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{{Infobox_gene}}
{{PBB_Controls
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'''Syndecan 1''' is a [[protein]] which in humans is encoded by the ''SDC1'' [[gene]].<ref name="pmid2324102">{{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–9 | date = Apr 1990 | pmid = 2324102 | doi =  | url = http://www.jbc.org/cgi/pmidlookup?view=long&pmid=2324102 }}</ref><ref name="pmid2173154">{{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–5 | date = Sep 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 }}</ref>
| require_manual_inspection = no
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}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Syndecan 1
| HGNCid = 10658
| Symbol = SDC1
| AltSymbols =; CD138; SDC; SYND1; syndecan
| OMIM = 186355
| ECnumber = 
| Homologene = 2252
| MGIid = 1349162
| GeneAtlas_image1 = PBB_GE_SDC1_201286_at_tn.png
| GeneAtlas_image2 = PBB_GE_SDC1_201287_s_at_tn.png
| Function = {{GNF_GO|id=GO:0008092 |text = cytoskeletal protein binding}}
| Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process =
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6382
    | Hs_Ensembl = ENSG00000115884
    | Hs_RefseqProtein = NP_001006947
    | Hs_RefseqmRNA = NM_001006946
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 2
    | Hs_GenLoc_start = 20264039
    | Hs_GenLoc_end = 20288675
    | Hs_Uniprot = P18827
    | Mm_EntrezGene = 20969
    | Mm_Ensembl = ENSMUSG00000020592
    | Mm_RefseqmRNA = NM_011519
    | Mm_RefseqProtein = NP_035649
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 12
    | Mm_GenLoc_start = 8797404
    | Mm_GenLoc_end = 8819683
    | Mm_Uniprot = Q3THY2
  }}
}}
'''[[Syndecan]] 1''' is a [[proteoglycan]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The protein encoded by this gene is a transmembrane (type I) [[heparan sulfate]] [[proteoglycan]] and is a member of the [[syndecan]] proteoglycan family. The syndecans mediate cell binding, [[cell signaling]], and [[cytoskeleton|cytoskeletal]] organization and syndecan receptors are required for internalization of the [[HIV| HIV-1]] [[Tat (HIV)|tat protein]]. The syndecan-1 protein functions as an [[integral membrane protein]] and participates in [[cell growth|cell proliferation]], [[cell migration]] and [[cell junction|cell-matrix]] interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors, with binding largely via heparan sulfate chains.
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Altered syndecan-1 expression has been detected in several different tumor types. While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.<ref>{{cite web | title = Entrez Gene: SDC1 syndecan 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6382| accessdate = }}</ref>
}}


==References==
An exception is the prosecretory mitogen [[lacritin]] that binds syndecan-1 only after heparanase modification.<ref name="pmid16982797">{{cite journal | vauthors = Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW | title = Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin | journal = The Journal of Cell Biology | volume = 174 | issue = 7 | pages = 1097–106 | date = Sep 2006 | pmid = 16982797 | pmc = 1666580 | doi = 10.1083/jcb.200511134 }}</ref><ref name="pmid23504321 [PubMed - indexed for MEDLINE]">{{cite journal | vauthors = Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW | title = Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity | journal = The Journal of Biological Chemistry | volume = 288 | issue = 17 | pages = 12090–101 | date = Apr 2013 | pmid = 23504321 | pmc = 3636894 | doi = 10.1074/jbc.M112.422717 }}</ref> Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial [[heparanase]] (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.<ref name="pmid16982797" /> Three SDC1 elements are required.  (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face.  (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" />  This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix.  (3) An N-terminal [[chondroitin sulfate]] chain that also likely binds to the cationic face.  Point mutagenesis of lacritin has narrowed the ligation site.<ref name="pmid23504321 [PubMed - indexed for MEDLINE]" />
{{reflist|2}}
 
==Further reading==
While several [[transcript variant|transcript]] variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.<ref>{{cite web | title = Entrez Gene: SDC1 syndecan 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6382| accessdate = }}</ref>
 
==Clinical significance==
Altered syndecan-1 expression has been detected in several different tumor types.
 
