COL4A3BP: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
m (Bot: HTTP→HTTPS)
 
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Collagen type IV alpha-3-binding protein''', also known as '''ceramide transfer protein''' (CERT) or '''StAR-related lipid transfer protein 11''' (STARD11) is a [[protein]] that in humans is encoded by the ''COL4A3BP'' [[gene]].<ref name="pmid10212244">{{cite journal | vauthors = Raya A, Revert F, Navarro S, Saus J | title = Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen | journal = The Journal of Biological Chemistry | volume = 274 | issue = 18 | pages = 12642–9 | date = Apr 1999 | pmid = 10212244 | pmc = | doi = 10.1074/jbc.274.18.12642 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: COL4A3BP collagen, type IV, alpha 3 (Goodpasture antigen) binding protein| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10087| accessdate = }}</ref>  The protein contains a [[pleckstrin homology domain]] at its amino terminus and a [[StAR-related transfer domain|START domain]] towards the end of the molecule.  It is a member of the [[phosphatidylcholine transfer protein#Structure|StarD2]] subfamily of START domain proteins.
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function and structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Collagen, type IV, alpha 3 (Goodpasture antigen) binding protein
| HGNCid = 2205
| Symbol = COL4A3BP
| AltSymbols =; CERT; CERTL; FLJ20597; GPBP; STARD11
| OMIM = 604677
| ECnumber = 
| Homologene = 4173
| MGIid = 1915268
| GeneAtlas_image1 = PBB_GE_COL4A3BP_219625_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005575 |text = cellular_component}}
| Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0006955 |text = immune response}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 10087
    | Hs_Ensembl = ENSG00000113163
    | Hs_RefseqProtein = NP_005704
    | Hs_RefseqmRNA = NM_005713
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 74702684
    | Hs_GenLoc_end = 74843719
    | Hs_Uniprot = Q9Y5P4
    | Mm_EntrezGene = 68018
    | Mm_Ensembl = ENSMUSG00000021669
    | Mm_RefseqmRNA = NM_023420
    | Mm_RefseqProtein = NP_075909
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 13
    | Mm_GenLoc_start = 97643434
    | Mm_GenLoc_end = 97738249
    | Mm_Uniprot = Q3TQF6
  }}
}}
'''Collagen, type IV, alpha 3 (Goodpasture antigen) binding protein''', also known as '''COL4A3BP''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: COL4A3BP collagen, type IV, alpha 3 (Goodpasture antigen) binding protein| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10087| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
Ceramide transferase protein (or CERT) is responsible for the transfer of [[ceramide]] from the [[endoplasmic reticulum]] (ER) to the [[Golgi apparatus]]. Ceramide plays a very important role in the metabolism and biosynthesis of [[sphingolipids|sphingolipid]]. More specifically, it is synthesized at the ER, then is transferred by CERT to Golgi where it is converted to [[sphingomyelin]] (SM).<ref name="pmid12011104">{{cite journal | vauthors = Merrill AH | title = De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway | journal = The Journal of Biological Chemistry | volume = 277 | issue = 29 | pages = 25843–6 | date = Jul 2002 | pmid = 12011104 | doi = 10.1074/jbc.R200009200 }}</ref>
{{PBB_Summary
 
| section_title =  
There are two pathways through which this transfer takes place: a major pathway, which is [[adenosine triphosphate|ATP]] and cytosol-dependent and a minor pathway, which is ATP- and cytosol-independent.<ref name="entrez" />
| summary_text = This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Two transcripts exist for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: COL4A3BP collagen, type IV, alpha 3 (Goodpasture antigen) binding protein| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10087| accessdate = }}</ref>
 
}}
CERT is a 68kDa protein<ref name="pmid14685229">{{cite journal | vauthors = Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M | title = Molecular machinery for non-vesicular trafficking of ceramide | journal = Nature | volume = 426 | issue = 6968 | pages = 803–9 | date = Dec 2003 | pmid = 14685229 | doi = 10.1038/nature02188 }}</ref> that consists of three different parts, each of which with a special role:
 
