3MA2

Complex membrane type-1 matrix metalloproteinase (MT1-MMP) with tissue inhibitor of metalloproteinase-1 (TIMP-1)

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A [auth D]	d3ma2d_	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	Matrix metalloproteases, catalytic domain	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth A]	d3ma2a_	Alpha and beta proteins (a+b)	Zincin-like	Metalloproteases ('zincins'), catalytic domain	Matrix metalloproteases, catalytic domain	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C [auth B]	d3ma2b_	All beta proteins	OB-fold	TIMP-like	Tissue inhibitor of metalloproteinases, TIMP	TIMP-1	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth C]	d3ma2c_	All beta proteins	OB-fold	TIMP-like	Tissue inhibitor of metalloproteinases, TIMP	TIMP-1	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A [auth D]	SCOP2B Superfamily	Metalloproteases (zincins) catalytic domain	8035557	3001975	SCOP2B (2022-06-29)
B [auth A]	SCOP2B Superfamily	Metalloproteases (zincins) catalytic domain	8035557	3001975	SCOP2B (2022-06-29)
C [auth B]	SCOP2B Superfamily	TIMP-like	8042955	3000488	SCOP2B (2022-06-29)
D [auth C]	SCOP2B Superfamily	TIMP-like	8042955	3000488	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A [auth D]	PF00413	e3ma2D1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: PF00413	ECOD (1.6)
B [auth A]	PF00413	e3ma2A1	A: mixed a+b and a/b	X: Zincin-like	H: Metalloproteases (zincins) catalytic domain (From Topology)	T: Metalloproteases (zincins) catalytic domain	F: PF00413	ECOD (1.6)
C [auth B]	PF00965	e3ma2B1	A: beta barrels	X: OB-fold	H: TIMP-like (From Topology)	T: TIMP-like	F: PF00965	ECOD (1.6)
D [auth C]	PF00965	e3ma2C1	A: beta barrels	X: OB-fold	H: TIMP-like (From Topology)	T: TIMP-like	F: PF00965	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A [auth D]	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)
B [auth A]	3.40.390.10	Alpha Beta	3-Layer(aba) Sandwich	Collagenase (Catalytic Domain)	Collagenase (Catalytic Domain)	CATH (4.3.0)
C [auth B]	2.40.50.120	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)		CATH (4.3.0)
D [auth C]	2.40.50.120	Mainly Beta	Beta Barrel	OB fold (Dihydrolipoamide Acetyltransferase, E2P)		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth D], B [auth A]	PF00413	Matrixin (Peptidase_M10)	Matrixin	The members of this family are enzymes that cleave peptides. These proteases require zinc for catalysis.	Domain
C [auth B], D [auth C]	PF00965	Tissue inhibitor of metalloproteinase (TIMP)	Tissue inhibitor of metalloproteinase	Members of this family are common in extracellular regions of vertebrate species	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth D], B [auth A]	Matrix metalloproteinase-14	peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity metalloendopeptidase activity metallopeptidase activity aminopeptidase activity metalloaminopeptidase activity exopeptidase activity metalloexopeptidase activity peptidase activity catalytic activity, acting on a protein serine hydrolase activity serine-type peptidase activity hydrolase activity serine-type endopeptidase activity catalytic activity endopeptidase activity metalloendopeptidase activity metallopeptidase activity aminopeptidase activity metalloaminopeptidase activity exopeptidase activity metalloexopeptidase activity cell adhesion molecule binding protein-containing complex binding protein binding binding integrin binding signaling receptor binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development system development cellular developmental process glial cell migration nervous system development neurogenesis gliogenesis cell differentiation astrocyte cell migration cellular process cell migration cell motility epithelium development tube development branching morphogenesis of an epithelial tube morphogenesis of an epithelium tissue development tissue morphogenesis anatomical structure morphogenesis tube morphogenesis morphogenesis of a branching structure epithelial tube morphogenesis morphogenesis of a branching epithelium skeletal system development cellular component organization extracellular matrix organization cellular component organization or biogenesis extracellular structure organization external encapsulating structure organization endochondral ossification replacement ossification endochondral bone morphogenesis ossification skeletal system morphogenesis animal organ morphogenesis bone morphogenesis bone development cell population proliferation chondrocyte proliferation female gonad development female sex differentiation development of primary female sexual characteristics ovarian follicle development regulation of cellular process regulation of developmental process positive regulation of biological process regulation of cell differentiation regulation of striated muscle cell differentiation muscle cell differentiation myotube differentiation muscle structure development positive regulation of developmental process positive regulation of myotube differentiation positive regulation of cell differentiation positive regulation of striated muscle cell differentiation regulation of myotube differentiation positive regulation of cellular process regulation of biological process biological regulation positive regulation of muscle cell differentiation regulation of muscle cell differentiation striated muscle cell differentiation craniofacial suture morphogenesis cranial skeletal system development response to decreased oxygen levels response to stimulus response to hypoxia response to stress response to oxygen levels response to abiotic stimulus protein localization regulation of