MMP9: Polycystic Ovarian Syndrome Database

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MMP9

Gene Information

Gene Ontology (GO)

Protein Information

Associated Diseases

Pathways

References

Gene Information

Gene Symbol

MMP9

Aliases

CLG4B, GELB, MANDP2, MMP-9

Entrez Gene ID

4318

Gene Name

Matrix metallopeptidase 9

Chromosomal Location

20q13.12

HGNC ID

HGNC:7176

Summary

Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades type IV and V collagens. Studies in rhesus monkeys suggest that the enzyme is involved in IL-8-induced mobilization of hematopoietic progenitor cells from bone marrow, and murine studies suggest a role in tumor-associated tissue remodeling. [provided by RefSeq, Jul 2008]

RefSeq DNA

NG_011468.1

RefSeq mRNA

NM_004994.3

e!Ensembl

Gene	ENSG00000100985
Transcript	ENST00000372330
Protein	ENSP00000361405

Gene Ontology (GO)

Show/Hide all(35 )

GO ID	Ontology	Function	Evidence	Reference
GO:0001934	Biological process	Positive regulation of protein phosphorylation	IMP	22984561
GO:0006508	Biological process	Proteolysis	IDA	2551898, 15863497, 19022250, 24164424
GO:0030198	Biological process	Extracellular matrix organization	IBA	21873635
GO:0030225	Biological process	Macrophage differentiation	TAS	2551898
GO:0030335	Biological process	Positive regulation of cell migration	IGI	28280358
GO:0030335	Biological process	Positive regulation of cell migration	TAS	23675531
GO:0030574	Biological process	Collagen catabolic process	IBA	21873635
GO:0034614	Biological process	Cellular response to reactive oxygen species	IDA	26514923
GO:0035987	Biological process	Endodermal cell differentiation	IEP	23154389
GO:0043066	Biological process	Negative regulation of apoptotic process	IMP	22984561
GO:0043388	Biological process	Positive regulation of DNA binding	IDA	22984561
GO:0045742	Biological process	Positive regulation of epidermal growth factor receptor signaling pathway	IMP	22984561
GO:0051549	Biological process	Positive regulation of keratinocyte migration	IMP	17704059
GO:0071276	Biological process	Cellular response to cadmium ion	IDA	26514923
GO:0090200	Biological process	Positive regulation of release of cytochrome c from mitochondria	IMP	22984561
GO:0150077	Biological process	Regulation of neuroinflammatory response	TAS	25049354
GO:1900122	Biological process	Positive regulation of receptor binding	IDA	24164424
GO:1904707	Biological process	Positive regulation of vascular smooth muscle cell proliferation	IMP	18667463
GO:2001243	Biological process	Negative regulation of intrinsic apoptotic signaling pathway	IMP	22984561
GO:2001258	Biological process	Negative regulation of cation channel activity	IDA	24164424
GO:2001268	Biological process	Negative regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway	IMP	22984561
GO:0005576	Cellular component	Extracellular region	HDA	27068509
GO:0005615	Cellular component	Extracellular space	IBA	21873635
GO:0005615	Cellular component	Extracellular space	IDA	2551898, 24236012, 25645918
GO:0062023	Cellular component	Collagen-containing extracellular matrix	HDA	28344315
GO:0070062	Cellular component	Extracellular exosome	HDA	23533145
GO:0004175	Molecular function	Endopeptidase activity	IDA	19022250
GO:0004222	Molecular function	Metalloendopeptidase activity	IBA	21873635
GO:0004222	Molecular function	Metalloendopeptidase activity	IDA	2551898, 9789069, 16192646, 24164424
GO:0004252	Molecular function	Serine-type endopeptidase activity	EXP	17428795
GO:0005515	Molecular function	Protein binding	IPI	2251898, 16512877, 21441952, 23123160, 23601700, 24330623
GO:0005518	Molecular function	Collagen binding	TAS	2551898
GO:0008237	Molecular function	Metallopeptidase activity	IDA	24236012, 26514923
GO:0008270	Molecular function	Zinc ion binding	TAS	2551898
GO:0042802	Molecular function	Identical protein binding	IPI	17937912, 18077379, 23601700

Protein Information

Protein Name

Matrix metalloproteinase-9, macrophage gelatinase, matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase), matrix metalloproteinase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase), type V collagenase

Function

May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.

Refseq Proteins

NP_004985.2

UniProt

P14780

PDB

1GKC, 1GKD, 1ITV, 1L6J, 1LKG, 2OVX, 2OVZ, 2OW0, 2OW1, 2OW2, 4H1Q, 4H2E, 4H3X, 4H82, 4HMA, 4JIJ, 4JQG, 4WZV, 4XCT, 5CUH, 5I12, 5TH6, 5TH9, 5UE3, 5UE4, 6ESM

Pfam

Pfam Accession	Pfam ID
PF00040	fn2
PF00045	Hemopexin
PF00413	Peptidase_M10
PF01471	PG_binding_1

Pathways
	KEGG	Reactome
	Endocrine resistance IL-17 signaling pathway TNF signaling pathway Leukocyte transendothelial migration Estrogen signaling pathway Relaxin signaling pathway Hepatitis B Pathways in cancer Transcriptional misregulation in cancer Proteoglycans in cancer MicroRNAs in cancer Prostate cancer Bladder cancer Fluid shear stress and atherosclerosis	Signaling by SCF-KIT Collagen degradation Degradation of the extracellular matrix Activation of Matrix Metalloproteinases Assembly of collagen fibrils and other multimeric structures EPH-ephrin mediated repulsion of cells Interleukin-4 and Interleukin-13 signaling Neutrophil degranulation Extra-nuclear estrogen signaling