It is a specific antigen on [[multiple myeloma]] cells.<ref name=ASH2013>[http://www.myelomabeacon.com/resources/mtgs/ash2013/abs/758/ Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients]</ref>
 
[[Indatuximab ravtansine]] targets this protein.
 
== Application ==
 
It is a useful marker for [[plasma cell]]s,<ref name="pmid18770841">{{cite journal | vauthors = Rawstron AC | title = Immunophenotyping of plasma cells | journal = Current Protocols in Cytometry | volume = Chapter 6 | issue =  | pages = Unit6.23 | date = May 2006 | pmid = 18770841 | doi = 10.1002/0471142956.cy0623s36 | isbn = 0-471-14295-6 }}</ref> but only if the cells tested are already known to be derived from blood.<ref name="pmid14983940">{{cite journal | vauthors = O'Connell FP, Pinkus JL, Pinkus GS | title = CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms | journal = American Journal of Clinical Pathology | volume = 121 | issue = 2 | pages = 254–63 | date = Feb 2004 | pmid = 14983940 | doi = 10.1309/617D-WB5G-NFWX-HW4L | url = http://ajcp.metapress.com/openurl.asp?genre=article&issn=0002-9173&volume=121&issue=2&spage=254 }}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = David G | title = Structural and functional diversity of the heparan sulfate proteoglycans | journal = Advances in Experimental Medicine and Biology | volume = 313 | issue =  | pages = 69–78 | year = 1992 | pmid = 1442271 | doi = 10.1007/978-1-4899-2444-5_7 }}
| citations =
* {{cite journal | vauthors = Jaakkola P, Jalkanen M | title = Transcriptional regulation of Syndecan-1 expression by growth factors | journal = Progress in Nucleic Acid Research and Molecular Biology | volume = 63 | issue =  | pages = 109–38 | year = 1999 | pmid = 10506830 | doi = 10.1016/S0079-6603(08)60721-7 | isbn = 978-0-12-540063-3 | series = Progress in Nucleic Acid Research and Molecular Biology }}
*{{cite journal | author=David G |title=Structural and functional diversity of the heparan sulfate proteoglycans. |journal=Adv. Exp. Med. Biol. |volume=313 |issue=  |pages= 69-78 |year= 1992 |pmid= 1442271 |doi= }}
* {{cite journal | vauthors = Wijdenes J, Dore JM, Clement C, Vermot-Desroches C | title = CD138 | journal = Journal of Biological Regulators and Homeostatic Agents | volume = 16 | issue = 2 | pages = 152–5 | year = 2003 | pmid = 12144130 | doi =  }}
*{{cite journal | author=Jaakkola P, Jalkanen M |title=Transcriptional regulation of Syndecan-1 expression by growth factors. |journal=Prog. Nucleic Acid Res. Mol. Biol. |volume=63 |issue=  |pages= 109-38 |year= 1999 |pmid= 10506830 |doi= }}
* {{cite journal | vauthors = Lories V, Cassiman JJ, Van den Berghe H, David G | title = Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts | journal = The Journal of Biological Chemistry | volume = 267 | issue = 2 | pages = 1116–22 | date = Jan 1992 | pmid = 1339431 | doi =  }}
*{{cite journal | author=Wijdenes J, Dore JM, Clement C, Vermot-Desroches C |title=CD138. |journal=J. Biol. Regul. Homeost. Agents |volume=16 |issue= 2 |pages= 152-5 |year= 2003 |pmid= 12144130 |doi=  }}
* {{cite journal | vauthors = Vainio S, Jalkanen M, Bernfield M, Saxén L | title = Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney | journal = Developmental Biology | volume = 152 | issue = 2 | pages = 221–32 | date = Aug 1992 | pmid = 1644217 | doi = 10.1016/0012-1606(92)90130-9 }}
