SUPERFAMILY 1.75 HMM library and genome assignments server

Alpha-macroglobulin receptor domain superfamily

SCOP classification
Root:   SCOP hierarchy in SUPERFAMILY [ 0] (11)
Class:   All beta proteins [ 48724] (174)
Fold:   Common fold of diphtheria toxin/transcription factors/cytochrome f [ 49379] (10)
Superfamily:   Alpha-macroglobulin receptor domain [ 49410]
Families:   Alpha-macroglobulin receptor domain [ 49411] (2)


Superfamily statistics
Genomes (150) Uniprot 2014_06 PDB chains (SCOP 1.75)
Domains 1,303 1,764 3
Proteins 1,292 1,753 3


Functional annotation
General category Regulation
Detailed category Receptor activity

Document:
Function annotation of SCOP domain superfamilies

Gene Ontology (high-coverage)

(show details)
GO term FDR (all) SDFO level Annotation (direct or inherited)
Biological Process (BP) response to stimulus 0.00004139 Least Informative Direct
Biological Process (BP) protein metabolic process 0.0006205 Least Informative Direct
Biological Process (BP) regulation of cellular process 1 Least Informative Inherited
Biological Process (BP) regulation of metabolic process 0.003096 Least Informative Inherited
Biological Process (BP) positive regulation of biological process 0.03178 Least Informative Inherited
Biological Process (BP) localization 0.07555 Least Informative Inherited
Biological Process (BP) single-organism metabolic process 0.1027 Least Informative Inherited
Biological Process (BP) regulation of protein metabolic process 0.000000000000001913 Moderately Informative Direct
Biological Process (BP) defense response 0.000000004599 Moderately Informative Direct
Biological Process (BP) positive regulation of response to stimulus 0.0000002478 Moderately Informative Direct
Biological Process (BP) immune system process 0.0000002853 Moderately Informative Direct
Biological Process (BP) multi-organism process 0.00003322 Moderately Informative Direct
Biological Process (BP) regulation of catalytic activity 0.1777 Moderately Informative Inherited
Biological Process (BP) regulation of cellular component organization 0.3357 Moderately Informative Inherited
Biological Process (BP) regulation of signal transduction 0.9434 Moderately Informative Inherited
Biological Process (BP) negative regulation of metabolic process 0.6242 Moderately Informative Inherited
Biological Process (BP) response to external stimulus 0.06059 Moderately Informative Inherited
Biological Process (BP) regulation of gene expression 1 Moderately Informative Inherited
Biological Process (BP) regulation of cellular biosynthetic process 1 Moderately Informative Inherited
Biological Process (BP) regulation of localization 0.001081 Moderately Informative Inherited
Biological Process (BP) positive regulation of cellular process 1 Moderately Informative Inherited
Biological Process (BP) positive regulation of metabolic process 0.9913 Moderately Informative Inherited
Biological Process (BP) regulation of phosphorus metabolic process 0.008024 Moderately Informative Inherited
Biological Process (BP) regulation of response to wounding 0 Informative Direct
Biological Process (BP) positive regulation of immune system process 0.000000006189 Informative Direct
Biological Process (BP) response to bacterium 0.00000001046 Informative Direct
Biological Process (BP) immune effector process 0.00000002979 Informative Direct
Biological Process (BP) regulation of peptidase activity 0.00000007479 Informative Direct
Biological Process (BP) positive regulation of transport 0.0000001785 Informative Direct
Biological Process (BP) regulation of immune response 0.0000006117 Informative Direct
Biological Process (BP) immune response 0.0000007005 Informative Direct
Biological Process (BP) regulation of response to external stimulus 0.00000105 Informative Direct
Biological Process (BP) regulation of protein phosphorylation 0.000001241 Informative Direct
Biological Process (BP) vesicle-mediated transport 0.000003569 Informative Direct
Biological Process (BP) regulation of immune effector process 0.00000389 Informative Direct
Biological Process (BP) regulation of vesicle-mediated transport 0.00002287 Informative Direct
Biological Process (BP) regulation of lipid metabolic process 0.00008105 Informative Direct
Biological Process (BP) negative regulation of catalytic activity 0.000402 Informative Direct
Biological Process (BP) regulation of defense response 0.00203 Informative Inherited
Biological Process (BP) positive regulation of cellular component organization 0.02035 Informative Inherited
Biological Process (BP) defense response to other organism 0.2848 Informative Inherited
Biological Process (BP) protein activation cascade 0 Highly Informative Direct
Biological Process (BP) humoral immune response 0 Highly Informative Direct
Biological Process (BP) regulation of acute inflammatory response 0 Highly Informative Direct
Biological Process (BP) phagocytosis 0.00000000004316 Highly Informative Direct
Biological Process (BP) regulation of humoral immune response 0.0000000005741 Highly Informative Direct
Biological Process (BP) regulation of lipid storage 0.000000001004 Highly Informative Direct
Biological Process (BP) regulation of G-protein coupled receptor protein signaling pathway 0.00000004906 Highly Informative Direct
Biological Process (BP) regulation of endocytosis 0.0000002257 Highly Informative Direct
Biological Process (BP) defense response to bacterium 0.000677 Highly Informative Direct
Molecular Function (MF) binding 0.4312 Least Informative Inherited
Molecular Function (MF) enzyme regulator activity 0.000000007008 Moderately Informative Direct
Molecular Function (MF) peptidase regulator activity 0.00000000000000467 Informative Direct
Molecular Function (MF) enzyme inhibitor activity 0.0000000000001454 Informative Direct
Molecular Function (MF) receptor binding 0.000001711 Informative Direct
Cellular Component (CC) extracellular region part 0.000007211 Moderately Informative Direct
Cellular Component (CC) vesicle 0.0007667 Moderately Informative Direct
Cellular Component (CC) extracellular space 0.00000001032 Informative Direct
Cellular Component (CC) extracellular membrane-bounded organelle 0.000003968 Informative Direct

