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Protein

Adenomatous polyposis coli protein

Gene

APC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.5 Publications

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • gamma-catenin binding Source: BHF-UCL
  • microtubule binding Source: UniProtKB
  • microtubule plus-end binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein kinase regulator activity Source: UniProtKB

GO - Biological processi

  • beta-catenin destruction complex assembly Source: Reactome
  • beta-catenin destruction complex disassembly Source: Reactome
  • bicellular tight junction assembly Source: UniProtKB
  • canonical Wnt signaling pathway Source: UniProtKB
  • cell adhesion Source: UniProtKB
  • cell cycle arrest Source: UniProtKB
  • cell fate specification Source: GO_Central
  • cell migration Source: UniProtKB
  • cellular component disassembly involved in execution phase of apoptosis Source: Reactome
  • cellular response to DNA damage stimulus Source: UniProtKB
  • mitotic cytokinesis Source: MGI
  • mitotic spindle assembly checkpoint Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: AgBase
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • negative regulation of microtubule depolymerization Source: UniProtKB
  • pattern specification process Source: GO_Central
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of cell migration Source: MGI
  • positive regulation of protein catabolic process Source: BHF-UCL
  • positive regulation of pseudopodium assembly Source: MGI
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: Reactome
  • protein complex assembly Source: UniProtKB
  • regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
  • regulation of cell differentiation Source: GO_Central
  • regulation of microtubule-based process Source: UniProtKB
  • Wnt signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000134982-MONOMER.
ZFISH:ENSG00000134982-MONOMER.
ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-HSA-195253. Degradation of beta-catenin by the destruction complex.
R-HSA-196299. Beta-catenin phosphorylation cascade.
R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-HSA-5339716. Misspliced GSK3beta mutants stabilize beta-catenin.
R-HSA-5358747. S33 mutants of beta-catenin aren't phosphorylated.
R-HSA-5358749. S37 mutants of beta-catenin aren't phosphorylated.
R-HSA-5358751. S45 mutants of beta-catenin aren't phosphorylated.
R-HSA-5358752. T41 mutants of beta-catenin aren't phosphorylated.
R-HSA-5467333. APC truncation mutants are not K63 polyubiquitinated.
R-HSA-5467337. APC truncation mutants have impaired AXIN binding.
R-HSA-5467340. AXIN missense mutants destabilize the destruction complex.
R-HSA-5467348. Truncations of AMER1 destabilize the destruction complex.
R-HSA-5689896. Ovarian tumor domain proteases.
SignaLinkiP25054.
SIGNORiP25054.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenomatous polyposis coli protein
Short name:
Protein APC
Alternative name(s):
Deleted in polyposis 2.5
Gene namesi
Name:APC
Synonyms:DP2.5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:583. APC.

Subcellular locationi

GO - Cellular componenti

  • adherens junction Source: UniProtKB-SubCell
  • beta-catenin destruction complex Source: UniProtKB
  • bicellular tight junction Source: UniProtKB
  • catenin complex Source: CACAO
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • kinetochore Source: UniProtKB
  • lamellipodium Source: UniProtKB
  • lateral plasma membrane Source: MGI
  • microtubule Source: UniProtKB-KW
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • ruffle membrane Source: UniProtKB
  • Wnt signalosome Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Microtubule

Pathology & Biotechi

Involvement in diseasei

Familial adenomatous polyposis (FAP)9 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA cancer predisposition syndrome characterized by adenomatous polyps of the colon and rectum, but also of upper gastrointestinal tract (ampullary, duodenal and gastric adenomas). This is a viciously premalignant disease with one or more polyps progressing through dysplasia to malignancy in untreated gene carriers with a median age at diagnosis of 40 years.
See also OMIM:175100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00961399R → W in FAP; unknown pathological significance. 1 PublicationCorresponds to variant rs139196838dbSNPEnsembl.1
Natural variantiVAR_005032171S → I in FAP. 1 Publication1
Natural variantiVAR_005033414R → C in FAP. Corresponds to variant rs137854567dbSNPEnsembl.1
Natural variantiVAR_009614722S → G in FAP. 1 Publication1
Natural variantiVAR_005034784S → T in FAP. 1
Natural variantiVAR_005038911E → G in FAP and colorectal tumor. 1
Natural variantiVAR_0096151057E → G in non-FAP; unknown pathological significance. 1 Publication1
Natural variantiVAR_0050441176P → L in FAP. 1
Natural variantiVAR_0096161184A → P in FAP. 1 Publication1
Natural variantiVAR_0050511313T → A in FAP and colorectal tumor. 1
Natural variantiVAR_0050531348R → W in FAP. 1 Publication1
Natural variantiVAR_0050562621S → C in FAP. Corresponds to variant rs72541816dbSNPEnsembl.1
Natural variantiVAR_0050572839L → F in FAP. 1
Hereditary desmoid disease (HDD)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant trait with 100% penetrance and possible variable expression among affected relatives. HDD patients show multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Desmoid tumors appears also as a complication of familial adenomatous polyposis.
See also OMIM:135290
Medulloblastoma (MDB)1 Publication
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionMalignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.
See also OMIM:155255
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0176531296A → V in MDB; sporadic. 1 Publication1
Natural variantiVAR_0176541472V → I in MDB; sporadic. 1 Publication1
Natural variantiVAR_0176551495S → G in MDB; sporadic. 1 Publication1
Gastric cancer (GASC)
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA malignant disease which starts in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. The term gastric cancer or gastric carcinoma refers to adenocarcinoma of the stomach that accounts for most of all gastric malignant tumors. Two main histologic types are recognized, diffuse type and intestinal type carcinomas. Diffuse tumors are poorly differentiated infiltrating lesions, resulting in thickening of the stomach. In contrast, intestinal tumors are usually exophytic, often ulcerating, and associated with intestinal metaplasia of the stomach, most often observed in sporadic disease.
See also OMIM:613659
Hepatocellular carcinoma (HCC)
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes.
See also OMIM:114550

