TIMP-like superfamily

SCOP classification

Root:	SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:	All beta proteins [ 48724] (174)
Fold:	OB-fold [ 50198] (16)
Superfamily:	TIMP-like [ 50242] (3)
Families:	Tissue inhibitor of metalloproteinases, TIMP [ 50243] (2)
	Netrin-like domain (NTR/C345C module) [ 89320] (2)
	The laminin-binding domain of agrin [ 63767]

Superfamily statistics

	Genomes (172)	Uniprot 2013_05	PDB chains (SCOP 1.75)
Domains	1,953	2,290	11
Proteins	1,934	2,275	11

Functional annotation

General category	Processes_IC
Detailed category	Proteases

Document: Function annotation of SCOP domain superfamilies

Gene Ontology (high-quality)

(show details)

	GO term	FDR (singleton)	FDR (all)	SDFO level	Annotation (direct or inherited)
Biological Process (BP)	multicellular organismal process	8.592e-05	1.139e-09	Least Informative	Direct
Biological Process (BP)	developmental process	1.698e-05	1.766e-11	Least Informative	Direct
Biological Process (BP)	response to stimulus	2.821e-05	1.108e-05	Least Informative	Direct
Biological Process (BP)	single-organism cellular process	6.462e-05	0.009798	Least Informative	Inherited
Biological Process (BP)	regulation of cellular process	4.371e-06	1	Least Informative	Inherited
Biological Process (BP)	regulation of metabolic process	0.002736	0.2661	Least Informative	Inherited
Biological Process (BP)	cellular component organization or biogenesis	0.0473	0.009356	Least Informative	Inherited
Biological Process (BP)	cell differentiation	6.245e-06	5.091e-10	Moderately Informative	Direct
Biological Process (BP)	negative regulation of cellular process	0.0002826	0.0004324	Moderately Informative	Direct
Biological Process (BP)	regulation of developmental process	2.433e-05	3.629e-10	Moderately Informative	Direct
Biological Process (BP)	regulation of multicellular organismal process	0.0001825	8.679e-08	Moderately Informative	Direct
Biological Process (BP)	nervous system development	0.04948	0.01384	Moderately Informative	Inherited
Biological Process (BP)	regulation of cellular metabolic process	0.000493	0.1806	Moderately Informative	Inherited
Biological Process (BP)	negative regulation of metabolic process	0.4154	1	Moderately Informative	Inherited
Biological Process (BP)	regulation of protein metabolic process	0.7304	0.0002258	Moderately Informative	Inherited
Biological Process (BP)	regulation of cell communication	0.04893	1.095e-11	Moderately Informative	Inherited
Biological Process (BP)	regulation of signaling	0.02412	4.324e-10	Moderately Informative	Inherited
Biological Process (BP)	regulation of response to stimulus	0.143	3.2e-10	Moderately Informative	Inherited
Biological Process (BP)	regulation of nitrogen compound metabolic process	0.08494	1	Moderately Informative	Inherited
Biological Process (BP)	regulation of cell proliferation	0.0009336	0.0001944	Informative	Direct
Biological Process (BP)	regulation of apoptotic process	0.0002065	1.139e-06	Informative	Direct
Biological Process (BP)	generation of neurons	3.225e-06	1.351e-09	Informative	Direct
Biological Process (BP)	regulation of nervous system development	0.0002824	0.02885	Informative	Inherited
Biological Process (BP)	regulation of cell development	1.588e-10	0.1249	Informative	Inherited
Biological Process (BP)	negative regulation of cellular metabolic process	0.4617	0.9187	Informative	Inherited
Biological Process (BP)	negative regulation of protein metabolic process	0.0001242	0.001416	Informative	Inherited
Biological Process (BP)	extracellular matrix organization	4.918e-07	5.994e-05	Highly Informative	Direct
Biological Process (BP)	regulation of neuron differentiation	3.29e-09	5.78e-06	Highly Informative	Direct
Molecular Function (MF)	binding	0.08492	0.01284	Least Informative	Inherited
Molecular Function (MF)	enzyme regulator activity	2.077e-14	2.231e-11	Moderately Informative	Direct
Molecular Function (MF)	protein binding	0.003425	9.05e-06	Moderately Informative	Inherited
Molecular Function (MF)	enzyme inhibitor activity	0	0.0001032	Informative	Direct
Molecular Function (MF)	receptor binding	3.119e-05	4.352e-09	Informative	Direct
Molecular Function (MF)	peptidase regulator activity	0	8.998e-12	Informative	Direct
Molecular Function (MF)	protein complex binding	4.134e-09	8.771e-05	Highly Informative	Direct
Cellular Component (CC)	extracellular region	2.73e-12	0	Moderately Informative	Direct
Cellular Component (CC)	cell surface	6.722e-12	2.516e-06	Informative	Direct
Cellular Component (CC)	extracellular matrix	0	0	Informative	Direct
Cellular Component (CC)	proteinaceous extracellular matrix	4.907e-13	1.761e-06	Highly Informative	Direct
Cellular Component (CC)	extracellular matrix part	0	0	Highly Informative	Direct

Document: GO annotation of SCOP domains

Gene Ontology (high-coverage)

(show details)

	GO term	FDR (all)	SDFO level	Annotation (direct or inherited)
Biological Process (BP)	multicellular organismal process	1.139e-09	Least Informative	Direct
Biological Process (BP)	developmental process	1.766e-11	Least Informative	Direct
Biological Process (BP)	response to stimulus	1.108e-05	Least Informative	Direct
Biological Process (BP)	single-organism cellular process	0.009798	Least Informative	Inherited
Biological Process (BP)	localization	0.9938	Least Informative	Inherited
Biological Process (BP)	regulation of cellular process	1	Least Informative	Inherited
Biological Process (BP)	regulation of metabolic process	0.2661	Least Informative	Inherited
Biological Process (BP)	protein metabolic process	0.4749	Least Informative	Inherited
Biological Process (BP)	cellular component organization or biogenesis	0.009356	Least Informative	Inherited
Biological Process (BP)	regulation of cell communication	1.095e-11	Moderately Informative	Direct
Biological Process (BP)	regulation of signaling	4.324e-10	Moderately Informative	Direct
Biological Process (BP)	cell differentiation	5.091e-10	Moderately Informative	Direct
Biological Process (BP)	single-organism developmental process	0.0005052	Moderately Informative	Direct
Biological Process (BP)	negative regulation of cellular process	0.0004324	Moderately Informative	Direct
Biological Process (BP)	regulation of response to stimulus	3.2e-10	Moderately Informative	Direct
Biological Process (BP)	regulation of developmental process	3.629e-10	Moderately Informative	Direct
Biological Process (BP)	regulation of multicellular organismal process	8.679e-08	Moderately Informative	Direct
Biological Process (BP)	regulation of protein metabolic process	0.0002258	Moderately Informative	Direct
Biological Process (BP)	macromolecule localization	0.1978	Moderately Informative	Inherited
Biological Process (BP)	cellular localization	0.6364	Moderately Informative	Inherited
Biological Process (BP)	tissue development	0.407	Moderately Informative	Inherited
Biological Process (BP)	regulation of cellular component organization	0.03413	Moderately Informative	Inherited
Biological Process (BP)	system process	1	Moderately Informative	Inherited
Biological Process (BP)	nervous system development	0.01384	Moderately Informative	Inherited
Biological Process (BP)	response to endogenous stimulus	0.1178	Moderately Informative	Inherited
Biological Process (BP)	response to organic substance	0.7957	Moderately Informative	Inherited
Biological Process (BP)	regulation of cellular metabolic process	0.1806	Moderately Informative	Inherited
Biological Process (BP)	negative regulation of metabolic process	1	Moderately Informative	Inherited
Biological Process (BP)	regulation of localization	0.01867	Moderately Informative	Inherited
Biological Process (BP)	signal transduction	1	Moderately Informative	Inherited
Biological Process (BP)	positive regulation of cellular process	0.1335	Moderately Informative	Inherited
Biological Process (BP)	regulation of biosynthetic process	1	Moderately Informative	Inherited
Biological Process (BP)	regulation of nitrogen compound metabolic process	1	Moderately Informative	Inherited
Biological Process (BP)	immune system process	0.01892	Moderately Informative	Inherited
Biological Process (BP)	anatomical structure morphogenesis	0.2172	Moderately Informative	Inherited
Biological Process (BP)	regulation of protein phosphorylation	6.813e-09	Informative	Direct
Biological Process (BP)	immune effector process	0.0008117	Informative	Direct
Biological Process (BP)	response to external stimulus	0.0001055	Informative	Direct
Biological Process (BP)	negative regulation of cell communication	7.477e-06	Informative	Direct
Biological Process (BP)	negative regulation of signaling	2.772e-06	Informative	Direct
Biological Process (BP)	cell projection organization	3.9e-05	Informative	Direct
Biological Process (BP)	regulation of growth	7.143e-05	Informative	Direct
Biological Process (BP)	locomotion	8.122e-05	Informative	Direct
Biological Process (BP)	regulation of cell proliferation	0.0001944	Informative	Direct
Biological Process (BP)	regulation of apoptotic process	1.139e-06	Informative	Direct
Biological Process (BP)	negative regulation of response to stimulus	7.344e-05	Informative	Direct
