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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)DescriptionActionsGraphical viewLength
Metal bindingi27Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner1

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 262 PublicationsAdd BLAST26
ChainiPRO_000003433127 – 220Metalloproteinase inhibitor 2Add BLAST194

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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 interactor.
MINTiMINT-1538893.
STRINGi9913.ENSBTAP00000014476.

Structurei

Secondary structure

1220
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi34 – 40Combined sources7
Beta strandi42 – 59Combined sources18
Beta strandi61 – 64Combined sources4
Beta strandi65 – 81Combined sources17
Beta strandi88 – 91Combined sources4
Helixi95 – 97Combined sources3
Beta strandi105 – 107Combined sources3
Beta strandi109 – 116Combined sources8
Beta strandi118 – 120Combined sources3
Beta strandi121 – 123Combined sources3
Beta strandi130 – 132Combined sources3
Helixi133 – 135Combined sources3
Helixi138 – 143Combined sources6
Turni144 – 146Combined sources3
Helixi147 – 151Combined sources5
Beta strandi154 – 158Combined sources5
Beta strandi160 – 162Combined sources3
Beta strandi171 – 174Combined sources4
Helixi176 – 179Combined sources4
Beta strandi183 – 185Combined sources3
Helixi186 – 190Combined sources5
Beta strandi192 – 195Combined sources4
Beta strandi197 – 204Combined sources8

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP16368.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 152NTRPROSITE-ProRule annotationAdd BLAST126

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni27 – 31Involved in metalloproteinase-binding5
Regioni95 – 96Involved in metalloproteinase-binding2

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)DescriptionActionsGraphical viewLength
Sequence conflicti15L → M in AAI02711 (Ref. 2) Curated1
Sequence conflicti42D → C AA sequence (PubMed:3005321).Curated1
Sequence conflicti56D → E AA sequence (PubMed:3005321).Curated1
Sequence conflicti68R → S AA sequence (PubMed:3005321).Curated1
Sequence conflicti88F → L in AAI02711 (Ref. 2) Curated1
Sequence conflicti94 – 95AA → SS in AAI02711 (Ref. 2) Curated2

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BQQX-ray2.75T27-210[»]
1BUVX-ray2.75T27-210[»]
2E2DX-ray2.00C28-206[»]
ProteinModelPortaliP16368.
SMRiP16368.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP16368. 1 interactor.
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.

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...

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: November 2, 2016
This is version 141 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.