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P23508

- CRCM_HUMAN

UniProt

P23508 - CRCM_HUMAN

Protein

Colorectal mutant cancer protein

Gene

MCC

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (11 Jan 2011)
      Previous versions | rss
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    Functioni

    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.3 Publications

    GO - Molecular functioni

    1. protein binding Source: UniProtKB
    2. receptor activity Source: ProtInc

    GO - Biological processi

    1. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
    2. negative regulation of epithelial cell migration Source: UniProtKB
    3. negative regulation of epithelial cell proliferation Source: UniProtKB
    4. signal transduction Source: ProtInc
    5. Wnt signaling pathway Source: UniProtKB-KW

    Keywords - Biological processi

    Wnt signaling pathway

    Enzyme and pathway databases

    SignaLinkiP23508.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Colorectal mutant cancer protein
    Short name:
    Protein MCC
    Gene namesi
    Name:MCC
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:6935. MCC.

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. lamellipodium Source: UniProtKB-SubCell
    3. nucleus Source: UniProtKB
    4. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi828 – 8281S → A: Reduced binding to SCRIB. 1 Publication
    Mutagenesisi828 – 8281S → D: Higher membrane localization, reduced formation of lamellipodia, accumulation of MYH10 at the cell cortex. 1 Publication

    Keywords - Diseasei

    Tumor suppressor

    Organism-specific databases

    PharmGKBiPA30679.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 829829Colorectal mutant cancer proteinPRO_0000079333Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei828 – 8281Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP23508.
    PaxDbiP23508.
    PRIDEiP23508.

    PTM databases

    PhosphoSiteiP23508.

    Expressioni

    Tissue specificityi

    Expressed in a variety of tissues.

    Gene expression databases

    ArrayExpressiP23508.
    BgeeiP23508.
    CleanExiHS_MCC.
    GenevestigatoriP23508.

    Organism-specific databases

    HPAiHPA037390.
    HPA037391.

    Interactioni

    Subunit structurei

    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 MYH10.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    GTF2E2P290842EBI-307531,EBI-2853321
    SCRIBQ141608EBI-307531,EBI-357345

    Protein-protein interaction databases

    BioGridi110333. 42 interactions.
    DIPiDIP-27599N.
    IntActiP23508. 13 interactions.
    MINTiMINT-1161194.
    STRINGi9606.ENSP00000386227.

    Structurei

    3D structure databases

    ProteinModelPortaliP23508.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi826 – 8294PDZ-binding

    Sequence similaritiesi

    Belongs to the MCC family.Curated

    Phylogenomic databases

    eggNOGiNOG122105.
    HOGENOMiHOG000111967.
    HOVERGENiHBG004762.
    OMAiPGKECAD.
    OrthoDBiEOG7B05C9.
    PhylomeDBiP23508.
    TreeFamiTF333056.

    Family and domain databases

    InterProiIPR019536. USH1C-bd_PDZ_domain.
    [Graphical view]
    PfamiPF10506. MCC-bdg_PDZ. 3 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P23508-1) [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

    MNSGVAMKYG NDSSAELSEL HSAALASLKG DIVELNKRLQ QTERERDLLE    50
    KKLAKAQCEQ SHLMREHEDV QERTTLRYEE RITELHSVIA ELNKKIDRLQ 100
    GTTIREEDEY SELRSELSQS QHEVNEDSRS MDQDQTSVSI PENQSTMVTA 150
    DMDNCSDLNS ELQRVLTGLE NVVCGRKKSS CSLSVAEVDK HIEQLTTASE 200
    HCDLAIKTVE EIEGVLGRDL YPNLAEERSR WEKELAGLRE ENESLTAMLC 250
    SKEEELNRTK ATMNAIREER DRLRRRVREL QTRLQSVQAT GPSSPGRLTS 300
    TNRPINPSTG ELSTSSSSND IPIAKIAERV KLSKTRSESS SSDRPVLGSE 350
    ISSIGVSSSV AEHLAHSLQD CSNIQEIFQT LYSHGSAISE SKIREFEVET 400
    ERLNSRIEHL KSQNDLLTIT LEECKSNAER MSMLVGKYES NATALRLALQ 450
    YSEQCIEAYE LLLALAESEQ SLILGQFRAA GVGSSPGDQS GDENITQMLK 500
    RAHDCRKTAE NAAKALLMKL DGSCGGAFAV AGCSVQPWES LSSNSHTSTT 550
    SSTASSCDTE FTKEDEQRLK DYIQQLKNDR AAVKLTMLEL ESIHIDPLSY 600
    DVKPRGDSQR LDLENAVLMQ ELMAMKEEMA ELKAQLYLLE KEKKALELKL 650
    STREAQEQAY LVHIEHLKSE VEEQKEQRMR SLSSTSSGSK DKPGKECADA 700
    ASPALSLAEL RTTCSENELA AEFTNAIRRE KKLKARVQEL VSALERLTKS 750
    SEIRHQQSAE FVNDLKRANS NLVAAYEKAK KKHQNKLKKL ESQMMAMVER 800
    HETQVRMLKQ RIALLEEENS RPHTNETSL 829
    Length:829
    Mass (Da):93,027
    Last modified:January 11, 2011 - v2
    Checksum:iC90611B2E91A7F60
    GO
    Isoform 2 (identifier: P23508-2) [UniParc]FASTAAdd to Basket

