| General information | | DisProt: | DP00519 | | Name: | Adenomatous polyposis coli protein [Isoform Long] | | Synonym(s): | APC_HUMAN
Protein APC
Deleted in polyposis 2.5
| | First appeared in release: | Release 3.5 (12/22/2006) | | UniProt: | P25054-1 | | UniGene: | Hs.158932 | | SwissProt: | APC_HUMAN | | TrEMBL: | | | NCBI (GI): | 97535708 | | Source organism: | Homo sapiens (Human) | | Sequence length: | 2843 | | Percent disordered: | 14% | | Homologues: | |
| Native sequence |
10 20 30 40 50 60
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MAAASYDQLL KQVEALKMEN SNLRQELEDN SNHLTKLETE ASNMKEVLKQ LQGSIEDEAM - 60
ASSGQIDLLE RLKELNLDSS NFPGVKLRSK MSLRSYGSRE GSVSSRSGEC SPVPMGSFPR - 120
RGFVNGSRES TGYLEELEKE RSLLLADLDK EEKEKDWYYA QLQNLTKRID SLPLTENFSL - 180
QTDMTRRQLE YEARQIRVAM EEQLGTCQDM EKRAQRRIAR IQQIEKDILR IRQLLQSQAT - 240
EAERSSQNKH ETGSHDAERQ NEGQGVGEIN MATSGNGQGS TTRMDHETAS VLSSSSTHSA - 300
PRRLTSHLGT KVEMVYSLLS MLGTHDKDDM SRTLLAMSSS QDSCISMRQS GCLPLLIQLL - 360
HGNDKDSVLL GNSRGSKEAR ARASAALHNI IHSQPDDKRG RREIRVLHLL EQIRAYCETC - 420
WEWQEAHEPG MDQDKNPMPA PVEHQICPAV CVLMKLSFDE EHRHAMNELG GLQAIAELLQ - 480
VDCEMYGLTN DHYSITLRRY AGMALTNLTF GDVANKATLC SMKGCMRALV AQLKSESEDL - 540
QQVIASVLRN LSWRADVNSK KTLREVGSVK ALMECALEVK KESTLKSVLS ALWNLSAHCT - 600
ENKADICAVD GALAFLVGTL TYRSQTNTLA IIESGGGILR NVSSLIATNE DHRQILRENN - 660
CLQTLLQHLK SHSLTIVSNA CGTLWNLSAR NPKDQEALWD MGAVSMLKNL IHSKHKMIAM - 720
GSAAALRNLM ANRPAKYKDA NIMSPGSSLP SLHVRKQKAL EAELDAQHLS ETFDNIDNLS - 780
PKASHRSKQR HKQSLYGDYV FDTNRHDDNR SDNFNTGNMT VLSPYLNTTV LPSSSSSRGS - 840
LDSSRSEKDR SLERERGIGL GNYHPATENP GTSSKRGLQI STTAAQIAKV MEEVSAIHTS - 900
QEDRSSGSTT ELHCVTDERN ALRRSSAAHT HSNTYNFTKS ENSNRTCSMP YAKLEYKRSS - 960
NDSLNSVSSS DGYGKRGQMK PSIESYSEDD ESKFCSYGQY PADLAHKIHS ANHMDDNDGE - 1020
LDTPINYSLK YSDEQLNSGR QSPSQNERWA RPKHIIEDEI KQSEQRQSRN QSTTYPVYTE - 1080
STDDKHLKFQ PHFGQQECVS PYRSRGANGS ETNRVGSNHG INQNVSQSLC QEDDYEDDKP - 1140
TNYSERYSEE EQHEEEERPT NYSIKYNEEK RHVDQPIDYS LKYATDIPSS QKQSFSFSKS - 1200
SSGQSSKTEH MSSSSENTST PSSNAKRQNQ LHPSSAQSRS GQPQKAATCK VSSINQETIQ - 1260
TYCVEDTPIC FSRCSSLSSL SSAEDEIGCN QTTQEADSAN TLQIAEIKEK IGTRSAEDPV - 1320
SEVPAVSQHP RTKSSRLQGS SLSSESARHK AVEFSSGAKS PSKSGAQTPK SPPEHYVQET - 1380
PLMFSRCTSV SSLDSFESRS IASSVQSEPC SGMVSGIISP SDLPDSPGQT MPPSRSKTPP - 1440
PPPQTAQTKR EVPKNKAPTA EKRESGPKQA AVNAAVQRVQ VLPDADTLLH FATESTPDGF - 1500
SCSSSLSALS LDEPFIQKDV ELRIMPPVQE NDNGNETESE QPKESNENQE KEAEKTIDSE - 1560
