Full text data of MESDC2
MESDC2
(KIAA0081, MESD)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
LDLR chaperone MESD (Mesoderm development candidate 2; Mesoderm development protein; Renal carcinoma antigen NY-REN-61; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
LDLR chaperone MESD (Mesoderm development candidate 2; Mesoderm development protein; Renal carcinoma antigen NY-REN-61; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q14696
ID MESD_HUMAN Reviewed; 234 AA.
AC Q14696; D3DW96; Q969U1;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-OCT-2002, sequence version 2.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=LDLR chaperone MESD;
DE AltName: Full=Mesoderm development candidate 2;
DE AltName: Full=Mesoderm development protein;
DE AltName: Full=Renal carcinoma antigen NY-REN-61;
DE Flags: Precursor;
GN Name=MESDC2; Synonyms=KIAA0081, MESD; ORFNames=UNQ1911/PRO4369;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S.,
RA Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III.
RT The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15014448; DOI=10.1038/sj.emboj.7600132;
RA Culi J., Springer T.A., Mann R.S.;
RT "Boca-dependent maturation of beta-propeller/EGF modules in low-
RT density lipoprotein receptor proteins.";
RL EMBO J. 23:1372-1380(2004).
RN [8]
RP FUNCTION, INTERACTION WITH LRP5 AND LRP6, AND SUBCELLULAR LOCATION.
RX PubMed=17488095; DOI=10.1021/bi700049g;
RA Koduri V., Blacklow S.C.;
RT "Requirement for natively unstructured regions of mesoderm development
RT candidate 2 in promoting low-density lipoprotein receptor-related
RT protein 6 maturation.";
RL Biochemistry 46:6570-6577(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Chaperone specifically assisting the folding of beta-
CC propeller/EGF modules within the family of low-density lipoprotein
CC receptors (LDLRs). Acts as a modulator of the Wnt pathway through
CC chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and
CC LRP6, to the plasma membrane. Essential for specification of
CC embryonic polarity and mesoderm induction.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with LRP5; the
CC interaction prevents LRP5 from forming aggregates and chaperones
CC LRP6 to the plasma membrane. Interacts with LRP6; the interaction
CC prevents LRP6 from forming aggregates and chaperones LRP6 to the
CC plasma membrane.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum.
CC -!- DOMAIN: The chaperone domain provides a folding template for
CC proper folding of the beta-propeller (BP) domains of LRP5/6 (By
CC similarity).
CC -!- DOMAIN: The escort domain ensures LRP5/6 safe-trafficking from the
CC ER to the Golgi by preventing premature ligand-binding (By
CC similarity).
CC -!- SIMILARITY: Belongs to the MESD family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07640.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D42039; BAA07640.2; ALT_INIT; mRNA.
DR EMBL; AY359110; AAQ89468.1; -; mRNA.
DR EMBL; CH471136; EAW99109.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99110.1; -; Genomic_DNA.
DR EMBL; BC009210; AAH09210.1; -; mRNA.
DR EMBL; BC012746; AAH12746.1; -; mRNA.
DR RefSeq; NP_055969.1; NM_015154.1.
DR UniGene; Hs.578450; -.
DR UniGene; Hs.732380; -.
DR ProteinModelPortal; Q14696; -.
DR SMR; Q14696; 40-234.
DR IntAct; Q14696; 8.
DR MINT; MINT-7006206; -.
DR STRING; 9606.ENSP00000261758; -.
DR PhosphoSite; Q14696; -.
DR DMDM; 24418861; -.
DR OGP; Q14696; -.
DR PaxDb; Q14696; -.
DR PeptideAtlas; Q14696; -.
DR PRIDE; Q14696; -.
DR Ensembl; ENST00000261758; ENSP00000261758; ENSG00000117899.
DR Ensembl; ENST00000561312; ENSP00000453430; ENSG00000117899.
DR GeneID; 23184; -.
DR KEGG; hsa:23184; -.
DR UCSC; uc002bfy.1; human.
