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Protein

Metalloproteinase inhibitor 3

Gene

TIMP3

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. May form part of a tissue-specific acute response to remodeling stimuli. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, MMP-14 and MMP-15.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi24Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner1

GO - Molecular functioni

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

GO - Biological processi

  • cellular response to organic substance Source: Ensembl
  • negative regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • negative regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
  • negative regulation of metalloendopeptidase activity Source: BHF-UCL
  • platelet degranulation Source: Reactome
  • positive regulation of TRAIL-activated apoptotic signaling pathway Source: BHF-UCL
  • response to organic substance Source: GO_Central
  • visual perception Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Metalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor

Keywords - Biological processi

Sensory transduction, Vision

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100234-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.

Protein family/group databases

MEROPSiI35.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 3
Alternative name(s):
Protein MIG-5
Tissue inhibitor of metalloproteinases 3
Short name:
TIMP-3
Gene namesi
Name:TIMP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:11822. TIMP3.

Subcellular locationi

GO - Cellular componenti

  • basement membrane Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: GO_Central
  • nucleus Source: UniProtKB
  • platelet dense granule lumen Source: Reactome
  • proteinaceous extracellular matrix Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Sorsby fundus dystrophy (SFD)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare autosomal dominant macular disorder with an age of onset in the fourth decade. It is characterized by loss of central vision from subretinal neovascularization and atrophy of the ocular tissues. Generally, macular disciform degeneration develops in the patients eye within 6 months to 6 years.
See also OMIM:136900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007508179S → C in SFD. 1 PublicationCorresponds to variant rs137853300dbSNPEnsembl.1
Natural variantiVAR_008290189G → C in SFD. 1 PublicationCorresponds to variant rs137853301dbSNPEnsembl.1
Natural variantiVAR_010901190G → C in SFD. 1 Publication1
Natural variantiVAR_007509191Y → C in SFD. 2 PublicationsCorresponds to variant rs137853299dbSNPEnsembl.1
Natural variantiVAR_007510204S → C in SFD. 1 PublicationCorresponds to variant rs137853298dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7078.
MalaCardsiTIMP3.
MIMi136900. phenotype.
OpenTargetsiENSG00000100234.
Orphaneti59181. Sorsby's fundus dystrophy.
PharmGKBiPA36528.

Polymorphism and mutation databases

BioMutaiTIMP3.
DMDMi730948.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000003434124 – 211Metalloproteinase inhibitor 3Add BLAST188

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi24 ↔ 91PROSITE-ProRule annotation1 Publication
Disulfide bondi26 ↔ 118PROSITE-ProRule annotation1 Publication
Disulfide bondi36 ↔ 143PROSITE-ProRule annotation1 Publication
Disulfide bondi145 ↔ 192PROSITE-ProRule annotation
Disulfide bondi150 ↔ 155PROSITE-ProRule annotation
Disulfide bondi163 ↔ 184PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP35625.
PaxDbiP35625.
PeptideAtlasiP35625.
PRIDEiP35625.

PTM databases

iPTMnetiP35625.
PhosphoSitePlusiP35625.

Expressioni

Gene expression databases

BgeeiENSG00000100234.
CleanExiHS_TIMP3.
GenevisibleiP35625. HS.

Organism-specific databases

HPAiCAB022187.

Interactioni

Subunit structurei

Interacts with EFEMP1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AGTR2P500527EBI-1748085,EBI-1748067

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112934. 20 interactors.
IntActiP35625. 3 interactors.
STRINGi9606.ENSP00000266085.

Structurei

Secondary structure

1211
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 37Combined sources7
Beta strandi39 – 42Combined sources4
Beta strandi45 – 52Combined sources8
Beta strandi55 – 57Combined sources3
Beta strandi59 – 65Combined sources7
Beta strandi69 – 71Combined sources3
Turni73 – 75Combined sources3
Beta strandi76 – 78Combined sources3
Beta strandi81 – 86Combined sources6
Helixi88 – 90Combined sources3
Beta strandi102 – 108Combined sources7
Turni124 – 126Combined sources3
Helixi129 – 136Combined sources8
Turni137 – 140Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3CKIX-ray2.30B24-144[»]
ProteinModelPortaliP35625.
SMRiP35625.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP35625.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 143NTRPROSITE-ProRule annotationAdd BLAST120

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni24 – 28Involved in metalloproteinase-binding5
Regioni88 – 89Involved in metalloproteinase-binding2
Regioni105 – 188Mediates interaction with EFEMP11 PublicationAdd BLAST84

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP35625.
KOiK16866.
OMAiCHYLPCF.
OrthoDBiEOG091G0NIC.
PhylomeDBiP35625.
TreeFamiTF317409.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015612. TIMP3.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF22. PTHR11844:SF22. 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.