# [[Pleckstrin homology domain]] (PH): It is the aminoterminal domain and it consists of about 100 aminoacid residues.<ref name="pmid10212244" /><ref name="pmid11007769">{{cite journal | vauthors = Raya A, Revert-Ros F, Martinez-Martinez P, Navarro S, Rosello E, Vieites B, Granero F, Forteza J, Saus J | title = Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis | journal = The Journal of Biological Chemistry | volume = 275 | issue = 51 | pages = 40392–9 | date = Dec 2000 | pmid = 11007769 | doi = 10.1074/jbc.M002769200 }}</ref>  The main function of this part of CERT is to recognize and bind various phosphatidyloinositol phosphates (PIPs) with different level of specificity.<ref name="pmid10926821">{{cite journal | vauthors = Lemmon MA, Ferguson KM | title = Signal-dependent membrane targeting by pleckstrin homology (PH) domains | journal = The Biochemical Journal | volume = 350 | issue =  1| pages = 1–18 | date = Aug 2000 | pmid = 10926821 | pmc = 1221219 | doi = 10.1042/0264-6021:3500001 }}</ref> The isomers of PIPs are distributed to various organelles: PI-4,5-diphosphate goes to the plasma membrane, PI-3-monophosphate to endosomes and PI-4-monophosphate to Golgi.<ref name="pmid12383794">{{cite journal | vauthors = De Matteis M, Godi A, Corda D | title = Phosphoinositides and the golgi complex | journal = Current Opinion in Cell Biology | volume = 14 | issue = 4 | pages = 434–47 | date = Aug 2002 | pmid = 12383794 | doi = 10.1016/S0955-0674(02)00357-5 }}</ref> PH domain of wild-type CERT has been found to recognize specifically PI4P and therefore CERT targets the Golgi apparatus or the  trans-Golgi network.<ref name="pmid14685229"/><ref name="pmid12007412">{{cite journal | vauthors = Levine TP, Munro S | title = Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components | journal = Current Biology | volume = 12 | issue = 9 | pages = 695–704 | date = Apr 2002 | pmid = 12007412 | doi = 10.1016/S0960-9822(02)00779-0 }}</ref><ref name="pmid12914695">{{cite journal | vauthors = Wang YJ, Wang J, Sun HQ, Martinez M, Sun YX, Macia E, Kirchhausen T, Albanesi JP, Roth MG, Yin HL | title = Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi | journal = Cell | volume = 114 | issue = 3 | pages = 299–310 | date = Aug 2003 | pmid = 12914695 | doi = 10.1016/S0092-8674(03)00603-2 }}</ref>
# [[StAR-related transfer domain|START domain]]: It consists of about 210 amino acid residues and has an important role in the transfer of ceramide, which is that it can recognize specifically only the natural D-erythro isomer of ceramide and extract it from the membrane.<ref name="pmid14685229"/>
# [[FFAT motif]] (two [[phenylalanine]]s in an acidic tract, that has a conserved sequence "EFFDAxE"): It is a short domain situated between PH and START domain and is the one responsible for the interaction of CERT with ER. More specifically, it binds to the ER resident type II membrane protein, [[vesicle-associated membrane protein]] (VAMP) associated protein (VAP), an interaction that is necessary for the transfer of ceramide from the ER to Golgi.<ref name="pmid12727870">{{cite journal | vauthors = Loewen CJ, Roy A, Levine TP | title = A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP | journal = The EMBO Journal | volume = 22 | issue = 9 | pages = 2025–35 | date = May 2003 | pmid = 12727870 | pmc = 156073 | doi = 10.1093/emboj/cdg201 }}</ref>
 
All of these domains are important for the transfer of ceramide, since first of all CERT will extract newly synthesized ceramide from the membrane with the help of its START domain. Then, ceramide will be transferred through the cytosol towards Golgi because of the interaction between the PH domain and PI4P. Finally, interaction with ER is facilitated through the binding of the [[FFAT motif]] with [[Vesicle-associated membrane protein]].
 
== Regulation ==
 
The transport of ceramide by CERT requires [[adenosine triphosphate|ATP]].<ref name="pmid10882735">{{cite journal | vauthors = Funakoshi T, Yasuda S, Fukasawa M, Nishijima M, Hanada K | title = Reconstitution of ATP- and cytosol-dependent transport of de novo synthesized ceramide to the site of sphingomyelin synthesis in semi-intact cells | journal = The Journal of Biological Chemistry | volume = 275 | issue = 39 | pages = 29938–45 | date = Sep 2000 | pmid = 10882735 | doi = 10.1074/jbc.M004470200 }}</ref>  CERT – when expressed in mammalian cells - has been found to receive a lot of possible phosphorylations at the serine repeat (SR) motif, which is close to the [[pleckstrin homology domain|PH]] domain.<ref name="Kumagai_2007">{{cite journal | vauthors = Kumagai K, Kawano M, Shinkai-Ouchi F, Nishijima M, Hanada K | title = Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT | journal = The Journal of Biological Chemistry | volume = 282 | issue = 24 | pages = 17758–66 | date = Jun 2007 | pmid = 17442665 | doi = 10.1074/jbc.M702291200 }}</ref>
 
It has been shown that the [[phosphorylation]] of this SR motif leads to inactivation of the PI4P-binding and ceramide transferring activities of CERT, since it induces an autoinhibitory reaction between the PH and START domains of CERT, transforming it from the active form to the inactive form.<ref name="Kumagai_2007"/>
 
[[Protein kinase D1|Protein kinase D]] (PKD) has been found to phosphorylate the SR motif of CERT.<ref name="pmid17591919">{{cite journal | vauthors = Fugmann T, Hausser A, Schöffler P, Schmid S, Pfizenmaier K, Olayioye MA | title = Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein | journal = The Journal of Cell Biology | volume = 178 | issue = 1 | pages = 15–22 | date = Jul 2007 | pmid = 17591919 | pmc = 2064413 | doi = 10.1083/jcb.200612017 }}</ref> Also, CERT is further phosphorylated by the [[Casein kinase 1|casein kinase 1 family]] leading to hyperphosphorylation of the SR motif.<ref name="pmid19005213">{{cite journal | vauthors = Tomishige N, Kumagai K, Kusuda J, Nishijima M, Hanada K | title = Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin | journal = Molecular Biology of the Cell | volume = 20 | issue = 1 | pages = 348–57 | date = Jan 2009 | pmid = 19005213 | pmc = 2613112 | doi = 10.1091/mbc.E08-07-0669 }}</ref>  On the other hand, the integral membrane protein [[protein phosphatase 2|protein phosphatase 2Cε ]] (PP2Cε), which is located on the endoplasmic reticulum induces dephosphorylation of CERT.<ref name="pmid18165232">{{cite journal | vauthors = Saito S, Matsui H, Kawano M, Kumagai K, Tomishige N, Hanada K, Echigo S, Tamura S, Kobayashi T | title = Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes | journal = The Journal of Biological Chemistry | volume = 283 | issue = 10 | pages = 6584–93 | date = Mar 2008 | pmid = 18165232 | doi = 10.1074/jbc.M707691200 }}</ref>  Dephosphorylated CERT is in the active form in order to be functional and transfer ceramide from ER to Golgi.<ref name="pmid20431265">{{cite journal | vauthors = Hanada K | title = Intracellular trafficking of ceramide by ceramide transfer protein | journal = Proceedings of the Japan Academy, Series B | volume = 86 | issue = 4 | pages = 426–37 | year = 2010 | pmid = 20431265 | pmc = 3417804 | doi = 10.2183/pjab.86.426 }}</ref>
 
== Inhibitor HPA-12 ==
 
The chemically synthesized compound N-(30hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecamide (HPA-12) has been found to be an inhibitor of CERT-mediated ceramide trafficking.<ref name="Kumagai_2005">{{cite journal | vauthors = Kumagai K, Yasuda S, Okemoto K, Nishijima M, Kobayashi S, Hanada K | title = CERT mediates intermembrane transfer of various molecular species of ceramides | journal = The Journal of Biological Chemistry | volume = 280 | issue = 8 | pages = 6488–95 | date = Feb 2005 | pmid = 15596449 | doi = 10.1074/jbc.M409290200 }}</ref>
More specifically, this drug inhibits the ATP-dependent transport of ceramide from ER to Golgi (and therefore the conversion of ceramide to sphingomyelin), but it does not inhibit protein trafficking. This suggests that Ceramide is still transformed to Glycosylceramide at Golgi. Moreover, it has been shown that it does not inhibit the Sphingomyelin synthase in vitro or in vivo.<ref name="Kumagai_2005"/>
Moreover, only the (1R, 3R) isomer of HPA-12 has been found to be an active inhibitor<ref name="Kumagai_2005"/> and the length of the chain as well as the two hydroxyl-groups are very important for the inhibitory activity.<ref name="pmid12904073">{{cite journal | vauthors = Nakamura Y, Matsubara R, Kitagawa H, Kobayashi S, Kumagai K, Yasuda S, Hanada K | title = Stereoselective synthesis and structure-activity relationship of novel ceramide trafficking inhibitors. (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide and its analogues | journal = Journal of Medicinal Chemistry | volume = 46 | issue = 17 | pages = 3688–95 | date = Aug 2003 | pmid = 12904073 | doi = 10.1021/jm0300779 }}</ref>
 
== Clinical significance ==
 
This gene encodes a kinase also known as Goodpasture antigen-binding protein that specifically phosphorylates the [[N-terminal]] region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture [[antigen]]. [[Goodpasture's syndrome]] is the result of an [[autoimmune]] response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Two transcripts exist for this gene.<ref name="entrez" />
 
==Model organisms==
[[Model organism]]s have been used in the study of COL4A3BP function. A conditional [[knockout mouse]] line called ''Col4a3bp<sup>tm1a(KOMP)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Col4a3bp#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, ((Sanger Institute Mouse Genetics Project)), Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Col4a3bp&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref> - in-depth bone and cartilage phenotyping<ref name="obcd_ref">{{cite web |url=http://www.boneandcartilage.com/ |title=OBCD Consortium}}</ref>  
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
|+ ''Col4a3bp'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" /><ref name="obcd_ref"/>
 
|-
| Peripheral blood leukocytes 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Insulin || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#C40000"|Abnormal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
 