DR CTD; 23184; -.
DR GeneCards; GC15M081244; -.
DR HGNC; HGNC:13520; MESDC2.
DR HPA; HPA039414; -.
DR MIM; 607783; gene.
DR neXtProt; NX_Q14696; -.
DR PharmGKB; PA30761; -.
DR eggNOG; NOG286690; -.
DR HOGENOM; HOG000230558; -.
DR InParanoid; Q14696; -.
DR OMA; IVGSNRA; -.
DR OrthoDB; EOG7XPZ76; -.
DR PhylomeDB; Q14696; -.
DR GeneWiki; MESDC2; -.
DR GenomeRNAi; 23184; -.
DR NextBio; 44647; -.
DR PRO; PR:Q14696; -.
DR ArrayExpress; Q14696; -.
DR Bgee; Q14696; -.
DR CleanEx; HS_MESDC2; -.
DR Genevestigator; Q14696; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0007498; P:mesoderm development; NAS:UniProtKB.
DR GO; GO:0006457; P:protein folding; ISS:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR019330; Mesoderm_development_cand-2.
DR Pfam; PF10185; Mesd; 1.
DR PROSITE; PS00014; ER_TARGET; FALSE_NEG.
PE 1: Evidence at protein level;
KW Chaperone; Complete proteome; Endoplasmic reticulum; Glycoprotein;
KW Reference proteome; Signal; Wnt signaling pathway.
FT SIGNAL 1 33 Potential.
FT CHAIN 34 234 LDLR chaperone MESD.
FT /FTId=PRO_0000096443.
FT REGION 1 164 Chaperone domain (By similarity).
FT REGION 165 204 Escort domain (By similarity).
FT MOTIF 231 234 Prevents secretion from ER.
FT CARBOHYD 201 201 N-linked (GlcNAc...) (Potential).
SQ SEQUENCE 234 AA; 26077 MW; 7F0D796A3CC4E339 CRC64;
MAASRWARKA VVLLCASDLL LLLLLLPPPG SCAAEGSPGT PDESTPPPRK KKKDIRDYND
ADMARLLEQW EKDDDIEEGD LPEHKRPSAP VDFSKIDPSK PESILKMTKK GKTLMMFVTV
SGSPTEKETE EITSLWQGSL FNANYDVQRF IVGSDRAIFM LRDGSYAWEI KDFLVGQDRC
ADVTLEGQVY PGKGGGSKEK NKTKQDKGKK KKEGDLKSRS SKEENRAGNK REDL
//
ID MESD_HUMAN Reviewed; 234 AA.
AC Q14696; D3DW96; Q969U1;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 25-OCT-2002, sequence version 2.
DT 22-JAN-2014, entry version 108.
DE RecName: Full=LDLR chaperone MESD;
DE AltName: Full=Mesoderm development candidate 2;
DE AltName: Full=Mesoderm development protein;
DE AltName: Full=Renal carcinoma antigen NY-REN-61;
DE Flags: Precursor;
GN Name=MESDC2; Synonyms=KIAA0081, MESD; ORFNames=UNQ1911/PRO4369;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Bone marrow;
RX PubMed=7788527; DOI=10.1093/dnares/2.1.37;
RA Nagase T., Miyajima N., Tanaka A., Sazuka T., Seki N., Sato S.,
RA Tabata S., Ishikawa K., Kawarabayasi Y., Kotani H., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. III.
RT The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by
RT analysis of cDNA clones from human cell line KG-1.";
RL DNA Res. 2:37-43(1995).
RN [2]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP IDENTIFICATION AS A RENAL CANCER ANTIGEN.
RC TISSUE=Renal cell carcinoma;
RX PubMed=10508479;
RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5;
RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H.,
RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T.,
RA Old L.J.;
RT "Antigens recognized by autologous antibody in patients with renal-
RT cell carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15014448; DOI=10.1038/sj.emboj.7600132;
RA Culi J., Springer T.A., Mann R.S.;
RT "Boca-dependent maturation of beta-propeller/EGF modules in low-
RT density lipoprotein receptor proteins.";
RL EMBO J. 23:1372-1380(2004).