Biological Process (BP)	generation of neurons	1.351e-09	Informative	Direct
Biological Process (BP)	cellular membrane organization	0.06461	Informative	Inherited
Biological Process (BP)	tissue morphogenesis	0.01668	Informative	Inherited
Biological Process (BP)	epithelium development	0.5041	Informative	Inherited
Biological Process (BP)	synaptic transmission	0.4427	Informative	Inherited
Biological Process (BP)	regulation of intracellular protein kinase cascade	0.6962	Informative	Inherited
Biological Process (BP)	regulation of response to stress	1	Informative	Inherited
Biological Process (BP)	positive regulation of signal transduction	0.6265	Informative	Inherited
Biological Process (BP)	regulation of nervous system development	0.02885	Informative	Inherited
Biological Process (BP)	regulation of cell development	0.1249	Informative	Inherited
Biological Process (BP)	response to hormone stimulus	0.1056	Informative	Inherited
Biological Process (BP)	response to organic cyclic compound	0.6159	Informative	Inherited
Biological Process (BP)	response to lipid	0.1137	Informative	Inherited
Biological Process (BP)	negative regulation of cellular metabolic process	0.9187	Informative	Inherited
Biological Process (BP)	negative regulation of protein metabolic process	0.001416	Informative	Inherited
Biological Process (BP)	regulation of locomotion	0.004598	Informative	Inherited
Biological Process (BP)	regulation of cellular component movement	0.01848	Informative	Inherited
Biological Process (BP)	regulation of lipid metabolic process	0.001897	Informative	Inherited
Biological Process (BP)	positive regulation of transport	0.00567	Informative	Inherited
Biological Process (BP)	immune response	0.0975	Informative	Inherited
Biological Process (BP)	positive regulation of immune system process	0.03917	Informative	Inherited
Biological Process (BP)	regulation of immune response	0.8247	Informative	Inherited
Biological Process (BP)	cellular component morphogenesis	0.004222	Informative	Inherited
Biological Process (BP)	activation of immune response	3.169e-05	Highly Informative	Direct
Biological Process (BP)	humoral immune response	4.605e-08	Highly Informative	Direct
Biological Process (BP)	axonogenesis	5.967e-09	Highly Informative	Direct
Biological Process (BP)	negative regulation of cell proliferation	0.0001631	Highly Informative	Direct
Biological Process (BP)	regulation of lipid storage	1.808e-08	Highly Informative	Direct
Biological Process (BP)	extracellular matrix organization	5.994e-05	Highly Informative	Direct
Biological Process (BP)	regulation of neuron differentiation	5.78e-06	Highly Informative	Direct
Biological Process (BP)	regulation of developmental growth	0.0005458	Highly Informative	Direct
Biological Process (BP)	protein activation cascade	7.599e-09	Highly Informative	Direct
Biological Process (BP)	protein localization to membrane	1.052e-06	Highly Informative	Direct
Biological Process (BP)	regulation of cellular response to stress	0.04004	Highly Informative	Inherited
Biological Process (BP)	regulation of G-protein coupled receptor protein signaling pathway	0.001502	Highly Informative	Inherited
Biological Process (BP)	negative regulation of signal transduction	0.006215	Highly Informative	Inherited
Molecular Function (MF)	binding	0.01284	Least Informative	Inherited
Molecular Function (MF)	protein binding	9.05e-06	Moderately Informative	Direct
Molecular Function (MF)	enzyme regulator activity	2.231e-11	Moderately Informative	Direct
Molecular Function (MF)	enzyme inhibitor activity	0.0001032	Informative	Direct
Molecular Function (MF)	receptor binding	4.352e-09	Informative	Direct
Molecular Function (MF)	peptidase regulator activity	8.998e-12	Informative	Direct
Molecular Function (MF)	glycosaminoglycan binding	5.208e-06	Highly Informative	Direct
Molecular Function (MF)	protein complex binding	8.771e-05	Highly Informative	Direct
Molecular Function (MF)	sulfur compound binding	3.037e-05	Highly Informative	Direct
Cellular Component (CC)	extracellular region	0	Moderately Informative	Direct
Cellular Component (CC)	cell projection	7.327e-05	Moderately Informative	Direct
Cellular Component (CC)	cell surface	2.516e-06	Informative	Direct
Cellular Component (CC)	extracellular matrix	0	Informative	Direct
Cellular Component (CC)	proteinaceous extracellular matrix	1.761e-06	Highly Informative	Direct
Cellular Component (CC)	extracellular matrix part	0	Highly Informative	Direct