|-
| Grip strength || bgcolor="#488ED3"|Normal
 
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#C40000"|Abnormal
 
|-
| Cytotoxic T Cell Function || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Influenza Challenge || bgcolor="#488ED3"|Normal
 
|-
|}
{{clear}}


==References==
==References==
{{reflist|2}}
{{reflist|35em}}
==Further reading==
 
{{refbegin | 2}}
== Further reading ==
{{PBB_Further_reading
{{refbegin|35em}}
| citations =
* {{cite journal | vauthors = Kalluri R | title = Goodpasture syndrome | journal = Kidney International | volume = 55 | issue = 3 | pages = 1120–2 | date = Mar 1999 | pmid = 10027952 | doi = 10.1046/j.1523-1755.1999.0550031120.x }}
*{{cite journal | author=Kalluri R |title=Goodpasture syndrome. |journal=Kidney Int. |volume=55 |issue= 3 |pages= 1120-2 |year= 1999 |pmid= 10027952 |doi= 10.1046/j.1523-1755.1999.0550031120.x }}
* {{cite journal | vauthors = Alpy F, Tomasetto C | title = Give lipids a START: the StAR-related lipid transfer (START) domain in mammals | journal = Journal of Cell Science | volume = 118 | issue = Pt 13 | pages = 2791–801 | date = Jul 2005 | pmid = 15976441 | doi = 10.1242/jcs.02485 }}
*{{cite journal | author=Alpy F, Tomasetto C |title=Give lipids a START: the StAR-related lipid transfer (START) domain in mammals. |journal=J. Cell. Sci. |volume=118 |issue= Pt 13 |pages= 2791-801 |year= 2005 |pmid= 15976441 |doi= 10.1242/jcs.02485 }}
* {{cite journal | vauthors = Raya A, Revert-Ros F, Martinez-Martinez P, Navarro S, Rosello E, Vieites B, Granero F, Forteza J, Saus J | title = Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis | journal = The Journal of Biological Chemistry | volume = 275 | issue = 51 | pages = 40392–9 | date = Dec 2000 | pmid = 11007769 | doi = 10.1074/jbc.M002769200 }}
*{{cite journal | author=Raya A, Revert F, Navarro S, Saus J |title=Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen. |journal=J. Biol. Chem. |volume=274 |issue= 18 |pages= 12642-9 |year= 1999 |pmid= 10212244 |doi=  }}
* {{cite journal | vauthors = Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M | title = Molecular machinery for non-vesicular trafficking of ceramide | journal = Nature | volume = 426 | issue = 6968 | pages = 803–9 | date = Dec 2003 | pmid = 14685229 | doi = 10.1038/nature02188 }}
*{{cite journal  | author=Raya A, Revert-Ros F, Martinez-Martinez P, ''et al.'' |title=Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis. |journal=J. Biol. Chem. |volume=275 |issue= 51 |pages= 40392-9 |year= 2001 |pmid= 11007769 |doi= 10.1074/jbc.M002769200 }}
* {{cite journal | vauthors = Kumagai K, Yasuda S, Okemoto K, Nishijima M, Kobayashi S, Hanada K | title = CERT mediates intermembrane transfer of various molecular species of ceramides | journal = The Journal of Biological Chemistry | volume = 280 | issue = 8 | pages = 6488–95 | date = Feb 2005 | pmid = 15596449 | doi = 10.1074/jbc.M409290200 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Borza DB, Bondar O, Colon S, Todd P, Sado Y, Neilson EG, Hudson BG | title = Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis | journal = The Journal of Biological Chemistry | volume = 280 | issue = 29 | pages = 27147–54 | date = Jul 2005 | pmid = 15917228 | doi = 10.1074/jbc.M504050200 }}
*{{cite journal  | author=Hanada K, Kumagai K, Yasuda S, ''et al.'' |title=Molecular machinery for non-vesicular trafficking of ceramide. |journal=Nature |volume=426 |issue= 6968 |pages= 803-9 |year= 2004 |pmid= 14685229 |doi= 10.1038/nature02188 }}
* {{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = Oct 2005 | pmid = 16189514 | doi = 10.1038/nature04209 }}
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
* {{cite journal | vauthors = Granero F, Revert F, Revert-Ros F, Lainez S, Martínez-Martínez P, Saus J | title = A human-specific TNF-responsive promoter for Goodpasture antigen-binding protein | journal = The FEBS Journal | volume = 272 | issue = 20 | pages = 5291–305 | date = Oct 2005 | pmid = 16218959 | doi = 10.1111/j.1742-4658.2005.04925.x }}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
* {{cite journal | vauthors = Longo I, Scala E, Mari F, Caselli R, Pescucci C, Mencarelli MA, Speciale C, Giani M, Bresin E, Caringella DA, Borochowitz ZU, Siriwardena K, Winship I, Renieri A, Meloni I | title = Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families | journal = Nephrology, Dialysis, Transplantation | volume = 21 | issue = 3 | pages = 665–71 | date = Mar 2006 | pmid = 16338941 | doi = 10.1093/ndt/gfi312 }}
*{{cite journal  | author=Kumagai K, Yasuda S, Okemoto K, ''et al.'' |title=CERT mediates intermembrane transfer of various molecular species of ceramides. |journal=J. Biol. Chem. |volume=280 |issue= 8 |pages= 6488-95 |year= 2005 |pmid= 15596449 |doi= 10.1074/jbc.M409290200 }}