RN [8]
RP FUNCTION, INTERACTION WITH LRP5 AND LRP6, AND SUBCELLULAR LOCATION.
RX PubMed=17488095; DOI=10.1021/bi700049g;
RA Koduri V., Blacklow S.C.;
RT "Requirement for natively unstructured regions of mesoderm development
RT candidate 2 in promoting low-density lipoprotein receptor-related
RT protein 6 maturation.";
RL Biochemistry 46:6570-6577(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Chaperone specifically assisting the folding of beta-
CC propeller/EGF modules within the family of low-density lipoprotein
CC receptors (LDLRs). Acts as a modulator of the Wnt pathway through
CC chaperoning the coreceptors of the canonical Wnt pathway, LRP5 and
CC LRP6, to the plasma membrane. Essential for specification of
CC embryonic polarity and mesoderm induction.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with LRP5; the
CC interaction prevents LRP5 from forming aggregates and chaperones
CC LRP6 to the plasma membrane. Interacts with LRP6; the interaction
CC prevents LRP6 from forming aggregates and chaperones LRP6 to the
CC plasma membrane.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum.
CC -!- DOMAIN: The chaperone domain provides a folding template for
CC proper folding of the beta-propeller (BP) domains of LRP5/6 (By
CC similarity).
CC -!- DOMAIN: The escort domain ensures LRP5/6 safe-trafficking from the
CC ER to the Golgi by preventing premature ligand-binding (By
CC similarity).
CC -!- SIMILARITY: Belongs to the MESD family.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07640.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D42039; BAA07640.2; ALT_INIT; mRNA.
DR EMBL; AY359110; AAQ89468.1; -; mRNA.
DR EMBL; CH471136; EAW99109.1; -; Genomic_DNA.
DR EMBL; CH471136; EAW99110.1; -; Genomic_DNA.
DR EMBL; BC009210; AAH09210.1; -; mRNA.
DR EMBL; BC012746; AAH12746.1; -; mRNA.
DR RefSeq; NP_055969.1; NM_015154.1.
DR UniGene; Hs.578450; -.
DR UniGene; Hs.732380; -.
DR ProteinModelPortal; Q14696; -.
DR SMR; Q14696; 40-234.
DR IntAct; Q14696; 8.
DR MINT; MINT-7006206; -.
DR STRING; 9606.ENSP00000261758; -.
DR PhosphoSite; Q14696; -.
DR DMDM; 24418861; -.
DR OGP; Q14696; -.
DR PaxDb; Q14696; -.
DR PeptideAtlas; Q14696; -.
DR PRIDE; Q14696; -.
DR Ensembl; ENST00000261758; ENSP00000261758; ENSG00000117899.
DR Ensembl; ENST00000561312; ENSP00000453430; ENSG00000117899.
DR GeneID; 23184; -.
DR KEGG; hsa:23184; -.
DR UCSC; uc002bfy.1; human.
DR CTD; 23184; -.
DR GeneCards; GC15M081244; -.
DR HGNC; HGNC:13520; MESDC2.
DR HPA; HPA039414; -.
DR MIM; 607783; gene.
DR neXtProt; NX_Q14696; -.
DR PharmGKB; PA30761; -.
DR eggNOG; NOG286690; -.
DR HOGENOM; HOG000230558; -.
DR InParanoid; Q14696; -.
DR OMA; IVGSNRA; -.
DR OrthoDB; EOG7XPZ76; -.
DR PhylomeDB; Q14696; -.
DR GeneWiki; MESDC2; -.
DR GenomeRNAi; 23184; -.
DR NextBio; 44647; -.
DR PRO; PR:Q14696; -.
DR ArrayExpress; Q14696; -.
DR Bgee; Q14696; -.
DR CleanEx; HS_MESDC2; -.
