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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi30 – 301Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partnerBy similarity

GO - Molecular functioni

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

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

HGNCiHGNC:11823. TIMP4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA36529.

Polymorphism and mutation databases

BioMutaiTIMP4.
DMDMi3915135.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929Sequence analysisAdd
BLAST
Chaini30 – 224195Metalloproteinase inhibitor 4PRO_0000034349Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
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

PaxDbiQ99727.
PRIDEiQ99727.

PTM databases

iPTMnetiQ99727.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ99727.
CleanExiHS_TIMP4.
GenevisibleiQ99727. HS.

Organism-specific databases

HPAiCAB002771.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112935. 1 interaction.
STRINGi9606.ENSP00000287814.

Structurei

3D structure databases

ProteinModelPortaliQ99727.
SMRiQ99727. Positions 30-210.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 156127NTRPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 345Involved in metalloproteinase-bindingBy similarity
Regioni99 – 1002Involved in metalloproteinase-bindingBy similarity

Sequence similaritiesi

Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiQ99727.
OMAiTISAPNE.
OrthoDBiEOG79GT74.
PhylomeDBiQ99727.
TreeFamiTF317409.

Family and domain databases

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

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ99727.
SMRiQ99727. Positions 30-210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112935. 1 interaction.
STRINGi9606.ENSP00000287814.

Protein family/group databases

MEROPSiI35.004.

PTM databases

iPTMnetiQ99727.

Polymorphism and mutation databases

BioMutaiTIMP4.
DMDMi3915135.

Proteomic databases

PaxDbiQ99727.
PRIDEiQ99727.

Protocols and materials databases

DNASUi7079.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7079.
GeneCardsiTIMP4.
HGNCiHGNC:11823. TIMP4.
HPAiCAB002771.
MIMi601915. gene.
neXtProtiNX_Q99727.
PharmGKBiPA36529.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4745. Eukaryota.
ENOG41103NU. LUCA.
GeneTreeiENSGT00390000004555.
HOGENOMiHOG000285981.
HOVERGENiHBG068749.
InParanoidiQ99727.
OMAiTISAPNE.
OrthoDBiEOG79GT74.
PhylomeDBiQ99727.
TreeFamiTF317409.

Miscellaneous databases

GeneWikiiTIMP4.
GenomeRNAii7079.
NextBioi27689.
PROiQ99727.
SOURCEiSearch...

Gene expression databases

BgeeiQ99727.
CleanExiHS_TIMP4.
GenevisibleiQ99727. HS.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4."
    Greene J., Wang M., Liu Y.E., Raymond L.A., Rosen C., Shi Y.E.
    J. Biol. Chem. 271:30375-30380(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Heart.
  2. "Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4) and localization of the TIMP4 and timp4 genes to human chromosome 3p25 and mouse chromosome 6, respectively."
    Olson T.M., Hirohata S., Ye J., Leco K., Seldin M.F., Apte S.S.
    Genomics 51:148-151(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Cerebellum.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.

Entry informationi

Entry nameiTIMP4_HUMAN
AccessioniPrimary (citable) accession number: Q99727
Secondary accession number(s): B2R7K6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: May 1, 1997
Last modified: March 16, 2016
This is version 133 of the entry and version 1 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

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

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.