| UniProt ID | FZR1_HUMAN | |
|---|---|---|
| UniProt AC | Q9UM11 | |
| Protein Name | Fizzy-related protein homolog | |
| Gene Name | FZR1 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 496 | |
| Subcellular Localization |
Isoform 2: Nucleus. Isoform 3: Cytoplasm. |
|
| Protein Description | Substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin-protein ligase complex. Associates with the APC/C in late mitosis, in replacement of CDC20, and activates the APC/C during anaphase and telophase. The APC/C remains active in degrading substrates to ensure that positive regulators of the cell cycle do not accumulate prematurely. At the G1/S transition FZR1 is phosphorylated, leading to its dissociation from the APC/C. Following DNA damage, it is required for the G2 DNA damage checkpoint: its dephosphorylation and reassociation with the APC/C leads to the ubiquitination of PLK1, preventing entry into mitosis. Acts as an adapter for APC/C to target the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. Through the regulation of RBBP8/CtIP protein turnover, may play a role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR). [PubMed: 25349192] | |
| Protein Sequence | MDQDYERRLLRQIVIQNENTMPRVTEMRRTLTPASSPVSSPSKHGDRFIPSRAGANWSVNFHRINENEKSPSQNRKAKDATSDNGKDGLAYSALLKNELLGAGIEKVQDPQTEDRRLQPSTPEKKGLFTYSLSTKRSSPDDGNDVSPYSLSPVSNKSQKLLRSPRKPTRKISKIPFKVLDAPELQDDFYLNLVDWSSLNVLSVGLGTCVYLWSACTSQVTRLCDLSVEGDSVTSVGWSERGNLVAVGTHKGFVQIWDAAAGKKLSMLEGHTARVGALAWNAEQLSSGSRDRMILQRDIRTPPLQSERRLQGHRQEVCGLKWSTDHQLLASGGNDNKLLVWNHSSLSPVQQYTEHLAAVKAIAWSPHQHGLLASGGGTADRCIRFWNTLTGQPLQCIDTGSQVCNLAWSKHANELVSTHGYSQNQILVWKYPSLTQVAKLTGHSYRVLYLAMSPDGEAIVTGAGDETLRFWNVFSKTRSTKVKWESVSVLNLFTRIR | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 5 | Phosphorylation | ---MDQDYERRLLRQ ---CCHHHHHHHHHH | 27642862 | ||
| 30 | Phosphorylation | RVTEMRRTLTPASSP HHHHHHHHCCCCCCC | 26055452 | ||
| 32 | Phosphorylation | TEMRRTLTPASSPVS HHHHHHCCCCCCCCC | 26055452 | ||
| 35 | Phosphorylation | RRTLTPASSPVSSPS HHHCCCCCCCCCCCC | 26055452 | ||
| 36 | Phosphorylation | RTLTPASSPVSSPSK HHCCCCCCCCCCCCC | 25159151 | ||
| 39 | O-linked_Glycosylation | TPASSPVSSPSKHGD CCCCCCCCCCCCCCC | 9569193 | ||
| 39 | Phosphorylation | TPASSPVSSPSKHGD CCCCCCCCCCCCCCC | 26055452 | ||
| 40 | O-linked_Glycosylation | PASSPVSSPSKHGDR CCCCCCCCCCCCCCC | 6431863 | ||
| 40 | Phosphorylation | PASSPVSSPSKHGDR CCCCCCCCCCCCCCC | 25159151 | ||
| 42 | O-linked_Glycosylation | SSPVSSPSKHGDRFI CCCCCCCCCCCCCCC | 29147679 | ||
| 42 | Phosphorylation | SSPVSSPSKHGDRFI CCCCCCCCCCCCCCC | 22617229 | ||
| 58 | Phosphorylation | SRAGANWSVNFHRIN CCCCCCEEEEEEECC | 28555341 | ||
| 69 | Acetylation | HRINENEKSPSQNRK EECCCCCCCHHHCCC | 22014574 | ||
| 70 | Phosphorylation | RINENEKSPSQNRKA ECCCCCCCHHHCCCC | 23401153 | ||
| 72 | Phosphorylation | NENEKSPSQNRKAKD CCCCCCHHHCCCCCC | 29255136 | ||
| 82 | Phosphorylation | RKAKDATSDNGKDGL CCCCCCCCCCCCCCH | 27642862 | ||
| 86 (in isoform 2) | Ubiquitination | - | - | ||