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi516K → E: Impairs interaction with KHDRBS1. 1 Publication1
Mutagenesisi549R → E: Impairs interaction with KHDRBS1. 1 Publication1
Mutagenesisi2841T → L: Loss of interaction with SCRIB. 1 Publication1
Mutagenesisi2843V → Q: Loss of interaction with SCRIB. 1 Publication1

Keywords - Diseasei

Disease mutation, Tumor suppressor

Organism-specific databases

DisGeNETi324.
MalaCardsiAPC.
MIMi114550. phenotype.
135290. phenotype.
155255. phenotype.
175100. phenotype.
613659. phenotype.
OpenTargetsiENSG00000134982.
Orphaneti247806. APC-related attenuated familial adenomatous polyposis.
873. Desmoid tumor.
261584. Familial adenomatous polyposis due to 5q22.2 microdeletion.
79665. Gardner syndrome.
99818. Turcot syndrome with polyposis.
PharmGKBiPA24875.

Polymorphism and mutation databases

BioMutaiAPC.
DMDMi97535708.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000646272 – 2843Adenomatous polyposis coli proteinAdd BLAST2842

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei107PhosphoserineBy similarity1
Modified residuei111PhosphoserineBy similarity1
Modified residuei744PhosphoserineCombined sources1
Modified residuei748PhosphoserineCombined sources1
Modified residuei780PhosphoserineCombined sources1
Modified residuei908PhosphoserineCombined sources1
Modified residuei987PhosphoserineBy similarity1
Modified residuei1038PhosphoserineBy similarity1
Modified residuei1042PhosphoserineCombined sources1
Modified residuei1360PhosphoserineCombined sources1
Modified residuei1371PhosphoserineCombined sources1
Modified residuei1385PhosphoserineCombined sources1
Modified residuei1392PhosphoserineBy similarity1
Modified residuei1395PhosphoserineBy similarity1
Modified residuei1438PhosphothreonineCombined sources1
Modified residuei1567PhosphoserineBy similarity1
Modified residuei1774PhosphoserineCombined sources1
Modified residuei1861PhosphoserineCombined sources1
Modified residuei1863PhosphoserineCombined sources1
Modified residuei1864PhosphoserineCombined sources1
Modified residuei1971PhosphoserineBy similarity1
Modified residuei1973PhosphoserineBy similarity1
Modified residuei2088PhosphoserineBy similarity1
Modified residuei2093PhosphoserineBy similarity1
Modified residuei2125PhosphoserineBy similarity1
Modified residuei2129PhosphoserineBy similarity1
Modified residuei2130PhosphoserineBy similarity1
Modified residuei2132PhosphoserineBy similarity1
Modified residuei2151PhosphothreonineCombined sources1
Modified residuei2260PhosphoserineCombined sources1
Modified residuei2270PhosphoserineCombined sources1
Modified residuei2283PhosphoserineCombined sources1
Modified residuei2473PhosphoserineCombined sources1
Modified residuei2535PhosphoserineCombined sources1
Modified residuei2569PhosphoserineCombined sources1
Modified residuei2671PhosphoserineCombined sources1
Modified residuei2674PhosphoserineCombined sources1
Modified residuei2679PhosphothreonineCombined sources1
Modified residuei2710PhosphoserineBy similarity1
Modified residuei2724PhosphoserineCombined sources1
Modified residuei2789PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by GSK3B.
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP25054.
MaxQBiP25054.
PaxDbiP25054.
PeptideAtlasiP25054.
PRIDEiP25054.

PTM databases

iPTMnetiP25054.
PhosphoSitePlusiP25054.

Expressioni

Tissue specificityi

Expressed in a variety of tissues.

Gene expression databases

BgeeiENSG00000134982.
CleanExiHS_APC.
ExpressionAtlasiP25054. baseline and differential.
GenevisibleiP25054. HS.

Organism-specific databases

HPAiCAB025994.
HPA013349.

