Reviewed, UniProtKB/Swiss-Prot P16035 (TIMP2_HUMAN)

Names and origin

Protein names

Recommended name:
    Metalloproteinase inhibitor 2
Alternative name(s):
    Tissue inhibitor of metalloproteinases 2
      Short name=TIMP-2
    CSC-21K

Gene names

Name:

TIMP2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. Known to act on MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19.
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
Molecular function	Metalloenzyme inhibitor Metalloprotease inhibitor
PTM	Disulfide bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Molecular function	metalloendopeptidase inhibitor activity Ref.3 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMA7	O14818	1	EBI-1033507,EBI-603272
SNCG	O76070	1	EBI-1033507,EBI-1053810

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 26

26

Ref.6 Ref.7 Ref.9

Chain

27 – 220

194

Metalloproteinase inhibitor 2

PRO_0000034335

Regions

Domain

27 – 152

126

NTR

Amino acid modifications

Disulfide bond

27 ↔ 98

Disulfide bond

29 ↔ 127

Disulfide bond

39 ↔ 152

Disulfide bond

154 ↔ 201

Disulfide bond

159 ↔ 164

Disulfide bond

172 ↔ 193

Experimental info

Sequence conflict

17 – 19

3

LAT → P in AAC50729. Ref.3

Sequence conflict

44 – 50

7

VIRAKAV → GKESGDP Ref.10

Sequence conflict

78

1

M → K Ref.6

Sequence conflict

78

1

M → K Ref.7

Sequence conflict

82

1

P → I Ref.6

Sequence conflict

82

1

P → I Ref.7

Sequence conflict

96

1

A → V in CAA38400. Ref.5

Sequence conflict

101

1

S → E Ref.6

Sequence conflict

101

1

S → E Ref.7

Sequence conflict

118

1

Missing Ref.6

Sequence conflict

118

1

Missing Ref.7

Sequence conflict

122

1

M → R Ref.6

Sequence conflict

122

1

M → R Ref.7

Sequence conflict

150

1

M → Q Ref.6

Sequence conflict

150

1

M → Q Ref.7

Sequence conflict

175

1

M → T Ref.6

Sequence conflict

175

1

M → T Ref.7

Secondary structure

1

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220

Helix Strand Turn

Details...

