TIMP2_RAT
ID TIMP2_RAT Reviewed; 220 AA.
AC P30121; Q546J4;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 3.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Metalloproteinase inhibitor 2;
DE AltName: Full=Tissue inhibitor of metalloproteinases 2;
DE Short=TIMP-2;
DE Flags: Precursor;
GN Name=Timp2; Synonyms=Timp-2;
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 [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Bone;
RX PubMed=8203893; DOI=10.1006/abbi.1994.1243;
RA Cook T.F., Burke J.S., Bergman K.D., Quinn C.O., Jeffrey J.J.,
RA Partridge N.C.;
RT "Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in
RT osteoblastic cells.";
RL Arch. Biochem. Biophys. 311:313-320(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RA Gibbons K.L., O'Grady R.L., Piper A.A.;
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8050496; DOI=10.1006/excr.1994.1215;
RA Santoro M., Battaglia C., Zhang L., Carlomagno F., Martelli M.L.,
RA Salvatore D., Fusco A.;
RT "Cloning of the rat tissue inhibitor of metalloproteinases type 2 (TIMP-2)
RT gene: analysis of its expression in normal and transformed thyroid cells.";
RL Exp. Cell Res. 213:398-403(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8792217;
RA Grima J., Calcagno K., Cheng C.Y.;
RT "Purification, cDNA cloning, and developmental changes in the steady-state
RT mRNA level of rat testicular tissue inhibitor of metalloproteases-2 (TIMP-
RT 2).";
RL J. Androl. 17:263-275(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Heart;
RX PubMed=11684074; DOI=10.1016/s0008-6363(01)00398-4;
RA Briest W., Hoelzl A., Rassler B., Deten A., Leicht M., Baba H.A.,
RA Zimmer H.G.;
RT "Cardiac remodeling after long term norepinephrine treatment in rats.";
RL Cardiovasc. Res. 52:265-273(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
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).
RN [7]
RP PROTEIN SEQUENCE OF 27-48.
RX PubMed=1309971; DOI=10.1016/0003-9861(92)90009-l;
RA Roswit W.T., McCourt D.W., Partridge N.C., Jeffrey J.J.;
RT "Purification and sequence analysis of two rat tissue inhibitors of
RT metalloproteinases.";
RL Arch. Biochem. Biophys. 292:402-410(1992).
CC -!- FUNCTION: Complexes with metalloproteinases (such as collagenases) and
CC irreversibly inactivates them by binding to their catalytic zinc
CC cofactor.
CC -!- SUBUNIT: Interacts (via the C-terminal) with MMP2 (via the C-terminal
CC PEX domain); the interaction inhibits the MMP2 activity. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: The activity of TIMP2 is dependent on the presence of disulfide
CC bonds.
CC -!- SIMILARITY: Belongs to the protease inhibitor I35 (TIMP) family.
CC {ECO:0000305}.
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DR EMBL; U14526; AAA21553.1; -; mRNA.
DR EMBL; L31884; AAA84581.1; -; mRNA.
DR EMBL; S72594; AAC60687.1; -; mRNA.
DR EMBL; S82718; AAB49507.1; -; mRNA.
DR EMBL; AJ409332; CAC35060.1; -; mRNA.
DR EMBL; BC084714; AAH84714.1; -; mRNA.
DR PIR; S45683; S45683.
DR RefSeq; NP_068824.1; NM_021989.2.
DR AlphaFoldDB; P30121; -.
DR BMRB; P30121; -.
DR SMR; P30121; -.
DR CORUM; P30121; -.
DR STRING; 10116.ENSRNOP00000004290; -.
DR MEROPS; I35.002; -.
DR PhosphoSitePlus; P30121; -.
DR PaxDb; P30121; -.
DR PRIDE; P30121; -.
DR Ensembl; ENSRNOT00000004290; ENSRNOP00000004290; ENSRNOG00000033143.
DR GeneID; 29543; -.
DR KEGG; rno:29543; -.
DR UCSC; RGD:61312; rat.
DR CTD; 7077; -.
DR RGD; 61312; Timp2.
DR eggNOG; KOG4745; Eukaryota.
DR GeneTree; ENSGT00940000153123; -.
DR HOGENOM; CLU_084029_0_0_1; -.
DR InParanoid; P30121; -.
DR OMA; DHYACIK; -.
DR OrthoDB; 1122531at2759; -.
DR PhylomeDB; P30121; -.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:P30121; -.
DR Proteomes; UP000002494; Chromosome 10.
DR Bgee; ENSRNOG00000003148; Expressed in lung and 20 other tissues.
DR Genevisible; P30121; RN.
DR GO; GO:0005604; C:basement membrane; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0030426; C:growth cone; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0008047; F:enzyme activator activity; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; IPI:RGD.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IMP:RGD.
DR GO; GO:0030414; F:peptidase inhibitor activity; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0007417; P:central nervous system development; IEP:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA: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:1905049; P:negative regulation of metallopeptidase activity; ISO:RGD.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:RGD.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:RGD.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IDA:RGD.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; IMP:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:RGD.
DR GO; GO:0043408; P:regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0032487; P:regulation of Rap protein signal transduction; IDA:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0009725; P:response to hormone; IBA:GO_Central.
DR GO; GO:0010033; P:response to organic substance; IBA:GO_Central.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0007283; P:spermatogenesis; NAS: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; IPR015613; TIMP2.
DR InterPro; IPR027465; TIMP_C.
DR InterPro; IPR030490; TIMP_CS.
DR PANTHER; PTHR11844; PTHR11844; 1.
DR PANTHER; PTHR11844:SF24; PTHR11844:SF24; 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 1: Evidence at protein level;
KW Direct protein sequencing; Disulfide bond; Metal-binding;
KW Metalloenzyme inhibitor; Metalloprotease inhibitor; Protease inhibitor;
KW Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..26
FT /evidence="ECO:0000269|PubMed:1309971"
FT CHAIN 27..220
FT /note="Metalloproteinase inhibitor 2"
FT /id="PRO_0000034337"
FT DOMAIN 27..152
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 27..30
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT REGION 95..96
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT BINDING 27
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 40
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT SITE 61
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT SITE 67
FT /note="Involved in metalloproteinase-binding"
FT /evidence="ECO:0000250|UniProtKB:P16035"
FT DISULFID 27..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 29..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 39..152
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 154..201
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 159..164
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 172..193
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT CONFLICT 7
FT /note="S -> T (in Ref. 1; AAA21553)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="E -> Q (in Ref. 1; AAA21553)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 220 AA; 24356 MW; 1C97A3F050C3AE7D CRC64;
MGAAARSLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND
IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG
KMHITLCDFI VPWDTLSITQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE
KSINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP
