P39876 (TIMP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Metalloproteinase inhibitor 3

Alternative name(s):
Tissue inhibitor of metalloproteinases 3
Short name=TIMP-3

Gene names

Name:	Timp3
Synonyms:	Sun, Timp-3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [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 › Mus › Mus

Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli.
Subunit structure	Interacts with EFEMP1 By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix.
Tissue specificity	Highest levels are found in kidney, lung and brain followed by ovary and uterus. Low levels are found in bone.
Induction	Highly induced by phorbol ester (PMA), EGF and transforming growth factor-beta 1. Also induced by dexamethasone.
Sequence similarities	Belongs to the protease inhibitor I35 (TIMP) family. [View classification] Contains 1 NTR domain.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Metalloenzyme inhibitor Metalloprotease inhibitor Protease inhibitor
PTM	Disulfide bond
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to organic substance Inferred from direct assay PubMed 11869290. Source: MGI negative regulation of membrane protein ectodomain proteolysis Inferred from electronic annotation. Source: Compara
Cellular_component	basement membrane Inferred from direct assay PubMed 12950084. Source: MGI
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Chain	24 – 211	188	Metalloproteinase inhibitor 3		PRO_0000034344
Regions
	Domain	24 – 143	120	NTR
	Region	24 – 28	5	Involved in metalloproteinase-binding By similarity
	Region	88 – 89	2	Involved in metalloproteinase-binding By similarity
	Region	105 – 188	84	Mediates interaction with EFEMP1 By similarity
Sites
	Metal binding	24	1	Zinc; via amino nitrogen and carbonyl oxygen; shared with metalloproteinase partner By similarity
Amino acid modifications
	Disulfide bond	24 ↔ 91		By similarity
	Disulfide bond	26 ↔ 118		By similarity
	Disulfide bond	36 ↔ 143		By similarity
	Disulfide bond	145 ↔ 192		By similarity
	Disulfide bond	150 ↔ 155		By similarity
	Disulfide bond	163 ↔ 184		By similarity
Experimental info
	Sequence conflict	31	1	P → S in AAH14713. Ref.7
	Sequence conflict	53	1	K → T in AAH14713. Ref.7
	Sequence conflict	148	1	K → N in AAH14713. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	P39876 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 184EDF5B8D69B07B	FASTA	211	24,182
	10 20 30 40 50 60 MTPWLGLVVL LSCWSLGHWG AEACTCSPSH PQDAFCNSDI VIRAKVVGKK LVKEGPFGTL 70 80 90 100 110 120 VYTIKQMKMY RGFSKMPHVQ YIHTEASESL CGLKLEVNKY QYLLTGRVYE GKMYTGLCNF 130 140 150 160 170 180 VERWDHLTLS QRKGLNYRYH LGCNCKIKSC YYLPCFVTSK NECLWTDMLS NFGYPGYQSK 190 200 210 HYACIRQKGG YCSWYRGWAP PDKSISNATD P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues." Leco K.J., Khokha R., Pavloff N., Hawkes S.P., Edwards D.R. J. Biol. Chem. 269:9352-9360(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning of five messenger RNAs differentially expressed in preneoplastic or neoplastic JB6 mouse epidermal cells: one is homologous to human tissue inhibitor of metalloproteinases-3." Sun Y., Hegamyer G., Colburn N.H. Cancer Res. 54:1139-1144(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Strain: BALB/c. Tissue: Lung and Skin.
[3]	"Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10." Apte S.S., Hayashi K., Seldin M.F., Mattei M.-G., Hayashi M., Olsen B.R. Dev. Dyn. 200:177-197(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lung.
[4]	"Molecular cloning of mouse tissue inhibitor of metalloproteinases-3 and its promoter. Specific lack of expression in neoplastic JB6 cells may reflect altered gene methylation." Sun Y., Hegamyer G., Kim H., Sithanandam K., Li H., Watts R., Colburn N.H. J. Biol. Chem. 270:19312-19319(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The gene structure of tissue inhibitor of metalloproteinases (TIMP)-3 and its inhibitory activities define the distinct TIMP gene family." Apte S.S., Olsen B.R., Murphy G. J. Biol. Chem. 270:14313-14318(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Sv.
[6]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Spinal ganglion.
[7]	"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]. Strain: FVB/N. Tissue: Kidney.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L27424 mRNA. Translation: AAA40447.1. Z30970 mRNA. Translation: CAA83218.1. L19622 mRNA. Translation: AAC37669.1. U26437 , U26433, U26434, U26435, U26436 Genomic DNA. Translation: AAA85860.1. AK083905 mRNA. Translation: BAC39055.1. BC014713 mRNA. Translation: AAH14713.1.
IPI	IPI00110370.
PIR	A53532.
RefSeq	NP_035725.1. NM_011595.2.
UniGene	Mm.4871.
3D structure databases
ProteinModelPortal	P39876.
SMR	P39876. Positions 24-199.
ModBase	Search...
Protein family/group databases
MEROPS	I35.003.
PTM databases
PhosphoSite	P39876.
Proteomic databases
PaxDb	P39876.
PRIDE	P39876.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000020234; ENSMUSP00000020234; ENSMUSG00000020044.
GeneID	21859.
KEGG	mmu:21859.
Organism-specific databases
CTD	7078.
MGI	MGI:98754. Timp3.
Phylogenomic databases
eggNOG	NOG250837.
HOGENOM	HOG000285981.
HOVERGEN	HBG068749.
InParanoid	P39876.
OMA	KEGYCSW.
OrthoDB	EOG47D9H3.
Gene expression databases
ArrayExpress	P39876.
Bgee	P39876.
CleanEx	MM_TIMP3.
Genevestigator	P39876.
GermOnline	ENSMUSG00000020044. Mus musculus.
Family and domain databases
InterPro	IPR001134. Netrin_domain. IPR001820. Prot_inh_TIMP. IPR008993. TIMP-like_OB-fold. IPR015612. Tissue_inhib_metalloprotease_3. [Graphical view]
PANTHER	PTHR11844. PTHR11844. 1 hit. PTHR11844:SF6. PTHR11844:SF6. 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	301360.
SOURCE	Search...

Entry information

Entry name

TIMP3_MOUSE

Accession

Primary (citable) accession number: P39876
Secondary accession number(s): Q91WL9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program