TIMP4_RAT
ID TIMP4_RAT Reviewed; 224 AA.
AC P81556;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 138.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9503367; DOI=10.1016/s0945-053x(98)90005-1;
RA Wu I., Moses M.A.;
RT "Molecular cloning and expression analysis of the cDNA encoding rat tissue
RT inhibitor of metalloproteinase-4.";
RL Matrix Biol. 16:339-342(1998).
CC -!- FUNCTION: Complexes with metalloproteinases (such as collagenases) and
CC irreversibly inactivates them by binding to their catalytic zinc
CC cofactor.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in retina, smooth muscle, skin, pancreas,
CC skeletal muscle, heart, brain, lung, kidney and testis. Not found in
CC cartilage, spleen and liver.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; AABR03031919; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001102863.1; NM_001109393.1.
DR AlphaFoldDB; P81556; -.
DR SMR; P81556; -.
DR STRING; 10116.ENSRNOP00000010748; -.
DR MEROPS; I35.004; -.
DR PaxDb; P81556; -.
DR GeneID; 680130; -.
DR KEGG; rno:680130; -.
DR UCSC; RGD:69077; rat.
DR CTD; 7079; -.
DR RGD; 69077; Timp4.
DR VEuPathDB; HostDB:ENSRNOG00000007955; -.
DR eggNOG; KOG4745; Eukaryota.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P81556; -.
DR OMA; EPWDNLS; -.
DR OrthoDB; 1122531at2759; -.
DR PhylomeDB; P81556; -.
DR TreeFam; TF317409; -.
DR PRO; PR:P81556; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000007955; Expressed in cerebellum and 16 other tissues.
DR Genevisible; P81556; RN.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0030017; C:sarcomere; IDA:RGD.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0002020; F:protease binding; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IEP:RGD.
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; ISO:RGD.
DR GO; GO:0042698; P:ovulation cycle; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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_0000034351"
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"
FT CONFLICT 85
FT /note="E -> G (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="S -> T (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 180
FT /note="D -> N (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="K -> M (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 224 AA; 25723 MW; AAAF44DE30F57A8B CRC64;
MPWSPLAALS WALVLRLLAL LWPPGRGEAC SCAPAHPQQH VCHSALVIRA KISSEKVVPA
SEDPADTQKM IRYEIKQIKM FKGFEKAKDI QYVYTPFDSS LCGVKLETNS QKQYLLTGQI
LSDGKVFIHL CNYIEPWEDL SLVQRESLNH HYHQNCGCQI TTCYAVPCTI SAPDECLWTD
WLLERKLYGY QAQHYVCMKH VDGICSWYRG HLHLRKEYVD IVQP