TIMP2_MOUSE
ID TIMP2_MOUSE Reviewed; 220 AA.
AC P25785;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 2.
DT 03-AUG-2022, entry version 164.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=1601312; DOI=10.1016/0378-1119(92)90591-c;
RA Shimizu S., Malik K., Sejima H., Kishi J.I., Hayakawa T., Koiwai O.;
RT "Cloning and sequencing of the cDNA encoding a mouse tissue inhibitor of
RT metalloproteinase-2.";
RL Gene 114:291-292(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1639268; DOI=10.1016/0378-1119(92)90731-4;
RA Leco K.J., Hayden L.J., Sharma R.R., Rocheleau H., Greenberg A.H.,
RA Edwards D.R.;
RT "Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and
RT Ha-ras-transformed murine fibroblasts.";
RL Gene 117:209-217(1992).
RN [3]
RP PRELIMINARY PROTEIN SEQUENCE OF 27-62.
RX PubMed=1851244; DOI=10.1016/s0934-8832(11)80222-2;
RA Kishi J.I., Ogawa K., Yamamoto S., Hayakawa T.;
RT "Purification and characterization of a new tissue inhibitor of
RT metalloproteinases (TIMP-2) from mouse colon 26 tumor cells.";
RL Matrix 11:10-16(1991).
RN [4]
RP TISSUE SPECIFICITY, AND INDUCTION BY INJURY.
RX PubMed=16985004; DOI=10.1152/physiolgenomics.00160.2006;
RA Jaworski D.M., Beem-Miller M., Lluri G., Barrantes-Reynolds R.;
RT "Potential regulatory relationship between the nested gene DDC8 and its
RT host gene tissue inhibitor of metalloproteinase-2.";
RL Physiol. Genomics 28:168-178(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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 -!- TISSUE SPECIFICITY: Detected in testis, retina, hippocampus and
CC cerebral cortex. {ECO:0000269|PubMed:16985004}.
CC -!- INDUCTION: After intracranial injury, expression peaks at 4 days post-
CC injury and slightly declines at 7 days post-injury.
CC {ECO:0000269|PubMed:16985004}.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X62622; CAA44491.1; -; mRNA.
DR EMBL; M82858; AAA40445.1; -; mRNA.
DR EMBL; M93954; AAA40446.1; -; mRNA.
DR PIR; JH0683; JH0683.
DR AlphaFoldDB; P25785; -.
DR BMRB; P25785; -.
DR SMR; P25785; -.
DR STRING; 10090.ENSMUSP00000017610; -.
DR MEROPS; I35.002; -.
DR PhosphoSitePlus; P25785; -.
DR CPTAC; non-CPTAC-3356; -.
DR MaxQB; P25785; -.
DR PaxDb; P25785; -.
DR PeptideAtlas; P25785; -.
DR PRIDE; P25785; -.
DR ProteomicsDB; 258885; -.
DR MGI; MGI:98753; Timp2.
DR eggNOG; KOG4745; Eukaryota.
DR InParanoid; P25785; -.
DR PhylomeDB; P25785; -.
DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR ChiTaRS; Timp2; mouse.
DR PRO; PR:P25785; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P25785; protein.
DR GO; GO:0005604; C:basement membrane; IDA:MGI.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0043005; C:neuron projection; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0008047; F:enzyme activator activity; IMP:MGI.
DR GO; GO:0005178; F:integrin binding; IDA:MGI.
DR GO; GO:0008191; F:metalloendopeptidase inhibitor activity; IMP:MGI.
DR GO; GO:0030414; F:peptidase inhibitor activity; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0071310; P:cellular response to organic substance; IDA:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
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:0045930; P:negative regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISO:MGI.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0043408; P:regulation of MAPK cascade; IDA:MGI.
DR GO; GO:0045664; P:regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0032487; P:regulation of Rap protein signal transduction; ISO:MGI.
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:0010033; P:response to organic substance; IBA:GO_Central.
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 CHAIN 27..220
FT /note="Metalloproteinase inhibitor 2"
FT /id="PRO_0000034336"
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 12
FT /note="L -> H (in Ref. 2; AAA40446)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="V -> L (in Ref. 2; AAA40446)"
FT /evidence="ECO:0000305"
FT CONFLICT 195
FT /note="K -> E (in Ref. 2; AAA40446)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 220 AA; 24328 MW; 1D0A16CEDA023F0D CRC64;
MGAAARSLRL ALGLLLLASL VRPADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND
IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG
KMHITLCDFI VPWDTLSITQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE
KSINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP
