Zinc homeostasis (Homo sapiens)

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(Difference between revisions)

Revision as of 10:18, 20 July 2024

Description

Zinc is a transition metal and catalytic cofactor involved in many biological processes such as proliferation, development and differentiation, regulation of DNA synthesis, genomic stability, cell activation, RNA transcription, immune function. Zinc homeostasis in cells is ensured by various protein families including zinc transporters, zinc-binding proteins (Metallothioneins, MTs), transcription factors (MTF1-2). ZnT (1-10) transporters are responsible of zinc efflux and are assigned to the SLC30A family while ZIP (1-14) transporters are responsible for the influx of zinc into the cytoplasm and are assigned to the SLC39A family. Zn2+ enters into the cell by the ZIP transporters, and once inside the cell is available to bind metalloproteins (MT) which deliver to ZnT, or the zinc can bind to directly ZnTs and then deliver in the organelles / vesicles or lead outside the cell. Elevated zinc levels have been reported in different tumour tissue, such as breast and lung cancer

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Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M.; ''Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.''; PLoS One. 2014 Jan 8;9(1):e85346, 2014 PubMed Europe PMC Scholia
Jeong J, Eide DJ; ''The SLC39 family of zinc transporters''; Mol Aspects Med. 2013, 2013 PubMed Europe PMC Scholia
Gumulec J, Raudenska M, Adam V, Kizek R, Masarik M; ''Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.''; PLoS One, 2014 PubMed Europe PMC Scholia
''Role of GAC63 in transcriptional activation mediated by beta-catenin.''; Chen YH; Yang CK; Xia M; Ou CY; Stallcup MR, 2007 PubMed Europe PMC Scholia
Miles AT, Hawksworth GM, Beattie JH, Rodilla V; ''Induction, regulation, degradation, and biological significance of mammalian metallothioneins.''; Crit Rev Biochem Mol Biol, 2000 PubMed Europe PMC Scholia
''Cellular zinc sensors: MTF-1 regulation of gene expression''; , 2001 PubMed Europe PMC Scholia
Miles AT, Hawksworth GM, Beattie JH, Rodilla V.; ''Induction, regulation, degradation, and biological significance of mammalian metallothioneins''; Crit Rev Biochem Mol Biol. 2000;35(1):35-70., 2000 PubMed Europe PMC Scholia
Huang L, Tepaamorndech S.; ''The SLC30 family of zinc transporters - a review of current understanding of their biological and pathophysiological roles''; , 2013 PubMed Europe PMC Scholia
''The taste of heavy metals: gene regulation by MTF-1''; , 2012 PubMed Europe PMC Scholia
Kambe T, Hashimoto A, Fujimoto S.; ''Current understanding of ZIP and ZnT zinc transporters in human health and diseases.''; Cell Mol Life Sci. , 2014 PubMed Europe PMC Scholia
''A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1).''; , 2012 PubMed Europe PMC Scholia