* {{cite journal | vauthors = Perry RJ, Ridgway ND | title = Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein | journal = Molecular Biology of the Cell | volume = 17 | issue = 6 | pages = 2604–16 | date = Jun 2006 | pmid = 16571669 | pmc = 1474796 | doi = 10.1091/mbc.E06-01-0060 }}
*{{cite journal | author=Borza DB, Bondar O, Colon S, ''et al.'' |title=Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis. |journal=J. Biol. Chem. |volume=280 |issue= 29 |pages= 27147-54 |year= 2005 |pmid= 15917228 |doi= 10.1074/jbc.M504050200 }}
* {{cite journal | vauthors = Kawano M, Kumagai K, Nishijima M, Hanada K | title = Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT | journal = The Journal of Biological Chemistry | volume = 281 | issue = 40 | pages = 30279–88 | date = Oct 2006 | pmid = 16895911 | doi = 10.1074/jbc.M605032200 }}
*{{cite journal | author=Rual JF, Venkatesan K, Hao T, ''et al.'' |title=Towards a proteome-scale map of the human protein-protein interaction network. |journal=Nature |volume=437 |issue= 7062 |pages= 1173-8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 }}
* {{cite journal | vauthors = Kharrat M, Makni S, Makni K, Kammoun K, Charfeddine K, Azaeiz H, Jarraya F, Ben Hmida M, Gubler MC, Ayadi H, Hachicha J | title = Autosomal dominant Alport's syndrome: study of a large Tunisian family | journal = Saudi Journal of Kidney Diseases and Transplantation | volume = 17 | issue = 3 | pages = 320–5 | date = Sep 2006 | pmid = 16970251 | doi =  }}
*{{cite journal | author=Granero F, Revert F, Revert-Ros F, ''et al.'' |title=A human-specific TNF-responsive promoter for Goodpasture antigen-binding protein. |journal=FEBS J. |volume=272 |issue= 20 |pages= 5291-305 |year= 2005 |pmid= 16218959 |doi= 10.1111/j.1742-4658.2005.04925.x }}
* {{cite journal | vauthors = Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M | title = Global, in vivo, and site-specific phosphorylation dynamics in signaling networks | journal = Cell | volume = 127 | issue = 3 | pages = 635–48 | date = Nov 2006 | pmid = 17081983 | doi = 10.1016/j.cell.2006.09.026 }}
*{{cite journal | author=Longo I, Scala E, Mari F, ''et al.'' |title=Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families. |journal=Nephrol. Dial. Transplant. |volume=21 |issue= 3 |pages= 665-71 |year= 2006 |pmid= 16338941 |doi= 10.1093/ndt/gfi312 }}
* {{cite journal | vauthors = Kumagai K, Kawano M, Shinkai-Ouchi F, Nishijima M, Hanada K | title = Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT | journal = The Journal of Biological Chemistry | volume = 282 | issue = 24 | pages = 17758–66 | date = Jun 2007 | pmid = 17442665 | doi = 10.1074/jbc.M702291200 }}
*{{cite journal | author=Perry RJ, Ridgway ND |title=Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein. |journal=Mol. Biol. Cell |volume=17 |issue= 6 |pages= 2604-16 |year= 2006 |pmid= 16571669 |doi= 10.1091/mbc.E06-01-0060 }}
*{{cite journal | author=Kawano M, Kumagai K, Nishijima M, Hanada K |title=Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. |journal=J. Biol. Chem. |volume=281 |issue= 40 |pages= 30279-88 |year= 2006 |pmid= 16895911 |doi= 10.1074/jbc.M605032200 }}
*{{cite journal | author=Kharrat M, Makni S, Makni K, ''et al.'' |title=Autosomal dominant Alport's syndrome: study of a large Tunisian family. |journal=Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia |volume=17 |issue= 3 |pages= 320-5 |year= 2006 |pmid= 16970251 |doi=  }}
*{{cite journal | author=Olsen JV, Blagoev B, Gnad F, ''et al.'' |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. |journal=Cell |volume=127 |issue= 3 |pages= 635-48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 }}
*{{cite journal | author=Kumagai K, Kawano M, Shinkai-Ouchi F, ''et al.'' |title=Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT. |journal=J. Biol. Chem. |volume=282 |issue= 24 |pages= 17758-66 |year= 2007 |pmid= 17442665 |doi= 10.1074/jbc.M702291200 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
* {{UCSC genome browser|COL4A3BP}}
* {{UCSC gene details|COL4A3BP}}

Latest revision as of 09:54, 30 August 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Collagen type IV alpha-3-binding protein, also known as ceramide transfer protein (CERT) or StAR-related lipid transfer protein 11 (STARD11) is a protein that in humans is encoded by the COL4A3BP gene.[1][2] The protein contains a pleckstrin homology domain at its amino terminus and a START domain towards the end of the molecule. It is a member of the StarD2 subfamily of START domain proteins.

