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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 (199) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 2,217 2,888 11
Proteins 2,197 2,871 11


Functional annotation
General category Processes_IC
Detailed category Proteases

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-quality)

(show details)
GO termFDR (singleton)FDR (all)SDFO levelAnnotation (direct or inherited)
Biological Process (BP)developmental process0.00053730.00000000002057Least InformativeDirect
Biological Process (BP)regulation of metabolic process00.01428Least InformativeInherited
Biological Process (BP)single-organism cellular process0.0020270.02165Least InformativeInherited
Biological Process (BP)multicellular organismal process0.0021010.000000004651Least InformativeInherited
Biological Process (BP)regulation of cellular process0.055391Least InformativeInherited
Biological Process (BP)response to stimulus0.0060390.000005044Least InformativeInherited
Biological Process (BP)regulation of signal transduction00.0003223Moderately InformativeDirect
Biological Process (BP)cell differentiation0.000066680.000000000001461Moderately InformativeDirect
Biological Process (BP)regulation of catalytic activity0.00000085840.00000355Moderately InformativeDirect
Biological Process (BP)regulation of nucleobase-containing compound metabolic process0.091161Moderately InformativeInherited
Biological Process (BP)regulation of phosphate metabolic process10.0000000001806Moderately InformativeInherited
Biological Process (BP)regulation of developmental process0.028120.0000002568Moderately InformativeInherited
Biological Process (BP)regulation of multicellular organismal process0.1070.0000664Moderately InformativeInherited
Biological Process (BP)nervous system development0.092270.07999Moderately InformativeInherited
Biological Process (BP)regulation of cell proliferation0.000000000043730.00000002192InformativeDirect
Biological Process (BP)negative regulation of catalytic activity00.0000005682InformativeDirect
Biological Process (BP)generation of neurons0.000016430.000000002485InformativeDirect
Biological Process (BP)regulation of peptidase activity00.000000000411InformativeDirect
Biological Process (BP)regulation of purine nucleotide metabolic process0.00000035130.000006464InformativeDirect
Biological Process (BP)regulation of nervous system development0.00000000011480.01153InformativeInherited
Biological Process (BP)regulation of cell development0.0000000003960.08708InformativeInherited
Biological Process (BP)negative regulation of endopeptidase activity00Highly InformativeDirect
Molecular Function (MF)binding0.000031480.0000000118Least InformativeDirect
Molecular Function (MF)enzyme regulator activity00Moderately InformativeDirect
Molecular Function (MF)enzyme inhibitor activity00.000000005363InformativeDirect
Molecular Function (MF)receptor binding00InformativeDirect
Molecular Function (MF)peptidase regulator activity00InformativeDirect
Molecular Function (MF)cytokine activity0.00098380.00003375Highly InformativeDirect
Molecular Function (MF)protein complex binding0.0000025190.0009441Highly InformativeDirect
Cellular Component (CC)extracellular region part00Moderately InformativeDirect
Cellular Component (CC)cell surface0.000000000075690.0000006696InformativeDirect
Cellular Component (CC)extracellular matrix00InformativeDirect
Cellular Component (CC)proteinaceous extracellular matrix0.000000000062570.00000004568Highly InformativeDirect
Cellular Component (CC)extracellular matrix part00Highly InformativeDirect

