Detail Information for IndEnz0002013397
IED ID IndEnz0002013397
Enzyme Type ID protease013397
Protein Name Metalloproteinase inhibitor 1
Erythroid-potentiating activity
EPA
Fibroblast collagenase inhibitor
Collagenase inhibitor
Tissue inhibitor of metalloproteinases 1
TIMP-1
Gene Name TIMP1 CLGI TIMP
Organism Homo sapiens (Human)
Taxonomic Lineage cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MAPFEPLASGILLLLWLIAPSRACTCVPPHPQTAFCNSDLVIRAKFVGTPEVNQTTLYQRYEIKMTKMYKGFQALGDAADIRFVYTPAMESVCGYFHRSHNRSEEFLIAGKLQDGLLHITTCSFVAPWNSLSLAQRRGFTKTYTVGCEECTVFPCLSIPCKLQSGTHCLWTDQLLQGSEKGFQSRHLACLPREPGLCTWQSLRSQIA
Enzyme Length 207
Uniprot Accession Number P01033
Absorption
Active Site
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity
DNA Binding
EC Number
Enzyme Function FUNCTION: Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. {ECO:0000269|PubMed:1420137, ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:17050530, ECO:0000269|PubMed:1730286, ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517, ECO:0000269|PubMed:8541540, ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:9065415}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Beta strand (13); Chain (1); Disulfide bond (6); Domain (1); Glycosylation (2); Helix (8); Metal binding (1); Modified residue (1); Mutagenesis (5); Region (3); Sequence conflict (2); Signal peptide (1); Site (2); Turn (3)
Keywords 3D-structure;Direct protein sequencing;Disulfide bond;Glycoprotein;Growth factor;Metal-binding;Metalloenzyme inhibitor;Metalloprotease inhibitor;Phosphoprotein;Protease inhibitor;Reference proteome;Secreted;Signal;Zinc
Interact With P08962; P27701; P20908
Induction
Subcellular Location SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1730286, ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3010309, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517, ECO:0000269|PubMed:8541540}.
Modified Residue MOD_RES 178; /note=Phosphoserine; by FAM20C; /evidence=ECO:0000269|PubMed:26091039
Post Translational Modification PTM: The activity of TIMP1 is dependent on the presence of disulfide bonds. {ECO:0000269|PubMed:10623524, ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:2163605, ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:3010309}.; PTM: N-glycosylated. {ECO:0000269|PubMed:16263699, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:16740002, ECO:0000269|PubMed:19139490, ECO:0000269|PubMed:3010309, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517}.
Signal Peptide SIGNAL 1..23; /evidence="ECO:0000269|PubMed:15340161, ECO:0000269|PubMed:1653055, ECO:0000269|PubMed:1730286, ECO:0000269|PubMed:3010309, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517"
Structure 3D NMR spectroscopy (2); X-ray crystallography (6)
Cross Reference PDB 1D2B; 1OO9; 1UEA; 2J0T; 3MA2; 3V96; 6MAV; 6N9D;