Interactioni

Subunit structurei

Forms homooligomers and heterooligomers with APC2. Interacts with DIAPH1 and DIAPH2 (By similarity). Interacts with PDZ domains of DLG1 and DLG3. Associates with catenins. Binds axin. Interacts with ARHGEF4 (via N-terminus). Interacts with MAPRE1 (via C-terminus); probably required for APC targeting to the growing microtubule plus ends. Interacts with MAPRE2 and MAPRE3 (via C-terminus). Found in a complex consisting of ARHGEF4, APC and CTNNB1. Interacts with SCRIB; may mediate APC targeting to adherens junctions of epithelial cells. Interacts with SPATA13 (via N-terminus and SH3 domain). Interacts with ASAP1 (via SH3 domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts at the cell membrane with AMER1 and AMER2 (via ARM repeats). Interacts with KHDRBS1.By similarity14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AMER1Q5JTC64EBI-727707,EBI-6169747
AMER3Q8N9448EBI-727707,EBI-8869590
CSNK1EP496748EBI-727707,EBI-749343
CTNNA1P352213EBI-727707,EBI-701918
CTNNB1P3522216EBI-727707,EBI-491549
Ctnnb1Q022488EBI-727707,EBI-397872From a different organism.
DVL1O146406EBI-727707,EBI-723489
DVL1P1P547922EBI-727707,EBI-7848109
DVL2O146412EBI-727707,EBI-740850
JUPP149233EBI-727707,EBI-702484
MAPRE1Q156915EBI-727707,EBI-1004115
SCRIBQ141604EBI-727707,EBI-357345

GO - Molecular functioni

  • beta-catenin binding Source: UniProtKB
  • gamma-catenin binding Source: BHF-UCL
  • microtubule binding Source: UniProtKB
  • microtubule plus-end binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi106821. 188 interactors.
DIPiDIP-33556N.
IntActiP25054. 180 interactors.
MINTiMINT-88204.
STRINGi9606.ENSP00000257430.

Structurei

Secondary structure

12843
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi6 – 53Combined sources48
Helixi132 – 169Combined sources38
Helixi180 – 204Combined sources25
Helixi208 – 238Combined sources31
Helixi328 – 338Combined sources11
Helixi343 – 350Combined sources8
Helixi353 – 360Combined sources8
Helixi377 – 393Combined sources17
Helixi407 – 425Combined sources19
Beta strandi429 – 431Combined sources3
Helixi433 – 435Combined sources3
Helixi441 – 444Combined sources4
Helixi446 – 457Combined sources12
Helixi460 – 468Combined sources9
Helixi471 – 486Combined sources16
Helixi492 – 508Combined sources17
Helixi513 – 521Combined sources9
Helixi523 – 531Combined sources9
Helixi532 – 534Combined sources3
Helixi538 – 552Combined sources15
Helixi557 – 565Combined sources9
Helixi568 – 578Combined sources11
Helixi582 – 596Combined sources15
Helixi600 – 608Combined sources9
Helixi612 – 619Combined sources8
Beta strandi625 – 627Combined sources3
Helixi630 – 646Combined sources17
Helixi650 – 657Combined sources8
Turni658 – 660Combined sources3
Helixi661 – 668Combined sources8
Helixi674 – 687Combined sources14
Helixi692 – 700Combined sources9
Helixi703 – 708Combined sources6
Turni709 – 712Combined sources4
Helixi716 – 730Combined sources15
Helixi735 – 737Combined sources3
Turni1027 – 1030Combined sources4
Helixi1470 – 1479Combined sources10
Helixi1520 – 1524Combined sources5
Helixi2036 – 2045Combined sources10
Beta strandi2840 – 2842Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DEBX-ray2.40A/B2-55[»]
1EMUX-ray1.90B2034-2049[»]
1JPPX-ray3.10C/D1021-1035[»]
1M5IX-ray2.00A126-250[»]
1T08X-ray2.10C1484-1498[»]
1TH1X-ray2.50C/D1362-1540[»]
1V18X-ray2.10B1482-1528[»]
2RQUNMR-B1578-1596[»]
3AU3X-ray2.10A396-732[»]
3NMWX-ray1.60A/B407-751[»]
3NMXX-ray2.30A/B/C407-751[»]
3NMZX-ray3.01A/B303-739[»]
3QHEX-ray2.40A/C396-732[»]
3RL7X-ray2.30G/H/I/J/K/L2833-2843[»]
3RL8X-ray2.20F2833-2843[»]
3T7UX-ray2.90A/B407-775[»]
4G69X-ray2.00B2833-2843[»]
4YJEX-ray1.90A407-751[»]
4YJLX-ray2.10A/B/C/D/E/F407-751[»]
4YK6X-ray1.70A407-751[»]
DisProtiDP00519.
ProteinModelPortaliP25054.
SMRiP25054.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP25054.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati453 – 495ARM 1Add BLAST43
Repeati505 – 547ARM 2Add BLAST43
Repeati548 – 591ARM 3Add BLAST44
Repeati592 – 638ARM 4Add BLAST47
Repeati639 – 683ARM 5Add BLAST45
Repeati684 – 725ARM 6Add BLAST42
Repeati726 – 767ARM 7Add BLAST42