DR Genevestigator; Q14696; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl.
DR GO; GO:0007498; P:mesoderm development; NAS:UniProtKB.
DR GO; GO:0006457; P:protein folding; ISS:UniProtKB.
DR GO; GO:0034394; P:protein localization to cell surface; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt receptor signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR019330; Mesoderm_development_cand-2.
DR Pfam; PF10185; Mesd; 1.
DR PROSITE; PS00014; ER_TARGET; FALSE_NEG.
PE 1: Evidence at protein level;
KW Chaperone; Complete proteome; Endoplasmic reticulum; Glycoprotein;
KW Reference proteome; Signal; Wnt signaling pathway.
FT SIGNAL 1 33 Potential.
FT CHAIN 34 234 LDLR chaperone MESD.
FT /FTId=PRO_0000096443.
FT REGION 1 164 Chaperone domain (By similarity).
FT REGION 165 204 Escort domain (By similarity).
FT MOTIF 231 234 Prevents secretion from ER.
FT CARBOHYD 201 201 N-linked (GlcNAc...) (Potential).
SQ SEQUENCE 234 AA; 26077 MW; 7F0D796A3CC4E339 CRC64;
MAASRWARKA VVLLCASDLL LLLLLLPPPG SCAAEGSPGT PDESTPPPRK KKKDIRDYND
ADMARLLEQW EKDDDIEEGD LPEHKRPSAP VDFSKIDPSK PESILKMTKK GKTLMMFVTV
SGSPTEKETE EITSLWQGSL FNANYDVQRF IVGSDRAIFM LRDGSYAWEI KDFLVGQDRC
ADVTLEGQVY PGKGGGSKEK NKTKQDKGKK KKEGDLKSRS SKEENRAGNK REDL
//
MIM
607783
*RECORD*
*FIELD* NO
607783
*FIELD* TI
*607783 MESODERM DEVELOPMENT CANDIDATE GENE 2; MESDC2
;;MESODERM DEVELOPMENT GENE; MESD;;
read moreKIAA0081;;
BOCA, DROSOPHILA, HOMOLOG OF; BOCA
MESDC2/SENP1 FUSION GENE, INCLUDED
*FIELD* TX
CLONING
By sequencing cDNAs randomly selected from a cDNA library derived from
the human immature myeloid cell line KG-1, Nagase et al. (1995) isolated
a cDNA encoding MESDC2, which they designated KIAA0081. The predicted
233-amino acid protein contains at least 1 putative transmembrane
region. Northern blot analysis detected expression in all tissues tested
except peripheral blood leukocytes.
Wines et al. (2001) cloned mouse Mesdc2, which encodes a 223-amino acid
protein that shares 82% identity with the 234-amino acid human protein.
MESDC2 was predicted to have an N-terminal transmembrane domain.
Northern blot analysis detected a 1.8-kb transcript in mouse embryos
throughout development and in all adult mouse tissues tested, except
skeletal muscle.
GENE FUNCTION
Hsieh et al. (2003) demonstrated that Mesdc2, a gene identified in the
mesoderm development (Mesd) deletion interval on mouse chromosome 7, is
essential for specification of embryonic polarity and mesoderm
induction. They determined that the patterning and cell differentiation
defects observed in Mesd deletion homozygotes result solely from loss of
the Mesdc2 gene, and therefore they renamed the gene Mesd. Hsieh et al.
(2003) showed that Mesd functions in the endoplasmic reticulum (ER) as a
specific chaperone for Lrp5 (603506) and Lrp6 (603507), which in
conjunction with frizzled (see 603408) are coreceptors for canonical Wnt
signal transduction. The authors proposed that disruption of embryonic
polarity and mesoderm differentiation in Mesd-deficient embryos likely
results from a primary defect in Wnt signaling. However, phenotypic
differences between Mesd-deficient and Wnt3 (165330) -/- embryos
suggested that Mesd may function on related members of the LDLR family.