P35625-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTPWLGLIVL LGSWSLGDWG AEACTCSPSH PQDAFCNSDI VIRAKVVGKK
60 70 80 90 100
LVKEGPFGTL VYTIKQMKMY RGFTKMPHVQ YIHTEASESL CGLKLEVNKY
110 120 130 140 150
QYLLTGRVYD GKMYTGLCNF VERWDQLTLS QRKGLNYRYH LGCNCKIKSC
160 170 180 190 200
YYLPCFVTSK NECLWTDMLS NFGYPGYQSK HYACIRQKGG YCSWYRGWAP
210
PDKSIINATD P
Length:211
Mass (Da):24,145
Last modified:February 1, 1995 - v2
Checksum:i15CF831028BABF7A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti16 – 23LGDWGAEA → WGTGAPR in CAA82918 (PubMed:8034652).Curated8
Sequence conflicti21 – 22AE → R in AAA21815 (PubMed:8188246).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_007508179S → C in SFD. 1 PublicationCorresponds to variant rs137853300dbSNPEnsembl.1
Natural variantiVAR_008290189G → C in SFD. 1 PublicationCorresponds to variant rs137853301dbSNPEnsembl.1
Natural variantiVAR_010901190G → C in SFD. 1 Publication1
Natural variantiVAR_007509191Y → C in SFD. 2 PublicationsCorresponds to variant rs137853299dbSNPEnsembl.1
Natural variantiVAR_007510204S → C in SFD. 1 PublicationCorresponds to variant rs137853298dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76227 mRNA. Translation: CAA53813.1.
S78453 mRNA. Translation: AAB34532.1.
U14394 mRNA. Translation: AAB60373.1.
U02571 mRNA. Translation: AAA17672.1.
Z30183 Genomic DNA. Translation: CAA82918.1.
U33114
, U33110, U33111, U33112, U33113 Genomic DNA. Translation: AAC50393.1.
U67195 mRNA. Translation: AAB07547.1.
CR456593 mRNA. Translation: CAG30479.1.
BT006848 mRNA. Translation: AAP35494.1.
AK314871 mRNA. Translation: BAG37386.1.
AL023282, Z98256 Genomic DNA. Translation: CAI17996.1.
Z98256, AL023282 Genomic DNA. Translation: CAI20115.1.
CH471095 Genomic DNA. Translation: EAW60038.1.
BC014277 mRNA. Translation: AAH14277.1.
L15078 mRNA. Translation: AAA21815.1.
U38955
, U38952, U38953, U38954 Genomic DNA. Translation: AAB17602.1.
CCDSiCCDS13911.1.
PIRiS45317.
RefSeqiNP_000353.1. NM_000362.4.
UniGeneiHs.644633.

Genome annotation databases

EnsembliENST00000266085; ENSP00000266085; ENSG00000100234.
GeneIDi7078.
KEGGihsa:7078.
UCSCiuc003anb.4. human.

Cross-referencesi

Web resourcesi

Mutations of the TIMP3 gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X76227 mRNA. Translation: CAA53813.1.
S78453 mRNA. Translation: AAB34532.1.
U14394 mRNA. Translation: AAB60373.1.
U02571 mRNA. Translation: AAA17672.1.
Z30183 Genomic DNA. Translation: CAA82918.1.
U33114
, U33110, U33111, U33112, U33113 Genomic DNA. Translation: AAC50393.1.
U67195 mRNA. Translation: AAB07547.1.
CR456593 mRNA. Translation: CAG30479.1.
BT006848 mRNA. Translation: AAP35494.1.
AK314871 mRNA. Translation: BAG37386.1.
AL023282, Z98256 Genomic DNA. Translation: CAI17996.1.
Z98256, AL023282 Genomic DNA. Translation: CAI20115.1.
CH471095 Genomic DNA. Translation: EAW60038.1.
BC014277 mRNA. Translation: AAH14277.1.
L15078 mRNA. Translation: AAA21815.1.
U38955
, U38952, U38953, U38954 Genomic DNA. Translation: AAB17602.1.
CCDSiCCDS13911.1.
PIRiS45317.
RefSeqiNP_000353.1. NM_000362.4.
UniGeneiHs.644633.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3CKIX-ray2.30B24-144[»]
ProteinModelPortaliP35625.
SMRiP35625.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112934. 20 interactors.
IntActiP35625. 3 interactors.
STRINGi9606.ENSP00000266085.

Protein family/group databases

MEROPSiI35.003.

PTM databases

iPTMnetiP35625.
PhosphoSitePlusiP35625.

Polymorphism and mutation databases

BioMutaiTIMP3.
DMDMi730948.

Proteomic databases

MaxQBiP35625.
PaxDbiP35625.
PeptideAtlasiP35625.
PRIDEiP35625.

Protocols and materials databases

DNASUi7078.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266085; ENSP00000266085; ENSG00000100234.
GeneIDi7078.
KEGGihsa:7078.
UCSCiuc003anb.4. human.

Organism-specific databases

CTDi7078.
DisGeNETi7078.
GeneCardsiTIMP3.
HGNCiHGNC:11822. TIMP3.
HPAiCAB022187.
MalaCardsiTIMP3.
MIMi136900. phenotype.
188826. gene.
neXtProtiNX_P35625.
OpenTargetsiENSG00000100234.
Orphaneti59181. Sorsby's fundus dystrophy.
PharmGKBiPA36528.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiP35625.
KOiK16866.
OMAiCHYLPCF.
OrthoDBiEOG091G0NIC.
PhylomeDBiP35625.
TreeFamiTF317409.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000100234-MONOMER.
ReactomeiR-HSA-114608. Platelet degranulation.

Miscellaneous databases

EvolutionaryTraceiP35625.
GeneWikiiTIMP3.
GenomeRNAii7078.
PROiP35625.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100234.
CleanExiHS_TIMP3.
GenevisibleiP35625. HS.

Family and domain databases

Gene3Di3.90.370.10. 1 hit.
InterProiIPR001134. Netrin_domain.
IPR001820. TIMP.
IPR008993. TIMP-like_OB-fold.
IPR015612. TIMP3.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
[Graphical view]
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF22. PTHR11844:SF22. 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 nameiTIMP3_HUMAN
AccessioniPrimary (citable) accession number: P35625
Secondary accession number(s): B2RBY9
, Q5THV4, Q9UC74, Q9UGS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 1, 1995
Last modified: November 2, 2016
This is version 174 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 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.