|
|
| (12 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1s1n.gif|left|200px]] | |
| | | | |
| - | {{Structure
| + | ==SH3 domain of human nephrocystin== |
| - | |PDB= 1s1n |SIZE=350|CAPTION= <scene name='initialview01'>1s1n</scene>
| + | <StructureSection load='1s1n' size='340' side='right'caption='[[1s1n]]' scene=''> |
| - | |SITE=
| + | == Structural highlights == |
| - | |LIGAND=
| + | <table><tr><td colspan='2'>[[1s1n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S1N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1S1N FirstGlance]. <br> |
| - | |ACTIVITY=
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | |GENE= NPHP1, NPH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1s1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1n OCA], [https://pdbe.org/1s1n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1s1n RCSB], [https://www.ebi.ac.uk/pdbsum/1s1n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1s1n ProSAT]</span></td></tr> |
| - | |DOMAIN=
| + | </table> |
| - | |RELATEDENTRY= | + | == Disease == |
| - | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1s1n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1s1n OCA], [http://www.ebi.ac.uk/pdbsum/1s1n PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1s1n RCSB]</span>
| + | [https://www.uniprot.org/uniprot/NPHP1_HUMAN NPHP1_HUMAN] Defects in NPHP1 are the cause of nephronophthisis type 1 (NPHP1) [MIM:[https://omim.org/entry/256100 256100]; also known as familial juvenile nephronophthisis 1. NPHP1 is an autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years.<ref>PMID:10839884</ref> Defects in NPHP1 are the cause of Senior-Loken syndrome type 1 (SLSN1) [MIM:[https://omim.org/entry/266900 266900]; also known as juvenile nephronophthisis with Leber amaurosis. SLSN is a renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney, with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.<ref>PMID:9856524</ref> Defects in NPHP1 are the cause of Joubert syndrome type 4 (JBTS4) [MIM:[https://omim.org/entry/609583 609583]. JBTS is an autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. JBTS4 is a phenotypically mild form.<ref>PMID:15138899</ref> |
| - | }}
| + | == Function == |
| - | | + | [https://www.uniprot.org/uniprot/NPHP1_HUMAN NPHP1_HUMAN] Together with BCAR1 it may play a role in the control of epithelial cell polarity. Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling. May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development. In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity). |
| - | '''SH3 domain of human nephrocystin'''
| + | == Evolutionary Conservation == |
| - | | + | [[Image:Consurf_key_small.gif|200px|right]] |
| - | | + | Check<jmol> |
| - | ==Overview== | + | <jmolCheckbox> |
| - | Human nephrocystin is a protein associated with juvenile NPH, an autosomal recessive, inherited kidney disease responsible for chronic renal failure in children. It contains an SH3 domain involved in signaling pathways controlling cell adhesion and cytoskeleton organization. The solution structure of this domain was solved by triple resonance NMR spectroscopy. Within the core, the structure is similar to those previously reported for other SH3 domains but exhibits a number of specific noncanonical features within the polyproline ligand binding site. Some of the key conserved residues are missing, and the N-Src loop exhibits an unusual twisted geometry, which results in a narrowing of the binding groove. This is induced by the replacement of a conserved Asp, Asn, or Glu residue by a Pro at one side of the N-Src loop. A systematic survey of other SH3 domains also containing a Pro at this position reveals that most of them belong to proteins involved in cell adhesion or motility. A variant of this domain, which carries a point mutation causing NPH, was also analyzed. This change, L180P, although it corresponds to a nonconserved and solvent-exposed position, causes a complete loss of the tertiary structure. Similar effects are also observed with the L180A variant. This could be a context-dependent effect resulting from an interaction between neighboring charged side-chains.