LDLR family members mediate diverse cellular processes ranging from
cargo transport to signaling.
Culi and Mann (2003) described boca, an evolutionarily conserved gene in
Drosophila melanogaster that encodes an ER protein homologous to the
mouse Mesdc2 protein. They showed that boca is specifically required for
the intracellular trafficking of members of the LDLR family. Two LDLRs
in flies, arrow (see 603507), which is required for wingless signal
transduction, and yolkless, which is required for yolk protein uptake
during oogenesis, were found to require boca function. Culi and Mann
(2003) concluded that boca is an essential component of the wingless
pathway but is more generally required for the activities of multiple
LDLR family members.
Veltman et al. (2005) identified a patient with an infantile
sacrococcygeal teratoma and a constitutional t(12;15)(q13;q25)
chromosomal translocation, resulting SENP1 (612157)/MESDC2 fusion gene.
Both reciprocal SENP1/MESDC2 (SEME) and MESDC2/SENP1 (MESE) fusion genes
were transcribed in tumor-derived cells, and their open reading frames
encoded aberrant proteins. In contrast to wildtype MESDC2, the
translocation-associated SEME protein was no longer targeted to the
endoplasmic reticulum, leading to a presumed loss-of-function as a
chaperone for the WNT coreceptors LRP5 (603506) and/or LRP6 (603507).
SUMO, a posttranslational modifier, plays an important role in several
cellular key processes and is cleaved from its substrates by wildtype
SENP1. In vitro studies revealed that translocation-associated MESE
proteins exhibited desumoylation capacities similar to those observed
for wildtype SENP1. Veltman et al. (2005) speculated that spatiotemporal
disturbances in desumoylating activities during critical stages of
embryonic development might be responsible for teratoma formation. The
constitutional t(12;15)(q13;q25) translocation suggested SENP1 and
MESDC2 as candidate genes for neonatal/infantile germ cell tumor
development.
MAPPING
Nagase et al. (1995) mapped the MESDC2 gene to chromosome 15 by analysis
of human-rodent hybrid cell lines.
By radiation hybrid analysis and sequencing a BAC contig, Wines et al.
(2001) mapped the MESCD2 gene to chromosome 15q23-q25. They mapped the
mouse Mesdc2 gene to a region of chromosome 7 that shares homology of
synteny with human chromosome 15q23-q25.
Veltman et al. (2005) stated that the MESDC2 gene maps to chromosome
15q25.
ANIMAL MODEL
Wines et al. (2001) identified Mesdc2 within a region of mouse
chromosome 7 that, when deleted, results in failure to form mesoderm and
embryonic lethality.
*FIELD* RF
1. Culi, J.; Mann, R. S.: Boca, an endoplasmic reticulum protein
required for Wingless signaling and trafficking of LDL receptor family
members in Drosophila. Cell 112: 343-354, 2003.
2. Hsieh, J.-C.; Lee, L.; Zhang, L.; Wefer, S.; Brown, K.; DeRossi,
C.; Wines, M. E.; Rosenquist, T.; Holdener, B. C.: Mesd encodes the
LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell 112:
355-367, 2003.
3. Nagase, T; Miyajima, N; Tanaka, A.; Sazuka, T.; Seki, N.; Sato,
S.; Tabata, S.; Ishikawa, K.; Kawarabayashi, Y.; Kotani, H.; Nomura,
N.: Prediction of the coding sequences of unidentified human genes.
III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced
by analysis of cDNA clones from human cell line KG-1. DNA Res. 2:
37-43, 1995.
4. Veltman, I. M.; Vreede, L. A.; Cheng, J.; Looijenga, L. H. J.;
Janssen, B.; Schoenmakers, E. F. P. M.; Yeh, E. T. H.; Geurts van
Kessel, A.: Fusion of the SUMO/sentrin-specific protease 1 gene SENP1
and the embryonic polarity-related mesoderm development gene MESDC2
in a patient with an infantile teratoma and a constitutional t(12;15)(q13;q25). Hum.