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni960 – 1337Responsible for down-regulation through a process mediated by direct ubiquitinationAdd BLAST378
Regioni1866 – 1893Highly chargedAdd BLAST28

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili2 – 61Sequence analysisAdd BLAST60
Coiled coili127 – 248Sequence analysisAdd BLAST122

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi2803 – 2806Microtubule tip localization signal4
Motifi2841 – 2843PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1 – 730Leu-richAdd BLAST730
Compositional biasi731 – 2832Ser-richAdd BLAST2102
Compositional biasi1131 – 1156Asp/Glu-rich (acidic)Add BLAST26
Compositional biasi1558 – 1577Asp/Glu-rich (acidic)Add BLAST20

Domaini

The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.By similarity

Sequence similaritiesi

Contains 7 ARM repeats.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiKOG2122. Eukaryota.
ENOG410XR2V. LUCA.
GeneTreeiENSGT00530000063749.
HOVERGENiHBG004264.
InParanoidiP25054.
KOiK02085.
OMAiISRGRTM.
OrthoDBiEOG091G00D4.
PhylomeDBiP25054.
TreeFamiTF106496.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
InterProiIPR026836. APC.
IPR009240. APC_15aa_rpt.
IPR009234. APC_basic_dom.
IPR026831. APC_dom.
IPR026818. Apc_fam.
IPR032038. APC_N.
IPR009223. APC_rpt.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR009232. EB1-bd.
IPR009224. SAMP.
[Graphical view]
PANTHERiPTHR12607. PTHR12607. 2 hits.
PTHR12607:SF11. PTHR12607:SF11. 2 hits.
PfamiPF05972. APC_15aa. 3 hits.
PF05956. APC_basic. 1 hit.
PF16689. APC_N_CC. 1 hit.
PF05923. APC_r. 7 hits.
PF00514. Arm. 2 hits.
PF05937. EB1_binding. 1 hit.
PF05924. SAMP. 3 hits.
[Graphical view]
SMARTiSM00185. ARM. 7 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF58050. SSF58050. 1 hit.
SSF82931. SSF82931. 1 hit.
PROSITEiPS50176. ARM_REPEAT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: P25054-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAASYDQLL KQVEALKMEN SNLRQELEDN SNHLTKLETE ASNMKEVLKQ
60 70 80 90 100
LQGSIEDEAM ASSGQIDLLE RLKELNLDSS NFPGVKLRSK MSLRSYGSRE
110 120 130 140 150
GSVSSRSGEC SPVPMGSFPR RGFVNGSRES TGYLEELEKE RSLLLADLDK
160 170 180 190 200
EEKEKDWYYA QLQNLTKRID SLPLTENFSL QTDMTRRQLE YEARQIRVAM
210 220 230 240 250
EEQLGTCQDM EKRAQRRIAR IQQIEKDILR IRQLLQSQAT EAERSSQNKH
260 270 280 290 300
ETGSHDAERQ NEGQGVGEIN MATSGNGQGS TTRMDHETAS VLSSSSTHSA
310 320 330 340 350
PRRLTSHLGT KVEMVYSLLS MLGTHDKDDM SRTLLAMSSS QDSCISMRQS
360 370 380 390 400
GCLPLLIQLL HGNDKDSVLL GNSRGSKEAR ARASAALHNI IHSQPDDKRG
410 420 430 440 450
RREIRVLHLL EQIRAYCETC WEWQEAHEPG MDQDKNPMPA PVEHQICPAV
460 470 480 490 500
CVLMKLSFDE EHRHAMNELG GLQAIAELLQ VDCEMYGLTN DHYSITLRRY
510 520 530 540 550
AGMALTNLTF GDVANKATLC SMKGCMRALV AQLKSESEDL QQVIASVLRN
560 570 580 590 600
LSWRADVNSK KTLREVGSVK ALMECALEVK KESTLKSVLS ALWNLSAHCT
610 620 630 640 650
ENKADICAVD GALAFLVGTL TYRSQTNTLA IIESGGGILR NVSSLIATNE
660 670 680 690 700
DHRQILRENN CLQTLLQHLK SHSLTIVSNA CGTLWNLSAR NPKDQEALWD
710 720 730 740 750
MGAVSMLKNL IHSKHKMIAM GSAAALRNLM ANRPAKYKDA NIMSPGSSLP
760 770 780 790 800
SLHVRKQKAL EAELDAQHLS ETFDNIDNLS PKASHRSKQR HKQSLYGDYV
810 820 830 840 850
FDTNRHDDNR SDNFNTGNMT VLSPYLNTTV LPSSSSSRGS LDSSRSEKDR
860 870 880 890 900
SLERERGIGL GNYHPATENP GTSSKRGLQI STTAAQIAKV MEEVSAIHTS
910 920 930 940 950