| 86 | Ubiquitination | DATSDNGKDGLAYSA CCCCCCCCCCHHHHH | 29967540 | ||
| 91 | Phosphorylation | NGKDGLAYSALLKNE CCCCCHHHHHHHHHH | 22817900 | ||
| 92 | Phosphorylation | GKDGLAYSALLKNEL CCCCHHHHHHHHHHH | 22817900 | ||
| 96 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 96 | Ubiquitination | LAYSALLKNELLGAG HHHHHHHHHHHHCCC | 21906983 | ||
| 96 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 96 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 106 (in isoform 2) | Ubiquitination | - | - | ||
| 106 | Ubiquitination | LLGAGIEKVQDPQTE HHCCCCCCCCCCCCC | 29967540 | ||
| 120 | Phosphorylation | EDRRLQPSTPEKKGL CCCCCCCCCCCCCCC | 25159151 | ||
| 121 | Phosphorylation | DRRLQPSTPEKKGLF CCCCCCCCCCCCCCE | 25159151 | ||
| 125 (in isoform 2) | Ubiquitination | - | - | ||
| 125 | Sumoylation | QPSTPEKKGLFTYSL CCCCCCCCCCEEEEE | - | ||
| 125 | Sumoylation | QPSTPEKKGLFTYSL CCCCCCCCCCEEEEE | - | ||
| 128 | Ubiquitination | TPEKKGLFTYSLSTK CCCCCCCEEEEEECC | 22817900 | ||
| 129 (in isoform 3) | Phosphorylation | - | 27251275 | ||
| 130 | Phosphorylation | EKKGLFTYSLSTKRS CCCCCEEEEEECCCC | 26074081 | ||
| 131 | Phosphorylation | KKGLFTYSLSTKRSS CCCCEEEEEECCCCC | 26074081 | ||
| 131 (in isoform 3) | Phosphorylation | - | 27251275 | ||
| 133 | Phosphorylation | GLFTYSLSTKRSSPD CCEEEEEECCCCCCC | 22199227 | ||
| 134 | Phosphorylation | LFTYSLSTKRSSPDD CEEEEEECCCCCCCC | 22199227 | ||
| 135 (in isoform 2) | Ubiquitination | - | - | ||
| 135 | Ubiquitination | FTYSLSTKRSSPDDG EEEEEECCCCCCCCC | - | ||
| 137 | Phosphorylation | YSLSTKRSSPDDGND EEEECCCCCCCCCCC | 23401153 | ||
| 138 | Phosphorylation | SLSTKRSSPDDGNDV EEECCCCCCCCCCCC | 22167270 | ||
| 146 | Phosphorylation | PDDGNDVSPYSLSPV CCCCCCCCCCCCCCC | 25159151 | ||
| 148 | Phosphorylation | DGNDVSPYSLSPVSN CCCCCCCCCCCCCCC | 22115753 | ||
| 149 | Phosphorylation | GNDVSPYSLSPVSNK CCCCCCCCCCCCCCH | 22617229 | ||
| 151 | Phosphorylation | DVSPYSLSPVSNKSQ CCCCCCCCCCCCHHH | 25159151 | ||
| 154 | Phosphorylation | PYSLSPVSNKSQKLL CCCCCCCCCHHHHHH | 30175587 | ||
| 156 | Ubiquitination | SLSPVSNKSQKLLRS CCCCCCCHHHHHHCC | 22817900 | ||
| 156 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 156 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 159 | Acetylation | PVSNKSQKLLRSPRK CCCCHHHHHHCCCCC | 22014574 | ||
| 159 | Ubiquitination | PVSNKSQKLLRSPRK CCCCHHHHHHCCCCC | 22817900 | ||
| 163 | Phosphorylation | KSQKLLRSPRKPTRK HHHHHHCCCCCCCCC | 17081983 | ||
| 173 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 173 (in isoform 2) | Ubiquitination | - | - | ||
| 173 | Ubiquitination | KPTRKISKIPFKVLD CCCCCCCCCCCEECC | 27667366 | ||
| 174 | Ubiquitination | PTRKISKIPFKVLDA CCCCCCCCCCEECCC | 22817900 | ||
| 174 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 188 | Ubiquitination | APELQDDFYLNLVDW CHHHCCCEEEEECCH | 22817900 | ||
| 191 | Ubiquitination | LQDDFYLNLVDWSSL HCCCEEEEECCHHHC | 22817900 | ||
| 205 | Ubiquitination | LNVLSVGLGTCVYLW CCCEECCCCHHHHHH | 27667366 | ||