Function and structure

Ceramide transferase protein (or CERT) is responsible for the transfer of ceramide from the endoplasmic reticulum (ER) to the Golgi apparatus. Ceramide plays a very important role in the metabolism and biosynthesis of sphingolipid. More specifically, it is synthesized at the ER, then is transferred by CERT to Golgi where it is converted to sphingomyelin (SM).[3]

There are two pathways through which this transfer takes place: a major pathway, which is ATP and cytosol-dependent and a minor pathway, which is ATP- and cytosol-independent.[2]

CERT is a 68kDa protein[4] that consists of three different parts, each of which with a special role:

  1. Pleckstrin homology domain (PH): It is the aminoterminal domain and it consists of about 100 aminoacid residues.[1][5] The main function of this part of CERT is to recognize and bind various phosphatidyloinositol phosphates (PIPs) with different level of specificity.[6] The isomers of PIPs are distributed to various organelles: PI-4,5-diphosphate goes to the plasma membrane, PI-3-monophosphate to endosomes and PI-4-monophosphate to Golgi.[7] PH domain of wild-type CERT has been found to recognize specifically PI4P and therefore CERT targets the Golgi apparatus or the trans-Golgi network.[4][8][9]
  2. START domain: It consists of about 210 amino acid residues and has an important role in the transfer of ceramide, which is that it can recognize specifically only the natural D-erythro isomer of ceramide and extract it from the membrane.[4]
  3. FFAT motif (two phenylalanines in an acidic tract, that has a conserved sequence "EFFDAxE"): It is a short domain situated between PH and START domain and is the one responsible for the interaction of CERT with ER. More specifically, it binds to the ER resident type II membrane protein, vesicle-associated membrane protein (VAMP) associated protein (VAP), an interaction that is necessary for the transfer of ceramide from the ER to Golgi.[10]

All of these domains are important for the transfer of ceramide, since first of all CERT will extract newly synthesized ceramide from the membrane with the help of its START domain. Then, ceramide will be transferred through the cytosol towards Golgi because of the interaction between the PH domain and PI4P. Finally, interaction with ER is facilitated through the binding of the FFAT motif with Vesicle-associated membrane protein.

Regulation

The transport of ceramide by CERT requires ATP.[11] CERT – when expressed in mammalian cells - has been found to receive a lot of possible phosphorylations at the serine repeat (SR) motif, which is close to the PH domain.[12]

It has been shown that the phosphorylation of this SR motif leads to inactivation of the PI4P-binding and ceramide transferring activities of CERT, since it induces an autoinhibitory reaction between the PH and START domains of CERT, transforming it from the active form to the inactive form.[12]

Protein kinase D (PKD) has been found to phosphorylate the SR motif of CERT.[13] Also, CERT is further phosphorylated by the casein kinase 1 family leading to hyperphosphorylation of the SR motif.[14] On the other hand, the integral membrane protein protein phosphatase 2Cε (PP2Cε), which is located on the endoplasmic reticulum induces dephosphorylation of CERT.[15] Dephosphorylated CERT is in the active form in order to be functional and transfer ceramide from ER to Golgi.[16]

Inhibitor HPA-12

The chemically synthesized compound N-(30hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecamide (HPA-12) has been found to be an inhibitor of CERT-mediated ceramide trafficking.[17] More specifically, this drug inhibits the ATP-dependent transport of ceramide from ER to Golgi (and therefore the conversion of ceramide to sphingomyelin), but it does not inhibit protein trafficking. This suggests that Ceramide is still transformed to Glycosylceramide at Golgi. Moreover, it has been shown that it does not inhibit the Sphingomyelin synthase in vitro or in vivo.[17] Moreover, only the (1R, 3R) isomer of HPA-12 has been found to be an active inhibitor[17] and the length of the chain as well as the two hydroxyl-groups are very important for the inhibitory activity.[18]

Clinical significance

This gene encodes a kinase also known as Goodpasture antigen-binding protein that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture's syndrome is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Two transcripts exist for this gene.[2]

Model organisms

Model organisms have been used in the study of COL4A3BP function. A conditional knockout mouse line called Col4a3bptm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[19] Male and female animals underwent a standardized phenotypic screen[20] to determine the effects of deletion.[21][22][23][24] Additional screens performed: - In-depth immunological phenotyping[25] - in-depth bone and cartilage phenotyping[26]

