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Protein

Metalloproteinase inhibitor 3

Gene

TIMP3

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. 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 partnerCombined sources1 Publication1
Sitei85Involved in metalloproteinase-bindingCombined sources1 Publication1

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

Keywordsi

Molecular functionMetalloenzyme inhibitor, Metalloprotease inhibitor, Protease inhibitor
Biological processSensory transduction, Vision
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation
SIGNORiP35625

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

EuPathDBiHostDB:ENSG00000100234.11
HGNCiHGNC:11822 TIMP3
MIMi188826 gene
neXtProtiNX_P35625

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

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 dbSNP:rs137853300EnsemblClinVar.1
Natural variantiVAR_008290189G → C in SFD. 1 PublicationCorresponds to variant dbSNP:rs137853301EnsemblClinVar.1
Natural variantiVAR_010901190G → C in SFD. 1 Publication1
Natural variantiVAR_007509191Y → C in SFD. 2 PublicationsCorresponds to variant dbSNP:rs137853299EnsemblClinVar.1
Natural variantiVAR_007510204S → C in SFD. 1 PublicationCorresponds to variant dbSNP:rs137853298EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

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

Chemistry databases

DrugBankiDB05383 pimagedine HCl

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 annotationCombined sources1 Publication
Disulfide bondi26 ↔ 118PROSITE-ProRule annotationCombined sources1 Publication
Disulfide bondi36 ↔ 143PROSITE-ProRule annotationCombined sources1 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
ProteomicsDBi55117

PTM databases

iPTMnetiP35625
PhosphoSitePlusiP35625

Expressioni

Gene expression databases

BgeeiENSG00000100234
CleanExiHS_TIMP3
GenevisibleiP35625 HS

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, 25 interactors
IntActiP35625, 3 interactors
MINTiP35625
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 – 27Involved in metalloproteinase-bindingCombined sources1 Publication4
Regioni88 – 89Involved in metalloproteinase-bindingCombined sources1 Publication2
Regioni105 – 188Mediates interaction with EFEMP11 PublicationAdd BLAST84

Sequence similaritiesi

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, 2 hits
InterProiView protein in InterPro
IPR001134 Netrin_domain
IPR001820 TIMP
IPR008993 TIMP-like_OB-fold
IPR015612 TIMP3
IPR027465 TIMP_C
IPR030490 TIMP_CS
PANTHERiPTHR11844 PTHR11844, 1 hit
PTHR11844:SF22 PTHR11844:SF22, 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

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 dbSNP:rs137853300EnsemblClinVar.1
Natural variantiVAR_008290189G → C in SFD. 1 PublicationCorresponds to variant dbSNP:rs137853301EnsemblClinVar.1
Natural variantiVAR_010901190G → C in SFD. 1 Publication1
Natural variantiVAR_007509191Y → C in SFD. 2 PublicationsCorresponds to variant dbSNP:rs137853299EnsemblClinVar.1
Natural variantiVAR_007510204S → C in SFD. 1 PublicationCorresponds to variant dbSNP:rs137853298EnsemblClinVar.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 Genomic DNA No translation available.
Z98256 Genomic DNA No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiTIMP3_HUMAN
AccessioniPrimary (citable) accession number: P35625
Secondary accession number(s): B2RBY9
, Q5THV4, Q9UC74, Q9UGS2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: February 1, 1995
Last modified: June 20, 2018
This is version 185 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. 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

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