KDLLDDSDDD DIEILEECII SAMPTKSSRK AKKPAQTASK LPPPVARKPS QLPVYKLLPS - 1620
QNRLQPQKHV SFTPGDDMPR VYCVEGTPIN FSTATSLSDL TIESPPNELA AGEGVRGGAQ - 1680
SGEFEKRDTI PTEGRSTDEA QGGKTSSVTI PELDDNKAEE GDILAECINS AMPKGKSHKP - 1740
FRVKKIMDQV QQASASSSAP NKNQLDGKKK KPTSPVKPIP QNTEYRTRVR KNADSKNNLN - 1800
AERVFSDNKD SKKQNLKNNS KVFNDKLPNN EDRVRGSFAF DSPHHYTPIE GTPYCFSRND - 1860
SLSSLDFDDD DVDLSREKAE LRKAKENKES EAKVTSHTEL TSNQQSANKT QAIAKQPINR - 1920
GQPKPILQKQ STFPQSSKDI PDRGAATDEK LQNFAIENTP VCFSHNSSLS SLSDIDQENN - 1980
NKENEPIKET EPPDSQGEPS KPQASGYAPK SFHVEDTPVC FSRNSSLSSL SIDSEDDLLQ - 2040
ECISSAMPKK KKPSRLKGDN EKHSPRNMGG ILGEDLTLDL KDIQRPDSEH GLSPDSENFD - 2100
WKAIQEGANS IVSSLHQAAA AACLSRQASS DSDSILSLKS GISLGSPFHL TPDQEEKPFT - 2160
SNKGPRILKP GEKSTLETKK IESESKGIKG GKKVYKSLIT GKVRSNSEIS GQMKQPLQAN - 2220
MPSISRGRTM IHIPGVRNSS SSTSPVSKKG PPLKTPASKS PSEGQTATTS PRGAKPSVKS - 2280
ELSPVARQTS QIGGSSKAPS RSGSRDSTPS RPAQQPLSRP IQSPGRNSIS PGRNGISPPN - 2340
KLSQLPRTSS PSTASTKSSG SGKMSYTSPG RQMSQQNLTK QTGLSKNASS IPRSESASKG - 2400
LNQMNNGNGA NKKVELSRMS STKSSGSESD RSERPVLVRQ STFIKEAPSP TLRRKLEESA - 2460
SFESLSPSSR PASPTRSQAQ TPVLSPSLPD MSLSTHSSVQ AGGWRKLPPN LSPTIEYNDG - 2520
RPAKRHDIAR SHSESPSRLP INRSGTWKRE HSKHSSSLPR VSTWRRTGSS SSILSASSES - 2580
SEKAKSEDEK HVNSISGTKQ SKENQVSAKG TWRKIKENEF SPTNSTSQTV SSGATNGAES - 2640
KTLIYQMAPA VSKTEDVWVR IEDCPINNPR SGRSPTGNTP PVIDSVSEKA NPNIKDSKDN - 2700
QAKQNVGNGS VPMRTVGLEN RLNSFIQVDA PDQKGTEIKP GQNNPVPVSE TNESSIVERT - 2760
PFSSSSSSKH SSPSGTVAAR VTPFNYNPSP RKSSADSTSA RPSQIPTPVN NNTKKRDSKT - 2820
DSTESSGTQS PKRHSGSYLV TSV
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| Functional narrative |
The tumor suppressor adenomatous polyposis coli (APC) is considered to be a gatekeeper in colorectal tumorigenesis. Truncational mutations of APC are found in Familial Adenomatous Polyposis (FAP) and more than 80% of sporadic colonic tumors. In addition to its roles in cytoskeletal and cell adhesion regulation it is well established that APC plays an essential role in the Wnt-regulated degradation of beta-catenin. The central region of APC includes three 15-amino acid repeats and seven 20-amino acid repeats. APC activity is correlated with its phosphorylation state. Mutations that truncate APC in the 20 residue repeat region, such as that in SW480 colon cancer cells, lead to the accumulation of high levels of beta-catenin. APC Forms homooligomers. Interacts with DIAPH1 and DIAPH2. Interacts with PDZ domains of DLG1 and DLG3. Associates with catenins. Binds axin. Interacts with the N-terminus of ARHGEF4, and the C-terminus of MAPRE1, MAPRE2 and MAPRE3. Found in a complex consisting of ARHGEF4, APC, and CTNNB1. Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state.
