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P23508 (CRCM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Colorectal mutant cancer protein

Short name=Protein MCC
Gene names
Name:MCC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length829 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Candidate for the putative colorectal tumor suppressor gene located at 5q21. Suppresses cell proliferation and the Wnt/b-catenin pathway in colorectal cancer cells. Inhibits DNA binding of b-catenin/TCF/LEF transcription factors. Involved in cell migration independently of RAC1, CDC42 and p21-activated kinase (PAK) activation. Ref.6 Ref.7 Ref.9

Subunit structure

Interacts with SCRIB (via phosphorylated PDZ-binding motif), EZR, SNX27, SLC9A3R1 and SLC9A3R2. Interacts with CTNNB1; the interaction is enhanced upon Wnt stimulation. Interacts with MYH10. Ref.6 Ref.7 Ref.9

Subcellular location

Cell membrane. Cell projectionlamellipodium. Nucleus. Cytoplasm. Note: Colocalizes with actin at the leading edge of polarized cells. Ref.6 Ref.7 Ref.9

Tissue specificity

Expressed in a variety of tissues.

Sequence similarities

Belongs to the MCC family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GTF2E2P290842EBI-307531,EBI-2853321
SCRIBQ141608EBI-307531,EBI-357345

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P23508-1)

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.
Isoform 2 (identifier: P23508-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-19: MNSGVAMKYGNDSSAELSE → MMAAAAAAAA...GGSYLELANT

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 829829Colorectal mutant cancer protein
PRO_0000079333

Regions

Motif826 – 8294PDZ-binding

Amino acid modifications

Modified residue8281Phosphoserine Ref.9

Natural variations

Alternative sequence1 – 1919MNSGV…AELSE → MMAAAAAAAAGSSSSGGGGG GSGSSSSSSDTSSTGEEERM RRLFQTCDGDGDGYISRNDL LMVCRQLNMEESVAEIMNQL GADENGKISFQDFTRCRMQL VREIRKEEVDLSAKSDNSCT KKLRDRIASWPTSSDNSLGA LSAARESWEYDSGARDLQSP DVQSQSALQKLLEYGGSSLH QQAALHKLLTQSPHIGNSVG GSYLELANT in isoform 2.
VSP_037660
Natural variant1901K → R. Ref.1 Ref.4 Ref.5
Corresponds to variant rs6594681 [ dbSNP | Ensembl ].
VAR_050905
Natural variant2671R → L in a colorectal cancer sample. Ref.10
VAR_005141
Natural variant4861P → L in a colorectal cancer sample. Ref.10
Corresponds to variant rs35269015 [ dbSNP | Ensembl ].
VAR_005142
Natural variant4901S → L in a colorectal cancer sample. Ref.10
VAR_005143
Natural variant5061R → Q in colorectal cancer samples; somatic mutation. Ref.1 Ref.10
VAR_005144
Natural variant6981A → V in colorectal cancer samples; somatic mutation. Ref.1 Ref.10
VAR_005145
Natural variant7511S → C.
Corresponds to variant rs17313892 [ dbSNP | Ensembl ].
VAR_033753

Experimental info

Mutagenesis8281S → A: Reduced binding to SCRIB. Ref.9
Mutagenesis8281S → D: Higher membrane localization, reduced formation of lamellipodia, accumulation of MYH10 at the cell cortex. Ref.9
Sequence conflict3531S → G in BAC87521. Ref.5
Isoform 2:
Sequence conflict251S → GSSSG in BAC87521. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2011. Version 2.
Checksum: C90611B2E91A7F60

FASTA82993,027
        10         20         30         40         50         60 
MNSGVAMKYG NDSSAELSEL HSAALASLKG DIVELNKRLQ QTERERDLLE KKLAKAQCEQ 

        70         80         90        100        110        120 
SHLMREHEDV QERTTLRYEE RITELHSVIA ELNKKIDRLQ GTTIREEDEY SELRSELSQS 

       130        140        150        160        170        180 
QHEVNEDSRS MDQDQTSVSI PENQSTMVTA DMDNCSDLNS ELQRVLTGLE NVVCGRKKSS 

       190        200        210        220        230        240 
CSLSVAEVDK HIEQLTTASE HCDLAIKTVE EIEGVLGRDL YPNLAEERSR WEKELAGLRE 

       250        260        270        280        290        300 
ENESLTAMLC SKEEELNRTK ATMNAIREER DRLRRRVREL QTRLQSVQAT GPSSPGRLTS 

       310        320        330        340        350        360 
TNRPINPSTG ELSTSSSSND IPIAKIAERV KLSKTRSESS SSDRPVLGSE ISSIGVSSSV 

       370        380        390        400        410        420 
AEHLAHSLQD CSNIQEIFQT LYSHGSAISE SKIREFEVET ERLNSRIEHL KSQNDLLTIT 

       430        440        450        460        470        480 
LEECKSNAER MSMLVGKYES NATALRLALQ YSEQCIEAYE LLLALAESEQ SLILGQFRAA 

       490        500        510        520        530        540 
GVGSSPGDQS GDENITQMLK RAHDCRKTAE NAAKALLMKL DGSCGGAFAV AGCSVQPWES 

       550        560        570        580        590        600 
LSSNSHTSTT SSTASSCDTE FTKEDEQRLK DYIQQLKNDR AAVKLTMLEL ESIHIDPLSY 

       610        620        630        640        650        660 
DVKPRGDSQR LDLENAVLMQ ELMAMKEEMA ELKAQLYLLE KEKKALELKL STREAQEQAY 

       670        680        690        700        710        720 
LVHIEHLKSE VEEQKEQRMR SLSSTSSGSK DKPGKECADA ASPALSLAEL RTTCSENELA 

       730        740        750        760        770        780 
AEFTNAIRRE KKLKARVQEL VSALERLTKS SEIRHQQSAE FVNDLKRANS NLVAAYEKAK 

       790        800        810        820 
KKHQNKLKKL ESQMMAMVER HETQVRMLKQ RIALLEEENS RPHTNETSL 

« Hide

Isoform 2 [UniParc].

