CCPDomain abundant in complement control proteins; SUSHI repeat; short complement-like repeat (SCR)
|SMART accession number:||SM00032|
|Description:||The complement control protein (CCP) modules (also known as short consensus repeats SCRs or SUSHI repeats) contain approximately 60 amino acid residues and have been identified in several proteins of the complement system. A missense mutation in seventh CCP domain causes deficiency of the b subunit of factor XIII.|
|Interpro abstract (IPR000436):|
Sushi domains are also known as Complement control protein (CCP) modules, or short consensus repeats (SCR), exist in a wide variety of complement and adhesion proteins. The structure is known for this domain, it is based on a beta-sandwich arrangement; one face made up of three beta-strands hydrogen-bonded to form a triple-stranded region at its centre and the other face formed from two separate beta-strands [(PUBMED:1829116)].
CD21 (also called C3d receptor, CR2, Epstein Barr virus receptor or EBV-R) is the receptor for EBV and for C3d, C3dg and iC3b. Complement components may activate B cells through CD21. CD21 is part of a large signal-transduction complex that also involves CD19, CD81, and Leu13.
Some of the proteins in this group are responsible for the molecular basis of the blood group antigens, surface markers on the outside of the red blood cell membrane. Most of these markers are proteins, but some are carbohydrates attached to lipids or proteins [Reid M.E., Lomas-Francis C. The Blood Group Antigen FactsBook Academic Press, London / San Diego, (1997)]. Complement decay-accelerating factor (Antigen CD55) belongs to the Cromer blood group system and is associated with Cr(a), Dr(a), Es(a), Tc(a/b/c), Wd(a), WES(a/b), IFC and UMC antigens. Complement receptor type 1 (C3b/C4b receptor) (Antigen CD35) belongs to the Knops blood group system and is associated with Kn(a/b), McC(a), Sl(a) and Yk(a) antigens.
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- Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing CCP domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with CCP domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing CCP domain in the selected taxonomic class.
- Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Hashiguchi T, Ichinose A
- Molecular and cellular basis of deficiency of the b subunit for factor XIII secondary to a Cys430-Phe mutation in the seventh Sushi domain.
- J Clin Invest. 1995; 95: 1002-8
- Display abstract
We studied the defect responsible for deficiency of the b subunit for factor XIII in the first known case of this condition. The patient is a compound heterozygote of two genetic defects: deletion of A-4161 at the acceptor splice junction of intron A, resulting in a loss of the obligatory AG splicing sequence; and, replacement of G-11499 by T in exon VIII, resulting in an amino acid substitution of Cys430 by Phe. To determine how the latter mutation impaired b subunit synthesis, recombinant b subunit bearing the mutation was expressed in BHK cells. The mutant as well as wild-type b subunit was synthesized by the cells. However, the apparent molecular weight of the mutant was slightly higher than those of the wild-type and plasma b subunits under nonreducing conditions, probably because of destruction of a disulfide bond. The mutant b subunit was secreted from the cells much less effectively than the wild type and remained susceptible to endoglycosidase H, indicating that it was not transported from the endoplasmic reticulum to the Golgi apparatus where the processing of oligosaccharides occurs. Immunofluorescence study suggested that the mutant protein was retained in the endoplasmic reticulum. These studies demonstrate that a Cys430-Phe mutation does not prevent the de novo synthesis of the b subunit, but alters the conformation of the mutant protein sufficiently to impair its intracellular transport, resulting in its deficiency in this patient.
- Norman DG, Barlow PN, Baron M, Day AJ, Sim RB, Campbell ID
- Three-dimensional structure of a complement control protein module in solution.