Molec. Genet. 14: 1955-1963, 2005.
5. Wines, M. E.; Lee, L.; Katari, M. S.; Zhang, L.; DeRossi, C.; Shi,
Y.; Perkins, S.; Feldman, M.; McCombie, W. R.; Holdener, B. C.: Identification
of mesoderm development (mesd) candidate genes by comparative mapping
and genome sequence analysis. Genomics 72: 88-98, 2001.
*FIELD* CN
Patricia A. Hartz: 10/9/2013
George E. Tiller - updated: 11/17/2008
Matthew B. Gross - updated: 5/13/2003
*FIELD* CD
Stylianos E. Antonarakis: 5/13/2003
*FIELD* ED
mgross: 10/18/2013
tpirozzi: 10/9/2013
wwang: 11/18/2008
wwang: 11/17/2008
mgross: 5/13/2003
*RECORD*
*FIELD* NO
607783
*FIELD* TI
*607783 MESODERM DEVELOPMENT CANDIDATE GENE 2; MESDC2
;;MESODERM DEVELOPMENT GENE; MESD;;
read moreKIAA0081;;
BOCA, DROSOPHILA, HOMOLOG OF; BOCA
MESDC2/SENP1 FUSION GENE, INCLUDED
*FIELD* TX
CLONING
By sequencing cDNAs randomly selected from a cDNA library derived from
the human immature myeloid cell line KG-1, Nagase et al. (1995) isolated
a cDNA encoding MESDC2, which they designated KIAA0081. The predicted
233-amino acid protein contains at least 1 putative transmembrane
region. Northern blot analysis detected expression in all tissues tested
except peripheral blood leukocytes.
Wines et al. (2001) cloned mouse Mesdc2, which encodes a 223-amino acid
protein that shares 82% identity with the 234-amino acid human protein.
MESDC2 was predicted to have an N-terminal transmembrane domain.
Northern blot analysis detected a 1.8-kb transcript in mouse embryos
throughout development and in all adult mouse tissues tested, except
skeletal muscle.
GENE FUNCTION
Hsieh et al. (2003) demonstrated that Mesdc2, a gene identified in the
mesoderm development (Mesd) deletion interval on mouse chromosome 7, is
essential for specification of embryonic polarity and mesoderm
induction. They determined that the patterning and cell differentiation
defects observed in Mesd deletion homozygotes result solely from loss of
the Mesdc2 gene, and therefore they renamed the gene Mesd. Hsieh et al.
(2003) showed that Mesd functions in the endoplasmic reticulum (ER) as a
specific chaperone for Lrp5 (603506) and Lrp6 (603507), which in
conjunction with frizzled (see 603408) are coreceptors for canonical Wnt
signal transduction. The authors proposed that disruption of embryonic
polarity and mesoderm differentiation in Mesd-deficient embryos likely
results from a primary defect in Wnt signaling. However, phenotypic
differences between Mesd-deficient and Wnt3 (165330) -/- embryos
suggested that Mesd may function on related members of the LDLR family.
LDLR family members mediate diverse cellular processes ranging from
cargo transport to signaling.
Culi and Mann (2003) described boca, an evolutionarily conserved gene in
Drosophila melanogaster that encodes an ER protein homologous to the
mouse Mesdc2 protein. They showed that boca is specifically required for
the intracellular trafficking of members of the LDLR family. Two LDLRs
in flies, arrow (see 603507), which is required for wingless signal
transduction, and yolkless, which is required for yolk protein uptake
during oogenesis, were found to require boca function. Culi and Mann
(2003) concluded that boca is an essential component of the wingless
pathway but is more generally required for the activities of multiple
LDLR family members.
Veltman et al. (2005) identified a patient with an infantile
sacrococcygeal teratoma and a constitutional t(12;15)(q13;q25)
chromosomal translocation, resulting SENP1 (612157)/MESDC2 fusion gene.
