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Protein

Metalloproteinase inhibitor 2

Gene

TIMP2

Organism
Homo sapiens (Human)
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. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi27Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • metalloendopeptidase inhibitor activity Source: ProtInc
  • protease binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000035862-MONOMER.
ReactomeiR-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-6798695. Neutrophil degranulation.

Protein family/group databases

MEROPSiI35.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 2
Alternative name(s):
CSC-21K
Tissue inhibitor of metalloproteinases 2
Short name:
TIMP-2
Gene namesi
Name:TIMP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:11821. TIMP2.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: BHF-UCL
  • extracellular region Source: Reactome
  • extracellular space Source: GO_Central
  • growth cone Source: Ensembl
  • neuronal cell body Source: Ensembl
  • proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi7077.
OpenTargetsiENSG00000035862.
PharmGKBiPA36527.

Polymorphism and mutation databases

BioMutaiTIMP2.
DMDMi135854.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 263 PublicationsAdd BLAST26
ChainiPRO_000003433527 – 220Metalloproteinase inhibitor 2Add BLAST194

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi27 ↔ 98PROSITE-ProRule annotation1 Publication
Disulfide bondi29 ↔ 127PROSITE-ProRule annotation1 Publication
Disulfide bondi39 ↔ 152PROSITE-ProRule annotation1 Publication
Disulfide bondi154 ↔ 201PROSITE-ProRule annotation1 Publication
Disulfide bondi159 ↔ 164PROSITE-ProRule annotation1 Publication
Disulfide bondi172 ↔ 193PROSITE-ProRule annotation1 Publication

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiP16035.
MaxQBiP16035.
PaxDbiP16035.
PeptideAtlasiP16035.
PRIDEiP16035.
TopDownProteomicsiP16035.

2D gel databases

DOSAC-COBS-2DPAGEP16035.

PTM databases

iPTMnetiP16035.
PhosphoSitePlusiP16035.

Expressioni

Inductioni

Down-regulated by TGFB1.1 Publication

Gene expression databases

BgeeiENSG00000035862.
CleanExiHS_TIMP2.
ExpressionAtlasiP16035. baseline and differential.
GenevisibleiP16035. HS.

Organism-specific databases

HPAiCAB010203.

Interactioni

Subunit structurei

Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MMP14P502812EBI-1033507,EBI-992788

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112933. 8 interactors.
IntActiP16035. 2 interactors.
STRINGi9606.ENSP00000262768.

Structurei

Secondary structure

1220
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi34 – 40Combined sources7
Beta strandi41 – 59Combined sources19
Beta strandi61 – 63Combined sources3
Beta strandi65 – 81Combined sources17
Beta strandi88 – 91Combined sources4
Helixi95 – 97Combined sources3
Turni104 – 107Combined sources4
Beta strandi109 – 118Combined sources10
Beta strandi121 – 123Combined sources3
Beta strandi130 – 132Combined sources3
Helixi133 – 135Combined sources3
Helixi138 – 143Combined sources6
Turni144 – 148Combined sources5
Helixi149 – 151Combined sources3
Beta strandi154 – 158Combined sources5
Beta strandi161 – 163Combined sources3
Beta strandi171 – 174Combined sources4
Helixi176 – 180Combined sources5
Beta strandi181 – 185Combined sources5
Helixi186 – 190Combined sources5
Beta strandi192 – 195Combined sources4
Beta strandi197 – 199Combined sources3
Beta strandi201 – 204Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BR9X-ray2.10A27-220[»]
1GXDX-ray3.10C/D27-220[»]
2TMPNMR-A27-153[»]
4ILWX-ray2.10A/B27-220[»]
ProteinModelPortaliP16035.
SMRiP16035.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP16035.

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.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP16035.
OMAiKMFKGPE.
OrthoDBiEOG091G0NIC.
PhylomeDBiP16035.
TreeFamiTF317409.

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.