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Revision	Action	Time	User	Comment
134312	view	11:07, 20 July 2024	Eweitz	Fix interaction z-index graphical discrepancy between PathVisio and Kaavio / Pvjs
134311	view	11:03, 20 July 2024	Eweitz	Modified description
134310	view	10:32, 20 July 2024	Eweitz	Mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134309	view	10:32, 20 July 2024	Eweitz	Mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134308	view	10:31, 20 July 2024	Eweitz	Transform Golgi graphics to mitigate discrepancy between PathVisio and Kaavio / Pvjs
134307	view	10:29, 20 July 2024	Eweitz	Try new Golgi object to mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134306	view	10:26, 20 July 2024	Eweitz	Mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134305	view	10:25, 20 July 2024	Eweitz	Mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134304	view	10:24, 20 July 2024	Eweitz	Mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134303	view	10:24, 20 July 2024	Eweitz	Mitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134302	view	10:18, 20 July 2024	Eweitz	Economize layout
134280	view	11:37, 19 July 2024	Eweitz	Use ChEBI identifier
134279	view	11:34, 19 July 2024	Eweitz	Vesicles secretory -> Secretory vesicles
134278	view	11:29, 19 July 2024	Eweitz	Change Zn++ to Zn2+, matching common Ca2+
134277	view	10:48, 19 July 2024	Eweitz	Standardize case
134276	view	10:46, 19 July 2024	Eweitz	Ontology Term : 'neuron' added !
134275	view	10:45, 19 July 2024	Eweitz	Ontology Term : 'type B pancreatic cell' added !
134274	view	10:44, 19 July 2024	Eweitz	Ontology Term : 'mammary gland epithelial cell' added !
134269	view	06:44, 19 July 2024	Egonw	Removed a template comment
120882	view	15:56, 27 January 2022	Egonw	Replaced an old HMDB identifier with the current one
120359	view	06:46, 29 November 2021	Egonw	Removed whitespace in the pubmed id
120272	view	12:50, 23 November 2021	Egonw	Removed whitespace in the pubmed id
120270	view	12:42, 23 November 2021	Egonw	Removed whitespace in the pubmed id
106738	view	13:22, 17 September 2019	MaintBot	HMDB identifier normalization
101992	view	19:18, 22 November 2018	Egonw	Removed whitespace in PubMed identifiers.
86971	view	14:28, 15 July 2016	Mkutmon	Ontology Term : 'homeostasis pathway' added !
84285	view	08:57, 3 February 2016	GIOVANNA VALENTI	connected interaction
84284	view	08:54, 3 February 2016	GIOVANNA VALENTI	connected interaction
84283	view	08:30, 3 February 2016	GIOVANNA VALENTI	Specify description
84282	view	08:26, 3 February 2016	GIOVANNA VALENTI	connected interaction
84281	view	08:25, 3 February 2016	GIOVANNA VALENTI	connected interaction
84280	view	08:23, 3 February 2016	GIOVANNA VALENTI	Periodical save, work in progress
84279	view	08:13, 3 February 2016	GIOVANNA VALENTI	Periodical save, work in progress
84278	view	21:45, 2 February 2016	Khanspers	updated transcription/translation
84277	view	21:44, 2 February 2016	Khanspers	replaced unconnected interactions with graphical lines
84274	view	20:57, 2 February 2016	Khanspers	Changed Zinc++ to Zn++
84273	view	19:27, 2 February 2016	Khanspers	simplify layout
84266	view	12:59, 2 February 2016	GIOVANNA VALENTI	connected interaction
84265	view	12:59, 2 February 2016	GIOVANNA VALENTI	connected interaction
84264	view	12:56, 2 February 2016	GIOVANNA VALENTI	Reverted to version '12:54, 2 February 2016' by GIOVANNA VALENTI
84263	view	12:54, 2 February 2016	GIOVANNA VALENTI	Specify description
84262	view	12:54, 2 February 2016	GIOVANNA VALENTI	Specify description
84261	view	12:52, 2 February 2016	GIOVANNA VALENTI	Specify description
84260	view	12:51, 2 February 2016	GIOVANNA VALENTI	Specify description
84259	view	12:46, 2 February 2016	GIOVANNA VALENTI	Periodical save, work in progress
84258	view	12:36, 2 February 2016	GIOVANNA VALENTI	Periodical save, work in progress
84257	view	12:26, 2 February 2016	GIOVANNA VALENTI	Periodical save, work in progress
84256	view	12:18, 2 February 2016	GIOVANNA VALENTI	connected interaction
84255	view	12:15, 2 February 2016	GIOVANNA VALENTI	Periodical save, work in progress
84254	view	12:05, 2 February 2016	GIOVANNA VALENTI	Periodical save, work in progress