Both reciprocal SENP1/MESDC2 (SEME) and MESDC2/SENP1 (MESE) fusion genes
were transcribed in tumor-derived cells, and their open reading frames
encoded aberrant proteins. In contrast to wildtype MESDC2, the
translocation-associated SEME protein was no longer targeted to the
endoplasmic reticulum, leading to a presumed loss-of-function as a
chaperone for the WNT coreceptors LRP5 (603506) and/or LRP6 (603507).
SUMO, a posttranslational modifier, plays an important role in several
cellular key processes and is cleaved from its substrates by wildtype
SENP1. In vitro studies revealed that translocation-associated MESE
proteins exhibited desumoylation capacities similar to those observed
for wildtype SENP1. Veltman et al. (2005) speculated that spatiotemporal
disturbances in desumoylating activities during critical stages of
embryonic development might be responsible for teratoma formation. The
constitutional t(12;15)(q13;q25) translocation suggested SENP1 and
MESDC2 as candidate genes for neonatal/infantile germ cell tumor
development.
MAPPING
Nagase et al. (1995) mapped the MESDC2 gene to chromosome 15 by analysis
of human-rodent hybrid cell lines.
By radiation hybrid analysis and sequencing a BAC contig, Wines et al.
(2001) mapped the MESCD2 gene to chromosome 15q23-q25. They mapped the
mouse Mesdc2 gene to a region of chromosome 7 that shares homology of
synteny with human chromosome 15q23-q25.
Veltman et al. (2005) stated that the MESDC2 gene maps to chromosome
15q25.
ANIMAL MODEL
Wines et al. (2001) identified Mesdc2 within a region of mouse
chromosome 7 that, when deleted, results in failure to form mesoderm and
embryonic lethality.
*FIELD* RF
1. Culi, J.; Mann, R. S.: Boca, an endoplasmic reticulum protein
required for Wingless signaling and trafficking of LDL receptor family
members in Drosophila. Cell 112: 343-354, 2003.
2. Hsieh, J.-C.; Lee, L.; Zhang, L.; Wefer, S.; Brown, K.; DeRossi,
C.; Wines, M. E.; Rosenquist, T.; Holdener, B. C.: Mesd encodes the
LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell 112:
355-367, 2003.
3. Nagase, T; Miyajima, N; Tanaka, A.; Sazuka, T.; Seki, N.; Sato,
S.; Tabata, S.; Ishikawa, K.; Kawarabayashi, Y.; Kotani, H.; Nomura,
N.: Prediction of the coding sequences of unidentified human genes.
III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced
by analysis of cDNA clones from human cell line KG-1. DNA Res. 2:
37-43, 1995.
4. Veltman, I. M.; Vreede, L. A.; Cheng, J.; Looijenga, L. H. J.;
Janssen, B.; Schoenmakers, E. F. P. M.; Yeh, E. T. H.; Geurts van
Kessel, A.: Fusion of the SUMO/sentrin-specific protease 1 gene SENP1
and the embryonic polarity-related mesoderm development gene MESDC2
in a patient with an infantile teratoma and a constitutional t(12;15)(q13;q25). Hum.
Molec. Genet. 14: 1955-1963, 2005.
5. Wines, M. E.; Lee, L.; Katari, M. S.; Zhang, L.; DeRossi, C.; Shi,
Y.; Perkins, S.; Feldman, M.; McCombie, W. R.; Holdener, B. C.: Identification
of mesoderm development (mesd) candidate genes by comparative mapping
and genome sequence analysis. Genomics 72: 88-98, 2001.
*FIELD* CN
Patricia A. Hartz: 10/9/2013
George E. Tiller - updated: 11/17/2008
Matthew B. Gross - updated: 5/13/2003
*FIELD* CD
Stylianos E. Antonarakis: 5/13/2003
*FIELD* ED
mgross: 10/18/2013
tpirozzi: 10/9/2013
wwang: 11/18/2008
wwang: 11/17/2008
mgross: 5/13/2003