QEDRSSGSTT ELHCVTDERN ALRRSSAAHT HSNTYNFTKS ENSNRTCSMP
960 970 980 990 1000
YAKLEYKRSS NDSLNSVSSS DGYGKRGQMK PSIESYSEDD ESKFCSYGQY
1010 1020 1030 1040 1050
PADLAHKIHS ANHMDDNDGE LDTPINYSLK YSDEQLNSGR QSPSQNERWA
1060 1070 1080 1090 1100
RPKHIIEDEI KQSEQRQSRN QSTTYPVYTE STDDKHLKFQ PHFGQQECVS
1110 1120 1130 1140 1150
PYRSRGANGS ETNRVGSNHG INQNVSQSLC QEDDYEDDKP TNYSERYSEE
1160 1170 1180 1190 1200
EQHEEEERPT NYSIKYNEEK RHVDQPIDYS LKYATDIPSS QKQSFSFSKS
1210 1220 1230 1240 1250
SSGQSSKTEH MSSSSENTST PSSNAKRQNQ LHPSSAQSRS GQPQKAATCK
1260 1270 1280 1290 1300
VSSINQETIQ TYCVEDTPIC FSRCSSLSSL SSAEDEIGCN QTTQEADSAN
1310 1320 1330 1340 1350
TLQIAEIKEK IGTRSAEDPV SEVPAVSQHP RTKSSRLQGS SLSSESARHK
1360 1370 1380 1390 1400
AVEFSSGAKS PSKSGAQTPK SPPEHYVQET PLMFSRCTSV SSLDSFESRS
1410 1420 1430 1440 1450
IASSVQSEPC SGMVSGIISP SDLPDSPGQT MPPSRSKTPP PPPQTAQTKR
1460 1470 1480 1490 1500
EVPKNKAPTA EKRESGPKQA AVNAAVQRVQ VLPDADTLLH FATESTPDGF
1510 1520 1530 1540 1550
SCSSSLSALS LDEPFIQKDV ELRIMPPVQE NDNGNETESE QPKESNENQE
1560 1570 1580 1590 1600
KEAEKTIDSE KDLLDDSDDD DIEILEECII SAMPTKSSRK AKKPAQTASK
1610 1620 1630 1640 1650
LPPPVARKPS QLPVYKLLPS QNRLQPQKHV SFTPGDDMPR VYCVEGTPIN
1660 1670 1680 1690 1700
FSTATSLSDL TIESPPNELA AGEGVRGGAQ SGEFEKRDTI PTEGRSTDEA
1710 1720 1730 1740 1750
QGGKTSSVTI PELDDNKAEE GDILAECINS AMPKGKSHKP FRVKKIMDQV
1760 1770 1780 1790 1800
QQASASSSAP NKNQLDGKKK KPTSPVKPIP QNTEYRTRVR KNADSKNNLN
1810 1820 1830 1840 1850
AERVFSDNKD SKKQNLKNNS KVFNDKLPNN EDRVRGSFAF DSPHHYTPIE
1860 1870 1880 1890 1900
GTPYCFSRND SLSSLDFDDD DVDLSREKAE LRKAKENKES EAKVTSHTEL
1910 1920 1930 1940 1950
TSNQQSANKT QAIAKQPINR GQPKPILQKQ STFPQSSKDI PDRGAATDEK
1960 1970 1980 1990 2000
LQNFAIENTP VCFSHNSSLS SLSDIDQENN NKENEPIKET EPPDSQGEPS
2010 2020 2030 2040 2050
KPQASGYAPK SFHVEDTPVC FSRNSSLSSL SIDSEDDLLQ ECISSAMPKK
2060 2070 2080 2090 2100
KKPSRLKGDN EKHSPRNMGG ILGEDLTLDL KDIQRPDSEH GLSPDSENFD
2110 2120 2130 2140 2150
WKAIQEGANS IVSSLHQAAA AACLSRQASS DSDSILSLKS GISLGSPFHL
2160 2170 2180 2190 2200
TPDQEEKPFT SNKGPRILKP GEKSTLETKK IESESKGIKG GKKVYKSLIT
2210 2220 2230 2240 2250
GKVRSNSEIS GQMKQPLQAN MPSISRGRTM IHIPGVRNSS SSTSPVSKKG
2260 2270 2280 2290 2300
PPLKTPASKS PSEGQTATTS PRGAKPSVKS ELSPVARQTS QIGGSSKAPS
2310 2320 2330 2340 2350
RSGSRDSTPS RPAQQPLSRP IQSPGRNSIS PGRNGISPPN KLSQLPRTSS
2360 2370 2380 2390 2400
PSTASTKSSG SGKMSYTSPG RQMSQQNLTK QTGLSKNASS IPRSESASKG
2410 2420 2430 2440 2450
LNQMNNGNGA NKKVELSRMS STKSSGSESD RSERPVLVRQ STFIKEAPSP
2460 2470 2480 2490 2500
TLRRKLEESA SFESLSPSSR PASPTRSQAQ TPVLSPSLPD MSLSTHSSVQ
2510 2520 2530 2540 2550
AGGWRKLPPN LSPTIEYNDG RPAKRHDIAR SHSESPSRLP INRSGTWKRE
2560 2570 2580 2590 2600
HSKHSSSLPR VSTWRRTGSS SSILSASSES SEKAKSEDEK HVNSISGTKQ
2610 2620 2630 2640 2650
SKENQVSAKG TWRKIKENEF SPTNSTSQTV SSGATNGAES KTLIYQMAPA
2660 2670 2680 2690 2700
VSKTEDVWVR IEDCPINNPR SGRSPTGNTP PVIDSVSEKA NPNIKDSKDN
2710 2720 2730 2740 2750
QAKQNVGNGS VPMRTVGLEN RLNSFIQVDA PDQKGTEIKP GQNNPVPVSE
2760 2770 2780 2790 2800
TNESSIVERT PFSSSSSSKH SSPSGTVAAR VTPFNYNPSP RKSSADSTSA
2810 2820 2830 2840
RPSQIPTPVN NNTKKRDSKT DSTESSGTQS PKRHSGSYLV TSV
Length:2,843
Mass (Da):311,646
Last modified:May 16, 2006 - v2
Checksum:i77E194AE4A91DC5A
GO
Isoform Short (identifier: P25054-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     312-412: Missing.