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/s1/1s1n_consurf.spt"</scriptWhenChecked> |
| - | | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| - | ==About this Structure== | + | <text>to colour the structure by Evolutionary Conservation</text> |
| - | 1S1N is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1S1N OCA].
| + | </jmolCheckbox> |
| - | | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1s1n ConSurf]. |
| - | ==Reference== | + | <div style="clear:both"></div> |
| - | Solution NMR structure of the SH3 domain of human nephrocystin and analysis of a mutation-causing juvenile nephronophthisis., le Maire A, Weber T, Saunier S, Broutin I, Antignac C, Ducruix A, Dardel F, Proteins. 2005 May 1;59(2):347-55. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15723349 15723349]
| + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Antignac, C.]] | + | [[Category: Antignac C]] |
| - | [[Category: Dardel, F.]] | + | [[Category: Dardel F]] |
| - | [[Category: Ducruix, A.]] | + | [[Category: Ducruix A]] |
| - | [[Category: Maire, A Le.]] | + | [[Category: Le Maire A]] |
| - | [[Category: Saunier, S.]] | + | [[Category: Saunier S]] |
| - | [[Category: Weber, T.]] | + | [[Category: Weber T]] |
| - | [[Category: beta barrel]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:36:04 2008''
| + | |
| Structural highlights
Disease
NPHP1_HUMAN Defects in NPHP1 are the cause of nephronophthisis type 1 (NPHP1) [MIM:256100; also known as familial juvenile nephronophthisis 1. NPHP1 is an autosomal recessive inherited disease characterized by anemia, polyuria, polydipsia, isosthenuria and death in uremia. Symmetrical destruction of the kidneys involving both tubules and glomeruli occurs. The underlying pathology is a chronic tubulo-interstitial nephropathy with characteristic tubular basement membrane thickening and medullary cyst formation. Associations with extrarenal symptoms, especially ocular lesions, are frequent. The age at death ranges from about 4 to 15 years.[1] Defects in NPHP1 are the cause of Senior-Loken syndrome type 1 (SLSN1) [MIM:266900; also known as juvenile nephronophthisis with Leber amaurosis. SLSN is a renal-retinal disorder characterized by progressive wasting of the filtering unit of the kidney, with or without medullary cystic renal disease, and progressive eye disease. Typically this disorder becomes apparent during the first year of life.[2] Defects in NPHP1 are the cause of Joubert syndrome type 4 (JBTS4) [MIM:609583. JBTS is an autosomal recessive disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. JBTS4 is a phenotypically mild form.[3]
Function
NPHP1_HUMAN Together with BCAR1 it may play a role in the control of epithelial cell polarity. Involved in the organization of apical junctions in kidney cells together with NPHP4 and RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 to cell matrix adhesions, thereby initiating phosphorylation of PTK2B/PYK2 and PTK2B/PYK2-dependent signaling. May play a role in the regulation of intraflagellar transport (IFT) during cilia assembly. Required for normal retina development. In connecting photoreceptor cilia influences the movement of some IFT proteins such as IFT88 and WDR19. Involved in spermatogenesis (By similarity).
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
References
- ↑ Betz R, Rensing C, Otto E, Mincheva A, Zehnder D, Lichter P, Hildebrandt F. Children with ocular motor apraxia type Cogan carry deletions in the gene (NPHP1) for juvenile nephronophthisis. J Pediatr. 2000 Jun;136(6):828-31. PMID:10839884
- ↑ Caridi G, Murer L, Bellantuono R, Sorino P, Caringella DA, Gusmano R, Ghiggeri GM. Renal-retinal syndromes: association of retinal anomalies and recessive nephronophthisis in patients with homozygous deletion of the NPH1 locus. Am J Kidney Dis. 1998 Dec;32(6):1059-62. PMID:9856524
- ↑ Parisi MA, Bennett CL, Eckert ML, Dobyns WB, Gleeson JG, Shaw DW, McDonald R, Eddy A, Chance PF, Glass IA. The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome. Am J Hum Genet. 2004 Jul;75(1):82-91. Epub 2004 May 11. PMID:15138899 doi:10.1086/421846
|
