| IED ID |
IndEnz0002005512 |
| Enzyme Type ID |
protease005512 |
| Protein Name |
Protein cereblon
|
| Gene Name |
CRBN AD-006 |
| Organism |
Homo sapiens (Human) |
| Taxonomic Lineage |
cellular organisms
Eukaryota
Opisthokonta
Metazoa
Eumetazoa
Bilateria
Deuterostomia
Chordata
Craniata
Vertebrata
Gnathostomata (jawed vertebrates)
Teleostomi
Euteleostomi
Sarcopterygii
Dipnotetrapodomorpha
Tetrapoda
Amniota
Mammalia
Theria
Eutheria
Boreoeutheria
Euarchontoglires
Primates
Haplorrhini
Simiiformes
Catarrhini
Hominoidea (apes)
Hominidae (great apes)
Homininae
Homo
Homo sapiens (Human)
|
| Enzyme Sequence |
MAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVEDQDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL |
| Enzyme Length |
442 |
| Uniprot Accession Number |
Q96SW2 |
| Absorption |
|
| Active Site |
|
| Activity Regulation |
|
| Binding Site |
|
| Calcium Binding |
|
| catalytic Activity |
|
| DNA Binding |
|
| EC Number |
|
| Enzyme Function |
FUNCTION: Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 or ILF2 (PubMed:33009960). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8 (PubMed:20223979, PubMed:24328678, PubMed:25043012, PubMed:25108355). Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons (PubMed:18414909, PubMed:29530986). Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (PubMed:18414909). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity). {ECO:0000250|UniProtKB:Q8C7D2, ECO:0000269|PubMed:18414909, ECO:0000269|PubMed:20223979, ECO:0000269|PubMed:24328678, ECO:0000269|PubMed:25043012, ECO:0000269|PubMed:25108355, ECO:0000269|PubMed:29530986, ECO:0000305}. |
| Temperature Dependency |
|
| PH Dependency |
|
| Pathway |
PATHWAY: Protein modification; protein ubiquitination. {ECO:0000269|PubMed:20223979, ECO:0000305|PubMed:25108355}. |
| nucleotide Binding |
|
| Features |
Alternative sequence (1); Beta strand (20); Chain (1); Domain (2); Erroneous initiation (1); Frameshift (2); Helix (16); Metal binding (4); Modified residue (1); Mutagenesis (3); Natural variant (1); Region (2); Sequence conflict (4); Turn (4) |
| Keywords |
3D-structure;Alternative splicing;Cytoplasm;Disease variant;Membrane;Mental retardation;Metal-binding;Nucleus;Phosphoprotein;Reference proteome;Ubl conjugation;Ubl conjugation pathway;Zinc |
| Interact With |
Q96A83-2; P48729; Q16531; O14901; Q8IVT2; Q9P286; D3DTS7; Q93062; Q16531; Q13422-7 |
| Induction |
|
| Subcellular Location |
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20223979}. Nucleus {ECO:0000269|PubMed:20223979}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. |
| Modified Residue |
MOD_RES 25; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:23186163 |
| Post Translational Modification |
PTM: Ubiquitinated, ubiquitination is mediated by its own DCX protein ligase complex. {ECO:0000269|PubMed:20223979, ECO:0000269|PubMed:25043012}. |
| Signal Peptide |
|
| Structure 3D |
X-ray crystallography (17) |
| Cross Reference PDB |
4M91;
4TZ4;
5FQD;
5HXB;
5V3O;
6BN7;
6BN8;
6BN9;
6BNB;
6BOY;
6H0F;
6H0G;
6UML;
6XK9;
7BQU;
7BQV;
7LPS;
|
| Mapped Pubmed ID |
19615732;
20131966;
20195357;
20360068;
20711500;
21232561;
21860026;
22552008;
22698399;
23026050;
23233657;
23434730;
23455924;
23983124;
23992230;
24118365;
24129344;
24166296;
24685145;
24687382;
24925210;
25284710;
25416956;
25569776;
26002965;
26021757;
26024445;
26119939;
26183205;
26186254;
26188093;
26909574;
26990986;
27142104;
27329811;
27338790;
27365142;
27417535;
27458004;
27460676;
27468689;
27601648;
27618360;
27751757;
28017969;
28083618;
28425720;
29272390;
29449372;
29892083;
29945920;
30190590;
30201761;
30234487;
30385546;
30458989;
30683842;
31115923;
31619706;
31620128;
31746254;
31865141;
31873151;
31964914;
31983437;
32061138;
32071327;
32132601;
32200025;
32219443;
32251415;
32333926;
32466489;
32677118;
32901087;
32929090;
33197925;
33206504;
33443552;
33830389;
33972400;
34035522;
34115836;
34373585;
34392531;
34489457;
34764413;
|
| Motif |
|
| Gene Encoded By |
|
| Mass |
50,546 |
| Kinetics |
|
| Metal Binding |
METAL 323; /note="Zinc"; /evidence="ECO:0000269|PubMed:25108355, ECO:0007744|PDB:4TZ4"; METAL 326; /note="Zinc"; /evidence="ECO:0000269|PubMed:25108355, ECO:0007744|PDB:4TZ4"; METAL 391; /note="Zinc"; /evidence="ECO:0000269|PubMed:25108355, ECO:0007744|PDB:4TZ4"; METAL 394; /note="Zinc"; /evidence="ECO:0000269|PubMed:25108355, ECO:0007744|PDB:4TZ4" |
| Rhea ID |
|
| Cross Reference Brenda |
|