*{{cite journal | author=Lories V, Cassiman JJ, Van den Berghe H, David G |title=Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts. |journal=J. Biol. Chem. |volume=267 |issue= 2 |pages= 1116-22 |year= 1992 |pmid= 1339431 |doi=  }}
* {{cite journal | vauthors = Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ | title = The molecular biology of heparan sulfate fibroblast growth factor receptors | journal = Annals of the New York Academy of Sciences | volume = 638 | issue =  | pages = 167–76 | year = 1992 | pmid = 1664683 | doi = 10.1111/j.1749-6632.1991.tb49027.x }}
*{{cite journal | author=Vainio S, Jalkanen M, Bernfield M, Saxén L |title=Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney. |journal=Dev. Biol. |volume=152 |issue= 2 |pages= 221-32 |year= 1992 |pmid= 1644217 |doi= }}
* {{cite journal | vauthors = Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J | title = Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2 | journal = Somatic Cell and Molecular Genetics | volume = 16 | issue = 5 | pages = 501–5 | date = Sep 1990 | pmid = 2173154 | doi = 10.1007/BF01233200 }}
*{{cite journal | author=Kiefer MC, Ishihara M, Swiedler SJ, ''et al.'' |title=The molecular biology of heparan sulfate fibroblast growth factor receptors. |journal=Ann. N. Y. Acad. Sci. |volume=638 |issue=  |pages= 167-76 |year= 1992 |pmid= 1664683 |doi= }}
* {{cite journal | vauthors = Mali M, Jaakkola P, Arvilommi AM, Jalkanen M | title = Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans | journal = The Journal of Biological Chemistry | volume = 265 | issue = 12 | pages = 6884–9 | date = Apr 1990 | pmid = 2324102 | doi =  }}
*{{cite journal | author=Ala-Kapee M, Nevanlinna H, Mali M, ''et al.'' |title=Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2. |journal=Somat. Cell Mol. Genet. |volume=16 |issue= 5 |pages= 501-5 |year= 1990 |pmid= 2173154 |doi= }}
* {{cite journal | vauthors = Sanderson RD, Lalor P, Bernfield M | title = B lymphocytes express and lose syndecan at specific stages of differentiation | journal = Cell Regulation | volume = 1 | issue = 1 | pages = 27–35 | date = Nov 1989 | pmid = 2519615 | pmc = 361422 | doi =  }}
*{{cite journal | author=Mali M, Jaakkola P, Arvilommi AM, Jalkanen M |title=Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans. |journal=J. Biol. Chem. |volume=265 |issue= 12 |pages= 6884-9 |year= 1990 |pmid= 2324102 |doi=  }}
* {{cite journal | vauthors = Asundi VK, Carey DJ | title = Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region | journal = The Journal of Biological Chemistry | volume = 270 | issue = 44 | pages = 26404–10 | date = Nov 1995 | pmid = 7592855 | doi = 10.1074/jbc.270.44.26404 }}
*{{cite journal | author=Sanderson RD, Lalor P, Bernfield M |title=B lymphocytes express and lose syndecan at specific stages of differentiation. |journal=Cell Regul. |volume=1 |issue= 1 |pages= 27-35 |year= 1992 |pmid= 2519615 |doi=  }}
* {{cite journal | vauthors = Zhang L, David G, Esko JD | title = Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27127–35 | date = Nov 1995 | pmid = 7592967 | doi = 10.1074/jbc.270.45.27127 }}
*{{cite journal | author=Asundi VK, Carey DJ |title=Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region. |journal=J. Biol. Chem. |volume=270 |issue= 44 |pages= 26404-10 |year= 1995 |pmid= 7592855 |doi= }}
* {{cite journal | vauthors = Barillari G, Gendelman R, Gallo RC, Ensoli B | title = The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 90 | issue = 17 | pages = 7941–5 | date = Sep 1993 | pmid = 7690138 | pmc = 47263 | doi = 10.1073/pnas.90.17.7941 }}