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 0.000000004651 Least Informative Direct
Biological Process (BP) developmental process 0.00000000002057 Least Informative Direct
Biological Process (BP) response to stimulus 0.000005044 Least Informative Direct
Biological Process (BP) localization 0.9791 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.01428 Least Informative Inherited
Biological Process (BP) single-organism cellular process 0.02165 Least Informative Inherited
Biological Process (BP) regulation of cellular process 1 Least Informative Inherited
Biological Process (BP) protein metabolic process 0.05143 Least Informative Inherited
Biological Process (BP) cellular component organization or biogenesis 0.06377 Least Informative Inherited
Biological Process (BP) regulation of signal transduction 0.0003223 Moderately Informative Direct
Biological Process (BP) regulation of phosphate metabolic process 0.0000000001806 Moderately Informative Direct
Biological Process (BP) cell differentiation 0.000000000001461 Moderately Informative Direct
Biological Process (BP) single-organism developmental process 0.0006521 Moderately Informative Direct
Biological Process (BP) regulation of catalytic activity 0.00000355 Moderately Informative Direct
Biological Process (BP) regulation of developmental process 0.0000002568 Moderately Informative Direct
Biological Process (BP) regulation of multicellular organismal process 0.0000664 Moderately Informative Direct
Biological Process (BP) regulation of protein metabolic process 0.0000521 Moderately Informative Direct
Biological Process (BP) regulation of nucleobase-containing compound metabolic process 1 Moderately Informative Inherited
Biological Process (BP) macromolecule localization 0.1021 Moderately Informative Inherited
Biological Process (BP) cellular localization 0.8066 Moderately Informative Inherited
Biological Process (BP) regulation of gene expression 1 Moderately Informative Inherited
Biological Process (BP) organ development 1 Moderately Informative Inherited
Biological Process (BP) tissue development 0.3997 Moderately Informative Inherited
Biological Process (BP) regulation of cellular component organization 0.02498 Moderately Informative Inherited
Biological Process (BP) system process 1 Moderately Informative Inherited
Biological Process (BP) regulation of biological quality 1 Moderately Informative Inherited
Biological Process (BP) response to endogenous stimulus 0.08723 Moderately Informative Inherited
Biological Process (BP) response to organic substance 0.7115 Moderately Informative Inherited
Biological Process (BP) positive regulation of cellular process 0.05203 Moderately Informative Inherited
Biological Process (BP) nervous system development 0.07999 Moderately Informative Inherited
Biological Process (BP) negative regulation of cellular process 0.1125 Moderately Informative Inherited
Biological Process (BP) signal transduction 1 Moderately Informative Inherited
Biological Process (BP) regulation of localization 0.06921 Moderately Informative Inherited
Biological Process (BP) regulation of cellular biosynthetic process 1 Moderately Informative Inherited
Biological Process (BP) positive regulation of response to stimulus 0.1154 Moderately Informative Inherited
Biological Process (BP) immune system process 0.001608 Moderately Informative Inherited
Biological Process (BP) anatomical structure morphogenesis 0.3301 Moderately Informative Inherited
Biological Process (BP) regulation of protein phosphorylation 0.00000001602 Informative Direct
Biological Process (BP) immune effector process 0.000005001 Informative Direct
Biological Process (BP) negative regulation of signaling 0.0005789 Informative Direct
Biological Process (BP) cell projection organization 0.0001247 Informative Direct
Biological Process (BP) regulation of growth 0.00002509 Informative Direct
Biological Process (BP) locomotion 0.00009043 Informative Direct
Biological Process (BP) regulation of cell proliferation 0.00000002192 Informative Direct
Biological Process (BP) regulation of apoptotic process 0.000001035 Informative Direct
Biological Process (BP) negative regulation of catalytic activity 0.0000005682 Informative Direct
Biological Process (BP) generation of neurons 0.000000002485 Informative Direct
Biological Process (BP) regulation of peptidase activity 0.000000000411 Informative Direct
Biological Process (BP) regulation of purine nucleotide metabolic process 0.000006464 Informative Direct
Biological Process (BP) cellular component morphogenesis 0.003953 Informative Inherited
Biological Process (BP) cellular component movement 0.003594 Informative Inherited
Biological Process (BP) cellular membrane organization 0.007987 Informative Inherited
Biological Process (BP) tissue morphogenesis 0.02817 Informative Inherited
Biological Process (BP) epithelium development 0.748 Informative Inherited
Biological Process (BP) synaptic transmission 0.3771 Informative Inherited
Biological Process (BP) positive regulation of immune system process 0.008061 Informative Inherited
Biological Process (BP) muscle structure development 0.03084 Informative Inherited
Biological Process (BP) response to hormone stimulus 0.1065 Informative Inherited
Biological Process (BP) response to organic cyclic compound 0.6155 Informative Inherited
Biological Process (BP) response to lipid 0.1142 Informative Inherited
Biological Process (BP) regulation of intracellular protein kinase cascade 1 Informative Inherited
Biological Process (BP) positive regulation of signal transduction 1 Informative Inherited
Biological Process (BP) regulation of nervous system development 0.01153 Informative Inherited
Biological Process (BP) regulation of cell development 0.08708 Informative Inherited
Biological Process (BP) regulation of immune effector process 0.001173 Informative Inherited
Biological Process (BP) negative regulation of cell communication 0.001146 Informative Inherited
Biological Process (BP) negative regulation of response to stimulus 0.004784 Informative Inherited
Biological Process (BP) muscle tissue development 0.06723 Informative Inherited
Biological Process (BP) regulation of lipid metabolic process 0.004821 Informative Inherited
Biological Process (BP) positive regulation of transport 0.0131 Informative Inherited
Biological Process (BP) immune response 0.006458 Informative Inherited
Biological Process (BP) regulation of immune response 0.8579 Informative Inherited
Biological Process (BP) regulation of defense response 0.4669 Informative Inherited
Biological Process (BP) regulation of response to external stimulus 0.159 Informative Inherited
Biological Process (BP) regulation of acute inflammatory response 0.000002087 Highly Informative Direct
Biological Process (BP) regulation of humoral immune response 0.000000001164 Highly Informative Direct
Biological Process (BP) humoral immune response 0.0000000000002818 Highly Informative Direct
Biological Process (BP) regulation of lipid storage 0.0000001288 Highly Informative Direct
Biological Process (BP) negative regulation of endopeptidase activity 0 Highly Informative Direct
Biological Process (BP) regulation of striated muscle tissue development 0.000005603 Highly Informative Direct
Biological Process (BP) extracellular matrix organization 0.00001121 Highly Informative Direct
Biological Process (BP) regulation of developmental growth 0.0000175 Highly Informative Direct
Biological Process (BP) muscle fiber development 0.00000004916 Highly Informative Direct
Biological Process (BP) regulation of protein processing 0.00000000001309 Highly Informative Direct
Biological Process (BP) protein activation cascade 0.00000000000004112 Highly Informative Direct
Biological Process (BP) neuron projection development 0.01879 Highly Informative Inherited
Biological Process (BP) cell part morphogenesis 0.009494 Highly Informative Inherited
Biological Process (BP) chemotaxis 0.002044 Highly Informative Inherited
Biological Process (BP) muscle organ development 0.07934 Highly Informative Inherited
Biological Process (BP) regulation of cellular response to stress 0.02692 Highly Informative Inherited
Biological Process (BP) regulation of G-protein coupled receptor protein signaling pathway 0.01088 Highly Informative Inherited
Biological Process (BP) cell morphogenesis involved in differentiation 0.0127 Highly Informative Inherited
Molecular Function (MF) binding 0.0000000118 Least Informative Direct
Molecular Function (MF) enzyme regulator activity 0 Moderately Informative Direct
Molecular Function (MF) anion binding 0.05718 Moderately Informative Inherited
Molecular Function (MF) enzyme inhibitor activity 0.000000005363 Informative Direct
Molecular Function (MF) receptor binding 0 Informative Direct
Molecular Function (MF) peptidase regulator activity 0 Informative Direct
Molecular Function (MF) carbohydrate derivative binding 0.00008334 Informative Direct
Molecular Function (MF) sulfur compound binding 0.00002489 Informative Direct
Molecular Function (MF) cytokine activity 0.00003375 Highly Informative Direct
Molecular Function (MF) heparin binding 0.0000007299 Highly Informative Direct
Molecular Function (MF) protein complex binding 0.0009441 Highly Informative Direct
Cellular Component (CC) extracellular region part 0 Moderately Informative Direct
Cellular Component (CC) vesicle 0.004642 Moderately Informative Inherited
Cellular Component (CC) cell surface 0.0000006696 Informative Direct
Cellular Component (CC) extracellular matrix 0 Informative Direct
Cellular Component (CC) extracellular membrane-bounded organelle 0.000006814 Informative Direct
Cellular Component (CC) proteinaceous extracellular matrix 0.00000004568 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 termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)organ system cancer0.04612Least InformativeInherited
Disease Ontology (DO)nervous system disease0.09887Least InformativeInherited
Disease Ontology (DO)connective tissue disease0.00003425Moderately InformativeDirect
Disease Ontology (DO)mouth disease0.007072Moderately InformativeInherited
Disease Ontology (DO)cell type cancer0.00793Moderately InformativeInherited
Disease Ontology (DO)sensory system disease0.298Moderately InformativeInherited
Disease Ontology (DO)artery disease0.8696Moderately InformativeInherited
Disease Ontology (DO)periodontitis0.0001247InformativeDirect
Disease Ontology (DO)myeloma0.000151InformativeDirect
Disease Ontology (DO)arthritis0.0004866InformativeDirect
Disease Ontology (DO)retinal disease0.01308InformativeInherited
Disease Ontology (DO)urinary system cancer0.02777InformativeInherited
Disease Ontology (DO)medulloblastoma0.0001838Highly InformativeDirect
Disease Ontology (DO)degeneration of macula and posterior pole0.0002277Highly InformativeDirect
Disease Ontology (DO)cerebrovascular disease0.009581Highly InformativeInherited

