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P70478 (APC_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 29, 2013. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Adenomatous polyposis coli protein

Short name=Protein APC
Gene names
Name:Apc
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length2842 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity.

Subunit structure

Forms homooligomers and heterooligomers with APC2. Interacts with DIAPH1 and DIAPH2. 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). Interacts at the cell membrane with AMER1 and AMER2 (via ARM repeats) By similarity. Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B. Ref.3

Subcellular location

Cell junctionadherens junction By similarity. Cytoplasmcytoskeleton By similarity. Cell projectionlamellipodium By similarity. Cell projectionruffle membrane By similarity. Cytoplasm By similarity. Cell membrane By similarity. Note: Associated with the microtubule network at the growing distal tip of microtubules. Accumulates in the lamellipodium and ruffle membrane in response to hepatocyte growth factor (HGF) treatment By similarity. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosophorylated form to the cell membrane By similarity.

Domain

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

Post-translational modification

Phosphorylated by GSK3B By similarity.

Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID By similarity.

Sequence similarities

Belongs to the adenomatous polyposis coli (APC) family.

Contains 7 ARM repeats.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Microtubule
   DiseaseTumor suppressor
   DomainCoiled coil
Repeat
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt receptor signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

cell cycle arrest

Inferred from sequence or structural similarity. Source: UniProtKB

cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

cytokinesis after mitosis

Inferred from electronic annotation. Source: InterPro

establishment or maintenance of cell polarity

Inferred from direct assay PubMed 12610628. Source: RGD

negative regulation of Wnt receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cyclin-dependent protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of microtubule depolymerization

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection development

Inferred from mutant phenotype PubMed 16303851. Source: RGD

pancreas development

Inferred from expression pattern PubMed 16688812. Source: RGD

positive regulation of apoptotic process

Inferred from electronic annotation. Source: InterPro

protein complex assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of glutamate metabolic process

Inferred from direct assay PubMed 19858196. Source: RGD

response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

response to alcohol

Inferred from expression pattern PubMed 18945221. Source: RGD

response to drug

Inferred from expression pattern PubMed 11689703. Source: RGD

   Cellular_componentadherens junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

axonal growth cone

Inferred from direct assay PubMed 15670646. Source: RGD

beta-catenin destruction complex

Inferred from sequence or structural similarity. Source: UniProtKB

cell body fiber

Inferred from direct assay PubMed 23001297. Source: RGD

cell cortex

Inferred from direct assay PubMed 18042042. Source: RGD

centrosome

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 15670646. Source: RGD

kinetochore

Inferred from sequence or structural similarity. Source: UniProtKB

lamellipodium

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule

Inferred from direct assay PubMed 16767746. Source: RGD

neuron projection terminus

Inferred from direct assay PubMed 18042042. Source: RGD

neuronal cell body

Inferred from direct assay PubMed 17507554. Source: RGD

nuclear membrane

Inferred from direct assay PubMed 18042042. Source: RGD

ruffle membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionbeta-catenin binding

Inferred from sequence or structural similarity. Source: UniProtKB

microtubule plus-end binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex binding

Inferred from direct assay PubMed 19858196. Source: RGD

protein kinase regulator activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Dlg4P310162EBI-631663,EBI-375655

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 28422842Adenomatous polyposis coli protein
PRO_0000064629

Regions

Repeat451 – 49343ARM 1
Repeat503 – 54543ARM 2
Repeat546 – 58944ARM 3
Repeat590 – 63647ARM 4
Repeat637 – 68145ARM 5
Repeat682 – 72342ARM 6
Repeat724 – 76542ARM 7
Region1864 – 189128Highly charged
Coiled coil1 – 6262 Potential
Coiled coil125 – 260136 Potential
Motif2802 – 28054Microtubule tip localization signal
Motif2840 – 28423PDZ-binding By similarity
Compositional bias1 – 728728Leu-rich
Compositional bias739 – 28312093Ser-rich
Compositional bias1130 – 115526Asp/Glu-rich (acidic)
Compositional bias1556 – 157520Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue7421Phosphoserine By similarity
Modified residue7781Phosphoserine By similarity
Modified residue10361Phosphoserine By similarity
Modified residue10401Phosphoserine By similarity
Modified residue11781Phosphoserine Ref.4
Modified residue13571Phosphoserine By similarity
Modified residue13681Phosphoserine By similarity
Modified residue15571Phosphoserine By similarity
Modified residue16951Phosphothreonine Ref.4
Modified residue17141Phosphoserine Ref.4
Modified residue18591Phosphoserine By similarity
Modified residue18611Phosphoserine By similarity
Modified residue18621Phosphoserine By similarity
Modified residue21511Phosphothreonine By similarity
Modified residue22601Phosphoserine By similarity
Modified residue22701Phosphoserine By similarity
Modified residue22831Phosphoserine By similarity
Modified residue24731Phosphoserine By similarity
Modified residue25351Phosphoserine By similarity
Modified residue26711Phosphoserine By similarity
Modified residue26741Phosphoserine By similarity
Modified residue26791Phosphothreonine By similarity
Modified residue27881Phosphoserine By similarity