Show »
Length:2,742
Mass (Da):300,439
Checksum:i49CF92BE7A81EBEC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti184M → L in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti184M → L in AAA60354 (PubMed:1678319).Curated1
Sequence conflicti970S → N in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti970S → N in AAA60354 (PubMed:1678319).Curated1
Sequence conflicti1309E → G in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti1309E → G in AAA60354 (PubMed:1678319).Curated1
Sequence conflicti1325 – 1331AVSQHPR → SSVHSTLE in AAA60353 (PubMed:1678319).Curated7
Sequence conflicti1325 – 1331AVSQHPR → SSVHSTLE in AAA60354 (PubMed:1678319).Curated7
Sequence conflicti1355S → P in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti1355S → P in AAA60354 (PubMed:1678319).Curated1
Sequence conflicti1591A → G in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti1591A → G in AAA60354 (PubMed:1678319).Curated1
Sequence conflicti2723N → T in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti2723N → T in AAA60354 (PubMed:1678319).Curated1
Sequence conflicti2755S → P in AAA60353 (PubMed:1678319).Curated1
Sequence conflicti2755S → P in AAA60354 (PubMed:1678319).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00961399R → W in FAP; unknown pathological significance. 1 PublicationCorresponds to variant rs139196838dbSNPEnsembl.1
Natural variantiVAR_005032171S → I in FAP. 1 Publication1
Natural variantiVAR_005033414R → C in FAP. Corresponds to variant rs137854567dbSNPEnsembl.1
Natural variantiVAR_009614722S → G in FAP. 1 Publication1
Natural variantiVAR_005034784S → T in FAP. 1
Natural variantiVAR_005035817G → C in gastric cancer. 1
Natural variantiVAR_053976870P → S.Corresponds to variant rs33974176dbSNPEnsembl.1
Natural variantiVAR_005036880I → T in colorectal carcinoma and gastric cancer; from a patient with MMRCS. 1 Publication1
Natural variantiVAR_012975890V → I in colorectal carcinoma; from a patient with MMRCS. 1 PublicationCorresponds to variant rs779998847dbSNPEnsembl.1
Natural variantiVAR_005037906S → Y in colorectal tumor. 1
Natural variantiVAR_005038911E → G in FAP and colorectal tumor. 1
Natural variantiVAR_005039942N → D in gastric cancer. 1
Natural variantiVAR_0050401027Y → C in colorectal tumor. 1
Natural variantiVAR_0096151057E → G in non-FAP; unknown pathological significance. 1 Publication1
Natural variantiVAR_0050411118N → D.1 PublicationCorresponds to variant rs140493115dbSNPEnsembl.1
Natural variantiVAR_0050421120G → E in gastric cancer. Corresponds to variant rs28933379dbSNPEnsembl.1
Natural variantiVAR_0089921171R → C.1 PublicationCorresponds to variant rs201830995dbSNPEnsembl.1
Natural variantiVAR_0050431171R → H in gastric cancer. Corresponds to variant rs372481703dbSNPEnsembl.1
Natural variantiVAR_0050441176P → L in FAP. 1
Natural variantiVAR_0096161184A → P in FAP. 1 Publication1
Natural variantiVAR_0050451197F → S in gastric cancer. 1
Natural variantiVAR_0357941254I → F in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_0050461259I → T in gastric cancer. 1
Natural variantiVAR_0050471292T → M.1 PublicationCorresponds to variant rs371113837dbSNPEnsembl.1
Natural variantiVAR_0176531296A → V in MDB; sporadic. 1 Publication1
Natural variantiVAR_0050481304I → V.1 PublicationCorresponds to variant rs770157475dbSNPEnsembl.1
Natural variantiVAR_0050491307I → K in 6% of Ashkenazi Jews; associated with slightly increased risk of colon and breast cancer. 4 PublicationsCorresponds to variant rs1801155dbSNPEnsembl.1
Natural variantiVAR_0050501312G → E in gastric cancer. 1
Natural variantiVAR_0050511313T → A in FAP and colorectal tumor. 1
Natural variantiVAR_0096171317E → Q May contribute to colorectal tumor development. 1 PublicationCorresponds to variant rs1801166dbSNPEnsembl.1
Natural variantiVAR_0050521326V → A in gastric cancer. 1
Natural variantiVAR_0050531348R → W in FAP. 1 Publication1
Natural variantiVAR_0651331395S → C in hepatoblastoma. 1 PublicationCorresponds to variant rs137854578dbSNPEnsembl.1
Natural variantiVAR_0050541422D → H in colorectal tumor. 1
Natural variantiVAR_0176541472V → I in MDB; sporadic. 1 Publication1
Natural variantiVAR_0176551495S → G in MDB; sporadic. 1 Publication1
Natural variantiVAR_0201411496T → S.Corresponds to variant rs2229996dbSNPEnsembl.1
Natural variantiVAR_0129761508A → V in colorectal carcinoma from a patient with MMRCS. 1 Publication1
Natural variantiVAR_0089931822V → D.4 PublicationsCorresponds to variant rs459552dbSNPEnsembl.1
Natural variantiVAR_0539771882R → T.Corresponds to variant rs34157245dbSNPEnsembl.1
Natural variantiVAR_0201421973S → T.Corresponds to variant rs4987109dbSNPEnsembl.1
Natural variantiVAR_0539782499V → L.Corresponds to variant rs33941929dbSNPEnsembl.1
Natural variantiVAR_0050552502G → S.1 PublicationCorresponds to variant rs2229995dbSNPEnsembl.1
Natural variantiVAR_0050562621S → C in FAP. Corresponds to variant rs72541816dbSNPEnsembl.1
Natural variantiVAR_0089942738I → T.1 Publication1
Natural variantiVAR_0050572839L → F in FAP. 1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004115312 – 412Missing in isoform Short. 1 PublicationAdd BLAST101