Helix

34 – 40

7

Beta strand

41 – 59

19

Beta strand

65 – 81

17

Beta strand

88 – 91

4

Helix

95 – 97

3

Beta strand

109 – 118

10

Beta strand

121 – 123

3

Beta strand

130 – 132

3

Helix

133 – 135

3

Helix

138 – 143

6

Turn

144 – 148

5

Helix

149 – 151

3

Beta strand

154 – 158

5

Beta strand

161 – 163

3

Beta strand

171 – 174

4

Helix

176 – 180

5

Helix

186 – 190

5

Beta strand

192 – 195

4

Beta strand

201 – 204

4

Sequences

	Sequence		Length	Mass (Da)
	P16035-1 [UniParc]. Last modified November 1, 1990. Version 2. Checksum: 603E5B1C9F94735D	FASTA	220	24,399
	10 20 30 40 50 60 MGAAARTLRL ALGLLLLATL LRPADACSCS PVHPQQAFCN ADVVIRAKAV SEKEVDSGND 70 80 90 100 110 120 IYGNPIKRIQ YEIKQIKMFK GPEKDIEFIY TAPSSAVCGV SLDVGGKKEY LIAGKAEGDG 130 140 150 160 170 180 KMHITLCDFI VPWDTLSTTQ KKSLNHRYQM GCECKITRCP MIPCYISSPD ECLWMDWVTE 190 200 210 220 KNINGHQAKF FACIKRSDGS CAWYRGAAPP KQEFLDIEDP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues." Stetler-Stevenson W.G., Brown P.D., Onisto M., Levy A.T., Liotta L.A. J. Biol. Chem. 265:13933-13938(1990) [PubMed: 2380196] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"cDNA cloning and expression of a metalloproteinase inhibitor related to tissue inhibitor of metalloproteinases." Boone T.C., Johnson M.J., de Clerck Y.A., Langley K.E. Proc. Natl. Acad. Sci. U.S.A. 87:2800-2804(1990) [PubMed: 2157214] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure and characterization of the human tissue inhibitor of metalloproteinases-2 gene." Hammani K., Blakis A., Morsette D., Bowcock A., Schmutte C., Henriet P., Declerck Y.A. J. Biol. Chem. 271:25498-25505(1996) [PubMed: 8810321] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta and Skin.
[5]	Malik K., Sejima H., Aoki T., Iwata K. Submitted (AUG-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 30-214.
[6]	"Tissue inhibitor of metalloproteinase (TIMP-2). A new member of the metalloproteinase inhibitor family." Stetler-Stevenson W.G., Krutzsch H.C., Liotta L.A. J. Biol. Chem. 264:17374-17378(1989) [PubMed: 2793861] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-219.
[7]	"TIMP-2: identification and characterization of a new member of the metalloproteinase inhibitor family." Stetler-Stevenson W.G., Krutzsch H.C., Liotta L.A. Matrix Suppl. 1:299-306(1992) [PubMed: 1480041] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-219.
[8]	"Human 72-kilodalton type IV collagenase forms a complex with a tissue inhibitor of metalloproteases designated TIMP-2." Goldberg G.I., Marmer B.L., Grant G.A., Eisen A.Z., Wilhelm S., He C. Proc. Natl. Acad. Sci. U.S.A. 86:8207-8211(1989) [PubMed: 2554304] [Abstract] Cited for: PROTEIN SEQUENCE OF 30-51; 124-141 AND 159-173.
[9]	"Isolation and characterization of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) from human rheumatoid synovial fluid." Osthues A., Knaueper V., Oberhoff R., Reinke H., Tschesche H. FEBS Lett. 296:16-20(1992) [PubMed: 1730286] [Abstract] Cited for: PROTEIN SEQUENCE OF 27-41. Tissue: Synovial fluid.
[10]	"Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2)." de Clerck Y.A., Darville M.I., Eeckhout Y., Rousseau G.G. Gene 139:185-191(1994) [PubMed: 8112602] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
[11]	"Three-dimensional structure of human tissue inhibitor of metalloproteinases-2 at 2.1-A resolution." Tuuttila A., Morgunova E., Bergmann U., Lindqvist Y., Maskos K., Fernandez-Catalan C., Bode W., Tryggvason K., Schneider G. J. Mol. Biol. 284:1133-1140(1998) [PubMed: 9837731] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-208.
[12]	"Solution structure of the active domain of tissue inhibitor of metalloproteinases-2. A new member of the OB fold protein family." Williamson R.A., Martorell G., Carr M.D., Murphy G., Docherty A.J.P., Freedman R.B., Feeney J. Biochemistry 33:11745-11759(1994) [PubMed: 7918391] [Abstract] Cited for: STRUCTURE BY NMR OF 27-153.
[13]	"High resolution structure of the N-terminal domain of tissue inhibitor of metalloproteinases-2 and characterization of its interaction site with matrix metalloproteinase-3." Muskett F.W., Frenkiel T.A., Feeney J., Freedman R.B., Carr M.D., Williamson R.A. J. Biol. Chem. 273:21736-21743(1998) [PubMed: 9705310] [Abstract] Cited for: STRUCTURE BY NMR OF 27-153.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBLGenBankDDBJ

J05593 mRNA. Translation: AAA61186.1.
S48568 mRNA. Translation: AAB19474.1.
U44385 , U44381, U44382, U44383 Genomic DNA. Translation: AAC50729.1.
M32304 mRNA. Translation: AAA59581.1.
BC052605 mRNA. Translation: AAH52605.1.
BC071586 mRNA. Translation: AAH71586.1.
X54533 mRNA. Translation: CAA38400.1.
S68860 Genomic DNA. Translation: AAD14025.1.

IPI

IPI00027166.

PIR

A37128.
I53729.

RefSeq

NP_003246.1.

UniGene

Hs.633514

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BR9	X-ray	2.10	A	27-220	[»]
1GXD	X-ray	3.10	C/D	27-220	[»]
2TMP	NMR	-	A	27-153	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P16035. 19 interactions.

Protein family/group databases

MEROPS

I35.002.

2-D gel databases

DOSAC-COBS-2DPAGE

P16035.

Proteomic databases

PeptideAtlas

P16035.

PRIDE

P16035.

Genome annotation databases

Ensembl

ENSG00000035862. Homo sapiens. [Contig view]

GeneID

7077.

KEGG

hsa:7077.

Organism-specific databases

GeneCards

GC17M074363.

H-InvDB

HIX0014228.

HGNC

HGNC:11821. TIMP2.

HPA

CAB010203.

MIM

188825. gene.

PharmGKB

PA36527.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P16035.

HOVERGEN

P16035.

OMA

P16035. VHPQQAF.

Gene expression databases

ArrayExpress

P16035.

Bgee

P16035.

CleanEx

HS_TIMP2.

GermOnline

ENSG00000035862. Homo sapiens.

Family and domain databases

InterPro

IPR001134. Netrin_domain.
IPR001820. Prot_inh_TIMP.
IPR015613. TIMP2.
[Graphical view]

PANTHER

PTHR11844. Prot_inh_TIMP. 1 hit.
PTHR11844:SF7. TIMP2. 1 hit.

Pfam

PF00965. TIMP. 1 hit.
[Graphical view]

SMART

SM00206. NTR. 1 hit.
[Graphical view]

PROSITE

PS50189. NTR. 1 hit.
PS00288. TIMP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27679.

SOURCE

Search...

Entry information

Entry name

TIMP2_HUMAN

Accession

Primary (citable) accession number: P16035
Secondary accession number(s): Q16121, Q93006, Q9UDF7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 1, 1990
Last modified:	June 16, 2009
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)