Checksum: 09C330B8B43832F1
Show »

FASTA1,019113,279

References

« Hide 'large scale' references
[1]"Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers."
Kinzler K.W., Nilbert M.C., Vogelstein B., Bryan T.M., Levy D.B., Smith K.J., Preisinger A.C., Hamilton S.R., Hedge P., Markham A., Carlson M., Joslyn G., Groden J., White R., Miki Y., Miyoshi Y., Nishisho I., Nakamura Y.
Science 251:1366-1370(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-190; GLN-506 AND VAL-698.
Tissue: Brain.
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ARG-190.
Tissue: Muscle.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-779 (ISOFORM 2), VARIANT ARG-190.
Tissue: Trachea.
[6]"Mutated in colorectal cancer, a putative tumor suppressor for serrated colorectal cancer, selectively represses beta-catenin-dependent transcription."
Fukuyama R., Niculaita R., Ng K.P., Obusez E., Sanchez J., Kalady M., Aung P.P., Casey G., Sizemore N.
Oncogene 27:6044-6055(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN WNT SIGNALING, SUBCELLULAR LOCATION, INTERACTION WITH CTNNB1.
[7]"MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells."
Arnaud C., Sebbagh M., Nola S., Audebert S., Bidaut G., Hermant A., Gayet O., Dusetti N.J., Ollendorff V., Santoni M.J., Borg J.P., Lecine P.
FEBS Lett. 583:2326-2332(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, INTERACTION WITH SCRIB; EZR; SNX27; SLC9A3R1 AND SLC9A3R2.
[8]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[9]"The PDZ-binding motif of MCC is phosphorylated at position -1 and controls lamellipodia formation in colon epithelial cells."
Pangon L., Van Kralingen C., Abas M., Daly R.J., Musgrove E.A., Kohonen-Corish M.R.
Biochim. Biophys. Acta 1823:1058-1067(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PDZ-BINDING MOTIF, PHOSPHORYLATION AT SER-828, INTERACTION WITH SCRIB AND MYH10, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-828.
[10]"Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients."
Nishisho I., Nakamura Y., Miyoshi Y., Miki Y., Ando H., Horii A., Koyama K., Utsunomiya J., Baba S., Hedge P., Markham A., Krush A.J., Petersen G.M., Hamilton S.R., Nilbert M.C., Levy D.B., Bryan T.M., Preisinger A.C. expand/collapse author list , Smith K.J., Su L.-K., Kinzler K.W., Vogelstein B.
Science 253:665-669(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-267; LEU-486; LEU-490; GLN-506 AND VAL-698.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M62397 mRNA. Translation: AAA52069.1.
AC008536 Genomic DNA. No translation available.
AC010431 Genomic DNA. No translation available.
AC079465 Genomic DNA. No translation available.
AC093208 Genomic DNA. No translation available.
AC106750 Genomic DNA. No translation available.
AC126917 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW48984.1.
CH471086 Genomic DNA. Translation: EAW48986.1.
BC009279 mRNA. Translation: AAH09279.1.
BC018919 mRNA. Translation: AAH18919.1.
AK128596 mRNA. Translation: BAC87521.1.
CCDSCCDS4111.1. [P23508-1]
CCDS43351.1. [P23508-2]
PIRA33166. A38434.
RefSeqNP_001078846.1. NM_001085377.1.
NP_002378.1. NM_002387.2.
UniGeneHs.593171.

3D structure databases

ProteinModelPortalP23508.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110333. 42 interactions.
DIPDIP-27599N.
IntActP23508. 12 interactions.
MINTMINT-1161194.
STRING9606.ENSP00000386227.

PTM databases

PhosphoSiteP23508.

Polymorphism databases

DMDM317373352.

Proteomic databases

MaxQBP23508.
PaxDbP23508.
PRIDEP23508.

Protocols and materials databases

DNASU4163.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000302475; ENSP00000305617; ENSG00000171444. [P23508-1]
ENST00000408903; ENSP00000386227; ENSG00000171444. [P23508-2]
GeneID4163.
KEGGhsa:4163.
UCSCuc003kqj.4. human. [P23508-1]
uc003kql.4. human. [P23508-2]

Organism-specific databases

CTD4163.
GeneCardsGC05M112388.
HGNCHGNC:6935. MCC.
HPAHPA037390.
HPA037391.
MIM159350. gene.
neXtProtNX_P23508.
PharmGKBPA30679.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG122105.
HOGENOMHOG000111967.
HOVERGENHBG004762.
OMAPGKECAD.
OrthoDBEOG7B05C9.
PhylomeDBP23508.
TreeFamTF333056.

Enzyme and pathway databases

SignaLinkP23508.

Gene expression databases

ArrayExpressP23508.
BgeeP23508.
CleanExHS_MCC.
GenevestigatorP23508.

Family and domain databases

InterProIPR019536. USH1C-bd_PDZ_domain.
[Graphical view]
PfamPF10506. MCC-bdg_PDZ. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMCC_(gene).
GenomeRNAi4163.
NextBio16402.
PROP23508.
SOURCESearch...

Entry information

Entry nameCRCM_HUMAN
AccessionPrimary (citable) accession number: P23508
Secondary accession number(s): D3DT05, Q6ZR04
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: January 11, 2011
Last modified: July 9, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM