Adenomatous polyposis coli protein - Rattus norvegicus (Rat)

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P70478 (APC_RAT) Reviewed, UniProtKB/Swiss-Prot

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

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Adenomatous polyposis coli protein
Short name=Protein APC

Gene names

Name:

Apc

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	2842 AA.
Sequence status	Complete.
Protein existence	Evidence 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 junction › adherens junction By similarity. Cytoplasm › cytoskeleton By similarity. Cell projection › lamellipodium By similarity. Cell projection › ruffle 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 process	Wnt signaling pathway
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Microtubule
Disease	Tumor suppressor
Domain	Coiled coil Repeat
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt 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_component	adherens 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_function	beta-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
Dlg4	P31016	2	EBI-631663,EBI-375655

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 2842

2842

Adenomatous polyposis coli protein

PRO_0000064629

Regions

Repeat

451 – 493

ARM 1

Repeat

503 – 545

ARM 2

Repeat

546 – 589

ARM 3

Repeat

590 – 636

ARM 4

Repeat

637 – 681

ARM 5

Repeat

682 – 723

ARM 6

Repeat

724 – 765

ARM 7

Region

1864 – 1891

Highly charged

Coiled coil

1 – 62

Potential

Coiled coil

125 – 260

136

Potential

Motif

2802 – 2805

Microtubule tip localization signal

Motif

2840 – 2842

PDZ-binding By similarity

Compositional bias

1 – 728

728

Leu-rich

Compositional bias

739 – 2831

2093

Ser-rich

Compositional bias

1130 – 1155

Asp/Glu-rich (acidic)

Compositional bias

1556 – 1575

Asp/Glu-rich (acidic)

Amino acid modifications

Modified residue

742

Phosphoserine By similarity

Modified residue

778

Phosphoserine By similarity

Modified residue

1036

Phosphoserine By similarity

Modified residue

1040

Phosphoserine By similarity

Modified residue

1178

Phosphoserine Ref.4

Modified residue

1357

Phosphoserine By similarity

Modified residue

1368

Phosphoserine By similarity

Modified residue

1557

Phosphoserine By similarity

Modified residue

1695

Phosphothreonine Ref.4

Modified residue

1714

Phosphoserine Ref.4

Modified residue

1859

Phosphoserine By similarity

Modified residue

1861

Phosphoserine By similarity

Modified residue

1862

Phosphoserine By similarity

Modified residue

2151

Phosphothreonine By similarity

Modified residue

2260

Phosphoserine By similarity

Modified residue

2270

Phosphoserine By similarity

Modified residue

2283

Phosphoserine By similarity

Modified residue

2473

Phosphoserine By similarity

Modified residue

2535

Phosphoserine By similarity

Modified residue

2671

Phosphoserine By similarity

Modified residue

2674

Phosphoserine By similarity

Modified residue

2679

Phosphothreonine By similarity

Modified residue

2788

Phosphoserine By similarity

Experimental info

Mutagenesis

523

C → R in an IQ-induced colon tumor.

Sequences

Sequence

Length

Mass (Da)

Tools

P70478 [UniParc].

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

FASTA

2,842

310,533

        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' referencesShow '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.
IPI	IPI00188859.
RefSeq	NP_036631.1. NM_012499.1.
UniGene	Rn.88057.
3D structure databases
ProteinModelPortal	P70478.
SMR	P70478. Positions 2-55, 128-237, 1467-1528.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70478. 1 interaction.
STRING	10116.ENSRNOP00000027691.
PTM databases
PhosphoSite	P70478.
Proteomic databases
PaxDb	P70478.
PRIDE	P70478.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24205.
KEGG	rno:24205.
UCSC	RGD:2123. rat.
Organism-specific databases
CTD	324.
RGD	2123. Apc.
Phylogenomic databases
eggNOG	NOG259696.
HOGENOM	HOG000033986.
HOVERGEN	HBG004264.
InParanoid	P70478.
KO	K02085.
OrthoDB	EOG4D26NZ.
Gene expression databases
ArrayExpress	P70478.
Genevestigator	P70478.
GermOnline	ENSRNOG00000020423. Rattus norvegicus.
Family and domain databases
Gene3D	1.25.10.10. 2 hits.
InterPro	IPR026836. 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]
PANTHER	PTHR12607. PTHR12607. 1 hit. PTHR12607:SF2. PTHR12607:SF2. 1 hit.
Pfam	PF05972. 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]
SMART	SM00185. ARM. 6 hits. [Graphical view]
SUPFAM	SSF48371. ARM-type_fold. 1 hit.
PROSITE	PS50176. ARM_REPEAT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	602593.

Entry information

Entry name

APC_RAT

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents