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Protein

Metalloproteinase inhibitor 2

Gene

TIMP2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi27 – 271Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Protein family/group databases

MEROPSiI35.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 2
Alternative name(s):
Collagenase inhibitor
Tissue inhibitor of metalloproteinases 2
Short name:
TIMP-2
Gene namesi
Name:TIMP2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 26262 PublicationsAdd
BLAST
Chaini27 – 220194Metalloproteinase inhibitor 2PRO_0000034331Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi27 ↔ 98
Disulfide bondi29 ↔ 127
Disulfide bondi39 ↔ 152
Disulfide bondi154 ↔ 201
Disulfide bondi159 ↔ 164
Disulfide bondi172 ↔ 193

Post-translational modificationi

The activity of TIMP2 is dependent on the presence of disulfide bonds.

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP16368.
PRIDEiP16368.

Interactioni

Subunit structurei

Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiP16368. 1 interaction.
MINTiMINT-1538893.
STRINGi9913.ENSBTAP00000014476.

Structurei

Secondary structure

1
220
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi34 – 407Combined sources
Beta strandi42 – 5918Combined sources
Beta strandi61 – 644Combined sources
Beta strandi65 – 8117Combined sources
Beta strandi88 – 914Combined sources
Helixi95 – 973Combined sources
Beta strandi105 – 1073Combined sources
Beta strandi109 – 1168Combined sources
Beta strandi118 – 1203Combined sources
Beta strandi121 – 1233Combined sources
Beta strandi130 – 1323Combined sources
Helixi133 – 1353Combined sources
Helixi138 – 1436Combined sources
Turni144 – 1463Combined sources
Helixi147 – 1515Combined sources
Beta strandi154 – 1585Combined sources
Beta strandi160 – 1623Combined sources
Beta strandi171 – 1744Combined sources
Helixi176 – 1794Combined sources
Beta strandi183 – 1853Combined sources
Helixi186 – 1905Combined sources
Beta strandi192 – 1954Combined sources
Beta strandi197 – 2048Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BQQX-ray2.75T27-210[»]
1BUVX-ray2.75T27-210[»]
2E2DX-ray2.00C28-206[»]
ProteinModelPortaliP16368.
SMRiP16368. Positions 27-210.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16368.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 152126NTRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni27 – 315Involved in metalloproteinase-binding
Regioni95 – 962Involved in metalloproteinase-binding

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP16368.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF24. PTHR11844:SF24. 1 hit.
PfamiPF00965. TIMP. 1 hit.
[Graphical view]
SMARTiSM00206. NTR. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiPS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P16368-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAAARSLPL AFCLLLLGTL LPRADACSCS PVHPQQAFCN ADIVIRAKAV
60 70 80 90 100
NKKEVDSGND IYGNPIKRIQ YEIKQIKMFK GPDQDIEFIY TAPAAAVCGV
110 120 130 140 150
SLDIGGKKEY LIAGKAEGNG NMHITLCDFI VPWDTLSATQ KKSLNHRYQM
160 170 180 190 200
GCECKITRCP MIPCYISSPD ECLWMDWVTE KNINGHQAKF FACIKRSDGS
210 220
CAWYRGAAPP KQEFLDIEDP
Length:220
Mass (Da):24,355
Last modified:May 1, 1991 - v2
Checksum:i9A5438737110E7B7
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti15 – 151L → M in AAI02711 (Ref. 2) Curated
Sequence conflicti42 – 421D → C AA sequence (PubMed:3005321).Curated
Sequence conflicti56 – 561D → E AA sequence (PubMed:3005321).Curated
Sequence conflicti68 – 681R → S AA sequence (PubMed:3005321).Curated
Sequence conflicti88 – 881F → L in AAI02711 (Ref. 2) Curated
Sequence conflicti94 – 952AA → SS in AAI02711 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32303 mRNA. Translation: AAA30636.1.
BC102710 mRNA. Translation: AAI02711.1.
AF144764 mRNA. Translation: AAD30304.1.
PIRiA35996.
RefSeqiNP_776897.2. NM_174472.4.
UniGeneiBt.111410.

Genome annotation databases

GeneIDi282093.
KEGGibta:282093.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M32303 mRNA. Translation: AAA30636.1.
BC102710 mRNA. Translation: AAI02711.1.
AF144764 mRNA. Translation: AAD30304.1.
PIRiA35996.
RefSeqiNP_776897.2. NM_174472.4.
UniGeneiBt.111410.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BQQX-ray2.75T27-210[»]
1BUVX-ray2.75T27-210[»]
2E2DX-ray2.00C28-206[»]
ProteinModelPortaliP16368.
SMRiP16368. Positions 27-210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP16368. 1 interaction.
MINTiMINT-1538893.
STRINGi9913.ENSBTAP00000014476.

Protein family/group databases

MEROPSiI35.002.

Proteomic databases

PaxDbiP16368.
PRIDEiP16368.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi282093.
KEGGibta:282093.

Organism-specific databases

CTDi7077.

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP16368.

Miscellaneous databases

EvolutionaryTraceiP16368.
NextBioi20805936.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015613. TIMP2.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF24. PTHR11844:SF24. 1 hit.
PfamiPF00965. TIMP. 1 hit.
[Graphical view]
SMARTiSM00206. NTR. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
PROSITEiPS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "cDNA cloning and expression of a metalloproteinase inhibitor related to tissue inhibitor of metalloproteinases."
    Boone T.C., Johnson M.J., de Clerck Y.A., Langley K.E.
    Proc. Natl. Acad. Sci. U.S.A. 87:2800-2804(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. NIH - Mammalian Gene Collection (MGC) project
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Crossbred X Angus.
    Tissue: Liver.
  3. "Involvement of fibroblasts and muscle cells in the expression of an extracellular proteolytic cascade in bovine skeletal muscle."
    Balcerzak D., Querengesser L., Dixon W.T., Baracos V.E.
    Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 22-218.
    Tissue: Skeletal muscle.
  4. "Purification and partial amino acid sequence of a bovine cartilage-derived collagenase inhibitor."
    Murray J.B., Allison K., Sudhalter J., Langer R.
    J. Biol. Chem. 261:4154-4159(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 27-71.
    Tissue: Cartilage.
  5. "Purification and characterization of two related but distinct metalloproteinase inhibitors secreted by bovine aortic endothelial cells."
    de Clerck Y.A., Yean T.D., Ratzkin B.J., Lu H.S., Langley K.E.
    J. Biol. Chem. 264:17445-17453(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 27-71.
  6. "Characterization of the functional domain of tissue inhibitor of metalloproteinases-2 (TIMP-2)."
    De Clerck Y.A., Yean T.D., Lee Y., Tomich J.M., Langley K.E.
    Biochem. J. 289:65-69(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-71.
  7. "Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor."
    Fernandez-Catalan C., Bode W., Huber R., Turk D., Calvete J.J., Lichte A., Tschesche H., Maskos K.
    EMBO J. 17:5238-5248(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 27-210 IN COMPLEX WITH MMP-1.
  8. "Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2."
    Maskos K., Lang R., Tschesche H., Bode W.
    J. Mol. Biol. 366:1222-1231(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 28-206 IN COMPLEX WITH MMP-13, DISULFIDE.

Entry informationi

Entry nameiTIMP2_BOVIN
AccessioniPrimary (citable) accession number: P16368
Secondary accession number(s): Q3SZU3, Q9TVB1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1990
Last sequence update: May 1, 1991
Last modified: May 11, 2016
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.