Interactions

STRING	MINT	IntAct
ENSP00000221930	P01137	P01137

View interactions

Associated Diseases

Show/Hide all(13 )

Disease group	Disease Name	References
Cardiovascular Diseases
	Acute Coronary Syndrome	20981132
	Aortic Aneurysm	16159824, 10231640, 17196988, 18178469
	Angina pectoris	20981132
	Aortic Rupture	18178469
	Myocardial Infarction	16310260, 24358288
	Aortic Diseases	15545515
	Hypertensive disease	21051829
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
	Marfan Syndrome	18178469
	Skeletal Dysplasia	19615667
Digestive System Diseases
	Gastric ulcer	17603938
	Oral submucosal fibrosis	16311067
	Liver Diseases	19784758, 22507835
	Cholestasis	28789951
	Periodontitis	24640096, 22808498
	Colitis	22119283
Ear Or Mastoid Diseases
Ear Or Mastoid Diseases	Meniere Disease	28787010
Endocrine System Diseases
	Diabetic Neuralgia	20213226
	PCOS	30551411, 23249695
Eye Diseases
Eye Diseases	Retinal Diseases	23075401
Immune System Diseases
Immune System Diseases	Lupus Nephritis	22479529
Neoplasms
	Astrocytoma	20188714
	Childhood Cerebral Astrocytoma	20188714
	Breast Cancer	19617202
	Intracranial Astrocytoma	20188714
	Liver Cancer	20084675
	Skin Cancer	18572023
	Glioblastoma Multiforme	16598420
	Pancreatic Neoplasm	22952646
	Cerebral Astrocytoma	20188714
	Glioblastoma	16598420
	Prostate cancer	16606632
	Lung Cancer	21789004
	Grade I Astrocytoma	20188714
	Colonic Neoplasms	15725655
	Oligoastrocytoma	20188714
	Bone Neoplasms	16475674
	Carcinoma	18572023
	Vulvar Cancer	26409448
Nervous System Diseases
	Cerebral Ischemia	15060315
	Middle Cerebral Artery Syndrome	19309543
	Diabetic Neuropathies	20213226
	Cerebral Artery Infarction	19309543
	Brain Infarction	19309543
	Cerebral Edema	15529013
	Cerebral Thrombosis	19309543
Nutritional and Metabolic Diseases
	Mandibuloacral dysplasia	18554282
	Tumoral calcinosis	15545515, 21193197
	Obesity	21156398
Psychiatric/Brain disorders
	Manic Disorder	24402212
	Bipolar Disorder	19536654, 24402212
	Schizophrenia	20510460, 19264454
	Obstructive Sleep Apnea	26169999, 23792205
Reproductive disorders
Reproductive disorders	Preeclampsia	27816668, 29670668, 29665148, 26317342, 21804632
Respiratory Tract Diseases
	Pulmonary Fibrosis	21468558
	Chronic Obstructive Pulmonary Disease	19299917
	Asthma	11742282, 15131573
	Airway Obstruction	19299917
	Emphysema	25106431
	Pulmonary Emphysema	25106431

References

Show/Hide all(7)

PubMed ID	Associated gene/s	Associated condition	Genetic Mutation	Diagnostic Criteria	Association with PCOS	Ethnicity	Conclusion
11279294	MMP-2 and TIMP-1	Follicular atresia, formation of multiple ovarian cysts		endocrine profile and ultrasonographic criteria	Related		A time-dependent increase in the production of MMP-9 was observed in cells from both normal and PCOS women, although the increase was more pronounced in the latter.
18362300	NGAL,estradiol, androgens, C-reactive protein	Vascular remodeling and plaque instability			Related		These findings indicate that NGAL and MMP-9/NGAL complex, two molecules that activate atherotic plaque erosion, is in lower concentrations in PCOS subjects.
12620479	TIMP-1			endocrine profile and ultrasonographic criteria	Related		In this preliminary study, similar and divergent patterns have emerged in the regulation of MMP-9 and TIMP-1 in human luteinized granulosa cells. Repressing MMP-9-TIMP-1 ratio may have an important modulatory effect on progesterone secretion.
16338908	MMP-2, TIMP-1	Cardiovascular risk,menstrual irregularities		Rotterdam criteria	Related		Obese women with PCOS have elevated serum concentrations of MMP-2 and -9.
20555001	MMP-2, TIMP-1, TIMP-2				Related		Significantly higher levels of MMP-2 and MMP-9 (p=0.02 and p<0.001, respectively) as well as TIMP-2 and TIMP-1 (p=0.006 and p<0.001, respectively) were found in the PCOS group compared to controls.
21437624	MMP-8, MMP-2, TIMP-1, TIMP-2				Related		The authors found evidence indicating that the balance between MMPs and TIMPs in women with PCOS is altered, probably due to androgen excess found in these women.
23249695	AP-1,EGR-1,MMP2,TF	Chronic low-grade inflammation,atherothrombosis,hyperandrogenism		NIH criteria	Related		Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls.

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