Experimental info

Mutagenesis5231C → R in an IQ-induced colon tumor.

Sequences

Sequence LengthMass (Da)Tools
P70478 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 3CBB2EA8A34E8F47

FASTA2,842310,533
        10         20         30         40         50         60 
MAAASYDQLL KQVEALKMEN SNLRQELEDN SNHLTELETE ASNMKEVLKQ LQGSIEDETM 

        70         80         90        100        110        120 
TSGQIDLLER LKEFNLDSNF PGVKLRSKMS LRSYGSREGS VSSRSGECSP VPMGSFPRRA 

       130        140        150        160        170        180 
FVNGSRESTG YLEELEKERS LLLADLDKEE KEKDWYYAQL QNLTKRIDSL PLTENFSLQT 

       190        200        210        220        230        240 
DMTRRQLEYE ARQIRAAMEE QLGTCQDMEK RAQRRIARIQ QIEKDILRVR QLLQSQAAEA 

       250        260        270        280        290        300 
ERSSQSKHET ASHEAERQLE GQGVAESNLA TSGSGQSSAA RVDHETAGVL SSSGTHSAPR 

       310        320        330        340        350        360 
RLTSHLGTKV EMVYSLLSML GTHDKDDMSR TLLAMSSSQD SCISMRQSGC LPLLIQLLHG 

       370        380        390        400        410        420 
NDKDSVLLGN SRGSKEARAR ASAALHNIIH SQPDDKRGRR EIRVLHLLEQ IRAYCETCWE 

       430        440        450        460        470        480 
WQEAHEQGMD QDKNPMPAPV EHQICPAVCV LMKLSFDEEH RHAMNELGGL QAIAELLQVD 

       490        500        510        520        530        540 
CEMHGLTDDH YSVTLRRYAG MALTNLTFGD VANKATLCSM KGCMRALVAQ LKSESEDLQQ 

       550        560        570        580        590        600 
VIASVLRNLS WRADVNSKKT LREVGSVKAL MECALEVKKE STLKSVLSAL WNLSAHCTEN 

       610        620        630        640        650        660 
KADICAVDGA LAFLVGTLTY RSQTNTLAII ESGGGILRNV SSLIATNEDH RQILRENNCL 

       670        680        690        700        710        720 
QTLLQHLKSH SLTIVSNACG TLWNLSARNP KDQEALWDMG AVSMLKNLIH SKHKMIAMGS 

       730        740        750        760        770        780 
AAALRNLMAN RPAKYKDANI MSPGSSLPSL HVRKQKALEA ELDAQHLSET FDNIDNLSPK 

       790        800        810        820        830        840 
ASHRSKQRHK QNLYGDYVFD ASRHDDNRSD NFNTGNMTVL SPYLNTTVLP SSSSSRGSLD 

       850        860        870        880        890        900 
SSRSEKDRSL ERERGIGLST YHSATENPGT SSKRGLQLSA TAAQIAKVME EVSALHTSQD 

       910        920        930        940        950        960 
DRSPASAAEL HCVAEERTAA RRSSASHTHP NTHNFAKSES SNRTCSMPYA KVEYKRSSND 

       970        980        990       1000       1010       1020 
SLNSVTSSDG YGKRGQMKPS VESYSEDDEG KFCSYGQYPA DLAHKIHSAN HMDDNGGELD 

      1030       1040       1050       1060       1070       1080 
TPINYSLKYS DEQLNSGRQS PSQNERWARP KHVIEDEIKQ NEQRQSRSQN TNFPVYSENT 

      1090       1100       1110       1120       1130       1140 
DDKHLKFQQH FGQQECVSPY RSRGTNGSET NRMGSSHAVN QNVNQSLCQE DDYEDDKPTN 

