UniProtKB - P30120 (TIMP1_RAT)
Metalloproteinase inhibitor 1
Timp1
Functioni
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. Also stimulates steroidogenesis by Leydig and ovarian granuloma cells; procathepsin L is required for maximal activity.
2 PublicationsSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 24 | Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity | 1 | |
Sitei | 37 | Involved in metalloproteinase-bindingBy similarity | 1 |
GO - Molecular functioni
- cytokine activity Source: UniProtKB
- growth factor activity Source: UniProtKB-KW
- metalloendopeptidase inhibitor activity Source: UniProtKB
- peptidase inhibitor activity Source: RGD
- protease binding Source: RGD
- zinc ion binding Source: RGD
GO - Biological processi
- aging Source: RGD
- cartilage development Source: RGD
- cell activation Source: RGD
- cellular response to UV-A Source: UniProtKB
- connective tissue replacement involved in inflammatory response wound healing Source: RGD
- negative regulation of apoptotic process Source: RGD
- negative regulation of catalytic activity Source: UniProtKB
- negative regulation of endopeptidase activity Source: UniProtKB
- negative regulation of membrane protein ectodomain proteolysis Source: RGD
- negative regulation of metallopeptidase activity Source: RGD
- negative regulation of trophoblast cell migration Source: RGD
- positive regulation of cell population proliferation Source: UniProtKB
- regulation of integrin-mediated signaling pathway Source: UniProtKB
- response to cytokine Source: RGD
- response to hormone Source: GO_Central
- response to organic substance Source: RGD
- response to peptide hormone Source: RGD
- steroid biosynthetic process Source: UniProtKB-KW
- wound healing Source: RGD
Keywordsi
Molecular function | Growth factor, Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor |
Biological process | Steroidogenesis |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-RNO-114608, Platelet degranulation R-RNO-1592389, Activation of Matrix Metalloproteinases R-RNO-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-RNO-8957275, Post-translational protein phosphorylation |
Names & Taxonomyi
Protein namesi | Recommended name: Metalloproteinase inhibitor 1Alternative name(s): Tissue inhibitor of metalloproteinases 1 Short name: TIMP-1 |
Gene namesi | Name:Timp1 Synonyms:Timp-1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 621675, Timp1 |
Subcellular locationi
Extracellular region or secreted
- Secreted 2 Publications
Extracellular region or secreted
- extracellular space Source: UniProtKB
Other locations
- basement membrane Source: RGD
- extracellular matrix Source: RGD
Keywords - Cellular componenti
SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | 2 PublicationsAdd BLAST | 23 | |
ChainiPRO_0000034329 | 24 – 217 | Metalloproteinase inhibitor 1Add BLAST | 194 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 24 ↔ 93 | PROSITE-ProRule annotation | ||
Disulfide bondi | 26 ↔ 122 | PROSITE-ProRule annotation | ||
Disulfide bondi | 36 ↔ 147 | PROSITE-ProRule annotation | ||
Glycosylationi | 77 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 101 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 150 ↔ 197 | PROSITE-ProRule annotation | ||
Disulfide bondi | 155 ↔ 160 | PROSITE-ProRule annotation | ||
Disulfide bondi | 168 ↔ 189 | PROSITE-ProRule annotation | ||
Modified residuei | 178 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | P30120 |
PRIDEi | P30120 |
PTM databases
GlyGeni | P30120, 2 sites |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSRNOG00000010208, Expressed in female gonad and 22 other tissues |
Genevisiblei | P30120, RN |
Interactioni
Subunit structurei
Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very low affinity for MMP14.
Interacts with CD63; identified in a complex with CD63 and ITGB1 (By similarity).
By similarityGO - Molecular functioni
- cytokine activity Source: UniProtKB
- growth factor activity Source: UniProtKB-KW
- protease binding Source: RGD
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000013745 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 24 – 147 | NTRPROSITE-ProRule annotationAdd BLAST | 124 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 24 – 27 | Involved in metalloproteinase-bindingBy similarity | 4 | |
Regioni | 90 – 91 | Involved in metalloproteinase-bindingBy similarity | 2 |
Sequence similaritiesi
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG4745, Eukaryota |
GeneTreei | ENSGT00940000161081 |
HOGENOMi | CLU_084029_0_0_1 |
InParanoidi | P30120 |
OMAi | TWQSLRP |
OrthoDBi | 1122531at2759 |
PhylomeDBi | P30120 |
TreeFami | TF317409 |
Family and domain databases
Gene3Di | 2.40.50.120, 1 hit 3.90.370.10, 1 hit |
InterProi | View protein in InterPro IPR001134, Netrin_domain IPR001820, TIMP IPR008993, TIMP-like_OB-fold IPR015611, TIMP1 IPR027465, TIMP_C IPR030490, TIMP_CS |
PANTHERi | PTHR11844, PTHR11844, 1 hit PTHR11844:SF20, PTHR11844:SF20, 1 hit |
Pfami | View protein in Pfam PF00965, TIMP, 1 hit |
SMARTi | View protein in SMART SM00206, NTR, 1 hit |
SUPFAMi | SSF50242, SSF50242, 1 hit |
PROSITEi | View protein in PROSITE PS50189, NTR, 1 hit PS00288, TIMP, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MAPFASLASG ILLLLSLIAS SKACSCAPTH PQTAFCNSDL VIRAKFMGSP
60 70 80 90 100
EIIETTLYQR YEIKMTKMLK GFDAVGNATG FRFAYTPAME SLCGYVHKSQ
110 120 130 140 150
NRSEEFLIAG RLRNGNLHIT ACSFLVPWHN LSPAQQKAFV KTYSAGCGVC
160 170 180 190 200
TVFPCSAIPC KLESDSHCLW TDQILMGSEK GYQSDHFACL PRNPDLCTWQ
210
YLGVSMTRSL PLAKAEA
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 80 – 81 | GF → DI in AAB08483 (PubMed:8707259).Curated | 2 | |
Sequence conflicti | 88 | A → V in AAA51653 (PubMed:7777858).Curated | 1 | |
Sequence conflicti | 103 | S → R in AAB08483 (PubMed:8707259).Curated | 1 | |
Sequence conflicti | 129 – 130 | HN → AS in AAB08483 (PubMed:8707259).Curated | 2 | |
Sequence conflicti | 136 – 140 | QKAFV → RKGLT in AAB08483 (PubMed:8707259).Curated | 5 | |
Sequence conflicti | 149 | V → L in AAA51653 (PubMed:7777858).Curated | 1 | |
Sequence conflicti | 157 | A → V in AAB08483 (PubMed:8707259).Curated | 1 | |
Sequence conflicti | 166 | S → T in AAB08483 (PubMed:8707259).Curated | 1 | |
Sequence conflicti | 185 – 187 | DHF → RHL in AAB08483 (PubMed:8707259).Curated | 3 | |
Sequence conflicti | 195 | D → G in AAB08483 (PubMed:8707259).Curated | 1 | |
Sequence conflicti | 201 | Y → S in AAB08483 (PubMed:8707259).Curated | 1 | |
Sequence conflicti | 204 – 205 | VS → SR in AAB08483 (PubMed:8707259).Curated | 2 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U06179 mRNA Translation: AAA85780.1 L31883 mRNA Translation: AAA85373.1 AY550026 mRNA Translation: AAS55641.1 BC099821 mRNA Translation: AAH99821.1 L29512 mRNA Translation: AAB08483.1 U16022 mRNA Translation: AAA51653.1 Sequence problems. |
PIRi | JC2557 |
RefSeqi | NP_446271.1, NM_053819.1 XP_006256670.1, XM_006256608.2 |
Genome annotation databases
Ensembli | ENSRNOT00000013745; ENSRNOP00000013745; ENSRNOG00000010208 |
GeneIDi | 116510 |
KEGGi | rno:116510 |
UCSCi | RGD:621675, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U06179 mRNA Translation: AAA85780.1 L31883 mRNA Translation: AAA85373.1 AY550026 mRNA Translation: AAS55641.1 BC099821 mRNA Translation: AAH99821.1 L29512 mRNA Translation: AAB08483.1 U16022 mRNA Translation: AAA51653.1 Sequence problems. |
PIRi | JC2557 |
RefSeqi | NP_446271.1, NM_053819.1 XP_006256670.1, XM_006256608.2 |
3D structure databases
AlphaFoldDBi | P30120 |
SMRi | P30120 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000013745 |
PTM databases
GlyGeni | P30120, 2 sites |
Proteomic databases
PaxDbi | P30120 |
PRIDEi | P30120 |
Genome annotation databases
Ensembli | ENSRNOT00000013745; ENSRNOP00000013745; ENSRNOG00000010208 |
GeneIDi | 116510 |
KEGGi | rno:116510 |
UCSCi | RGD:621675, rat |
Organism-specific databases
CTDi | 7076 |
RGDi | 621675, Timp1 |
Phylogenomic databases
eggNOGi | KOG4745, Eukaryota |
GeneTreei | ENSGT00940000161081 |
HOGENOMi | CLU_084029_0_0_1 |
InParanoidi | P30120 |
OMAi | TWQSLRP |
OrthoDBi | 1122531at2759 |
PhylomeDBi | P30120 |
TreeFami | TF317409 |
Enzyme and pathway databases
Reactomei | R-RNO-114608, Platelet degranulation R-RNO-1592389, Activation of Matrix Metalloproteinases R-RNO-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-RNO-8957275, Post-translational protein phosphorylation |
Miscellaneous databases
PROi | PR:P30120 |
Gene expression databases
Bgeei | ENSRNOG00000010208, Expressed in female gonad and 22 other tissues |
Genevisiblei | P30120, RN |
Family and domain databases
Gene3Di | 2.40.50.120, 1 hit 3.90.370.10, 1 hit |
InterProi | View protein in InterPro IPR001134, Netrin_domain IPR001820, TIMP IPR008993, TIMP-like_OB-fold IPR015611, TIMP1 IPR027465, TIMP_C IPR030490, TIMP_CS |
PANTHERi | PTHR11844, PTHR11844, 1 hit PTHR11844:SF20, PTHR11844:SF20, 1 hit |
Pfami | View protein in Pfam PF00965, TIMP, 1 hit |
SMARTi | View protein in SMART SM00206, NTR, 1 hit |
SUPFAMi | SSF50242, SSF50242, 1 hit |
PROSITEi | View protein in PROSITE PS50189, NTR, 1 hit PS00288, TIMP, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TIMP1_RAT | |
Accessioni | P30120Primary (citable) accession number: P30120 Secondary accession number(s): P70533, Q53YM7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 1, 1993 |
Last sequence update: | November 1, 1995 | |
Last modified: | May 25, 2022 | |
This is version 167 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families