P16035-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGAAARTLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV
60 70 80 90 100
SEKEVDSGND IYGNPIKRIQ YEIKQIKMFK GPEKDIEFIY TAPSSAVCGV
110 120 130 140 150
SLDVGGKKEY LIAGKAEGDG KMHITLCDFI VPWDTLSTTQ KKSLNHRYQM
160 170 180 190 200
GCECKITRCP MIPCYISSPD ECLWMDWVTE KNINGHQAKF FACIKRSDGS
210 220
CAWYRGAAPP KQEFLDIEDP
Length:220
Mass (Da):24,399
Last modified:November 1, 1990 - v2
Checksum:i603E5B1C9F94735D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti17 – 19LAT → P in AAC50729 (PubMed:8810321).Curated3
Sequence conflicti44 – 50VIRAKAV → GKESGDP (PubMed:8112602).Curated7
Sequence conflicti78M → K AA sequence (PubMed:2793861).Curated1
Sequence conflicti78M → K AA sequence (PubMed:1480041).Curated1
Sequence conflicti82P → I AA sequence (PubMed:2793861).Curated1
Sequence conflicti82P → I AA sequence (PubMed:1480041).Curated1
Sequence conflicti96A → V in CAA38400 (Ref. 5) Curated1
Sequence conflicti101S → E AA sequence (PubMed:2793861).Curated1
Sequence conflicti101S → E AA sequence (PubMed:1480041).Curated1
Sequence conflicti118Missing AA sequence (PubMed:2793861).Curated1
Sequence conflicti118Missing AA sequence (PubMed:1480041).Curated1
Sequence conflicti122M → R AA sequence (PubMed:2793861).Curated1
Sequence conflicti122M → R AA sequence (PubMed:1480041).Curated1
Sequence conflicti150M → Q AA sequence (PubMed:2793861).Curated1
Sequence conflicti150M → Q AA sequence (PubMed:1480041).Curated1
Sequence conflicti175M → T AA sequence (PubMed:2793861).Curated1
Sequence conflicti175M → T AA sequence (PubMed:1480041).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05593 mRNA. Translation: AAA61186.1.
S48568 mRNA. Translation: AAB19474.1.
U44385
, U44381, U44382, U44383 Genomic DNA. Translation: AAC50729.1.
M32304 mRNA. Translation: AAA59581.1.
BC052605 mRNA. Translation: AAH52605.1.
BC071586 mRNA. Translation: AAH71586.1.
X54533 mRNA. Translation: CAA38400.1.
S68860 Genomic DNA. Translation: AAD14025.1.
CCDSiCCDS11758.1.
PIRiA37128.
I53729.
RefSeqiNP_003246.1. NM_003255.4.
UniGeneiHs.633514.

Genome annotation databases

EnsembliENST00000262768; ENSP00000262768; ENSG00000035862.
GeneIDi7077.
KEGGihsa:7077.
UCSCiuc002jwf.4. human.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
J05593 mRNA. Translation: AAA61186.1.
S48568 mRNA. Translation: AAB19474.1.
U44385
, U44381, U44382, U44383 Genomic DNA. Translation: AAC50729.1.
M32304 mRNA. Translation: AAA59581.1.
BC052605 mRNA. Translation: AAH52605.1.
BC071586 mRNA. Translation: AAH71586.1.
X54533 mRNA. Translation: CAA38400.1.
S68860 Genomic DNA. Translation: AAD14025.1.
CCDSiCCDS11758.1.
PIRiA37128.
I53729.
RefSeqiNP_003246.1. NM_003255.4.
UniGeneiHs.633514.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BR9X-ray2.10A27-220[»]
1GXDX-ray3.10C/D27-220[»]
2TMPNMR-A27-153[»]
4ILWX-ray2.10A/B27-220[»]
ProteinModelPortaliP16035.
SMRiP16035.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112933. 8 interactors.
IntActiP16035. 2 interactors.
STRINGi9606.ENSP00000262768.

Protein family/group databases

MEROPSiI35.002.

PTM databases

iPTMnetiP16035.
PhosphoSitePlusiP16035.

Polymorphism and mutation databases

BioMutaiTIMP2.
DMDMi135854.

2D gel databases

DOSAC-COBS-2DPAGEP16035.

Proteomic databases

EPDiP16035.
MaxQBiP16035.
PaxDbiP16035.
PeptideAtlasiP16035.
PRIDEiP16035.
TopDownProteomicsiP16035.

Protocols and materials databases

DNASUi7077.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262768; ENSP00000262768; ENSG00000035862.
GeneIDi7077.
KEGGihsa:7077.
UCSCiuc002jwf.4. human.

Organism-specific databases

CTDi7077.
DisGeNETi7077.
GeneCardsiTIMP2.
HGNCiHGNC:11821. TIMP2.
HPAiCAB010203.
MIMi188825. gene.
neXtProtiNX_P16035.
OpenTargetsiENSG00000035862.
PharmGKBiPA36527.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP16035.
OMAiKMFKGPE.
OrthoDBiEOG091G0NIC.
PhylomeDBiP16035.
TreeFamiTF317409.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000035862-MONOMER.
ReactomeiR-HSA-1592389. Activation of Matrix Metalloproteinases.
R-HSA-6798695. Neutrophil degranulation.

Miscellaneous databases

ChiTaRSiTIMP2. human.
EvolutionaryTraceiP16035.
GeneWikiiTIMP2.
GenomeRNAii7077.
PROiP16035.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000035862.
CleanExiHS_TIMP2.
ExpressionAtlasiP16035. baseline and differential.
GenevisibleiP16035. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P16035
Secondary accession number(s): Q16121, Q93006, Q9UDF7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 1, 1990
Last modified: November 30, 2016
This is version 177 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.