      1150       1160       1170       1180       1190       1200 
YSERYSEEEQ HEEEERPTNY SIKYNEEKHH VDQPIDYSLK YATDISSSQK PSFSFSKTPS 

      1210       1220       1230       1240       1250       1260 
VQGTKTEHNS PSSEAASAPS SNAKRQSQLH PSSAQRNGQT PKGTACKVPS INQETMQTYC 

      1270       1280       1290       1300       1310       1320 
VEDTPICFSR CSSLSSLSSA EDEIGCDQTT QEADSANTLQ IAEIKENDVT RSAQDPASDV 

      1330       1340       1350       1360       1370       1380 
PAVSQSTRTK PSRLQASGLA SESARHKAVE FSSGAKSPSK SGAQTPKSPP EHYVQETPLV 

      1390       1400       1410       1420       1430       1440 
FSRCTSVSSL DSFESRSIAS SVQSEPCSGM VSGIVSPSDL PDSPGQTMPP SRSKTPPPPP 

      1450       1460       1470       1480       1490       1500 
PPQPVQTKRE VPKTKVPAAE QREGGPKQTA VSAAVQRVQV LPDADTLLHF ATESTPDGFS 

      1510       1520       1530       1540       1550       1560 
CSSSLSALSL DEPFIQKDVE LRIMPPVQEN DNGNETEPEQ PEESNENQDK EVEKPDSEKD 

      1570       1580       1590       1600       1610       1620 
LLDDSDDDDI EILEECIISA MPTKSSRKAK KLAQTASKLP PPVARKPSQL PVYKLLPSQS 

      1630       1640       1650       1660       1670       1680 
RLQAQKHVSF TPGDDVPRVY CVEGTPINFS TATSLSDLTI ESPPNELAAG DGVRASVQSG 

      1690       1700       1710       1720       1730       1740 
EFEKRDTIPT EGRSTDEAQR GKVSSIAIPD LDGSKAEEGD ILAECINSAL PKGRSHKPFR 

      1750       1760       1770       1780       1790       1800 
VKKIMDQVQQ ASMTSSGTNK NQIDTKKKKP TSPVKPMPQN TEYRTRVRKN TDSKVNVNTE 

      1810       1820       1830       1840       1850       1860 
ETFSDNKDSK KQSLKNNPKD LNDKLPDNED RVRGGFTFDS PHHYAPIEGT PYCFSRNDSL 

      1870       1880       1890       1900       1910       1920 
SSLDFDDDDV DLSREKAELR KGKESKDSEA KVTCHTEPSS SQQSARKAQA STKHPVNRGP 

      1930       1940       1950       1960       1970       1980 
SKPLLQEQPT FPQSSKDVPD RGAATDEKLQ NFAIENTPVC FSRNSSLSSL SDVDQENNNN 

      1990       2000       2010       2020       2030       2040 
EETGPVRDAE PANAQGQPGK PQASGYAPKS FHVEDTPVCF SRNSSLSSLS IDSEDDLLRE 

      2050       2060       2070       2080       2090       2100 
CISSAMPKKR RPSRLKGEGE WQSPRKVGSV LAEDLTLDLK DIQRPESEHG LSPDSENFDW 

      2110       2120       2130       2140       2150       2160 
KAIQEGANSI VSSLHQAAAA AACLSRQASS DSDSILSLKS GVSLGSPFHL TPDQEEKPFT 

      2170       2180       2190       2200       2210       2220 
SHKGPRILKP GEKSTLEAKK IESENKGIKG GKKVYKSLIT GKIRSNSEIS SQMKQPLQTN 

      2230       2240       2250       2260       2270       2280 
MPSISRGRTM IHIPGVRNSS SSTSPVSKKG PPLKTPASKS PSEGPVATTS PRGTKPAVKS 

      2290       2300       2310       2320       2330       2340 
ELSPITRQTS HISGSNKGPS RSGSRDSTPS RPTQQPLSRP MQSPGRNSIS PGRNGISTPN 

      2350       2360       2370       2380       2390       2400 
KLSQLPRTSS PSTASTKSSG SGKMSYTSPG RQLSQQNLSK QTGLSKNASS IPRSESASKG 

      2410       2420       2430       2440       2450       2460 
LNQMNNSNGS NKKVELSRMS STKSSGSESD RSERPALVRQ STFIKEAPSP TLRRKLEESA 

      2470       2480       2490       2500       2510       2520 
SFESLSPSSR PDSPTRSQAQ TPVLSPSLPD MSLSTHPSVQ AGGWRKLPPN LSPTIEYSDG 