Document: GO annotation of SCOP domains

Disease Ontology (DO)

(show details)

	DO term	FDR (all)	SDDO level	Annotation (direct or inherited)
Disease Ontology (DO)	organ system cancer	0.04612	Least Informative	Inherited
Disease Ontology (DO)	nervous system disease	0.05623	Least Informative	Inherited
Disease Ontology (DO)	cell type cancer	0.008169	Moderately Informative	Inherited
Disease Ontology (DO)	hematologic cancer	0.06068	Moderately Informative	Inherited
Disease Ontology (DO)	gastrointestinal system disease	0.06087	Moderately Informative	Inherited
Disease Ontology (DO)	sensory system disease	0.3311	Moderately Informative	Inherited
Disease Ontology (DO)	vascular disease	0.3817	Moderately Informative	Inherited
Disease Ontology (DO)	bone disease	0.4976	Moderately Informative	Inherited
Disease Ontology (DO)	periodontitis	0.0001278	Informative	Direct
Disease Ontology (DO)	myeloma	0.0001478	Informative	Direct
Disease Ontology (DO)	arthritis	0.0004972	Informative	Direct
Disease Ontology (DO)	retinal degeneration	0.001666	Informative	Inherited
Disease Ontology (DO)	kidney cancer	0.001765	Informative	Inherited
Disease Ontology (DO)	aneurysm disease	0.006661	Informative	Inherited
Disease Ontology (DO)	medulloblastoma	0.0001914	Highly Informative	Direct
Disease Ontology (DO)	degeneration of macula and posterior pole	0.0002723	Highly Informative	Direct

Document: DO annotation of SCOP domains

Mouse Phenotype (MP)

(show details)

	MP term	FDR (all)	SDMP level	Annotation (direct or inherited)
Mammalian Phenotype (MP)	cardiovascular system phenotype	0.05133	Least Informative	Inherited
Mammalian Phenotype (MP)	nervous system phenotype	0.2149	Least Informative	Inherited
Mammalian Phenotype (MP)	immune system phenotype	0.2937	Least Informative	Inherited
Mammalian Phenotype (MP)	abnormal cardiovascular system physiology	0.3565	Moderately Informative	Inherited
Mammalian Phenotype (MP)	embryogenesis phenotype	0.3712	Moderately Informative	Inherited
Mammalian Phenotype (MP)	abnormal blood vessel physiology	0.09242	Informative	Inherited
Mammalian Phenotype (MP)	abnormal embryonic tissue morphology	0.229	Informative	Inherited
Mammalian Phenotype (MP)	abnormal neutrophil morphology	2.497e-05	Highly Informative	Direct
Mammalian Phenotype (MP)	abnormal somite size	7.059e-05	Highly Informative	Direct
Mammalian Phenotype (MP)	impaired somite development	0.00123	Highly Informative	Inherited
Mammalian Phenotype (MP)	abnormal neural tube closure	0.02495	Highly Informative	Inherited

Document: MP annotation of SCOP domains

Worm Phenotype (WP)

(show details) Document: WP annotation of SCOP domains

Fly Phenotype (FP)

(show details)

	FP term	FDR (all)	SDFP level	Annotation (direct or inherited)
Fly Phenotype (FP)	neuroanatomy defective	0	Moderately Informative	Direct

Document: FP annotation of SCOP domains

Fly Anatomy (FA)

(show details)

	FA term	FDR (all)	SDFA level	Annotation (direct or inherited)
Fly Anatomy (FA)	organ system	0	Least Informative	Direct
Fly Anatomy (FA)	cell	0	Least Informative	Direct

Document: FA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)

	XA term	FDR (all)	SDXA level	Annotation (direct or inherited)
Xenopus ANatomical entity (XAN)	alimentary system	0.2731	Least Informative	Inherited
Xenopus ANatomical entity (XAN)	portion of tissue	0.5879	Least Informative	Inherited
Xenopus ANatomical entity (XAN)	embryo	0.6745	Least Informative	Inherited
Xenopus ANatomical entity (XAN)	embryonic structure	0.05697	Moderately Informative	Inherited
Xenopus ANatomical entity (XAN)	ectoderm	0.7236	Moderately Informative	Inherited
Xenopus ANatomical entity (XAN)	neural plate	5.796e-05	Informative	Direct
Xenopus ANatomical entity (XAN)	endoderm	0.0001744	Informative	Direct
Xenopus ANatomical entity (XAN)	anatomical direction	0.003001	Informative	Inherited
Xenopus ANatomical entity (XAN)	optic field	1.273e-05	Highly Informative	Direct
Xenopus ANatomical entity (XAN)	chordal neural plate	1.856e-05	Highly Informative	Direct
Xenopus ANatomical entity (XAN)	foregut	0.0002055	Highly Informative	Direct
Xenopus DEvelopment stage (XDE)	embryonic stage	8.721e-05	Least Informative	Direct