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| Map of ordered and disordered regions |
Note: 'Mouse' over a region to see the start and stop residues. Click on a region to see detailed information.
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| Region 1 | | Type: | Disordered | | Name: | central region | | Location: | 1362 - 1745 | | Length: | 384 | | Region sequence: |
SKSGAQTPKSPPEHYVQETPLMFSRCTSVSSLDSFESRSIASSVQSEPCSGMVSGIISPS
DLPDSPGQTMPPSRSKTPPPPPQTAQTKREVPKNKAPTAEKRESGPKQAAVNAAVQRVQV
LPDADTLLHFATESTPDGFSCSSSLSALSLDEPFIQKDVELRIMPPVQENDNGNETESEQ
PKESNENQEKEAEKTIDSEKDLLDDSDDDDIEILEECIISAMPTKSSRKAKKPAQTASKL
PPPVARKPSQLPVYKLLPSQNRLQPQKHVSFTPGDDMPRVYCVEGTPINFSTATSLSDLT
IESPPNELAAGEGVRGGAQSGEFEKRDTIPTEGRSTDEAQGGKTSSVTIPELDDNKAEEG
DILAECINSAMPKGKSHKPFRVKK | | Modification type: | Fragment
Native
| | PDB: | | | Structural/functional type: | Function arises from the disordered state
| | Functional classes: | Molecular assembly
| | Functional subclasses: | Protein-protein binding
| Detection methods:
- Circular dichroism (CD) spectroscopy, far-UV (277 K; pH: 7.5; 1 mm path length; phosphate (buffer) 10 mM)
- Nuclear magnetic resonance (NMR) (298 K; pH: 7.5; 2H2O 10 %; DTT-d10 1 mM; PBS (buffer); protein (sample) 0.2 mM)
| References:
- Liu J, Xing Y, Hinds TR, Zheng J, Xu W. "The Third 20 Amino Acid Repeat Is the Tightest Binding Site of APC for beta-Catenin." J Mol Biol. 2006; 360(1): 133-44. PubMed: 16753179
| Comments:The central region of APC (residues ∼1000–∼2100)
is highly hydrophilic. It contains only a total of 18.9%
of hydrophobic residues, but 20.0% of serine/
threonine and 8.0% of proline. Using various
programs, including FoldIndex, PONDR and
DisEMBL it is predicted that all this central region of APC is largely unstructured. Experimental data were measured only for the the longest APC fragment (APC 1362-1745) that could be obtained in large quantity.
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| References |
- Hanson CA, Miller JR. "Non-traditional roles for the Adenomatous Polyposis Coli (APC) tumor suppressor protein." Gene. 2005; 361: 1-12. PubMed: 16185824
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