Document: DO annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)nervous system phenotype0.2491Least InformativeInherited
Mammalian Phenotype (MP)hematopoietic system phenotype0.295Least InformativeInherited
Mammalian Phenotype (MP)immune system phenotype0.3698Least InformativeInherited
Mammalian Phenotype (MP)abnormal nervous system development0.1392Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hematopoietic cell number0.3248Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal skeleton morphology0.7106Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal embryogenesis/ development1Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal vertebrae morphology0.03043InformativeInherited
Mammalian Phenotype (MP)abnormal neural tube morphology/development0.1841InformativeInherited
Mammalian Phenotype (MP)fused somites0.00000129Highly InformativeDirect
Mammalian Phenotype (MP)craniorachischisis0.000003721Highly InformativeDirect
Mammalian Phenotype (MP)abnormal rostral-caudal body axis extension0.000005683Highly InformativeDirect
Mammalian Phenotype (MP)decreased somite size0.00003468Highly InformativeDirect
Mammalian Phenotype (MP)abnormal neutrophil morphology0.00004058Highly InformativeDirect
Mammalian Phenotype (MP)incomplete somite formation0.0001615Highly InformativeDirect
Mammalian Phenotype (MP)abnormal granulocyte number0.0003341Highly InformativeDirect
Mammalian Phenotype (MP)abnormal neural tube closure0.02826Highly InformativeInherited