- J Mol Biol. 1991; 219: 717-25
- Display abstract
The complement control protein (CCP) modules (also known as short consensus repeats) are defined by a consensus sequence within a stretch of about 60 amino acid residues. These modules have been identified more than 140 times in over 20 proteins, including 12 proteins of the complement system. The solution structure of the 16th CCP module from human complement factor H has been determined by a combination of 2-dimensional nuclear magnetic resonance spectroscopy and restrained simulated annealing. In all, 548 structurally important nuclear Overhauser enhancement cross-peaks were quantified as distance restraints and, together with 41 experimentally measured angle restraints, were incorporated into a simulated annealing protocol to determine a family of closely related structures that satisfied the experimental observations. The CCP structure is shown to be based on a beta-sandwich arrangement; one face made up of three beta-strands hydrogen-bonded to form a triple-stranded region at its centre and the other face formed from two separate beta-strands. Both faces of the molecule contribute highly conserved hydrophobic side-chains to a compact core. The regions between the beta-strands are composed of both well-defined turns and less well-defined loops. Analysis of CCP sequence alignments, in light of the determined structure, reveals a high degree of conservation amongst residues of obvious structural importance, while almost all insertions, deletions or replacements observed in the known sequences are found in the less well-defined loop regions. On the basis of these observations it is postulated that models of other CCP modules that are based on the structure presented here will be accurate. Certain families of CCP modules differ from the consensus in that they contain extra cysteine residues. As a test of structural consensus, the extra disulphide bridges are shown to be easily accommodated within the determined CCP model.
- Ripoche J, Day AJ, Harris TJ, Sim RB
- The complete amino acid sequence of human complement factor H.
- Biochem J. 1988; 249: 593-602
- Display abstract
The complete amino acid sequence of the human complement system regulatory protein, factor H, has been derived from sequencing three overlapping cDNA clones. The sequence consists of 1213 amino acids arranged in 20 homologous units, each about 60 amino acids long, and an 18-residue leader sequence. The 60-amino-acid-long repetitive units are homologous with those found in a large number of other complement and non-complement proteins. Two basic C-terminal residues, deduced from the cDNA sequence, are absent from factor H isolated from outdated plasma. A tyrosine/histidine polymorphism was observed within the seventh homologous repeat unit of factor H. This is likely to represent a difference between the two major allelic variants of factor H. The nature of the cDNA clones indicates that there is likely to be an alternative splicing mechanism, resulting in the formation of at least two species of factor H mRNA.
- Disease (disease genes where sequence variants are found in this domain)
SwissProt sequences and OMIM curated human diseases associated with missense mutations within the CCP domain.
Protein Disease Beta-2-glycoprotein 1 (P02749) (SMART) OMIM:138700: APOLIPOPROTEIN H; APOH P-selectin (P16109) (SMART) OMIM:173610: Platelet alpha/delta storage pool deficiency Complement C2 (P06681) (SMART) OMIM:217000: C2 deficiency Coagulation factor XIII B chain (P05160) (SMART) OMIM:134580: Factor XIIIB deficiency
- Metabolism (metabolic pathways involving proteins which contain this domain)