Document: GO annotation of SCOP domains

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)mouth disease0.0002511Moderately InformativeDirect
Disease Ontology (DO)skin disease0.006827Moderately InformativeInherited
Disease Ontology (DO)urinary system disease0.007773Moderately InformativeInherited
Disease Ontology (DO)periodontitis0.0000685InformativeDirect
Disease Ontology (DO)psoriasis0.0002561InformativeDirect
Disease Ontology (DO)proteinuria0.000007004Highly InformativeDirect

Document: DO annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)immune system phenotype0.009404Least InformativeInherited
Mammalian Phenotype (MP)mortality/aging0.4758Least InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.00007284Moderately InformativeDirect
Mammalian Phenotype (MP)liver/biliary system phenotype0.008422Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system physiology0.09399Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal embryogenesis/ development1Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal hepatobiliary system physiology0.0002446InformativeDirect
Mammalian Phenotype (MP)abnormal sensitivity to induced morbidity/mortality0.0004312InformativeDirect
Mammalian Phenotype (MP)abnormal female reproductive system physiology0.01231InformativeInherited
Mammalian Phenotype (MP)abnormal extraembryonic tissue morphology0.01477InformativeInherited
Mammalian Phenotype (MP)increased sensitivity to induced morbidity/mortality0.0001363Highly InformativeDirect
Mammalian Phenotype (MP)abnormal pregnancy0.0001927Highly InformativeDirect
Mammalian Phenotype (MP)abnormal trophoblast layer morphology0.0001974Highly InformativeDirect
Mammalian Phenotype (MP)abnormal placenta labyrinth morphology0.000268Highly InformativeDirect

Document: MP annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)alimentary system0Least InformativeDirect
Xenopus ANatomical entity (XAN)genital system0Least InformativeDirect
Xenopus ANatomical entity (XAN)male organism0Least InformativeDirect
Xenopus ANatomical entity (XAN)viscus0Least InformativeDirect
Xenopus ANatomical entity (XAN)portion of tissue0Least InformativeDirect
Xenopus ANatomical entity (XAN)gonad0Least InformativeDirect
Xenopus ANatomical entity (XAN)embryo0.2367Least InformativeInherited
Xenopus ANatomical entity (XAN)surface structure0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)immune system0Moderately InformativeDirect
Xenopus ANatomical entity (XAN)embryonic structure0.1077Moderately InformativeInherited
Xenopus ANatomical entity (XAN)liver and biliary system0InformativeDirect
Xenopus ANatomical entity (XAN)solid compound organ0InformativeDirect
Xenopus ANatomical entity (XAN)endoderm0.00005797InformativeDirect
Xenopus ANatomical entity (XAN)adipose tissue0Highly InformativeDirect
Xenopus ANatomical entity (XAN)midgut0.00000003052Highly InformativeDirect
Xenopus ANatomical entity (XAN)hindgut0.0000001143Highly InformativeDirect
Xenopus ANatomical entity (XAN)foregut0.000007508Highly InformativeDirect