References

  1. ↑ 1.0 1.1 Raya A, Revert F, Navarro S, Saus J (Apr 1999). "Characterization of a novel type of serine/threonine kinase that specifically phosphorylates the human goodpasture antigen". The Journal of Biological Chemistry. 274 (18): 12642–9. doi:10.1074/jbc.274.18.12642. PMID 10212244.
  2. ↑ 2.0 2.1 2.2 "Entrez Gene: COL4A3BP collagen, type IV, alpha 3 (Goodpasture antigen) binding protein".
  3. ↑ Merrill AH (Jul 2002). "De novo sphingolipid biosynthesis: a necessary, but dangerous, pathway". The Journal of Biological Chemistry. 277 (29): 25843–6. doi:10.1074/jbc.R200009200. PMID 12011104.
  4. ↑ 4.0 4.1 4.2 Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M (Dec 2003). "Molecular machinery for non-vesicular trafficking of ceramide". Nature. 426 (6968): 803–9. doi:10.1038/nature02188. PMID 14685229.
  5. ↑ Raya A, Revert-Ros F, Martinez-Martinez P, Navarro S, Rosello E, Vieites B, Granero F, Forteza J, Saus J (Dec 2000). "Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis". The Journal of Biological Chemistry. 275 (51): 40392–9. doi:10.1074/jbc.M002769200. PMID 11007769.
  6. ↑ Lemmon MA, Ferguson KM (Aug 2000). "Signal-dependent membrane targeting by pleckstrin homology (PH) domains". The Biochemical Journal. 350 (1): 1–18. doi:10.1042/0264-6021:3500001. PMC 1221219. PMID 10926821.
  7. ↑ De Matteis M, Godi A, Corda D (Aug 2002). "Phosphoinositides and the golgi complex". Current Opinion in Cell Biology. 14 (4): 434–47. doi:10.1016/S0955-0674(02)00357-5. PMID 12383794.
  8. ↑ Levine TP, Munro S (Apr 2002). "Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components". Current Biology. 12 (9): 695–704. doi:10.1016/S0960-9822(02)00779-0. PMID 12007412.
  9. ↑ Wang YJ, Wang J, Sun HQ, Martinez M, Sun YX, Macia E, Kirchhausen T, Albanesi JP, Roth MG, Yin HL (Aug 2003). "Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi". Cell. 114 (3): 299–310. doi:10.1016/S0092-8674(03)00603-2. PMID 12914695.
  10. ↑ Loewen CJ, Roy A, Levine TP (May 2003). "A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP". The EMBO Journal. 22 (9): 2025–35. doi:10.1093/emboj/cdg201. PMC 156073. PMID 12727870.
  11. ↑ Funakoshi T, Yasuda S, Fukasawa M, Nishijima M, Hanada K (Sep 2000). "Reconstitution of ATP- and cytosol-dependent transport of de novo synthesized ceramide to the site of sphingomyelin synthesis in semi-intact cells". The Journal of Biological Chemistry. 275 (39): 29938–45. doi:10.1074/jbc.M004470200. PMID 10882735.
  12. ↑ 12.0 12.1 Kumagai K, Kawano M, Shinkai-Ouchi F, Nishijima M, Hanada K (Jun 2007). "Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT". The Journal of Biological Chemistry. 282 (24): 17758–66. doi:10.1074/jbc.M702291200. PMID 17442665.
  13. ↑ Fugmann T, Hausser A, Schöffler P, Schmid S, Pfizenmaier K, Olayioye MA (Jul 2007). "Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein". The Journal of Cell Biology. 178 (1): 15–22. doi:10.1083/jcb.200612017. PMC 2064413. PMID 17591919.
  14. ↑ Tomishige N, Kumagai K, Kusuda J, Nishijima M, Hanada K (Jan 2009). "Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin". Molecular Biology of the Cell. 20 (1): 348–57. doi:10.1091/mbc.E08-07-0669. PMC 2613112. PMID 19005213.
  15. ↑ Saito S, Matsui H, Kawano M, Kumagai K, Tomishige N, Hanada K, Echigo S, Tamura S, Kobayashi T (Mar 2008). "Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes". The Journal of Biological Chemistry. 283 (10): 6584–93. doi:10.1074/jbc.M707691200. PMID 18165232.
  16. ↑ Hanada K (2010). "Intracellular trafficking of ceramide by ceramide transfer protein". Proceedings of the Japan Academy, Series B. 86 (4): 426–37. doi:10.2183/pjab.86.426. PMC 3417804. PMID 20431265.
  17. ↑ 17.0 17.1 17.2 Kumagai K, Yasuda S, Okemoto K, Nishijima M, Kobayashi S, Hanada K (Feb 2005). "CERT mediates intermembrane transfer of various molecular species of ceramides". The Journal of Biological Chemistry. 280 (8): 6488–95. doi:10.1074/jbc.M409290200. PMID 15596449.
  18. ↑ Nakamura Y, Matsubara R, Kitagawa H, Kobayashi S, Kumagai K, Yasuda S, Hanada K (Aug 2003). "Stereoselective synthesis and structure-activity relationship of novel ceramide trafficking inhibitors. (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide and its analogues". Journal of Medicinal Chemistry. 46 (17): 3688–95. doi:10.1021/jm0300779. PMID 12904073.
  19. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  20. ↑ 20.0 20.1 "International Mouse Phenotyping Consortium".
  21. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  22. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  23. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  24. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  25. ↑ 25.0 25.1 "Infection and Immunity Immunophenotyping (3i) Consortium".
  26. ↑ 26.0 26.1 "OBCD Consortium".