      2530       2540       2550       2560       2570       2580 
RPSKRHDIAR SHSESPSRLP VNRAGTWKRE HSKHSSSLPR VSTWRRTGSS SSILSASSES 

      2590       2600       2610       2620       2630       2640 
SEKAKSEDEK HVNSVPGPRQ MKENQVPTKG TWRKIKESEI SPTNTVSQTT SSGAASGAES 

      2650       2660       2670       2680       2690       2700 
KTLIYQMAPA VSRTEDVWVR IEDCPINNPR SGRSPTGNTP PVIDSISEKG NPSIKDSKDT 

      2710       2720       2730       2740       2750       2760 
QGKQSVGSGS PVQTVGLENR LNSFIQVEAP EQKGTETKAG QGSPAPVAET GETCMAERTP 

      2770       2780       2790       2800       2810       2820 
FSSSSSSKHS SPSGTVAARV TPFNYNPSPR KSSADSTSAR PSQIPTPVGS STKKRDSKTD 

      2830       2840 
STESSGAQSP KRHSGSYLVT SV 

« Hide

References

« Hide 'large scale' references
[1]"cDNA cloning of the rat APC gene and assignment to chromosome 18."
Toyota M., Ushijima T., Kakiuchi H., Watanabe M., Imai K., Yachi A., Sugimura T., Nagao M.
Mamm. Genome 6:746-748(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: Fischer 344/N.
Tissue: Brain.
[2]"Specific 5'-GGGA-3'-->5'-GGA-3' mutation of the Apc gene in rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine."
Kakiuchi H., Watanabe M., Ushijima T., Toyota M., Imai K., Weisburger J.H., Sugimura T., Nagao M.
Proc. Natl. Acad. Sci. U.S.A. 92:910-914(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
Strain: Fischer 344/N and Sprague-Dawley.
[3]"The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway."
Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.
Genes Dev. 20:1933-1945(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH MACF1; CTNNB1; AXIN1 AND GSK3B.
[4]"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1178; THR-1695 AND SER-1714, MASS SPECTROMETRY.
Tissue: Renal collecting duct.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D38629 mRNA. Translation: BAA07609.1.
IPIIPI00188859.
RefSeqNP_036631.1. NM_012499.1.
UniGeneRn.88057.

3D structure databases

ProteinModelPortalP70478.
SMRP70478. Positions 2-55, 128-237, 1467-1528.
ModBaseSearch...

Protein-protein interaction databases

IntActP70478. 1 interaction.
STRING10116.ENSRNOP00000027691.

PTM databases

PhosphoSiteP70478.

Proteomic databases

PaxDbP70478.
PRIDEP70478.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID24205.
KEGGrno:24205.
UCSCRGD:2123. rat.

Organism-specific databases

CTD324.
RGD2123. Apc.

Phylogenomic databases

eggNOGNOG259696.
HOGENOMHOG000033986.
HOVERGENHBG004264.
InParanoidP70478.
KOK02085.
OrthoDBEOG4D26NZ.

Gene expression databases

ArrayExpressP70478.
GenevestigatorP70478.
GermOnlineENSRNOG00000020423. Rattus norvegicus.

Family and domain databases

Gene3D1.25.10.10. 2 hits.
InterProIPR026836. APC.
IPR009240. APC_15aa_rpt.
IPR009234. APC_basic_dom.
IPR009223. APC_Cys-rich_rpt.
IPR026831. APC_dom.
IPR026818. Apc_fam.
IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000225. Armadillo.
IPR009232. EB1-bd.
IPR009224. SAMP.
[Graphical view]
PANTHERPTHR12607. PTHR12607. 1 hit.
PTHR12607:SF2. PTHR12607:SF2. 1 hit.
PfamPF05972. APC_15aa. 4 hits.
PF05956. APC_basic. 1 hit.
PF05923. APC_crr. 7 hits.
PF00514. Arm. 3 hits.
PF05937. EB1_binding. 1 hit.
PF05924. SAMP. 3 hits.
PF11414. Suppressor_APC. 1 hit.
[Graphical view]
SMARTSM00185. ARM. 6 hits.
[Graphical view]
SUPFAMSSF48371. ARM-type_fold. 1 hit.
PROSITEPS50176. ARM_REPEAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio602593.

Entry information

Entry nameAPC_RAT
AccessionPrimary (citable) accession number: P70478
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 1, 1997
Last modified: May 29, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families