ID   DYM_HUMAN               Reviewed;         669 AA.
AC   Q7RTS9; A8K5I8; B2RCF9; B4DKI7; Q3ZTS8; Q6P2P5; Q8N2M0; Q9BVE9; Q9NPU7;
DT   05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT   15-DEC-2003, sequence version 1.
DT   24-JAN-2024, entry version 147.
DE   RecName: Full=Dymeclin;
DE   AltName: Full=Dyggve-Melchior-Clausen syndrome protein;
GN   Name=DYM;
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 [GENOMIC DNA], INVOLVEMENT IN DMC, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=12554689; DOI=10.1093/hmg/ddg029;
RA   El Ghouzzi V., Dagoneau N., Kinning E., Thauvin-Robinet C., Chemaitilly W.,
RA   Prost-Squarcioni C., Al-Gazali L.I., Verloes A., Le Merrer M., Munnich A.,
RA   Trembath R.C., Cormier-Daire V.;
RT   "Mutations in a novel gene dymeclin (FLJ20071) are responsible for Dyggve-
RT   Melchior-Clausen syndrome.";
RL   Hum. Mol. Genet. 12:357-364(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Cervix, Testis, and Tongue;
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   [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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain, and Cervix;
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-524 (ISOFORM 1).
RA   Kemmer D., Podowski R., Hodges E., Roth P., Lenhard B., Sonnhammer E.L.L.,
RA   Wasserman W.W., Hoog C.;
RT   "Characterization of human proteins containing evolutionary conserved
RT   domains of unknown function.";
RL   Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 446-669.
RC   TISSUE=Melanoma;
RX   PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA   Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA   Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA   Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA   Wiemann S., Schupp I.;
RT   "The full-ORF clone resource of the German cDNA consortium.";
RL   BMC Genomics 8:399-399(2007).
RN   [7]
RP   TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MYRISTOYLATION AT GLY-2,
RP   MUTAGENESIS OF GLY-2, CHARACTERIZATION OF VARIANT SMC1 LYS-87, AND
RP   CHARACTERIZATION OF VARIANT DMC TYR-469.
RX   PubMed=18996921; DOI=10.1093/hmg/ddn371;
RA   Dimitrov A., Paupe V., Gueudry C., Sibarita J.-B., Raposo G.,
RA   Vielemeyer O., Gilbert T., Csaba Z., Attie-Bitach T., Cormier-Daire V.,
RA   Gressens P., Rustin P., Perez F., El Ghouzzi V.;
RT   "The gene responsible for Dyggve-Melchior-Clausen syndrome encodes a novel
RT   peripheral membrane protein dynamically associated with the Golgi
RT   apparatus.";
RL   Hum. Mol. Genet. 18:440-453(2009).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GOLM1 AND PPIB, AND
RP   INVOLVEMENT IN DCM.
RX   PubMed=21280149; DOI=10.1002/humu.21413;
RA   Denais C., Dent C.L., Southgate L., Hoyle J., Dafou D., Trembath R.C.,
RA   Machado R.D.;
RT   "Dymeclin, the gene underlying Dyggve-Melchior-Clausen syndrome, encodes a
RT   protein integral to extracellular matrix and Golgi organization and is
RT   associated with protein secretion pathways critical in bone development.";
RL   Hum. Mutat. 32:231-239(2011).
RN   [9]
RP   MYRISTOYLATION AT GLY-2, CLEAVAGE OF INITIATOR METHIONINE, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RX   PubMed=25255805; DOI=10.1038/ncomms5919;
RA   Thinon E., Serwa R.A., Broncel M., Brannigan J.A., Brassat U., Wright M.H.,
RA   Heal W.P., Wilkinson A.J., Mann D.J., Tate E.W.;
RT   "Global profiling of co- and post-translationally N-myristoylated proteomes
RT   in human cells.";
RL   Nat. Commun. 5:4919-4919(2014).
RN   [10]
RP   VARIANT DMC TYR-469, AND VARIANT SMC1 LYS-87.
RX   PubMed=12491225; DOI=10.1086/346176;
RA   Cohn D.H., Ehtesham N., Krakow D., Unger S., Shanske A., Reinker K.,
RA   Powell B.R., Rimoin D.L.;
RT   "Mental retardation and abnormal skeletal development (Dyggve-Melchior-
RT   Clausen dysplasia) due to mutations in a novel, evolutionarily conserved
RT   gene.";
RL   Am. J. Hum. Genet. 72:419-428(2003).
RN   [11]
RP   VARIANT SMC1 ARG-542.
RX   PubMed=19005420; DOI=10.1097/mcd.0b013e32831868ea;
RA   Santos H.G., Fernandes H.C., Nunes J.L., Almeida M.R.;
RT   "Portuguese case of Smith-McCort syndrome caused by a new mutation in the
RT   dymeclin (FLJ20071) gene.";
RL   Clin. Dysmorphol. 18:41-44(2009).
CC   -!- FUNCTION: Necessary for correct organization of Golgi apparatus.
CC       Involved in bone development. {ECO:0000269|PubMed:21280149}.
CC   -!- SUBUNIT: Interacts with GOLM1 and PPIB. {ECO:0000269|PubMed:21280149}.