localization cellular localization protein localization to cell periphery regulation of protein localization protein localization to plasma membrane localization within membrane regulation of protein localization to cell periphery protein localization to membrane localization regulation of cellular localization cellular macromolecule localization macromolecule localization regulation of protein localization to plasma membrane regulation of protein localization to membrane regulation of leukocyte differentiation regulation of leukocyte activation regulation of cell activation mononuclear cell differentiation positive regulation of B cell differentiation lymphocyte differentiation regulation of cell development positive regulation of cell activation positive regulation of leukocyte activation regulation of immune system process positive regulation of immune system process positive regulation of cell development positive regulation of multicellular organismal process leukocyte differentiation cell development lymphocyte activation leukocyte activation positive regulation of lymphocyte activation regulation of B cell differentiation B cell differentiation positive regulation of hemopoiesis regulation of B cell activation regulation of multicellular organismal process regulation of lymphocyte differentiation regulation of multicellular organismal development hemopoiesis B cell activation cell activation positive regulation of B cell activation immune system process regulation of hemopoiesis positive regulation of leukocyte differentiation positive regulation of lymphocyte differentiation regulation of lymphocyte activation response to chemical response to odorant endothelial cell proliferation epithelial cell proliferation regulation of growth regulation of cellular component organization growth positive regulation of cell growth regulation of cell growth cell growth positive regulation of growth collagen catabolic process catabolic process metabolic process collagen metabolic process cell-substrate junction assembly negative regulation of biological process negative regulation of cell-substrate junction organization negative regulation of cell-matrix adhesion negative regulation of cell adhesion cellular component biogenesis cell adhesion cellular component assembly negative regulation of cell junction assembly cell junction assembly negative regulation of cellular process regulation of cell-substrate junction organization focal adhesion assembly negative regulation of cellular component organization regulation of cell-substrate adhesion regulation of cell adhesion cell-substrate adhesion regulation of cellular component biogenesis negative regulation of focal adhesion assembly regulation of cell junction assembly cell junction organization cell-matrix adhesion regulation of cell-matrix adhesion cell-substrate junction organization negative regulation of cell-substrate adhesion regulation of focal adhesion assembly regulation of cell-substrate junction assembly response to organic substance response to hormone response to endogenous stimulus response to estrogen blood vessel morphogenesis angiogenesis vasculature development circulatory system development anatomical structure formation involved in morphogenesis blood vessel development head development embryonic organ morphogenesis embryonic cranial skeleton morphogenesis chordate embryonic development embryonic morphogenesis embryo development embryo development ending in birth or egg hatching embryonic skeletal system development embryonic organ development embryonic skeletal system morphogenesis formation of primary germ layer gastrulation endoderm development endoderm formation endodermal cell differentiation respiratory tube development lung development respiratory system development regulation of protein maturation positive regulation of protein maturation cellular biosynthetic process positive regulation of protein metabolic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of protein processing protein maturation regulation of primary metabolic process positive regulation of metabolic process organic substance metabolic process regulation of proteolysis positive regulation of biosynthetic process proteolysis organic substance biosynthetic process positive regulation of macromolecule metabolic process protein metabolic process regulation of biosynthetic process organonitrogen compound metabolic process cellular metabolic process regulation of protein metabolic process primary metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process positive regulation of gene expression positive regulation of proteolysis regulation of protein processing protein processing regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular biosynthetic process tissue remodeling cellular component disassembly extracellular matrix disassembly positive regulation of locomotion regulation of cell motility macrophage migration positive regulation of cell migration regulation of macrophage migration positive regulation of cell motility regulation of cell migration myeloid leukocyte migration positive regulation of mononuclear cell migration regulation of mononuclear cell migration locomotion positive regulation of macrophage migration regulation of leukocyte migration positive regulation of leukocyte migration leukocyte migration regulation of locomotion mononuclear cell migration cellular response to stimulus negative regulation of signaling signaling regulation of signal transduction negative regulation of cell communication cell communication signal transduction regulation of signaling cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of