External references

DataNodes

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Name	Type	Database reference	Comment
MT1A	GeneProduct	4489 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1B	GeneProduct	4490 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1E	GeneProduct	4493 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1F	GeneProduct	4494 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1G	GeneProduct	4495 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1H	GeneProduct	4496 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1L	GeneProduct	4500 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1M	GeneProduct	4499 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT1X	GeneProduct	4501 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT2A	GeneProduct	4502 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT3	GeneProduct	4504 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MT4	GeneProduct	84560 (Entrez Gene)	zinc is chelated by cytoplasmic proteins, such as MTs
MTF1	GeneProduct	ENSG00000188786 (Ensembl)	Metal-response element-binding transcription factor-1 (MTF-1) functions as a cellular zinc sensor which coordinates the expression of genes involved in zinc homeostasis.
SLC30A10	GeneProduct	55532 (Entrez Gene)
SLC30A1	GeneProduct	7779 (Entrez Gene)	SLC30A1 (ZnT1) transporter is responsible of zinc efflux
SLC30A2	GeneProduct	7780 (Entrez Gene)
SLC30A3	GeneProduct	7781 (Entrez Gene)
SLC30A4	GeneProduct	7782 (Entrez Gene)
SLC30A5	GeneProduct	64924 (Entrez Gene)
SLC30A6	GeneProduct	55676 (Entrez Gene)
SLC30A7	GeneProduct	148867 (Entrez Gene)
SLC30A8	GeneProduct	169026 (Entrez Gene)	http://www.ncbi.nlm.nih.gov/gene/169026
SLC30A9	GeneProduct	10463 (Entrez Gene)
SLC39A10	GeneProduct	57181 (Entrez Gene)
SLC39A11	GeneProduct	201266 (Entrez Gene)
SLC39A12	GeneProduct	221074 (Entrez Gene)
SLC39A1	GeneProduct	27173 (Entrez Gene)	SLC39A1 (ZIP1) transporter is responsible for the influx of zinc into the cytoplasm
SLC39A13	GeneProduct	91252 (Entrez Gene)
SLC39A14	GeneProduct	23516 (Entrez Gene)
SLC39A2	GeneProduct	29986 (Entrez Gene)
SLC39A3	GeneProduct	29985 (Entrez Gene)
SLC39A4	GeneProduct	55630 (Entrez Gene)
SLC39A5	GeneProduct	283375 (Entrez Gene)
SLC39A6	GeneProduct	25800 (Entrez Gene)
SLC39A7	GeneProduct	7922 (Entrez Gene)
SLC39A8	GeneProduct	64116 (Entrez Gene)
SLC39A9	GeneProduct	55334 (Entrez Gene)
Zn2+	Metabolite	CHEBI:29105 (ChEBI)

Annotated Interactions

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Zinc homeostasis (Homo sapiens)

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Revision as of 10:18, 20 July 2024

