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FLASH GENE

Symbol

MMP12

contributors: mct - updated : 30-11-2015

HGNC name	matrix metalloproteinase 12 (macrophage elastase)
HGNC id	7158

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	member of the MMP cluster
STRUCTURE	12.25 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002426 10 - 1877 NP_002417 - 470 - 2001 11704502

EXPRESSION

Type

widely

constitutive of

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive esophagus       highly Reproductive female system placenta     highly   female system breast mammary gland   highly Respiratory lung           respiratory tract larynx     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune macrophage

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta,cells ,chondrocytes of hypertrophic cartilage (spinal column,ribs )

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a cysteine residue essential for latency and involved in autocatalytic activation
	a catalytic domain with the zinc-binding site (the cysteine switch)that alone binds and degrades collagens I and III
	a hinge region
	a hemopexin-like C terminal domain

conjugated

HemoP , MetalloP

HOMOLOGY

Homologene

FAMILY	MMP family
	peptidase M10A family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION

extracellular

basic FUNCTION	regulator in matrix remodeling
	playing a role in extracellular matrix remodeling during fetal bone development and in chondrocytes malignant transformation
	macrophage metalloelastase, essential for macrophage migration
	MMP9 and MMP12 promote intimal thickening by independent cleavage of N-cadherin, which elevates vascular smooth muscle cell proliferation via beta-catenin signalling
	remodeling of elastotic areas in sun damaged skin
	generation of angiostatin-like fragment
	macrophage-secreting proteinase
	its overexpression in myeloid lineage cells plays a key role in modulating myelopoiesis, immune suppression, and lung tumorigenesis

CELLULAR PROCESS	nucleotide, repair
	cell migration & motility

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding,
	zinc Zn2+
	calcium Ca2+

protein	binding TIMPs in a 1:1 stoechiometry
	is a PGRN proteolytic enzyme, and SLPI an inhibitor of MMP12-induced PGRN proteolysis
	MMP12 regulates adipose tissue expansion, insulin sensitivity, and expression of NOS2

cell & other

REGULATION

activated by

proteinases

inhibited by

TFPI2

Other	regulated by the Ca2+ (may be involved in controlling the activity of MMP12)
	regulation by a PPAR alpha agonist in human monocyte-derived macrophages

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in ulcerative colitis and Crohn's disease and in colorectal carcinoma with better prognosis constitutional     --over   with ADAMDEC1, in bronchoalveolar lavage samples from patients with sarcoidosis, correlating with disease severity tumoral     --over   correlated with poor prognosis of hepatocellular carcinoma constitutional     --over   in atherosclerotic lesions

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	MMP12 mRNA may be a valuable prognostic marker for both overall survival and tumour recurrence of hepatocellular carcinoma patients after liver resection
Therapy target
	System Type Disorder Pubmed allergy asthm   In allergen-sensitized sheep pharmacologic inhibition of MMP12 downregulates both early and late airway responses in response to allergic stimuli

ANIMAL & CELL MODELS