Mapped Pubmed ID 11104795; 11278729; 11606052; 11705862; 11762702; 11796725; 11876751; 11935340; 11940298; 11960372; 12032189; 12034345; 12063180; 12082592; 12147251; 12150976; 12218659; 12376362; 12406369; 12452001; 12475252; 12479097; 12496489; 12538453; 12612199; 12614934; 12620441; 12626459; 12634064; 12704667; 12717827; 12771930; 12791318; 12846741; 12861139; 12869573; 12873541; 12904305; 12921631; 12951656; 12970724; 14517716; 1460289; 14605322; 14622947; 14648584; 14652000; 14661256; 14669348; 14688084; 14710472; 14871825; 14962256; 14973177; 14983226; 15028476; 15051730; 15073104; 15116091; 15161657; 15248826; 15277439; 15287862; 15313474; 15363817; 15363818; 15465038; 15479729; 15485866; 15494493; 15515157; 15516987; 15530852; 15557756; 15616792; 15754326; 15754388; 15818737; 15841325; 15867221; 15888067; 15890357; 15896974; 15944607; 16005367; 16019435; 16042227; 16061701; 16100012; 16103240; 16107690; 16169070; 16188099; 16191301; 16205632; 16219294; 16236134; 16248458; 16269968; 16280123; 16288711; 16372907; 16407831; 16410344; 16496359; 16555295; 16606674; 16615041; 16631927; 16754484; 16767366; 16772717; 16786122; 16840178; 16864898; 16877361; 16880228; 16931892; 16935611; 16940985; 16960901; 16996520; 17008230; 17009408; 17012236; 17045024; 17071711; 17114213; 17136882; 17162914; 17182940; 17192464; 17202148; 17205957; 17209789; 17222415; 17226791; 17299802; 17301822; 17340613; 17350093; 17380436; 17409012; 17456311; 17478562; 17489740; 17493602; 17543340; 17549663; 17564313; 17572495; 17572998; 17589947; 17634538; 17660250; 17703334; 17726014; 17763191; 17786346; 17878270; 17893005; 17899257; 17920311; 17928006; 17998244; 18025061; 18034264; 18042068; 18049028; 18063811; 18159069; 18214300; 18217401; 18236174; 18273688; 18291374; 18298349; 18385523; 18391843; 18395263; 18474748; 18477480; 18487063; 18502033; 18630499; 18634035; 18636124; 18645261; 18683786; 18692810; 18704317; 18787947; 18850474; 18854176; 18945772; 18984437; 19012952; 19019896; 19020757; 19036126; 19124156; 19141395; 19185846; 19246282; 19288452; 19331801; 19336475; 19358835; 19383295; 19383343; 19383344; 19387352; 19390929; 19430729; 19464975; 19506087; 19513566; 19524176; 19551542; 19560452; 19596921; 19608737; 19609944; 19629003; 19637058; 19653096; 19717938; 19723899; 19728856; 19747478; 19758569; 19766963; 19781774; 19796534; 19814619; 19863693; 19875168; 19887890; 19889076; 19904223; 19911067; 19913121; 19927649; 20021931; 20030715; 20039537; 20041335; 20051489; 20095885; 20111696; 20193458; 20215736; 20298300; 20305574; 20361393; 20371206; 20388222; 20423842; 20450704; 20452482; 20459644; 20484597; 20493732; 20514432; 20533294; 20545111; 20556397; 20584750; 20587546; 20595097; 20616161; 20628086; 20628624; 20646231; 20655547; 20673868; 20685094; 20707923; 20798956; 20838751; 20853162; 20854182; 20889295; 20921293; 21041986; 21086628; 21094936; 21115936; 21128246; 21163810; 21165404; 21167221; 21211402; 21283828; 21427648; 21437624; 21437772; 21454617; 21463121; 21487066; 21524282; 21535601; 21547130; 21586274; 21684102; 21709637; 21720458; 21731773; 21745383; 21763297; 21786179; 21858035; 21860087; 21881840; 21882477; 21903858; 21928345; 21946941; 21963718; 21969093; 21993004; 21995626; 22016393; 22051851; 22110238; 22122951; 22139647; 22177802; 22199358; 22200256; 22200690; 22200710; 22204652; 22223664; 22257687; 22286923; 22289852; 22291969; 22305865; 22364921; 22397869; 22402936; 22457727; 22465225; 22516898; 22532131; 22544540; 22558080; 22645431; 22667130; 22671570; 22706255; 22712305; 22718114; 22739984; 22788708; 22820628; 22851691; 22859303; 22883459; 22901654; 22906271; 22957045; 