Document: XA annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)

	KW term	FDR (all)	SDKW level	Annotation (direct or inherited)
Biological process	Differentiation	0	Moderately Informative	Direct
Biological process	Inflammatory response	0	Informative	Direct
Biological process	Innate immunity	0	Informative	Direct
Biological process	Wnt signaling pathway	0	Informative	Direct
Biological process	Complement pathway	0	Highly Informative	Direct
Biological process	Complement alternate pathway	1.975e-13	Highly Informative	Direct
Cellular component	Secreted	0	Moderately Informative	Direct
Cellular component	Extracellular matrix	9.209e-11	Informative	Direct
Domain	Signal	0	Least Informative	Direct
Domain	Laminin EGF-like domain	0	Highly Informative	Direct
Molecular function	Zinc	3.779e-12	Least Informative	Direct
Post-translational modification	Developmental protein	0	Moderately Informative	Direct
Post-translational modification	Protease inhibitor	0	Informative	Direct
Post-translational modification	Metalloenzyme inhibitor	0	Highly Informative	Direct
Post-translational modification	Glycoprotein	0	Least Informative	Direct
Post-translational modification	Disulfide bond	0	Least Informative	Direct
Post-translational modification	Cleavage on pair of basic residues	4.744e-08	Moderately Informative	Direct
Post-translational modification	Sulfation	5.913e-06	Informative	Direct
Post-translational modification	Thioester bond	0	Highly Informative	Direct

Document: KW annotation of SCOP domains

InterPro annotation

Cross references IPR008993 SSF50242 Protein matches

Abstract
Tissue inhibitors of metalloproteinases (TIMP) are a family of proteins that can form complexes with extracellular matrix metalloproteinases (such as collagenases) and irreversibly inactivate them [ PubMed 2793861]. TIMP and related proteins contains a five-stranded antiparallel beta-sheet that is rolled over on itself to form a closed beta-barrel, and two short helices, which pack close to one another on the same barrel face. A comparison of the delta TIMP-2 structure with other known protein folds reveals that the beta-barrel topology is homologous to that seen in proteins of the oligosaccharide/oligonucleotide binding (OB) fold family, a five-stranded beta-sheet coiled to form a closed beta-barrel capped by an alpha-helix located between the third and fourth strands [ PubMed 7918391].

Other proteins contain domains with a similar OB-like fold:

Netrin-like domain (NTR/C345C module), found in procollagen c-proteinase enhancer protein PCOLCE, and in the complement C5 domain.

Laminin-binding domain, found in agrin.

InterPro database

PDBeMotif information about ligands, sequence and structure motifs

Cross references

PDB entries
Ligand binding statistics
Nucleic-acid binding statistics
Occurrence of secondary structure elements
Occurrence of small 3D structural motifs

PDBeMotif resource

Jump to [ Top of page · SCOP classification · InterPro annotation · PDBeMotif links · Functional annotation · Gene Ontology (high-quality) · Gene Ontology (high-coverage) · Disease Ontology (DO) · Mouse Phenotype (MP) · Worm Phenotype (WP) · Fly Phenotype (FP) · Fly Anatomy (FA) · Xenopus Anatomy (XA) · UniProtKB KeyWords (KW) ]

Internal database links

Browse genome assignments for this superfamily. The SUPERFAMILY hidden Markov model library has been used to carry out SCOP domain assignments to all genomes at the superfamily level.

Alignments of sequences to 6 models in this superfamily are available by clicking on the 'Alignments' icon above. PDB sequences less than 40% identical are shown by default, but any other sequence(s) may be aligned. Select PDB sequences, genome sequences, or paste in or upload your own sequences.

Browse and view proteins in genomes which have different domain combinations including a TIMP-like domain.

Examine the distribution of domain superfamilies, or families, across the major taxonomic kingdoms or genomes within a kingdom. This gives an immediate impression of how superfamilies, or families, are restricted to certain kingdoms of life.

Explore domain occurrence network where nodes represent genomes and edges are domain architectures (shared between genomes) containing the superfamily of interest.

There are 6 hidden Markov models representing the TIMP-like superfamily. Information on how the models are built, and plots showing hydrophobicity, match emmission probabilities and insertion/deletion probabilities can be inspected.

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TIMP-like superfamily