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

    Show »
    Length:1,019
    Mass (Da):113,279
    Checksum:i09C330B8B43832F1
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti353 – 3531S → G in BAC87521. (PubMed:14702039)Curated
    Isoform 2 (identifier: P23508-2)
    Sequence conflicti25 – 251S → GSSSG in BAC87521. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti190 – 1901K → R.3 Publications
    Corresponds to variant rs6594681 [ dbSNP | Ensembl ].
    VAR_050905
    Natural varianti267 – 2671R → L in a colorectal cancer sample. 1 Publication
    VAR_005141
    Natural varianti486 – 4861P → L in a colorectal cancer sample. 1 Publication
    Corresponds to variant rs35269015 [ dbSNP | Ensembl ].
    VAR_005142
    Natural varianti490 – 4901S → L in a colorectal cancer sample. 1 Publication
    VAR_005143
    Natural varianti506 – 5061R → Q in colorectal cancer samples; somatic mutation. 2 Publications
    VAR_005144
    Natural varianti698 – 6981A → V in colorectal cancer samples; somatic mutation. 2 Publications
    VAR_005145
    Natural varianti751 – 7511S → C.
    Corresponds to variant rs17313892 [ dbSNP | Ensembl ].
    VAR_033753

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1919MNSGV…AELSE → MMAAAAAAAAGSSSSGGGGG GSGSSSSSSDTSSTGEEERM RRLFQTCDGDGDGYISRNDL LMVCRQLNMEESVAEIMNQL GADENGKISFQDFTRCRMQL VREIRKEEVDLSAKSDNSCT KKLRDRIASWPTSSDNSLGA LSAARESWEYDSGARDLQSP DVQSQSALQKLLEYGGSSLH QQAALHKLLTQSPHIGNSVG GSYLELANT in isoform 2. 1 PublicationVSP_037660Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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.
    CCDSiCCDS4111.1. [P23508-1]
    CCDS43351.1. [P23508-2]
    PIRiA38434. A33166.
    RefSeqiNP_001078846.1. NM_001085377.1.
    NP_002378.1. NM_002387.2.
    UniGeneiHs.593171.

    Genome annotation databases

    EnsembliENST00000302475; ENSP00000305617; ENSG00000171444. [P23508-1]
    ENST00000408903; ENSP00000386227; ENSG00000171444. [P23508-2]
    GeneIDi4163.
    KEGGihsa:4163.
    UCSCiuc003kqj.4. human. [P23508-1]
    uc003kql.4. human. [P23508-2]

    Polymorphism databases

    DMDMi317373352.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    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 .
    CCDSi CCDS4111.1. [P23508-1 ]
    CCDS43351.1. [P23508-2 ]
    PIRi A38434. A33166.
    RefSeqi NP_001078846.1. NM_001085377.1.
    NP_002378.1. NM_002387.2.
    UniGenei Hs.593171.

    3D structure databases

    ProteinModelPortali P23508.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110333. 42 interactions.
    DIPi DIP-27599N.
    IntActi P23508. 13 interactions.
    MINTi MINT-1161194.
    STRINGi 9606.ENSP00000386227.

    PTM databases

    PhosphoSitei P23508.

    Polymorphism databases

    DMDMi 317373352.

    Proteomic databases

    MaxQBi P23508.
    PaxDbi P23508.
    PRIDEi P23508.

    Protocols and materials databases

    DNASUi 4163.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302475 ; ENSP00000305617 ; ENSG00000171444 . [P23508-1 ]
    ENST00000408903 ; ENSP00000386227 ; ENSG00000171444 . [P23508-2 ]
    GeneIDi 4163.
    KEGGi hsa:4163.
    UCSCi uc003kqj.4. human. [P23508-1 ]
    uc003kql.4. human. [P23508-2 ]

    Organism-specific databases

    CTDi 4163.
    GeneCardsi GC05M112388.
    HGNCi HGNC:6935. MCC.
    HPAi HPA037390.
    HPA037391.
    MIMi 159350. gene.
    neXtProti NX_P23508.
    PharmGKBi PA30679.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG122105.
    HOGENOMi HOG000111967.
    HOVERGENi HBG004762.
    OMAi PGKECAD.
    OrthoDBi EOG7B05C9.
    PhylomeDBi P23508.
    TreeFami TF333056.

    Enzyme and pathway databases

    SignaLinki P23508.

    Miscellaneous databases

    GeneWikii MCC_(gene).
    GenomeRNAii 4163.
    NextBioi 16402.
    PROi P23508.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P23508.
    Bgeei P23508.
    CleanExi HS_MCC.
    Genevestigatori P23508.

    Family and domain databases

    InterProi IPR019536. USH1C-bd_PDZ_domain.
    [Graphical view ]
    Pfami PF10506. MCC-bdg_PDZ. 3 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. 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.
      , 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. 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.
      , 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. Cited for: VARIANTS LEU-267; LEU-486; LEU-490; GLN-506 AND VAL-698.

    Entry informationi

    Entry nameiCRCM_HUMAN
    AccessioniPrimary (citable) accession number: P23508
    Secondary accession number(s): D3DT05, Q6ZR04
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1991
    Last sequence update: January 11, 2011
    Last modified: October 1, 2014
    This is version 122 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

    Keywords - Technical termi

    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3