| 231 | Ubiquitination | DLSVEGDSVTSVGWS CCEECCCCEEEEEEE | 21963094 | ||
| 262 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 262 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 262 | Ubiquitination | IWDAAAGKKLSMLEG EHHHHCCCCEECCCC | 21906983 | ||
| 263 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 263 | Ubiquitination | WDAAAGKKLSMLEGH HHHHCCCCEECCCCC | 22817900 | ||
| 263 (in isoform 1) | Ubiquitination | - | 21890473 | ||
| 294 | Ubiquitination | GSRDRMILQRDIRTP CCCCCEEEECCCCCC | 21890473 | ||
| 295 | Ubiquitination | SRDRMILQRDIRTPP CCCCEEEECCCCCCC | 22817900 | ||
| 300 | Phosphorylation | ILQRDIRTPPLQSER EEECCCCCCCCCCHH | - | ||
| 320 | Ubiquitination | RQEVCGLKWSTDHQL HHCCCCCEECCCCCC | 21963094 | ||
| 320 (in isoform 2) | Ubiquitination | - | - | ||
| 336 (in isoform 2) | Ubiquitination | - | - | ||
| 336 | Ubiquitination | ASGGNDNKLLVWNHS CCCCCCCCEEEEECC | - | ||
| 343 | Phosphorylation | KLLVWNHSSLSPVQQ CEEEEECCCCCHHHH | - | ||
| 346 | Phosphorylation | VWNHSSLSPVQQYTE EEECCCCCHHHHHHH | - | ||
| 352 | Ubiquitination | LSPVQQYTEHLAAVK CCHHHHHHHHHHHHH | 21963094 | ||
| 391 (in isoform 3) | Ubiquitination | - | 21890473 | ||
| 429 | Ubiquitination | QNQILVWKYPSLTQV CCCEEEEECCCHHHH | - | ||
| 429 (in isoform 2) | Ubiquitination | - | - | ||
| 475 | Ubiquitination | RFWNVFSKTRSTKVK EEEECCCCCCCCCCC | - | ||
| 475 (in isoform 2) | Ubiquitination | - | - | ||
| 480 (in isoform 2) | Ubiquitination | - | 21890473 | ||
| 480 | Ubiquitination | FSKTRSTKVKWESVS CCCCCCCCCCEEEEE | - | ||
| 485 | Phosphorylation | STKVKWESVSVLNLF CCCCCEEEEEEHHHH | 29759185 | ||
| 487 | Phosphorylation | KVKWESVSVLNLFTR CCCEEEEEEHHHHHC | 29759185 | ||
| 493 | Phosphorylation | VSVLNLFTRIR---- EEEHHHHHCCC---- | 29759185 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
| 40 | S | Phosphorylation | Kinase | CDK2 | P24941 | PSP |
| 40 | S | Phosphorylation | Kinase | CDK5 | Q00535 | PSP |
| 40 | S | Phosphorylation | Kinase | CDK5 | Q03114 | PSP |
| 121 | T | Phosphorylation | Kinase | CDK2 | P24941 | PSP |
| 121 | T | Phosphorylation | Kinase | CDK5 | Q00535 | PSP |
| 121 | T | Phosphorylation | Kinase | CDK5 | Q03114 | PSP |
| 151 | S | Phosphorylation | Kinase | CDK2 | P24941 | PSP |
| 151 | S | Phosphorylation | Kinase | CDK-FAMILY | - | GPS |
| 151 | S | Phosphorylation | Kinase | CDK_GROUP | - | PhosphoELM |
| 163 | S | Phosphorylation | Kinase | CDK2 | P24941 | PSP |
| 163 | S | Phosphorylation | Kinase | CDK5 | Q00535 | PSP |
| 163 | S | Phosphorylation | Kinase | CDK5 | Q03114 | PSP |
| 163 | S | Phosphorylation | Kinase | CDK-FAMILY | - | GPS |
| 163 | S | Phosphorylation | Kinase | CDK_GROUP | - | PhosphoELM |
| - | K | Ubiquitination | E3 ubiquitin ligase | BTRC | Q9Y297 | PMID:23972993 |
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of FZR1_HUMAN !! | ||||||
| Kegg Drug | ||||||
|---|---|---|---|---|---|---|
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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