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@@ Line 2: / Line 2: @@
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    <Comment Source="WikiPathways-description">Zinc is a transition metal and catalytic cofactor involved in many biological processes such as proliferation, development and differentiation, regulation of DNA synthesis, genomic stability, cell activation, RNA transcription, immune function. Zinc homeostasis in cells is ensured by various protein families including zinc transporters, zinc-binding proteins (Metallothioneins, MTs), transcription factors (MTF1-2). ZnT (1-10) transporters are responsible of zinc efflux and are assigned to the SLC30A family while ZIP (1-14) transporters are responsible for the influx of zinc into the cytoplasm and are assigned to the SLC39A family. Zn2+ enters into the cell by the ZIP transporters, and once inside the cell is available to bind metalloproteins (MT) which deliver to ZnT, or the zinc can bind to directly ZnTs and then deliver in the organelles / vesicles or lead outside the cell. Elevated zinc levels have been reported in different tumour tissue, such as breast and lung cancer</Comment>
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-      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">neuron</bp:TERM>
+       <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">11831458</bp:ID>
-      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0000540</bp:ID>
-      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
-    </bp:openControlledVocabulary>
-    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
-      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">homeostasis pathway</bp:TERM>
-      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PW:0000355</bp:ID>
-      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pathway Ontology</bp:Ontology>
-    </bp:openControlledVocabulary>
-     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="eaf">
-       <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">10755665</bp:ID>
        <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
-       <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Induction, regulation, degradation, and biological significance of mammalian metallothioneins.</bp:TITLE>
+       <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cellular zinc sensors: MTF-1 regulation of gene expression</bp:TITLE>
-       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Crit Rev Biochem Mol Biol</bp:SOURCE>
+       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string"></bp:SOURCE>
-       <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2000</bp:YEAR>
+       <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2001</bp:YEAR>
-      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Miles AT</bp:AUTHORS>
-      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hawksworth GM</bp:AUTHORS>
-      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Beattie JH</bp:AUTHORS>
-      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Rodilla V</bp:AUTHORS>
      </bp:PublicationXref>
-     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d4c">
+     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="e00">
        <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">24416395</bp:ID>
        <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
        <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.</bp:TITLE>
-       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PLoS One</bp:SOURCE>
+       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PLoS One. 2014 Jan 8;9(1):e85346</bp:SOURCE>
        <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2014</bp:YEAR>
        <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Gumulec J</bp:AUTHORS>
        <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Raudenska M</bp:AUTHORS>
-       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Adam V</bp:AUTHORS>
+       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Adam V, Kizek R</bp:AUTHORS>
-       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kizek R</bp:AUTHORS>
+       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Masarik M.</bp:AUTHORS>
-       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Masarik M</bp:AUTHORS>
+    </bp:PublicationXref>
+    <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="fb5">
+      <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">24710731</bp:ID>
+      <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
+      <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Current understanding of ZIP and ZnT zinc transporters in human health and diseases.</bp:TITLE>
+      <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Mol Life Sci. </bp:SOURCE>
+      <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2014</bp:YEAR>
+       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kambe T</bp:AUTHORS>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hashimoto A</bp:AUTHORS>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Fujimoto S.</bp:AUTHORS>
      </bp:PublicationXref>
      <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
@@ Line 914: / Line 899: @@
        <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
      </bp:openControlledVocabulary>
-     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b6b">
+     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="eaf">
-       <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">22289350</bp:ID>
+       <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">10755665</bp:ID>
        <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
-       <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The taste of heavy metals: gene regulation by MTF-1</bp:TITLE>
+       <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Induction, regulation, degradation, and biological significance of mammalian metallothioneins.</bp:TITLE>
-       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string"></bp:SOURCE>
+       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Crit Rev Biochem Mol Biol</bp:SOURCE>
-       <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2012</bp:YEAR>
+       <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2000</bp:YEAR>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Miles AT</bp:AUTHORS>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hawksworth GM</bp:AUTHORS>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Beattie JH</bp:AUTHORS>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Rodilla V</bp:AUTHORS>
      </bp:PublicationXref>
-    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
-      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">mammary gland epithelial cell</bp:TERM>
-      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0002327</bp:ID>
-      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
-    </bp:openControlledVocabulary>
      <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="cc2">
        <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">17344318</bp:ID>
@@ Line 932: / Line 916: @@
        <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Chen YH; Yang CK; Xia M; Ou CY; Stallcup MR</bp:SOURCE>
        <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2007</bp:YEAR>
+    </bp:PublicationXref>
+    <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b85">
+      <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">22057392</bp:ID>
+      <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
+      <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">A conserved cysteine cluster, essential for transcriptional activity, mediates homodimerization of human metal-responsive transcription factor-1 (MTF-1).</bp:TITLE>
+      <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string"></bp:SOURCE>
+      <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2012</bp:YEAR>
      </bp:PublicationXref>
      <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b06">
@@ Line 942: / Line 933: @@
        <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Eide DJ</bp:AUTHORS>
      </bp:PublicationXref>
-     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c8b">
+     <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
-       <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">11831458</bp:ID>
+      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">neuron</bp:TERM>
-       <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
+       <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0000540</bp:ID>
-       <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cellular zinc sensors: MTF-1 regulation of gene expression</bp:TITLE>
+       <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
-       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string"></bp:SOURCE>
+    </bp:openControlledVocabulary>
-       <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2001</bp:YEAR>
+    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
-     </bp:PublicationXref>
+       <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">mammary gland epithelial cell</bp:TERM>
-     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="e00">
+       <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">CL:0002327</bp:ID>
+       <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Cell Type</bp:Ontology>
+     </bp:openControlledVocabulary>
+     <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d4c">
        <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">24416395</bp:ID>
        <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB>
        <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Metallothionein - immunohistochemical cancer biomarker: a meta-analysis.</bp:TITLE>
-       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PLoS One. 2014 Jan 8;9(1):e85346</bp:SOURCE>
+       <bp:SOURCE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PLoS One</bp:SOURCE>
        <bp:YEAR rdf:datatype="http://www.w3.org/2001/XMLSchema#string">2014</bp:YEAR>
        <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Gumulec J</bp:AUTHORS>
        <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Raudenska M</bp:AUTHORS>
-       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Adam V, Kizek R</bp:AUTHORS>
+       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Adam V</bp:AUTHORS>
-       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Masarik M.</bp:AUTHORS>
+      <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Kizek R</bp:AUTHORS>
+       <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Masarik M</bp:AUTHORS>
      </bp:PublicationXref>
      <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="fcd">
@@ Line 969: / Line 964: @@
        <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Tepaamorndech S.</bp:AUTHORS>
      </bp:PublicationXref>
+    <bp:openControlledVocabulary xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#">
+      <bp:TERM xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">homeostasis pathway</bp:TERM>
+      <bp:ID xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PW:0000355</bp:ID>
+      <bp:Ontology xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Pathway Ontology</bp:Ontology>
+    </bp:openControlledVocabulary>
    </Biopax>
 </Pathway>