Document: XA annotation of SCOP domains

DrugBank ATC (DB)

(show details)
DB termFDR (all)SDDB levelAnnotation (direct or inherited)
Drugbank ATC_code (DB)antiinfectives for systemic use0Least InformativeDirect
Drugbank ATC_code (DB)immunoglobulins, normal human0.0000000002527InformativeDirect

Document: DB annotation of SCOP domains

UniProtKB KeyWords (KW)

(show details)
KW termFDR (all)SDKW levelAnnotation (direct or inherited)
Biological processLipid metabolism0.001508Moderately InformativeInherited
Biological processInflammatory response0InformativeDirect
Biological processInnate immunity0InformativeDirect
Biological processFatty acid metabolism0.000007964InformativeDirect
Biological processComplement pathway0Highly InformativeDirect
Biological processComplement alternate pathway0.00000000001376Highly InformativeDirect
Cellular componentSecreted0Moderately InformativeDirect
DomainSignal0Least InformativeDirect
Post-translational modificationProtease inhibitor0InformativeDirect
Post-translational modificationToxin0.0000101InformativeDirect
Post-translational modificationGlycoprotein0Least InformativeDirect
Post-translational modificationDisulfide bond0.000000000000001793Least InformativeDirect
Post-translational modificationCleavage on pair of basic residues0Moderately InformativeDirect
Post-translational modificationSulfation0.00000002637InformativeDirect
Post-translational modificationThioester bond0Highly InformativeDirect

Document: KW annotation of SCOP domains

InterPro annotation
Cross references IPR009048 SSF49410 Protein matches
Abstract

This entry represents the receptor-binding domain (RBD) of alpha-2-macroglobulin proteins. The RBD is located at the C-terminus, its structure having an immunoglobulin-like fold consists of a sandwich of nine strands in two sheets with a Greek-key topology [PubMed11106161, PubMed9634697].

The alpha-macroglobulin (aM) family of proteins includes protease inhibitors [PubMed2473064], typified by the human tetrameric a2-macroglobulin (a2M); they belong to the MEROPS proteinase inhibitor family I39, clan IL. These protease inhibitors share several defining properties, which include (i) the ability to inhibit proteases from all catalytic classes, (ii) the presence of a 'bait region' and a thiol ester, (iii) a similar protease inhibitory mechanism and (iv) the inactivation of the inhibitory capacity by reaction of the thiol ester with small primary amines. aM protease inhibitors inhibit by steric hindrance [PubMed2472396]. The mechanism involves protease cleavage of the bait region, a segment of the aM that is particularly susceptible to proteolytic cleavage, which initiates a conformational change such that the aM collapses about the protease. In the resulting aM-protease complex, the active site of the protease is sterically shielded, thus substantially decreasing access to protein substrates. Two additional events occur as a consequence of bait region cleavage, namely (i) the h-cysteinyl-g-glutamyl thiol ester becomes highly reactive and (ii) a major conformational change exposes a conserved COOH-terminal receptor binding domain [PubMed2469470] (RBD). RBD exposure allows the aM protease complex to bind to clearance receptors and be removed from circulation [PubMed2430968]. Tetrameric, dimeric, and, more recently, monomeric aM protease inhibitors have been identified [PubMed9914899, PubMed10426429].


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-coverage) · Disease Ontology (DO) · Mouse Phenotype (MP) · Xenopus Anatomy (XA) · DrugBank ATC (DB) · 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 3 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 Alpha-macroglobulin receptor domain 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 3 hidden Markov models representing the Alpha-macroglobulin receptor domain 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-coverage) · Disease Ontology (DO) · Mouse Phenotype (MP) · Xenopus Anatomy (XA) · DrugBank ATC (DB) · UniProtKB KeyWords (KW) · Internal database links ]