Document: MP annotation of SCOP domains

Worm Phenotype (WP)

(show details) Document: WP annotation of SCOP domains

Fly Phenotype (FP)

(show details)
FP termFDR (all)SDFP levelAnnotation (direct or inherited)
Fly Phenotype (FP)neuroanatomy defective0Moderately InformativeDirect

Document: FP annotation of SCOP domains

Fly Anatomy (FA)

(show details)
FA termFDR (all)SDFA levelAnnotation (direct or inherited)
Fly Anatomy (FA)larva0Least InformativeDirect
Fly Anatomy (FA)organ system0Least InformativeDirect
Fly Anatomy (FA)cell0Least InformativeDirect
Fly Anatomy (FA)late embryo0Moderately InformativeDirect

Document: FA annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)alimentary system0.2729Least InformativeInherited
Xenopus ANatomical entity (XAN)portion of tissue0.6008Least InformativeInherited
Xenopus ANatomical entity (XAN)embryo0.6964Least InformativeInherited
Xenopus ANatomical entity (XAN)embryonic structure0.07709Moderately InformativeInherited
Xenopus ANatomical entity (XAN)ectoderm0.7453Moderately InformativeInherited
Xenopus ANatomical entity (XAN)pre-chordal neural plate0.000003368InformativeDirect
Xenopus ANatomical entity (XAN)chordal neural plate0.00005509InformativeDirect
Xenopus ANatomical entity (XAN)endoderm0.0002913InformativeDirect
Xenopus ANatomical entity (XAN)anatomical direction0.0007332InformativeDirect
Xenopus ANatomical entity (XAN)primordium0.00102InformativeInherited
Xenopus ANatomical entity (XAN)stomodeal-hypophyseal primordium0.00005524Highly InformativeDirect
Xenopus ANatomical entity (XAN)optic field0.00006832Highly InformativeDirect
Xenopus ANatomical entity (XAN)foregut0.0004182Highly InformativeDirect
Xenopus ANatomical entity (XAN)axial mesoderm0.0008206Highly InformativeDirect
Xenopus DEvelopment stage (XDE)embryonic stage0.00008859Least InformativeDirect

Document: XA annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processDifferentiation0Moderately InformativeDirect
Biological processInflammatory response0InformativeDirect
Biological processInnate immunity0InformativeDirect
Biological processWnt signaling pathway0InformativeDirect
Biological processComplement pathway0Highly InformativeDirect
Biological processComplement alternate pathway0.00000000001375Highly InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
Cellular componentExtracellular matrix0.00000000001962InformativeDirect
DomainSignal0Least InformativeDirect
DomainLaminin EGF-like domain0Highly InformativeDirect
Molecular functionZinc0.000000000009183Least InformativeDirect
Post-translational modificationDevelopmental protein0Moderately InformativeDirect
Post-translational modificationProtease inhibitor0InformativeDirect
Post-translational modificationGrowth factor8.845e-16InformativeDirect
Post-translational modificationToxin0.001925InformativeInherited
Post-translational modificationMetalloenzyme inhibitor0Highly InformativeDirect
Post-translational modificationGlycoprotein0Least InformativeDirect
Post-translational modificationDisulfide bond0Least InformativeDirect
Post-translational modificationCleavage on pair of basic residues0.000000000001982Moderately InformativeDirect
Post-translational modificationSulfation0.000005606InformativeDirect
Post-translational modificationThioester bond0Highly InformativeDirect

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 [PubMed2793861]. 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 [PubMed7918391].

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.


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 ]