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M73548 mRNA. Translation: AAA60353.1.
M73548 mRNA. Translation: AAA60354.1.
M74088 mRNA. Translation: AAA03586.1.
CH471086 Genomic DNA. Translation: EAW49002.1.
CH471086 Genomic DNA. Translation: EAW49007.1.
S78214 Genomic DNA. Translation: AAB21145.2. Sequence problems.
CCDSiCCDS4107.1. [P25054-1]
PIRiA37261. RBHUAP.
RefSeqiNP_000029.2. NM_000038.5. [P25054-1]
NP_001120982.1. NM_001127510.2. [P25054-1]
UniGeneiHs.158932.

Genome annotation databases

EnsembliENST00000257430; ENSP00000257430; ENSG00000134982. [P25054-1]
ENST00000508376; ENSP00000427089; ENSG00000134982. [P25054-1]
GeneIDi324.
KEGGihsa:324.
UCSCiuc003kpy.5. human. [P25054-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Colon cancer gene variant databases Adenomatous Polyposis Coli (APC)

Leiden Open Variation Database (LOVD)

Atlas of Genetics and Cytogenetics in Oncology and Haematology
SHMPD

The Singapore human mutation and polymorphism database

Wikipedia

APC entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M73548 mRNA. Translation: AAA60353.1.
M73548 mRNA. Translation: AAA60354.1.
M74088 mRNA. Translation: AAA03586.1.
CH471086 Genomic DNA. Translation: EAW49002.1.
CH471086 Genomic DNA. Translation: EAW49007.1.
S78214 Genomic DNA. Translation: AAB21145.2. Sequence problems.
CCDSiCCDS4107.1. [P25054-1]
PIRiA37261. RBHUAP.
RefSeqiNP_000029.2. NM_000038.5. [P25054-1]
NP_001120982.1. NM_001127510.2. [P25054-1]
UniGeneiHs.158932.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DEBX-ray2.40A/B2-55[»]
1EMUX-ray1.90B2034-2049[»]
1JPPX-ray3.10C/D1021-1035[»]
1M5IX-ray2.00A126-250[»]
1T08X-ray2.10C1484-1498[»]
1TH1X-ray2.50C/D1362-1540[»]
1V18X-ray2.10B1482-1528[»]
2RQUNMR-B1578-1596[»]
3AU3X-ray2.10A396-732[»]
3NMWX-ray1.60A/B407-751[»]
3NMXX-ray2.30A/B/C407-751[»]
3NMZX-ray3.01A/B303-739[»]
3QHEX-ray2.40A/C396-732[»]
3RL7X-ray2.30G/H/I/J/K/L2833-2843[»]
3RL8X-ray2.20F2833-2843[»]
3T7UX-ray2.90A/B407-775[»]
4G69X-ray2.00B2833-2843[»]
4YJEX-ray1.90A407-751[»]
4YJLX-ray2.10A/B/C/D/E/F407-751[»]
4YK6X-ray1.70A407-751[»]
DisProtiDP00519.
ProteinModelPortaliP25054.
SMRiP25054.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106821. 188 interactors.
DIPiDIP-33556N.
IntActiP25054. 180 interactors.
MINTiMINT-88204.
STRINGi9606.ENSP00000257430.