signal transduction Notch signaling pathway negative regulation of Notch signaling pathway regulation of response to stimulus regulation of Notch signaling pathway regulation of cell communication response to mechanical stimulus response to external stimulus response to oxidative stress response to organic cyclic compound zymogen activation	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle endosome intracellular vesicle intracellular membrane-bounded organelle macropinosome endomembrane system intracellular organelle cytoplasmic vesicle organelle vesicle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle endosome intracellular vesicle intracellular membrane-bounded organelle macropinosome endomembrane system intracellular organelle cytoplasmic vesicle organelle vesicle pinosome cytoskeleton intracellular non-membrane-bounded organelle non-membrane-bounded organelle intermediate filament cytoskeleton extracellular region extracellular space anchoring junction cell junction focal adhesion cell-substrate junction pigment granule melanosome cell periphery plasma membrane membrane extracellular matrix external encapsulating structure Golgi apparatus membrane-enclosed lumen intracellular organelle lumen Golgi lumen organelle lumen nucleus
C [auth B], D [auth C]	Metalloproteinase inhibitor 1	protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity enzyme binding protease binding enzyme regulator activity molecular function inhibitor activity peptidase regulator activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity growth factor activity receptor ligand activity signaling receptor activator activity enzyme binding protease binding enzyme regulator activity molecular function inhibitor activity peptidase regulator activity enzyme inhibitor activity peptidase inhibitor activity endopeptidase regulator activity metalloendopeptidase inhibitor activity endopeptidase inhibitor activity cytokine activity cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	developmental process multicellular organism development multicellular organismal process skeletal system development connective tissue development anatomical structure development animal organ development tissue development cartilage development system development response to organic substance response to stimulus response to hormone response to chemical developmental process multicellular organism development multicellular organismal process skeletal system development connective tissue development anatomical structure development animal organ development tissue development cartilage development system development response to organic substance response to stimulus response to hormone response to chemical response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to oxygen-containing compound response to nitrogen compound regulation of biological process regulation of cellular process negative regulation of programmed cell death regulation of apoptotic process biological regulation negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process cellular process apoptotic process programmed cell death wound healing connective tissue replacement involved in inflammatory response wound healing wound healing involved in inflammatory response defense response response to stress inflammatory response to wounding tissue remodeling connective tissue replacement inflammatory response response to wounding response to cytokine regulation of molecular function regulation of catalytic activity negative regulation of molecular function negative regulation of catalytic activity cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation positive regulation of biological process positive regulation of cellular process negative regulation of hydrolase activity negative regulation of proteolysis regulation of primary metabolic process negative regulation of peptidase activity organic substance metabolic process regulation of proteolysis proteolysis protein metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process organonitrogen compound metabolic process regulation of protein metabolic process negative regulation of metabolic process regulation of peptidase activity primary metabolic process regulation of macromolecule metabolic process regulation of metallopeptidase activity regulation of hydrolase activity negative regulation of metallopeptidase activity metabolic process macromolecule metabolic process regulation of metabolic process negative regulation of endopeptidase activity regulation of endopeptidase activity multi-multicellular organism process negative regulation of locomotion regulation of cell motility regulation of trophoblast cell migration regulation of reproductive process reproductive process ameboidal-type cell migration regulation of cell migration cell migration regulation of multicellular organismal process cell motility female pregnancy embryo implantation negative regulation of trophoblast cell migration locomotion negative regulation of cell migration trophoblast cell migration negative regulation of reproductive process regulation of locomotion negative regulation of cell motility negative regulation of multicellular organismal process multi-organism reproductive process negative regulation of membrane protein ectodomain proteolysis negative regulation of cellular catabolic process catabolic process macromolecule catabolic process negative regulation of cellular metabolic process negative regulation of protein catabolic process cellular catabolic process membrane protein proteolysis membrane protein ectodomain proteolysis organonitrogen compound