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Protein

Metalloproteinase inhibitor 2

Gene

TIMP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 partnerCombined sources1 Publication1
Sitei40Involved in metalloproteinase-bindingCombined sources1 Publication1
Sitei61Involved in metalloproteinase-bindingCombined sources1 Publication1
Sitei67Involved in metalloproteinase-bindingCombined sources1 Publication1

GO - Molecular functioni

  • integrin binding Source: Ensembl
  • metalloendopeptidase inhibitor activity Source: GO_Central
  • peptidase inhibitor activity Source: UniProtKB
  • protease binding Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionMetalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-6798695 Neutrophil degranulation
SIGNORiP16035

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

EuPathDBiHostDB:ENSG00000035862.12
HGNCiHGNC:11821 TIMP2
MIMi188825 gene
neXtProtiNX_P16035

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi53263
TopDownProteomicsiP16035

2D gel databases

DOSAC-COBS-2DPAGEiP16035

PTM databases

iPTMnetiP16035
PhosphoSitePlusiP16035

Expressioni

Inductioni

Down-regulated by TGFB1.1 Publication

Gene expression databases

BgeeiENSG00000035862 Expressed in 231 organ(s), highest expression level in decidua
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, 11 interactors
IntActiP16035, 4 interactors
MINTiP16035
STRINGi9606.ENSP00000262768

Structurei

Secondary structure

1220
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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 – 30Involved in metalloproteinase-bindingCombined sources1 Publication4
Regioni95 – 96Involved in metalloproteinase-bindingCombined sources1 Publication2

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745 Eukaryota
ENOG41103NU LUCA
GeneTreeiENSGT00390000004555
HOGENOMiHOG000285981
HOVERGENiHBG068749
InParanoidiP16035
KOiK22583
OMAiPEECLWT
OrthoDBiEOG091G0NIC
PhylomeDBiP16035
TreeFamiTF317409

Family and domain databases

Gene3Di3.90.370.10, 1 hit
InterProiView protein in InterPro
IPR001134 Netrin_domain
IPR001820 TIMP
IPR008993 TIMP-like_OB-fold
IPR015613 TIMP2
IPR027465 TIMP_C
IPR030490 TIMP_CS
PANTHERiPTHR11844 PTHR11844, 1 hit
PTHR11844:SF24 PTHR11844:SF24, 1 hit
PfamiView protein in Pfam
PF00965 TIMP, 1 hit
SMARTiView protein in SMART
SM00206 NTR, 1 hit
SUPFAMiSSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS50189 NTR, 1 hit
PS00288 TIMP, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DFW2B4DFW2_HUMAN
TIMP metallopeptidase inhibitor 2, ...
TIMP2 hCG_95573
143Annotation score:
K7EIX4K7EIX4_HUMAN
Metalloproteinase inhibitor 2
TIMP2
109Annotation score:

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

Similar proteinsi

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, 11 interactors
IntActiP16035, 4 interactors
MINTiP16035
STRINGi9606.ENSP00000262768

Protein family/group databases

MEROPSiI35.002

PTM databases

iPTMnetiP16035
PhosphoSitePlusiP16035

Polymorphism and mutation databases

BioMutaiTIMP2
DMDMi135854

2D gel databases

DOSAC-COBS-2DPAGEiP16035

Proteomic databases

EPDiP16035
MaxQBiP16035
PaxDbiP16035
PeptideAtlasiP16035
PRIDEiP16035
ProteomicsDBi53263
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
EuPathDBiHostDB:ENSG00000035862.12
GeneCardsiTIMP2
HGNCiHGNC:11821 TIMP2
HPAiCAB010203
MIMi188825 gene
neXtProtiNX_P16035
OpenTargetsiENSG00000035862
PharmGKBiPA36527
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4745 Eukaryota
ENOG41103NU LUCA
GeneTreeiENSGT00390000004555
HOGENOMiHOG000285981
HOVERGENiHBG068749
InParanoidiP16035
KOiK22583
OMAiPEECLWT
OrthoDBiEOG091G0NIC
PhylomeDBiP16035
TreeFamiTF317409

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-6798695 Neutrophil degranulation
SIGNORiP16035

Miscellaneous databases

ChiTaRSiTIMP2 human
EvolutionaryTraceiP16035
GeneWikiiTIMP2
GenomeRNAii7077
PROiPR:P16035
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000035862 Expressed in 231 organ(s), highest expression level in decidua
CleanExiHS_TIMP2
ExpressionAtlasiP16035 baseline and differential
GenevisibleiP16035 HS

Family and domain databases

Gene3Di3.90.370.10, 1 hit
InterProiView protein in InterPro
IPR001134 Netrin_domain
IPR001820 TIMP
IPR008993 TIMP-like_OB-fold
IPR015613 TIMP2
IPR027465 TIMP_C
IPR030490 TIMP_CS
PANTHERiPTHR11844 PTHR11844, 1 hit
PTHR11844:SF24 PTHR11844:SF24, 1 hit
PfamiView protein in Pfam
PF00965 TIMP, 1 hit
SMARTiView protein in SMART
SM00206 NTR, 1 hit
SUPFAMiSSF50242 SSF50242, 1 hit
PROSITEiView protein in PROSITE
PS50189 NTR, 1 hit
PS00288 TIMP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTIMP2_HUMAN
AccessioniPrimary (citable) accession number: P16035
Secondary accession number(s): Q16121, Q93006, Q9UDF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 1, 1990
Last modified: November 7, 2018
This is version 192 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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