*{{cite journal | author=Zhang L, David G, Esko JD |title=Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans. |journal=J. Biol. Chem. |volume=270 |issue= 45 |pages= 27127-35 |year= 1995 |pmid= 7592967 |doi= }}
* {{cite journal | vauthors = Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M | title = Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family | journal = Genomics | volume = 21 | issue = 3 | pages = 597–601 | date = Jun 1994 | pmid = 7959737 | doi = 10.1006/geno.1994.1319 }}
*{{cite journal | author=Barillari G, Gendelman R, Gallo RC, Ensoli B |title=The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 17 |pages= 7941-5 |year= 1993 |pmid= 7690138 |doi= }}
* {{cite journal | vauthors = Sneed TB, Stanley DJ, Young LA, Sanderson RD | title = Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells | journal = Cellular Immunology | volume = 153 | issue = 2 | pages = 456–67 | date = Feb 1994 | pmid = 8118875 | doi = 10.1006/cimm.1994.1042 }}
*{{cite journal | author=Spring J, Goldberger OA, Jenkins NA, ''et al.'' |title=Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family. |journal=Genomics |volume=21 |issue= 3 |pages= 597-601 |year= 1994 |pmid= 7959737 |doi= 10.1006/geno.1994.1319 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Sneed TB, Stanley DJ, Young LA, Sanderson RD |title=Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells. |journal=Cell. Immunol. |volume=153 |issue= 2 |pages= 456-67 |year= 1994 |pmid= 8118875 |doi= 10.1006/cimm.1994.1042 }}
* {{cite journal | vauthors = Kokenyesi R, Bernfield M | title = Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1 | journal = The Journal of Biological Chemistry | volume = 269 | issue = 16 | pages = 12304–9 | date = Apr 1994 | pmid = 8163535 | doi =  }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D | title = HIV-tat protein is a heparin-binding angiogenic growth factor | journal = Oncogene | volume = 12 | issue = 2 | pages = 289–97 | date = Jan 1996 | pmid = 8570206 | doi =  }}
*{{cite journal | author=Kokenyesi R, Bernfield M |title=Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1. |journal=J. Biol. Chem. |volume=269 |issue= 16 |pages= 12304-9 |year= 1994 |pmid= 8163535 |doi=  }}
* {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 }}
*{{cite journal | author=Albini A, Benelli R, Presta M, ''et al.'' |title=HIV-tat protein is a heparin-binding angiogenic growth factor. |journal=Oncogene |volume=12 |issue= 2 |pages= 289-97 |year= 1996 |pmid= 8570206 |doi=  }}
* {{cite journal | vauthors = Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A | title = The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p | journal = Human Genetics | volume = 99 | issue = 3 | pages = 295–7 | date = Mar 1997 | pmid = 9050911 | doi = 10.1007/s004390050360 }}
*{{cite journal | author=Bonaldo MF, Lennon G, Soares MB |title=Normalization and subtraction: two approaches to facilitate gene discovery. |journal=Genome Res. |volume=6 |issue= 9 |pages= 791-806 |year= 1997 |pmid= 8889548 |doi= }}
*{{cite journal | author=Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A |title=The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p. |journal=Hum. Genet. |volume=99 |issue= 3 |pages= 295-7 |year= 1997 |pmid= 9050911 |doi= }}
}}
{{refend}}
{{refend}}