catabolic process negative regulation of catabolic process regulation of membrane protein ectodomain proteolysis cellular metabolic process regulation of cellular metabolic process regulation of catabolic process protein catabolic process regulation of cellular catabolic process organic substance catabolic process regulation of protein catabolic process cellular response to stimulus regulation of integrin-mediated signaling pathway regulation of signaling integrin-mediated signaling pathway cell surface receptor signaling pathway signaling regulation of signal transduction cell communication regulation of response to stimulus regulation of cell communication signal transduction response to light stimulus cellular response to radiation response to UV cellular response to environmental stimulus cellular response to UV-A cellular response to light stimulus response to radiation response to abiotic stimulus cellular response to abiotic stimulus cellular response to UV response to UV-A	basement membrane cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle basement membrane cell periphery extracellular matrix external encapsulating structure collagen-containing extracellular matrix cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen endoplasmic reticulum cytoplasm vesicle lumen intracellular vesicle cytoplasmic vesicle lumen secretory granule lumen cytoplasmic vesicle secretory granule secretory vesicle platelet alpha granule platelet alpha granule lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth D], B [auth A]	IPR021158	Peptidase M10A, cysteine switch, zinc binding site	Binding Site
A [auth D], B [auth A]	IPR021190	Peptidase M10A	Family
A [auth D], B [auth A]	IPR002477	Peptidoglycan binding-like	Domain
A [auth D], B [auth A]	IPR006026	Peptidase, metallopeptidase	Domain
A [auth D], B [auth A]	IPR033739	Peptidase M10A, catalytic domain	Domain
A [auth D], B [auth A]	IPR018486	Hemopexin, conserved site	Conserved Site
A [auth D], B [auth A]	IPR036375	Hemopexin-like domain superfamily	Homologous Superfamily
A [auth D], B [auth A]	IPR036365	PGBD-like superfamily	Homologous Superfamily
A [auth D], B [auth A]	IPR001818	Peptidase M10, metallopeptidase	Domain
A [auth D], B [auth A]	IPR021805	Peptidase M10A, matrix metallopeptidase, C-terminal	Domain
A [auth D], B [auth A]	IPR024079	Metallopeptidase, catalytic domain superfamily	Homologous Superfamily
A [auth D], B [auth A]	IPR018487	Hemopexin-like repeats	Repeat
A [auth D], B [auth A]	IPR000585	Hemopexin-like domain	Domain
A [auth D], B [auth A]	IPR036366	PGBD superfamily	Homologous Superfamily
C [auth B], D [auth C]	IPR001820	Protease inhibitor I35 (TIMP)	Family
C [auth B], D [auth C]	IPR027465	Proteinase inhibitor I35b (TIMP), C-terminal	Homologous Superfamily
C [auth B], D [auth C]	IPR001134	Netrin domain	Domain
C [auth B], D [auth C]	IPR008993	Tissue inhibitor of metalloproteinases-like, OB-fold	Homologous Superfamily
C [auth B], D [auth C]	IPR030490	Tissue inhibitor of metalloproteinase, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth D], B [auth A]	Pharos: P50281	Winchester syndrome abdominal aortic aneurysm Neoplasm Invasiveness breast carcinoma tubular adenocarcinoma esophageal cancer adenocarcinoma breast cancer granular cell carcinoma lung carcinoma malignant mesothelioma non-small cell lung carcinoma pilocytic astrocytoma prostate carcinoma cribriform carcinoma Winchester syndrome abdominal aortic aneurysm Neoplasm Invasiveness breast carcinoma tubular adenocarcinoma esophageal cancer adenocarcinoma breast cancer granular cell carcinoma lung carcinoma malignant mesothelioma non-small cell lung carcinoma pilocytic astrocytoma prostate carcinoma cribriform carcinoma hypertensive disorder malignant ependymoma neoplasm of esophagus osteosarcoma atypical teratoid rhabdoid tumor plantar fibromatosis cancer psoriasis cribriform carcinoma of breast glioblastoma lung adenocarcinoma malignant glioma malignant pancreatic neoplasm medulloblastoma pancreatic ductal adenocarcinoma Torg-Winchester syndrome chronic obstructive pulmonary disease cystic fibrosis
C [auth B], D [auth C]	Pharos: P01033	aortic valve insufficiency Wilson disease oral submucous fibrosis IgA glomerulonephritis heart disease type 2 diabetes mellitus hypertensive disorder vascular disease adult acute respiratory distress syndrome Inflammation cholangitis extrahepatic cholestasis pulmonary fibrosis heart valve disease alcoholic liver cirrhosis aortic valve insufficiency Wilson disease oral submucous fibrosis IgA glomerulonephritis heart disease type 2 diabetes mellitus hypertensive disorder vascular disease adult acute respiratory distress syndrome Inflammation cholangitis extrahepatic cholestasis pulmonary fibrosis heart valve disease alcoholic liver cirrhosis autoimmune disease calcinosis varicose disease osteosarcoma esophageal adenocarcinoma pilocytic astrocytoma gastric carcinoma subependymal giant cell astrocytoma juvenile dermatomyositis Becker muscular dystrophy liver disease malignant colon neoplasm malignant mesothelioma medulloblastoma ductal breast carcinoma in situ ovarian cancer glioblastoma tuberculosis ulcerative colitis idiopathic interstitial pneumonia interstitial cystitis limb-girdle muscular dystrophy lung adenocarcinoma malignant ependymoma congestive heart failure malignant pancreatic neoplasm diabetes mellitus Emery-Dreifuss muscular dystrophy pancreatic ductal adenocarcinoma invasive ductal breast carcinoma Barrett esophagus lung cancer cancer malignant glioma Crohn disease maturity-onset diabetes of the young myopathy Duchenne muscular dystrophy

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.