22965799; 22971139; 22975753; 22985578; 23016931; 23043898; 23057632; 23060593; 23064462; 23086340; 23107442; 23122949; 23175213; 23179318; 23223421; 23318123; 23388475; 23407481; 23412981; 23457635; 23509357; 23525523; 23548070; 23555182; 23555662; 23557756; 23563628; 23583449; 23585206; 23592002; 23640497; 23650722; 23660069; 23661104; 23673111; 23706069; 23763354; 23768069; 23773968; 23817219; 23834019; 23841813; 23881388; 23893334; 23900236; 23909892; 23962148; 23967200; 23967215; 23993112; 23998545; 24039251; 24042342; 24068394; 24113427; 24118356; 24143225; 24174628; 24212294; 24283658; 24330623; 24347177; 24389602; 24427345; 24447332; 24457057; 24479343; 24651234; 24727739; 24728097; 24743777; 24819588; 24895412; 24913092; 24976505; 24986570; 25016699; 25128867; 25137018; 25153995; 25183545; 25233933; 25234944; 25263437; 25300296; 25316052; 25335732; 25360794; 25436070; 25466591; 25470073; 25470608; 2551898; 25532000; 25549087; 25578494; 25594187; 25608838; 25623427; 25665057; 25674294; 25689086; 25693084; 25712810; 25756591; 25765004; 25854270; 25868389; 25883077; 25895516; 25932641; 25951835; 25998046; 26002577; 26077878; 26120586; 26193199; 26197083; 26213230; 26254391; 26268417; 26329758; 26342670; 26366732; 26399271; 26490574; 26539028; 26626455; 26681056; 26708839; 26718740; 26722039; 26730601; 26769731; 26782378; 26782559; 26844501; 26856083; 26861446; 26979530; 26995105; 27033700; 27089280; 27113051; 27121520; 27129797; 27130446; 27160811; 27258564; 27296149; 27297362; 27302771; 27304059; 27329669; 27506299; 27509063; 27561093; 27619981; 27644693; 27689613; 27903985; 28030805; 28098912; 28131910; 28192449; 28197741; 28278213; 28288890; 28293015; 28375112; 28509321; 28510611; 28554303; 28578515; 28682675; 28696822; 28739509; 28765154; 28887854; 28925394; 28992358; 29038419; 29250646; 29250654; 29263043; 29298087; 29394913; 29417309; 29453088; 29504111; 29523123; 29651326; 29658577; 29692608; 29752166; 29753168; 29929486; 29930267; 29979898; 29989318; 30010105; 30035371; 30037277; 30134384; 30187906; 30192205; 30221334; 30227310; 30238981; 30243515; 30254012; 30281655; 30317247; 30412498; 30458003; 30473539; 30482778; 30486830; 30523734; 30561224; 30626536; 30676640; 30695426; 30806727; 31018823; 31040180; 31074490; 31086224; 31273966; 31397194; 31545548; 31588644; 31625350; 31653704; 31658546; 31669537; 31861382; 31894031; 31910731; 32034211; 32049862; 32071226; 32200451; 32258173; 32303531; 32325785; 32423054; 32431079; 32447063; 32522594; 32535335; 32587306; 32607676; 32643898; 32652878; 32702237; 32915403; 32945513; 32955903; 32961536; 33005257; 33064893; 33070147; 33093251; 33123912; 33183761; 33186519; 33294960; 33355364; 33358398; 33404139; 33419373; 33482846; 33556788; 33569677; 33587449; 33601303; 33775157; 33814420; 33831331; 33941611; 34043679; 34170085; 34257518; 34270579; 34280134; 34391782; 34533565; 34555302; 34592197; 34659209; 34685701; 6457647; 7593617; 8063757; 8163946; 8467233; 8537680; 8621622; 8668165; 8742066; 8871669; 9354687; 9918218;
Motif
Gene Encoded By
Mass 23,171
Kinetics
Metal Binding METAL 24; /note=Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner; /evidence=ECO:0000269|PubMed:22427646
Rhea ID
Cross Reference Brenda 3.4.24.22;