P30121 (TIMP2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metalloproteinase inhibitor 2

Alternative name(s):
Tissue inhibitor of metalloproteinases 2
Short name=TIMP-2

Gene names

Name:	Timp2
Synonyms:	Timp-2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	220 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.
Subunit structure	Interacts (via the C-terminal) with MMP2 (via the C-terminal PEX domain); the interaction inhibits the MMP2 activity By similarity.
Subcellular location	Secreted.
Post-translational modification	The activity of TIMP2 is dependent on the presence of disulfide bonds.
Sequence similarities	Belongs to the protease inhibitor I35 (TIMP) family. [View classification] Contains 1 NTR domain.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Metalloenzyme inhibitor Metalloprotease inhibitor Protease inhibitor
PTM	Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from expression pattern PubMed 18278151. Source: RGD cellular response to organic substance Inferred from electronic annotation. Source: Compara central nervous system development Inferred from expression pattern PubMed 11044612. Source: RGD negative regulation of Ras protein signal transduction Inferred from direct assay PubMed 15901773. Source: RGD negative regulation of cell proliferation Inferred from direct assay PubMed 15901773. Source: RGD negative regulation of mitotic cell cycle Inferred from direct assay PubMed 15901773. Source: RGD negative regulation of proteolysis Inferred from mutant phenotype PubMed 17532789. Source: RGD positive regulation of MAPK cascade Inferred from direct assay PubMed 15901773. Source: RGD positive regulation of adenylate cyclase activity Inferred from mutant phenotype PubMed 15901773. Source: RGD positive regulation of neuron differentiation Inferred from direct assay PubMed 15901773. Source: RGD regulation of Rap protein signal transduction Inferred from direct assay PubMed 15901773. Source: RGD response to cytokine stimulus Inferred from expression pattern PubMed 17822627. Source: RGD response to drug Inferred from expression pattern PubMed 17491697. Source: RGD spermatogenesis Non-traceable author statement Ref.4. Source: RGD
Cellular_component	basement membrane Inferred from electronic annotation. Source: Compara cell surface Inferred from direct assay PubMed 15901773. Source: RGD extracellular space Inferred from direct assay PubMed 15901773. Source: RGD growth cone Inferred from direct assay PubMed 15901773. Source: RGD neuronal cell body Inferred from direct assay PubMed 15901773. Source: RGD
Molecular_function	enzyme activator activity Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase inhibitor activity Inferred from mutant phenotype PubMed 15901773. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Ref.7
	Chain	27 – 220	194	Metalloproteinase inhibitor 2		PRO_0000034337
Regions
	Domain	27 – 152	126	NTR
	Region	27 – 31	5	Involved in metalloproteinase-binding By similarity
	Region	95 – 96	2	Involved in metalloproteinase-binding By similarity
Sites
	Metal binding	27	1	Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner By similarity
Amino acid modifications
	Disulfide bond	27 ↔ 98		By similarity
	Disulfide bond	29 ↔ 127		By similarity
	Disulfide bond	39 ↔ 152		By similarity
	Disulfide bond	154 ↔ 201		By similarity
	Disulfide bond	159 ↔ 164		By similarity
	Disulfide bond	172 ↔ 193		By similarity
Experimental info
	Sequence conflict	7	1	S → T in AAA21553. Ref.1
	Sequence conflict	153	1	E → Q in AAA21553. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P30121 [UniParc]. Last modified October 1, 1996. Version 3. Checksum: 1C97A3F050C3AE7D	FASTA	220	24,356
	10 20 30 40 50 60 MGAAARSLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND 70 80 90 100 110 120 IYGNPIKRIQ YEIKQIKMFK GPDKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG 130 140 150 160 170 180 KMHITLCDFI VPWDTLSITQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE 190 200 210 220 KSINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells." Cook T.F., Burke J.S., Bergman K.D., Quinn C.O., Jeffrey J.J., Partridge N.C. Arch. Biochem. Biophys. 311:313-320(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Bone.
[2]	Gibbons K.L., O'Grady R.L., Piper A.A. Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary gland.
[3]	"Cloning of the rat tissue inhibitor of metalloproteinases type 2 (TIMP-2) gene: analysis of its expression in normal and transformed thyroid cells." Santoro M., Battaglia C., Zhang L., Carlomagno F., Martelli M.L., Salvatore D., Fusco A. Exp. Cell Res. 213:398-403(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Purification, cDNA cloning, and developmental changes in the steady-state mRNA level of rat testicular tissue inhibitor of metalloproteases-2 (TIMP-2)." Grima J., Calcagno K., Cheng C.Y. J. Androl. 17:263-275(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Testis.
[5]	"Cardiac remodeling after long term norepinephrine treatment in rats." Briest W., Hoelzl A., Rassler B., Deten A., Leicht M., Baba H.A., Zimmer H.G. Cardiovasc. Res. 52:265-273(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Heart.
[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: Ovary.
[7]	"Purification and sequence analysis of two rat tissue inhibitors of metalloproteinases." Roswit W.T., McCourt D.W., Partridge N.C., Jeffrey J.J. Arch. Biochem. Biophys. 292:402-410(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-48.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U14526 mRNA. Translation: AAA21553.1. L31884 mRNA. Translation: AAA84581.1. S72594 mRNA. Translation: AAC60687.1. S82718 mRNA. Translation: AAB49507.1. AJ409332 mRNA. Translation: CAC35060.1. BC084714 mRNA. Translation: AAH84714.1.
IPI	IPI00205807.
PIR	S45683.
RefSeq	NP_068824.1. NM_021989.2.
UniGene	Rn.10161.
3D structure databases
ProteinModelPortal	P30121.
SMR	P30121. Positions 27-208.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000004290.
Protein family/group databases
MEROPS	I35.002.
Proteomic databases
PaxDb	P30121.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000004290; ENSRNOP00000004290; ENSRNOG00000003148.
GeneID	29543.
KEGG	rno:29543.
UCSC	RGD:61312. rat.
Organism-specific databases
CTD	7077.
RGD	61312. Timp2.
Phylogenomic databases
eggNOG	NOG243625.
GeneTree	ENSGT00390000004555.
HOGENOM	HOG000285981.
HOVERGEN	HBG068749.
OrthoDB	EOG4XPQGS.
Gene expression databases
ArrayExpress	P30121.
Genevestigator	P30121.
GermOnline	ENSRNOG00000003148. Rattus norvegicus.
Family and domain databases
InterPro	IPR001134. Netrin_domain. IPR001820. Prot_inh_TIMP. IPR008993. TIMP-like_OB-fold. IPR015613. TIMP2. [Graphical view]
PANTHER	PTHR11844. PTHR11844. 1 hit. PTHR11844:SF7. PTHR11844:SF7. 1 hit.
Pfam	PF00965. TIMP. 1 hit. [Graphical view]
SMART	SM00206. NTR. 1 hit. [Graphical view]
SUPFAM	SSF50242. TIMP_like. 1 hit.
PROSITE	PS50189. NTR. 1 hit. PS00288. TIMP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	609549.

Entry information

Entry name

TIMP2_RAT

Accession

Primary (citable) accession number: P30121
Secondary accession number(s): Q546J4

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	October 1, 1996
Last modified:	April 3, 2013
This is version 103 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program