MCRI1_HUMAN
ID MCRI1_HUMAN Reviewed; 97 AA.
AC C9JLW8; Q6ZUL0;
DT 18-MAY-2010, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Mapk-regulated corepressor-interacting protein 1 {ECO:0000303|PubMed:25728771};
DE AltName: Full=Granulin-2 {ECO:0000303|PubMed:26184334};
DE AltName: Full=Protein FAM195B;
GN Name=MCRIP1 {ECO:0000303|PubMed:25728771, ECO:0000312|HGNC:HGNC:28007};
GN Synonyms=FAM195B, GRAN2 {ECO:0000303|PubMed:26184334};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Small intestine;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-79, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21 AND SER-24, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP INTERACTION WITH DDX6 AND MCRIP2, AND SUBCELLULAR LOCATION.
RX PubMed=26184334; DOI=10.3390/biom5031441;
RA Bish R., Cuevas-Polo N., Cheng Z., Hambardzumyan D., Munschauer M.,
RA Landthaler M., Vogel C.;
RT "Comprehensive protein interactome analysis of a key RNA helicase:
RT detection of novel stress granule proteins.";
RL Biomolecules 5:1441-1466(2015).
RN [10]
RP PHOSPHORYLATION AT SER-21 AND THR-30, SUBCELLULAR LOCATION, INTERACTION
RP WITH CTBP1 AND CTBP2, AND FUNCTION.
RX PubMed=25728771; DOI=10.1016/j.molcel.2015.01.023;
RA Ichikawa K., Kubota Y., Nakamura T., Weng J.S., Tomida T., Saito H.,
RA Takekawa M.;
RT "MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during
RT epithelial-mesenchymal transition by regulating the co-repressor CtBP.";
RL Mol. Cell 58:35-46(2015).
CC -!- FUNCTION: The phosphorylation status of MCRIP1 functions as a molecular
CC switch to regulate epithelial-mesenchymal transition. Unphosphorylated
CC MCRIP1 binds to and inhibits the transcriptional corepressor CTBP(s).
CC When phosphorylated by MAPK/ERK, MCRIP1 releases CTBP(s) resulting in
CC transcriptional silencing of the E-cadherin gene and induction of
CC epithelial-mesenchymal transition (PubMed:25728771).
CC {ECO:0000269|PubMed:25728771}.
CC -!- SUBUNIT: Interacts (unphosphorylated form, via the PXDLS motif) with
CC CTBP1, competitively inhibiting CTBP-ZEB1 interaction
CC (PubMed:25728771). Interacts with CTBP2 (PubMed:25728771). Interacts
CC with MCRIP2 (PubMed:26184334). Interacts with DDX6 (PubMed:26184334).
CC {ECO:0000269|PubMed:25728771, ECO:0000269|PubMed:26184334}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25728771,
CC ECO:0000269|PubMed:26184334}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:26184334}.
CC -!- PTM: Phosphorylation by MAPK3/1 (ERK1/2) regulates MCRIP1 binding to
CC CTBP(s) (PubMed:25728771). {ECO:0000269|PubMed:25728771}.
CC -!- SIMILARITY: Belongs to the MCRIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC86211.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305};
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DR EMBL; AK125584; BAC86211.1; ALT_SEQ; mRNA.
DR EMBL; AC174470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471099; EAW89687.1; -; Genomic_DNA.
DR CCDS; CCDS45814.1; -.
DR RefSeq; NP_001087236.1; NM_001093767.2.
DR RefSeq; NP_997251.2; NM_207368.4.
DR AlphaFoldDB; C9JLW8; -.
DR BioGRID; 131518; 37.
DR IntAct; C9JLW8; 10.
DR MINT; C9JLW8; -.
DR STRING; 9606.ENSP00000461433; -.
DR GlyGen; C9JLW8; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; C9JLW8; -.
DR PhosphoSitePlus; C9JLW8; -.
DR BioMuta; MCRIP1; -.
DR EPD; C9JLW8; -.
DR jPOST; C9JLW8; -.
DR MassIVE; C9JLW8; -.
DR MaxQB; C9JLW8; -.
DR PaxDb; C9JLW8; -.
DR PeptideAtlas; C9JLW8; -.
DR PRIDE; C9JLW8; -.
DR ProteomicsDB; 10766; -.
DR TopDownProteomics; C9JLW8; -.
DR Antibodypedia; 63491; 34 antibodies from 10 providers.
DR DNASU; 348262; -.
DR Ensembl; ENST00000455127.7; ENSP00000409009.2; ENSG00000225663.8.
DR Ensembl; ENST00000538396.5; ENSP00000445543.1; ENSG00000225663.8.
DR Ensembl; ENST00000574190.5; ENSP00000458720.1; ENSG00000225663.8.
DR Ensembl; ENST00000576730.5; ENSP00000458707.1; ENSG00000225663.8.
DR Ensembl; ENST00000672201.1; ENSP00000500493.1; ENSG00000288213.1.
DR Ensembl; ENST00000672501.1; ENSP00000499966.1; ENSG00000288213.1.
DR Ensembl; ENST00000673154.1; ENSP00000500382.1; ENSG00000288213.1.
DR Ensembl; ENST00000673369.1; ENSP00000500656.1; ENSG00000288213.1.
DR GeneID; 348262; -.
DR KEGG; hsa:348262; -.
DR MANE-Select; ENST00000455127.7; ENSP00000409009.2; NM_207368.5; NP_997251.2.
DR UCSC; uc010wuy.3; human.
DR CTD; 348262; -.
DR GeneCards; MCRIP1; -.
DR HGNC; HGNC:28007; MCRIP1.
DR HPA; ENSG00000225663; Low tissue specificity.
DR MIM; 616514; gene.
DR neXtProt; NX_C9JLW8; -.
DR OpenTargets; ENSG00000225663; -.
DR PharmGKB; PA165431912; -.
DR VEuPathDB; HostDB:ENSG00000225663; -.
DR eggNOG; ENOG502S25D; Eukaryota.
DR GeneTree; ENSGT00940000161850; -.
DR HOGENOM; CLU_161057_0_0_1; -.
DR InParanoid; C9JLW8; -.
DR OMA; QNHERND; -.
DR PhylomeDB; C9JLW8; -.
DR TreeFam; TF326620; -.
DR PathwayCommons; C9JLW8; -.
DR SignaLink; C9JLW8; -.
DR SIGNOR; C9JLW8; -.
DR BioGRID-ORCS; 348262; 13 hits in 1077 CRISPR screens.
DR GenomeRNAi; 348262; -.
DR Pharos; C9JLW8; Tdark.
DR PRO; PR:C9JLW8; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; C9JLW8; protein.
DR Bgee; ENSG00000225663; Expressed in right testis and 94 other tissues.
DR ExpressionAtlas; C9JLW8; baseline and differential.
DR Genevisible; C9JLW8; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0010717; P:regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR InterPro; IPR029428; MCRIP.
DR Pfam; PF14799; FAM195; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..97
FT /note="Mapk-regulated corepressor-interacting protein 1"
FT /id="PRO_0000393954"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 80..84
FT /note="PXDLS motif"
FT /evidence="ECO:0000305"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:25728771,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 30
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:25728771"
FT MOD_RES 41
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q3UGS4"
FT MOD_RES 79
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
SQ SEQUENCE 97 AA; 10920 MW; D92176E755159A81 CRC64;
MTSSPVSRVV YNGKRTSSPR SPPSSSEIFT PAHEENVRFI YEAWQGVERD LRGQVPGGER
GLVEEYVEKV PNPSLKTFKP IDLSDLKRRS TQDAKKS
