TIMP4_HUMAN
ID TIMP4_HUMAN Reviewed; 224 AA.
AC Q99727; B2R7K6;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=Metalloproteinase inhibitor 4;
DE AltName: Full=Tissue inhibitor of metalloproteinases 4;
DE Short=TIMP-4;
DE Flags: Precursor;
GN Name=TIMP4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RX PubMed=8939999; DOI=10.1074/jbc.271.48.30375;
RA Greene J., Wang M., Liu Y.E., Raymond L.A., Rosen C., Shi Y.E.;
RT "Molecular cloning and characterization of human tissue inhibitor of
RT metalloproteinase 4.";
RL J. Biol. Chem. 271:30375-30380(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9693046; DOI=10.1006/geno.1998.5362;
RA Olson T.M., Hirohata S., Ye J., Leco K., Seldin M.F., Apte S.S.;
RT "Cloning of the human tissue inhibitor of metalloproteinase-4 gene (TIMP4)
RT and localization of the TIMP4 and timp4 genes to human chromosome 3p25 and
RT mouse chromosome 6, respectively.";
RL Genomics 51:148-151(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Complexes with metalloproteinases (such as collagenases) and
CC irreversibly inactivates them by binding to their catalytic zinc
CC cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP-9.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Abundant in heart and present at low levels in many
CC other tissues.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; U76456; AAB40391.1; -; mRNA.
DR EMBL; AF057532; AAC34422.1; -; Genomic_DNA.
DR EMBL; AF057528; AAC34422.1; JOINED; Genomic_DNA.
DR EMBL; AF057529; AAC34422.1; JOINED; Genomic_DNA.
DR EMBL; AF057530; AAC34422.1; JOINED; Genomic_DNA.
DR EMBL; AF057531; AAC34422.1; JOINED; Genomic_DNA.
DR EMBL; BT019627; AAV38433.1; -; mRNA.
DR EMBL; AK313018; BAG35853.1; -; mRNA.
DR EMBL; CH471055; EAW64122.1; -; Genomic_DNA.
DR EMBL; BC010553; AAH10553.1; -; mRNA.
DR CCDS; CCDS2608.1; -.
DR RefSeq; NP_003247.1; NM_003256.3.
DR AlphaFoldDB; Q99727; -.
DR SMR; Q99727; -.
DR BioGRID; 112935; 21.
DR STRING; 9606.ENSP00000287814; -.
DR MEROPS; I35.004; -.
DR iPTMnet; Q99727; -.
DR PhosphoSitePlus; Q99727; -.
DR BioMuta; TIMP4; -.
DR DMDM; 3915135; -.
DR MassIVE; Q99727; -.
DR PaxDb; Q99727; -.
DR PeptideAtlas; Q99727; -.
DR PRIDE; Q99727; -.
DR ProteomicsDB; 78441; -.
DR Antibodypedia; 3455; 593 antibodies from 36 providers.
DR DNASU; 7079; -.
DR Ensembl; ENST00000287814.5; ENSP00000287814.4; ENSG00000157150.5.
DR GeneID; 7079; -.
DR KEGG; hsa:7079; -.
DR MANE-Select; ENST00000287814.5; ENSP00000287814.4; NM_003256.4; NP_003247.1.
DR UCSC; uc003bwo.4; human.
DR CTD; 7079; -.
DR DisGeNET; 7079; -.
DR GeneCards; TIMP4; -.
DR HGNC; HGNC:11823; TIMP4.
DR HPA; ENSG00000157150; Tissue enhanced (adipose tissue, breast).
DR MIM; 601915; gene.
DR neXtProt; NX_Q99727; -.
DR OpenTargets; ENSG00000157150; -.
DR PharmGKB; PA36529; -.
DR VEuPathDB; HostDB:ENSG00000157150; -.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000159798; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; Q99727; -.
DR OMA; EPWDNLS; -.
DR OrthoDB; 799740at2759; -.
DR PhylomeDB; Q99727; -.
DR TreeFam; TF317409; -.
DR PathwayCommons; Q99727; -.
DR SignaLink; Q99727; -.
DR BioGRID-ORCS; 7079; 8 hits in 1068 CRISPR screens.
DR ChiTaRS; TIMP4; human.
DR GeneWiki; TIMP4; -.
DR GenomeRNAi; 7079; -.
DR Pharos; Q99727; Tbio.
DR PRO; PR:Q99727; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q99727; protein.
DR Bgee; ENSG00000157150; Expressed in adipose tissue of abdominal region and 152 other tissues.
DR Genevisible; Q99727; HS.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030017; C:sarcomere; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0051045; P:negative regulation of membrane protein ectodomain proteolysis; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0042698; P:ovulation cycle; IEA:Ensembl.
DR GO; GO:0034097; P:response to cytokine; IBA:GO_Central.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 3.90.370.10; -; 1.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR001820; TIMP.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR InterPro; IPR015614; TIMP4.
DR InterPro; IPR027465; TIMP_C.
DR InterPro; IPR030490; TIMP_CS.
DR PANTHER; PTHR11844; PTHR11844; 1.
DR PANTHER; PTHR11844:SF26; PTHR11844:SF26; 1.
DR Pfam; PF00965; TIMP; 1.
DR SMART; SM00206; NTR; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR PROSITE; PS50189; NTR; 1.
DR PROSITE; PS00288; TIMP; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Metal-binding; Metalloenzyme inhibitor;
KW Metalloprotease inhibitor; Protease inhibitor; Reference proteome;
KW Secreted; Signal; Zinc.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..224
FT /note="Metalloproteinase inhibitor 4"
FT /id="PRO_0000034349"
FT DOMAIN 30..156
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 30..33
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT REGION 99..100
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT BINDING 30
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with metalloproteinase partner"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT SITE 69
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT DISULFID 30..102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 32..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 42..156
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 158..205
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 163..168
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 176..197
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
SQ SEQUENCE 224 AA; 25503 MW; 39C7187D78D99442 CRC64;
MPGSPRPAPS WVLLLRLLAL LRPPGLGEAC SCAPAHPQQH ICHSALVIRA KISSEKVVPA
SADPADTEKM LRYEIKQIKM FKGFEKVKDV QYIYTPFDSS LCGVKLEANS QKQYLLTGQV
LSDGKVFIHL CNYIEPWEDL SLVQRESLNH HYHLNCGCQI TTCYTVPCTI SAPNECLWTD
WLLERKLYGY QAQHYVCMKH VDGTCSWYRG HLPLRKEFVD IVQP
