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Protein

Metalloproteinase inhibitor 4

Gene

TIMP4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 and MMP-9.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi30Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity1
Sitei69Involved in metalloproteinase-bindingBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Protein family/group databases

MEROPSiI35.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Metalloproteinase inhibitor 4
Alternative name(s):
Tissue inhibitor of metalloproteinases 4
Short name:
TIMP-4
Gene namesi
Name:TIMP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000157150.4.
HGNCiHGNC:11823. TIMP4.

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

DisGeNETi7079.
OpenTargetsiENSG00000157150.
PharmGKBiPA36529.

Polymorphism and mutation databases

BioMutaiTIMP4.
DMDMi3915135.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000003434930 – 224Metalloproteinase inhibitor 4Add BLAST195

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 102PROSITE-ProRule annotation
Disulfide bondi32 ↔ 131PROSITE-ProRule annotation
Disulfide bondi42 ↔ 156PROSITE-ProRule annotation
Disulfide bondi158 ↔ 205PROSITE-ProRule annotation
Disulfide bondi163 ↔ 168PROSITE-ProRule annotation
Disulfide bondi176 ↔ 197PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ99727.
PaxDbiQ99727.
PeptideAtlasiQ99727.
PRIDEiQ99727.

PTM databases

iPTMnetiQ99727.
PhosphoSitePlusiQ99727.

Expressioni

Tissue specificityi

Abundant in heart and present at low levels in many other tissues.

Gene expression databases

BgeeiENSG00000157150.
CleanExiHS_TIMP4.
GenevisibleiQ99727. HS.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112935. 4 interactors.
STRINGi9606.ENSP00000287814.

Structurei

3D structure databases

ProteinModelPortaliQ99727.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 156NTRPROSITE-ProRule annotationAdd BLAST127

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni30 – 33Involved in metalloproteinase-bindingBy similarity4
Regioni99 – 100Involved in metalloproteinase-bindingBy similarity2

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiQ99727.
OMAiTISAPNE.
OrthoDBiEOG091G0NIC.
PhylomeDBiQ99727.
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.
IPR015614. TIMP4.
IPR027465. TIMP_C.
IPR030490. TIMP_CS.
PANTHERiPTHR11844. PTHR11844. 1 hit.
PTHR11844:SF26. PTHR11844:SF26. 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.

Q99727-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGSPRPAPS WVLLLRLLAL LRPPGLGEAC SCAPAHPQQH ICHSALVIRA
60 70 80 90 100
KISSEKVVPA SADPADTEKM LRYEIKQIKM FKGFEKVKDV QYIYTPFDSS
110 120 130 140 150
LCGVKLEANS QKQYLLTGQV LSDGKVFIHL CNYIEPWEDL SLVQRESLNH
160 170 180 190 200
HYHLNCGCQI TTCYTVPCTI SAPNECLWTD WLLERKLYGY QAQHYVCMKH
210 220
VDGTCSWYRG HLPLRKEFVD IVQP
Length:224
Mass (Da):25,503
Last modified:May 1, 1997 - v1
Checksum:i39C7187D78D99442
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U76456 mRNA. Translation: AAB40391.1.
AF057532
, AF057528, AF057529, AF057530, AF057531 Genomic DNA. Translation: AAC34422.1.
BT019627 mRNA. Translation: AAV38433.1.
AK313018 mRNA. Translation: BAG35853.1.
CH471055 Genomic DNA. Translation: EAW64122.1.
BC010553 mRNA. Translation: AAH10553.1.
CCDSiCCDS2608.1.
RefSeqiNP_003247.1. NM_003256.3.
UniGeneiHs.591665.

Genome annotation databases

EnsembliENST00000287814; ENSP00000287814; ENSG00000157150.
GeneIDi7079.
KEGGihsa:7079.
UCSCiuc003bwo.4. human.

Similar proteinsi

Entry informationi

Entry nameiTIMP4_HUMAN
AccessioniPrimary (citable) accession number: Q99727
Secondary accession number(s): B2R7K6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 1, 1997
Last modified: October 25, 2017
This is version 145 of the entry and version 1 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: 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. SIMILARITY comments
    Index of protein domains and families