Further reading

  • Kalluri R (Mar 1999). "Goodpasture syndrome". Kidney International. 55 (3): 1120–2. doi:10.1046/j.1523-1755.1999.0550031120.x. PMID 10027952.
  • Alpy F, Tomasetto C (Jul 2005). "Give lipids a START: the StAR-related lipid transfer (START) domain in mammals". Journal of Cell Science. 118 (Pt 13): 2791–801. doi:10.1242/jcs.02485. PMID 15976441.
  • Raya A, Revert-Ros F, Martinez-Martinez P, Navarro S, Rosello E, Vieites B, Granero F, Forteza J, Saus J (Dec 2000). "Goodpasture antigen-binding protein, the kinase that phosphorylates the goodpasture antigen, is an alternatively spliced variant implicated in autoimmune pathogenesis". The Journal of Biological Chemistry. 275 (51): 40392–9. doi:10.1074/jbc.M002769200. PMID 11007769.
  • Hanada K, Kumagai K, Yasuda S, Miura Y, Kawano M, Fukasawa M, Nishijima M (Dec 2003). "Molecular machinery for non-vesicular trafficking of ceramide". Nature. 426 (6968): 803–9. doi:10.1038/nature02188. PMID 14685229.
  • Kumagai K, Yasuda S, Okemoto K, Nishijima M, Kobayashi S, Hanada K (Feb 2005). "CERT mediates intermembrane transfer of various molecular species of ceramides". The Journal of Biological Chemistry. 280 (8): 6488–95. doi:10.1074/jbc.M409290200. PMID 15596449.
  • Borza DB, Bondar O, Colon S, Todd P, Sado Y, Neilson EG, Hudson BG (Jul 2005). "Goodpasture autoantibodies unmask cryptic epitopes by selectively dissociating autoantigen complexes lacking structural reinforcement: novel mechanisms for immune privilege and autoimmune pathogenesis". The Journal of Biological Chemistry. 280 (29): 27147–54. doi:10.1074/jbc.M504050200. PMID 15917228.
  • Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
  • Granero F, Revert F, Revert-Ros F, Lainez S, Martínez-Martínez P, Saus J (Oct 2005). "A human-specific TNF-responsive promoter for Goodpasture antigen-binding protein". The FEBS Journal. 272 (20): 5291–305. doi:10.1111/j.1742-4658.2005.04925.x. PMID 16218959.
  • Longo I, Scala E, Mari F, Caselli R, Pescucci C, Mencarelli MA, Speciale C, Giani M, Bresin E, Caringella DA, Borochowitz ZU, Siriwardena K, Winship I, Renieri A, Meloni I (Mar 2006). "Autosomal recessive Alport syndrome: an in-depth clinical and molecular analysis of five families". Nephrology, Dialysis, Transplantation. 21 (3): 665–71. doi:10.1093/ndt/gfi312. PMID 16338941.
  • Perry RJ, Ridgway ND (Jun 2006). "Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein". Molecular Biology of the Cell. 17 (6): 2604–16. doi:10.1091/mbc.E06-01-0060. PMC 1474796. PMID 16571669.
  • Kawano M, Kumagai K, Nishijima M, Hanada K (Oct 2006). "Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT". The Journal of Biological Chemistry. 281 (40): 30279–88. doi:10.1074/jbc.M605032200. PMID 16895911.
  • Kharrat M, Makni S, Makni K, Kammoun K, Charfeddine K, Azaeiz H, Jarraya F, Ben Hmida M, Gubler MC, Ayadi H, Hachicha J (Sep 2006). "Autosomal dominant Alport's syndrome: study of a large Tunisian family". Saudi Journal of Kidney Diseases and Transplantation. 17 (3): 320–5. PMID 16970251.
  • Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
  • Kumagai K, Kawano M, Shinkai-Ouchi F, Nishijima M, Hanada K (Jun 2007). "Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT". The Journal of Biological Chemistry. 282 (24): 17758–66. doi:10.1074/jbc.M702291200. PMID 17442665.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=COL4A3BP&oldid=1420455"