN}
{BEGIN}
*************************************************
* Visual pigments (opsins) retinal binding site *
*************************************************

Visual pigments [1,2] are the light-absorbing  molecules that  mediate vision.
They consist of  an apoprotein, opsin,  covalently  linked  to the chromophore
cis-retinal.  Vision is  effected through  the absorption of a  photon by cis-
retinal  which is isomerized to  trans-retinal.  This isomerization leads to a
change  of conformation  of the protein. Opsins are integral membrane proteins
with  seven transmembrane regions that belong to family 1 of G-protein coupled
receptors (see <PDOC00210>).

In vertebrates four different pigments are generally found.   Rod cells, which
mediate vision in dim light, contain the pigment rhodopsin.  Cone cells, which
function in bright light, are responsible  for  color vision and contain three
or more color pigments (for example, in mammals: red, blue and green).

In Drosophila, the  eye   is composed   of 800   facets  or   ommatidia.  Each
ommatidium contains eight photoreceptor cells (R1-R8):  the R1 to R6 cells are
outer cells,  R7  and R8 inner cells. Each of the three types of cells (R1-R6,
R7 and R8) expresses a specific opsin.

Proteins evolutionary related to opsins include squid retinochrome, also known
as retinal  photoisomerase, which converts various isomers of retinal into 11-
cis retinal and mammalian retinal pigment  epithelium (RPE) RGR [3], a protein
that may also act in retinal isomerization.

The attachment  site  for  retinal in the above proteins is a conserved lysine
residue in  the  middle  of  the  seventh  transmembrane helix. The pattern we
developed includes this residue.

-Consensus pattern: [LIVMWAC]-[PGAC]-x(3)-[SAC]-K-[STALIMR]-[GSACPNV]-[STACP]-
                    x(2)-[DENF]-[AP]-x(2)-[IY]
                    [K is the retinal binding site]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: NONE.
-Last update: July 1998 / Pattern and text revised.

[ 1] Applebury M.L., Hargrave P.A.
     Vision Res. 26:1881-1895(1986).
[ 2] Fryxell K.J., Meyerowitz E.M.
     J. Mol. Evol. 33:367-378(1991).
[ 3] Shen D., Jiang M., Hao W., Tao L., Salazar M., Fong H.K.W.
     Biochemistry 33:13117-13125(1994).
{END}