PTM databases

iPTMnetiP25054.
PhosphoSitePlusiP25054.

Polymorphism and mutation databases

BioMutaiAPC.
DMDMi97535708.

Proteomic databases

EPDiP25054.
MaxQBiP25054.
PaxDbiP25054.
PeptideAtlasiP25054.
PRIDEiP25054.

Protocols and materials databases

DNASUi324.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257430; ENSP00000257430; ENSG00000134982. [P25054-1]
ENST00000508376; ENSP00000427089; ENSG00000134982. [P25054-1]
GeneIDi324.
KEGGihsa:324.
UCSCiuc003kpy.5. human. [P25054-1]

Organism-specific databases

CTDi324.
DisGeNETi324.
GeneCardsiAPC.
GeneReviewsiAPC.
HGNCiHGNC:583. APC.
HPAiCAB025994.
HPA013349.
MalaCardsiAPC.
MIMi114550. phenotype.
135290. phenotype.
155255. phenotype.
175100. phenotype.
611731. gene.
613659. phenotype.
neXtProtiNX_P25054.
OpenTargetsiENSG00000134982.
Orphaneti247806. APC-related attenuated familial adenomatous polyposis.
873. Desmoid tumor.
261584. Familial adenomatous polyposis due to 5q22.2 microdeletion.
79665. Gardner syndrome.
99818. Turcot syndrome with polyposis.
PharmGKBiPA24875.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2122. Eukaryota.
ENOG410XR2V. LUCA.
GeneTreeiENSGT00530000063749.
HOVERGENiHBG004264.
InParanoidiP25054.
KOiK02085.
OMAiISRGRTM.
OrthoDBiEOG091G00D4.
PhylomeDBiP25054.
TreeFamiTF106496.

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000134982-MONOMER.
ZFISH:ENSG00000134982-MONOMER.
ReactomeiR-HSA-111465. Apoptotic cleavage of cellular proteins.
R-HSA-195253. Degradation of beta-catenin by the destruction complex.
R-HSA-196299. Beta-catenin phosphorylation cascade.
R-HSA-3769402. Deactivation of the beta-catenin transactivating complex.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-HSA-5339716. Misspliced GSK3beta mutants stabilize beta-catenin.
R-HSA-5358747. S33 mutants of beta-catenin aren't phosphorylated.
R-HSA-5358749. S37 mutants of beta-catenin aren't phosphorylated.
R-HSA-5358751. S45 mutants of beta-catenin aren't phosphorylated.
R-HSA-5358752. T41 mutants of beta-catenin aren't phosphorylated.
R-HSA-5467333. APC truncation mutants are not K63 polyubiquitinated.
R-HSA-5467337. APC truncation mutants have impaired AXIN binding.
R-HSA-5467340. AXIN missense mutants destabilize the destruction complex.
R-HSA-5467348. Truncations of AMER1 destabilize the destruction complex.
R-HSA-5689896. Ovarian tumor domain proteases.
SignaLinkiP25054.
SIGNORiP25054.

Miscellaneous databases

ChiTaRSiAPC. human.
EvolutionaryTraceiP25054.
GeneWikiiAdenomatous_polyposis_coli.
GenomeRNAii324.
PROiP25054.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134982.
CleanExiHS_APC.
ExpressionAtlasiP25054. baseline and differential.
GenevisibleiP25054. HS.

Family and domain databases

Gene3Di1.25.10.10. 2 hits.
InterProiIPR026836. APC.
IPR009240. APC_15aa_rpt.
IPR009234. APC_basic_dom.
IPR026831. APC_dom.
IPR026818. Apc_fam.
IPR032038. APC_N.
IPR009223. APC_rpt.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR009232. EB1-bd.
IPR009224. SAMP.
[Graphical view]
PANTHERiPTHR12607. PTHR12607. 2 hits.
PTHR12607:SF11. PTHR12607:SF11. 2 hits.
PfamiPF05972. APC_15aa. 3 hits.
PF05956. APC_basic. 1 hit.
PF16689. APC_N_CC. 1 hit.
PF05923. APC_r. 7 hits.
PF00514. Arm. 2 hits.
PF05937. EB1_binding. 1 hit.
PF05924. SAMP. 3 hits.
[Graphical view]
SMARTiSM00185. ARM. 7 hits.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 1 hit.
SSF58050. SSF58050. 1 hit.
SSF82931. SSF82931. 1 hit.
PROSITEiPS50176. ARM_REPEAT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPC_HUMAN
AccessioniPrimary (citable) accession number: P25054
Secondary accession number(s): D3DT03
, Q15162, Q15163, Q93042
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 16, 2006
Last modified: November 30, 2016
This is version 216 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

APC mutations have led to some interesting observations. (1) the great majority of the mutations found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with the number of colorectal polyps in FAP patients. Inactivation of both alleles of the APC gene seems to be required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.