==External links==
== External links ==
* {{MeshName|Syndecan-1}}
* {{MeshName|Syndecan-1}}


{{biochemistry-stub}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}
{{Clusters of differentiation by lineage}}
{{Proteoglycans}}
{{Proteoglycans}}


[[Category:Proteoglycans]]
[[Category:Proteoglycans]]

Latest revision as of 00:15, 10 June 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene.[1][2]

Function

The protein encoded by this gene is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors, with binding largely via heparan sulfate chains.

An exception is the prosecretory mitogen lacritin that binds syndecan-1 only after heparanase modification.[3][4] Binding utilizes an enzyme-regulated 'off-on' switch in which active epithelial heparanase (HPSE) cleaves off heparan sulfate to expose a binding site in the N-terminal region of syndecan-1's core protein.[3] Three SDC1 elements are required. (1) The heparanase-exposed hydrophobic sequence GAGAL that promotes the alpha helicity of lacritin's C-terminal amphipathic alpha helix form and likely binds to the hydrophobic face. (2) Heparanase-cleaved heparan sulfate that is 3-O sulfated.[4] This likely interacts with the cationic face of lacritin's C-terminal amphipathic alpha helix. (3) An N-terminal chondroitin sulfate chain that also likely binds to the cationic face. Point mutagenesis of lacritin has narrowed the ligation site.[4]

While several transcript variants may exist for this gene, the full-length natures of only two have been described to date. These two represent the major variants of this gene and encode the same protein.[5]

Clinical significance

Altered syndecan-1 expression has been detected in several different tumor types.

It is a specific antigen on multiple myeloma cells.[6]

Indatuximab ravtansine targets this protein.

Application

It is a useful marker for plasma cells,[7] but only if the cells tested are already known to be derived from blood.[8]

References

  1. Mali M, Jaakkola P, Arvilommi AM, Jalkanen M (Apr 1990). "Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans". The Journal of Biological Chemistry. 265 (12): 6884–9. PMID 2324102.
  2. Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (Sep 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–5. doi:10.1007/BF01233200. PMID 2173154.
  3. 3.0 3.1 Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW (Sep 2006). "Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin". The Journal of Cell Biology. 174 (7): 1097–106. doi:10.1083/jcb.200511134. PMC 1666580. PMID 16982797.
  4. 4.0 4.1 4.2 Zhang Y, Wang N, Raab RW, McKown RL, Irwin JA, Kwon I, van Kuppevelt TH, Laurie GW (Apr 2013). "Targeting of heparanase-modified syndecan-1 by prosecretory mitogen lacritin requires conserved core GAGAL plus heparan and chondroitin sulfate as a novel hybrid binding site that enhances selectivity". The Journal of Biological Chemistry. 288 (17): 12090–101. doi:10.1074/jbc.M112.422717. PMC 3636894. PMID 23504321.
  5. "Entrez Gene: SDC1 syndecan 1".
  6. Indatuximab Ravtansine (BT062) In Combination With Lenalidomide and Low-Dose Dexamethasone In Patients With Relapsed and/Or Refractory Multiple Myeloma: Clinical Activity In Len/Dex-Refractory Patients
  7. Rawstron AC (May 2006). "Immunophenotyping of plasma cells". Current Protocols in Cytometry. Chapter 6: Unit6.23. doi:10.1002/0471142956.cy0623s36. ISBN 0-471-14295-6. PMID 18770841.
  8. O'Connell FP, Pinkus JL, Pinkus GS (Feb 2004). "CD138 (syndecan-1), a plasma cell marker immunohistochemical profile in hematopoietic and nonhematopoietic neoplasms". American Journal of Clinical Pathology. 121 (2): 254–63. doi:10.1309/617D-WB5G-NFWX-HW4L. PMID 14983940.[permanent dead link]