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% proteins involved KEGG pathway ID Description 53.44 map04610 Complement and coagulation cascades 13.23 map04640 Hematopoietic cell lineage 12.70 map04514 Cell adhesion molecules (CAMs) 8.99 map04060 Cytokine-cytokine receptor interaction 3.70 map04080 Neuroactive ligand-receptor interaction 2.12 map04662 B cell receptor signaling pathway 1.59 map00350 Tyrosine metabolism 1.06 map00680 Methane metabolism 1.06 map00940 Phenylpropanoid biosynthesis 1.06 map00360 Phenylalanine metabolism 0.53 map04512 ECM-receptor interaction 0.53 map04510 Focal adhesion
This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with CCP domain which could be assigned to a KEGG orthologous group, and not all proteins containing CCP domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
- Structure (3D structures containing this domain)
3D Structures of CCP domains in PDB
PDB code Main view Title 1c1z CRYSTAL STRUCTURE OF HUMAN BETA-2-GLYCOPROTEIN-I (APOLIPOPROTEIN-H) 1ckl N-TERMINAL TWO DOMAINS OF HUMAN CD46 (MEMBRANE COFACTOR PROTEIN, MCP) 1e5g Solution structure of central CP module pair of a pox virus complement inhibitor 1elv CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COMPLEMENT C1S PROTEASE 1g40 CRYSTAL STRUCTURE OF A COMPLEMENT PROTEIN THAT REGULATES BOTH PATHWAYS OF COMPLEMENT ACTIVATION AND BINDS HEPARAN SULFATE PROTEOGLYCANS 1g44 CRYSTAL STRUCTURE OF A COMPLEMENT CONTROL PROTEIN THAT REGULATES BOTH PATHWAYS OF COMPLEMENT ACTIVATION AND BINDS HEPARAN SULFATE PROTEOGLYCANS 1ghq CR2-C3D COMPLEX STRUCTURE 1gkg Structure Determination and Rational Mutagenesis reveal binding surface of immune adherence receptor, CR1 (CD35) 1gkn Structure Determination and Rational Mutagenesis reveal binding surface of immune adherence receptor, CR1 (CD35) 1gpz The crystal structure of the zymogen catalytic domain of complement protease C1r 1h03 Human CD55 domains 3 & 4 1h04 Human CD55 domains 3 & 4 1h2p Human CD55 domains 3 & 4 1h2q Human CD55 domains 3 & 4 1haq FOUR MODELS OF HUMAN FACTOR H DETERMINED BY SOLUTION SCATTERING CURVE-FITTING AND HOMOLOGY MODELLING 1hcc THREE-DIMENSIONAL STRUCTURE OF A COMPLEMENT CONTROL PROTEIN MODULE IN SOLUTION 1hfh SOLUTION STRUCTURE OF A PAIR OF COMPLEMENT MODULES BY NUCLEAR MAGNETIC RESONANCE 1hfi SOLUTION STRUCTURE OF A PAIR OF COMPLEMENT MODULES BY NUCLEAR MAGNETIC RESONANCE 1ly2 Crystal structure of unliganded human CD21 SCR1-SCR2 (Complement receptor type 2) 1m11 structural model of human decay-accelerating factor bound to echovirus 7 from cryo-electron microscopy 1md7 Monomeric structure of the zymogen of complement protease C1r 1md8 Monomeric structure of the active catalytic domain of complement protease C1r 1ntj Model of rat Crry determined by solution scattering, curve fitting and homology modelling 1ntl Model of mouse Crry-Ig determined by solution scattering, curve fitting and homology modelling 1nwv SOLUTION STRUCTURE OF A FUNCTIONALLY ACTIVE COMPONENT OF DECAY ACCELERATING FACTOR 1ojv Decay accelerating factor (CD55): the structure of an intact human complement regulator. 1ojw Decay accelerating factor (CD55): the structure of an intact human complement regulator. 1ojy Decay accelerating factor (cd55): the structure of an intact human complement regulator. 1ok1 Decay accelerating factor (cd55) : the structure of an intact human complement regulator. 1ok2 Decay accelerating factor (CD55): the structure of an intact human complement regulator. 1ok3 Decay accelerating factor (cd55): the structure of an intact human complement regulator. 1ok9 Decay accelerating factor (CD55): The structure of an intact human complement regulator. 1ppq NMR structure of 16th module of Immune Adherence Receptor, Cr1 (Cd35) 1q3x Crystal structure of the catalytic region of human MASP-2 1qub CRYSTAL STRUCTURE OF THE GLYCOSYLATED FIVE-DOMAIN HUMAN BETA2-GLYCOPROTEIN I PURIFIED FROM BLOOD PLASMA 1rid Vaccinia Complement Protein in Complex with Heparin 1srz Solution structure of the second complement control protein (CCP) module of the GABA(B)R1a receptor, Pro-119 trans conformer 1ss2 Solution structure of the second complement control protein (CCP) module of the GABA(B)R1a receptor, Pro-119 cis conformer 1uot HUMAN CD55 DOMAINS 3 & 4 1upn Complex of Echovirus type 12 with domains 3 and 4 of its receptor decay accelerating factor (CD55) by cryo electron microscopy at 16 A 1vvc C-TERMINAL HALF OF VACCINIA VIRUS COMPLEMENT CONTROL PROTEIN, NMR, MINIMIZED AVERAGE STRUCTURE 1vvd C-TERMINAL HALF OF VACCINIA VIRUS COMPLEMENT CONTROL PROTEIN, NMR, 21 STRUCTURES 1vve C-TERMINAL HALF OF VACCINIA VIRUS COMPLEMENT CONTROL PROTEIN, NMR, 21 STRUCTURES 1w2r Solution structure of CR2 SCR 1-2 by X-ray scattering 1w2s Solution structure of CR2 SCR 1-2 in its complex with C3d by X-ray scattering 1y8e VCP:Suramin Complex 1z92 structure of interleukin-2 with its alpha receptor 1zjk Crystal structure of the zymogen catalytic region of human MASP-2 2a55 Solution structure of the two N-terminal CCP modules of C4b-binding protein (C4BP) alpha-chain. 2aty Complement receptor chimaeric conjugate CR2-Ig 2b5i cytokine receptor complex 2bzm Solution structure of the primary host recognition region of complement factor H 2c8i Complex Of Echovirus Type 12 With Domains 1, 2, 3 and 4 Of Its Receptor Decay Accelerating Factor (Cd55) By Cryo Electron Microscopy At 16 A 2ehf Solution structure of the third Sushi domain from human CUB and sushi domain-containing protein 1 2erj Crystal structure of the heterotrimeric interleukin-2 receptor in complex with interleukin-2 2ers Solution structure of the Interleukin-15 receptor sushi domain 2g7i Structure of Human Complement Factor H Carboxyl Terminal Domains 19-20: a Basis for Atypical Hemolytic Uremic Syndrome 2gsx Complement Receptor Type 2 2ic4 Solution structure of the His402 allotype of the Factor H SCR6-SCR7-SCR8 fragment 2jgw Structure of CCP module 7 of complement factor H - The AMD at risk varient (402H) 2jgx Structure of CCP module 7 of complement factor H - The AMD Not at risk varient (402Y) 2kms Combined high- and low-resolution techniques reveal compact structure in central portion of factor H despite long inter-modular linkers 2mcy CR1 Sushi domains 2 and 3 2mcz CR1 Sushi domains 1 and 2 2o39 Human Adenovirus type 11 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP) 2ok5 Human Complement factor B 2psm Crystal structure of Interleukin 15 in complex with Interleukin 15 receptor alpha 2q7z Solution Structure of the 30 SCR domains of human Complement Receptor 1 2qfg Solution Structure of the N-terminal SCR-1/5 fragment of Complement Factor H. 2qfh Solution Structure of the C-terminal SCR-16/20 fragment of Complement Factor H. 2qy0 Active dimeric structure of the catalytic domain of C1r reveals enzyme-product like contacts 2qzd Fitted structure of SCR4 of DAF into cryoEM density 2qzf SCR1 of DAF from 1ojv fitted into cryoEM density 2qzh SCR2/3 of DAF from the NMR structure 1nwv fitted into a cryoEM reconstruction of CVB3-RD complexed with DAF 2rlp NMR structure of CCP modules 1-2 of complement factor H 2rlq NMR structure of CCP modules 2-3 of complement factor H 2uwn Crystal structure of Human Complement Factor H, SCR domains 6-8 (H402 risk variant), in complex with ligand. 2v8e Crystal structure of Human Complement Factor H, SCR domains 6-8 (H402 risk variant), in complex with ligand. 2w80 Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs 6-7 of human complement factor H 2w81 Structure of a complex between Neisseria meningitidis factor H binding protein and CCPs 6-7 of human complement factor H 2wii Complement C3b in complex with factor H domains 1-4 2xqw Structure of Factor H domains 19-20 in complex with complement C3d 2xrb Structure of the N-terminal four domains of the complement regulator Rat Crry 2xrd Structure of the N-terminal four domains of the complement regulator Rat Crry 2xwb Crystal Structure of Complement C3b in complex with Factors B and D 2xwj Crystal Structure of Complement C3b in Complex with Factor B 2yby Structure of domains 6 and 7 of the mouse complement regulator Factor H 2yra Solution structure of the zinc finger domains (1-87) from human F-box only protein 2z3q Crystal structure of the IL-15/IL-15Ra complex 2z3r Crystal structure of the IL-15/IL-15Ra complex 3erb The Crystal Structure of C2b, a Fragment of Complement Component C2 produced during C3-convertase Formation 3gau Solution structure of Human Complement Factor H in 50 mM NaCl buffer 3gav Solution structure of Human Complement Factor H in 137 mM NaCl buffer 3gaw Solution structure of Human Complement Factor H in 250 mM NaCl buffer 3gov Crystal structure of the catalytic region of human MASP-1 3hrz Cobra Venom Factor (CVF) in complex with human factor B 3hs0 Cobra Venom Factor (CVF) in complex with human factor B 3inb Structure of the measles virus hemagglutinin bound to the CD46 receptor 3iu3 Crystal structure of the Fab fragment of therapeutic antibody Basiliximab in complex with IL-2Ra (CD25) ectodomain 3iyp The Interaction of Decay-accelerating Factor with Echovirus 7 3j24 CryoEM reconstruction of complement decay-accelerating factor 3kxv Structure of complement Factor H variant Q1139A 3kzj Structure of complement Factor H variant R1203A 3l89 Human Adenovirus type 21 knob in complex with domains SCR1 and SCR2 of CD46 (membrane cofactor protein, MCP) 3nfp Crystal structure of the Fab fragment of therapeutic antibody daclizumab in complex with IL-2Ra (CD25) ectodomain 3o8e Structure of extracelllar portion of CD46 in complex with Adenovirus type 11 knob 3oed The structure of the complex between complement receptor CR2 and its ligand complement fragment C3d 3oxu Complement components factor H CCP19-20 and C3d in complex 3r62 Structure of complement regulator Factor H mutant, T1184R. 3rj3 Complement components factor H CCP19-20 (S1191L mutant) and C3D in complex 3sw0 Structure of the C-terminal region (modules 18-20) of complement regulator Factor H 3t5o Crystal Structure of human Complement Component C6 3tvj Catalytic fragment of MASP-2 in complex with its specific inhibitor developed by directed evolution on SGCI scaffold 3zd1 STRUCTURE OF THE TWO C-TERMINAL DOMAINS OF COMPLEMENT FACTOR H RELATED PROTEIN 2 3zd2 THE STRUCTURE OF THE TWO N-TERMINAL DOMAINS OF COMPLEMENT FACTOR H RELATED PROTEIN 1 SHOWS FORMATION OF A NOVEL DIMERISATION INTERFACE 4a5w Crystal structure of C5b6 4aqb MBL-Ficolin Associated Protein-1, MAP-1 aka MAP44 4ayd Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria meningitidis FHbp Variant 1 R106A mutant 4aye Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria meningitidis FHbp Variant 1 E283AE304A mutant 4ayi Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria meningitidis FHbp Variant 3 Wild type 4aym Structure of a complex between CCPs 6 and 7 of Human Complement Factor H and Neisseria meningitidis FHbp Variant 3 P106A mutant 4b2r Solution structure of CCP modules 10-11 of complement factor H 4b2s Solution structure of CCP modules 11-12 of complement factor H 4djz Catalytic fragment of masp-1 in complex with its specific inhibitor developed by directed evolution on sgci scaffold 4e0s Crystal Structure of C5b-6 4f4o Structure of the Haptoglobin-Haemoglobin Complex 4fxg Complement C4 in complex with MASP-2 4gs7 Structure of the Interleukin-15 quaternary complex 4igd Crystal structure of the zymogen catalytic region of Human MASP-1 4j1y The X-ray crystal structure of human complement protease C1s zymogen 4j38 Structure of Borrelia burgdorferi Outer surface protein E in complex with Factor H domains 19-20 4jhs Crystal structure of a C-terminal two domain fragment of human beta-2-glycoprotein 1 4k12 Structural Basis for Host Specificity of Factor H Binding by Streptococcus pneumoniae 4kkd The X-ray crystal structure of Mannose-binding lectin-associated serine proteinase-3 reveals the structural basis for enzyme inactivity associated with the 3MC syndrome 4los C1s CUB2-CCP1 4lot C1s CUB2-CCP1-CCP2
- Links (links to other resources describing this domain)
PFAM sushi INTERPRO IPR000436