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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 (156) Uniprot 2018_03 genome PDB chains (SCOP 1.75)
Domains 1,401 4,467 3
Proteins 1,383 4,416 3

Functional annotation
General category Regulation
Detailed category Receptor activity

Function annotation of SCOP domain superfamilies

Disease Ontology (DO)

(show details)
DO termFDR (all)SDDO levelAnnotation (direct or inherited)
Disease Ontology (DO)skin disease0.007247Moderately InformativeInherited
Disease Ontology (DO)urinary system disease0.00755Moderately InformativeInherited
Disease Ontology (DO)gastrointestinal system disease0.06046Moderately InformativeInherited
Disease Ontology (DO)periodontal disease0.00009727InformativeDirect
Disease Ontology (DO)proteinuria0.000007075Highly InformativeDirect
Disease Ontology (DO)psoriasis0.0002616Highly InformativeDirect

Document: DO annotation of SCOP domains

Human Phenotype (HP)

(show details)
HP termFDR (all)SDHP levelAnnotation (direct or inherited)
Phenotypic Abnormality (PA)Abnormality of nervous system morphology0.4251Least InformativeInherited
Phenotypic Abnormality (PA)Abnormality of immune system physiology0.05085Moderately InformativeInherited
Phenotypic Abnormality (PA)Abnormality of complement system0.00000008403InformativeDirect
Phenotypic Abnormality (PA)Unusual CNS infection0.0003035InformativeDirect

Document: HP annotation of SCOP domains

Mouse Phenotype (MP)

(show details)
MP termFDR (all)SDMP levelAnnotation (direct or inherited)
Mammalian Phenotype (MP)immune system phenotype0.008901Least InformativeInherited
Mammalian Phenotype (MP)mortality/aging0.2002Least InformativeInherited
Mammalian Phenotype (MP)abnormal inflammatory response0.0000486Moderately InformativeDirect
Mammalian Phenotype (MP)abnormal induced morbidity/mortality0.0009336Moderately InformativeDirect
Mammalian Phenotype (MP)liver/biliary system phenotype0.008722Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal reproductive system physiology0.08472Moderately InformativeInherited
Mammalian Phenotype (MP)embryo phenotype0.105Moderately InformativeInherited
Mammalian Phenotype (MP)abnormal liver physiology0.0001295InformativeDirect
Mammalian Phenotype (MP)abnormal sensitivity to induced morbidity/mortality0.0002725InformativeDirect
Mammalian Phenotype (MP)altered susceptibility to bacterial infection0.00156InformativeInherited
Mammalian Phenotype (MP)increased susceptibility to infection0.003606InformativeInherited
Mammalian Phenotype (MP)abnormal extraembryonic tissue morphology0.009194InformativeInherited
Mammalian Phenotype (MP)abnormal female reproductive system physiology0.01022InformativeInherited
Mammalian Phenotype (MP)increased sensitivity to induced morbidity/mortality0.00008764Highly InformativeDirect
Mammalian Phenotype (MP)abnormal trophoblast layer morphology0.0001318Highly InformativeDirect
Mammalian Phenotype (MP)abnormal pregnancy0.0001345Highly InformativeDirect
Mammalian Phenotype (MP)abnormal placenta labyrinth morphology0.0002073Highly InformativeDirect
Mammalian Phenotype (MP)increased susceptibility to bacterial infection0.0007725Highly InformativeDirect

Document: MP annotation of SCOP domains

Xenopus Anatomy (XA)

(show details)
XA termFDR (all)SDXA levelAnnotation (direct or inherited)
Xenopus ANatomical entity (XAN)trunk0Least InformativeDirect
Xenopus ANatomical entity (XAN)tissue0Least InformativeDirect
Xenopus ANatomical entity (XAN)embryo0.13Least InformativeInherited
Xenopus ANatomical entity (XAN)alimentary system0.1039Moderately InformativeInherited
Xenopus ANatomical entity (XAN)embryonic structure0.2276Moderately InformativeInherited
Xenopus ANatomical entity (XAN)surface structure0.0008479InformativeDirect
Xenopus ANatomical entity (XAN)endoderm0.00212InformativeInherited
Xenopus ANatomical entity (XAN)anatomical space0.006031InformativeInherited
Xenopus ANatomical entity (XAN)hindgut0.000001098Highly InformativeDirect
Xenopus ANatomical entity (XAN)archenteron0.000007589Highly InformativeDirect
Xenopus ANatomical entity (XAN)foregut0.0006662Highly InformativeDirect

Document: XA annotation of SCOP domains

InterPro annotation
Cross references IPR009048 SSF49410 Protein matches

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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Xenopus Anatomy (XA) ]

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 · Disease Ontology (DO) · Human Phenotype (HP) · Mouse Phenotype (MP) · Xenopus Anatomy (XA) · Internal database links ]