Further reading

  • David G (1992). "Structural and functional diversity of the heparan sulfate proteoglycans". Advances in Experimental Medicine and Biology. 313: 69–78. doi:10.1007/978-1-4899-2444-5_7. PMID 1442271.
  • Jaakkola P, Jalkanen M (1999). "Transcriptional regulation of Syndecan-1 expression by growth factors". Progress in Nucleic Acid Research and Molecular Biology. Progress in Nucleic Acid Research and Molecular Biology. 63: 109–38. doi:10.1016/S0079-6603(08)60721-7. ISBN 978-0-12-540063-3. PMID 10506830.
  • Wijdenes J, Dore JM, Clement C, Vermot-Desroches C (2003). "CD138". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 152–5. PMID 12144130.
  • Lories V, Cassiman JJ, Van den Berghe H, David G (Jan 1992). "Differential expression of cell surface heparan sulfate proteoglycans in human mammary epithelial cells and lung fibroblasts". The Journal of Biological Chemistry. 267 (2): 1116–22. PMID 1339431.
  • Vainio S, Jalkanen M, Bernfield M, Saxén L (Aug 1992). "Transient expression of syndecan in mesenchymal cell aggregates of the embryonic kidney". Developmental Biology. 152 (2): 221–32. doi:10.1016/0012-1606(92)90130-9. PMID 1644217.
  • Kiefer MC, Ishihara M, Swiedler SJ, Crawford K, Stephans JC, Barr PJ (1992). "The molecular biology of heparan sulfate fibroblast growth factor receptors". Annals of the New York Academy of Sciences. 638: 167–76. doi:10.1111/j.1749-6632.1991.tb49027.x. PMID 1664683.
  • Ala-Kapee M, Nevanlinna H, Mali M, Jalkanen M, Schröder J (Sep 1990). "Localization of gene for human syndecan, an integral membrane proteoglycan and a matrix receptor, to chromosome 2". Somatic Cell and Molecular Genetics. 16 (5): 501–5. doi:10.1007/BF01233200. PMID 2173154.
  • Mali M, Jaakkola P, Arvilommi AM, Jalkanen M (Apr 1990). "Sequence of human syndecan indicates a novel gene family of integral membrane proteoglycans". The Journal of Biological Chemistry. 265 (12): 6884–9. PMID 2324102.
  • Sanderson RD, Lalor P, Bernfield M (Nov 1989). "B lymphocytes express and lose syndecan at specific stages of differentiation". Cell Regulation. 1 (1): 27–35. PMC 361422. PMID 2519615.
  • Asundi VK, Carey DJ (Nov 1995). "Self-association of N-syndecan (syndecan-3) core protein is mediated by a novel structural motif in the transmembrane domain and ectodomain flanking region". The Journal of Biological Chemistry. 270 (44): 26404–10. doi:10.1074/jbc.270.44.26404. PMID 7592855.
  • Zhang L, David G, Esko JD (Nov 1995). "Repetitive Ser-Gly sequences enhance heparan sulfate assembly in proteoglycans". The Journal of Biological Chemistry. 270 (45): 27127–35. doi:10.1074/jbc.270.45.27127. PMID 7592967.
  • Barillari G, Gendelman R, Gallo RC, Ensoli B (Sep 1993). "The Tat protein of human immunodeficiency virus type 1, a growth factor for AIDS Kaposi sarcoma and cytokine-activated vascular cells, induces adhesion of the same cell types by using integrin receptors recognizing the RGD amino acid sequence". Proceedings of the National Academy of Sciences of the United States of America. 90 (17): 7941–5. doi:10.1073/pnas.90.17.7941. PMC 47263. PMID 7690138.
  • Spring J, Goldberger OA, Jenkins NA, Gilbert DJ, Copeland NG, Bernfield M (Jun 1994). "Mapping of the syndecan genes in the mouse: linkage with members of the myc gene family". Genomics. 21 (3): 597–601. doi:10.1006/geno.1994.1319. PMID 7959737.
  • Sneed TB, Stanley DJ, Young LA, Sanderson RD (Feb 1994). "Interleukin-6 regulates expression of the syndecan-1 proteoglycan on B lymphoid cells". Cellular Immunology. 153 (2): 456–67. doi:10.1006/cimm.1994.1042. PMID 8118875.
  • Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Kokenyesi R, Bernfield M (Apr 1994). "Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1". The Journal of Biological Chemistry. 269 (16): 12304–9. PMID 8163535.
  • Albini A, Benelli R, Presta M, Rusnati M, Ziche M, Rubartelli A, Paglialunga G, Bussolino F, Noonan D (Jan 1996). "HIV-tat protein is a heparin-binding angiogenic growth factor". Oncogene. 12 (2): 289–97. PMID 8570206.
  • Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
  • Kaukonen J, Alanen-Kurki L, Jalkanen M, Palotie A (Mar 1997). "The mapping and visual ordering of the human syndecan-1 and N-myc genes near the telomeric region of chromosome 2p". Human Genetics. 99 (3): 295–7. doi:10.1007/s004390050360. PMID 9050911.

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