CC   -!- INTERACTION:
CC       Q7RTS9; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-2871106, EBI-712073;
CC       Q7RTS9; P23284: PPIB; NbExp=4; IntAct=EBI-2871106, EBI-359252;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm. Golgi apparatus. Membrane
CC       {ECO:0000305}; Lipid-anchor {ECO:0000305}. Note=Sequence analysis
CC       programs clearly predict 1 transmembrane region. However,
CC       PubMed:18996921 shows that it is not a stably anchored transmembrane
CC       protein but it weakly associates with the Golgi apparatus and shuttles
CC       between the Golgi and the cytosol.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q7RTS9-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q7RTS9-2; Sequence=VSP_036442, VSP_036443;
CC   -!- TISSUE SPECIFICITY: Expressed in most embryo-fetal and adult tissues.
CC       Abundant in primary chondrocytes, osteoblasts, cerebellum, kidney,
CC       lung, stomach, heart, pancreas and fetal brain. Very low or no
CC       expression in the spleen, thymus, esophagus, bladder and thyroid gland.
CC       {ECO:0000269|PubMed:12554689, ECO:0000269|PubMed:18996921}.
CC   -!- PTM: Myristoylated in vitro; myristoylation is not essential for
CC       protein targeting to Golgi compartment. {ECO:0000269|PubMed:18996921}.
CC   -!- DISEASE: Dyggve-Melchior-Clausen syndrome (DMC) [MIM:223800]: A rare
CC       autosomal recessive disorder belonging to the group of
CC       spondyloepimetaphyseal dysplasias. DMC is characterized by progressive
CC       short stature with short trunk dwarfism, microcephaly, protruding
CC       sternum, and psychomotor retardation. Radiological features include a
CC       platyspondyly with double vertebral humps, an epiphyso-metaphyseal
CC       dysplasia and lacy pelvis iliac crests. {ECO:0000269|PubMed:12491225,
CC       ECO:0000269|PubMed:12554689, ECO:0000269|PubMed:18996921}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Smith-McCort dysplasia 1 (SMC1) [MIM:607326]: A rare autosomal
CC       recessive osteochondrodysplasia with skeletal features identical to
CC       those of Dyggve-Melchior-Clausen syndrome, but with normal intelligence
CC       and no microcephaly. It is characterized by short limbs and trunk with
CC       barrel-shaped chest. The radiographic phenotype includes platyspondyly,
CC       generalized abnormalities of the epiphyses and metaphyses, and a
CC       distinctive lacy appearance of the iliac crest.
CC       {ECO:0000269|PubMed:12491225, ECO:0000269|PubMed:18996921,
CC       ECO:0000269|PubMed:19005420}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the dymeclin family. {ECO:0000305}.
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DR   EMBL; BK000950; DAA00396.1; -; Genomic_DNA.
DR   EMBL; AK074611; BAC11088.1; -; mRNA.
DR   EMBL; AK091256; BAG52319.1; -; mRNA.
DR   EMBL; AK291303; BAF83992.1; -; mRNA.
DR   EMBL; AK296579; BAG59199.1; -; mRNA.
DR   EMBL; AK315091; BAG37556.1; -; mRNA.
DR   EMBL; CH471096; EAW62933.1; -; Genomic_DNA.
DR   EMBL; BC001252; AAH01252.2; -; mRNA.
DR   EMBL; BC064394; AAH64394.1; -; mRNA.
DR   EMBL; AY364250; AAQ76809.1; -; mRNA.
DR   EMBL; AL390156; CAB99092.1; -; mRNA.
DR   CCDS; CCDS11937.1; -. [Q7RTS9-1]
DR   CCDS; CCDS92459.1; -. [Q7RTS9-2]
DR   RefSeq; NP_060123.3; NM_017653.3. [Q7RTS9-1]
DR   AlphaFoldDB; Q7RTS9; -.
DR   BioGRID; 120165; 168.
DR   ELM; Q7RTS9; -.
DR   IntAct; Q7RTS9; 22.
DR   STRING; 9606.ENSP00000269445; -.
DR   GlyCosmos; Q7RTS9; 2 sites, 1 glycan.
DR   GlyGen; Q7RTS9; 3 sites, 2 O-linked glycans (3 sites).
DR   iPTMnet; Q7RTS9; -.
DR   PhosphoSitePlus; Q7RTS9; -.
DR   BioMuta; DYM; -.
DR   DMDM; 68565365; -.
DR   EPD; Q7RTS9; -.
DR   jPOST; Q7RTS9; -.
DR   MassIVE; Q7RTS9; -.
DR   MaxQB; Q7RTS9; -.
DR   PaxDb; 9606-ENSP00000269445; -.
DR   PeptideAtlas; Q7RTS9; -.
DR   ProteomicsDB; 68896; -. [Q7RTS9-1]
DR   ProteomicsDB; 68897; -. [Q7RTS9-2]
DR   Pumba; Q7RTS9; -.
DR   Antibodypedia; 22572; 152 antibodies from 22 providers.
DR   DNASU; 54808; -.
DR   Ensembl; ENST00000269445.10; ENSP00000269445.6; ENSG00000141627.14. [Q7RTS9-1]
DR   Ensembl; ENST00000442713.6; ENSP00000395942.2; ENSG00000141627.14. [Q7RTS9-2]
DR   GeneID; 54808; -.
DR   KEGG; hsa:54808; -.
DR   UCSC; uc002ldi.2; human. [Q7RTS9-1]
DR   AGR; HGNC:21317; -.
DR   CTD; 54808; -.
DR   DisGeNET; 54808; -.
DR   GeneCards; DYM; -.
DR   HGNC; HGNC:21317; DYM.
DR   HPA; ENSG00000141627; Low tissue specificity.
DR   MalaCards; DYM; -.
DR   MIM; 223800; phenotype.
DR   MIM; 607326; phenotype.
DR   MIM; 607461; gene.
DR   neXtProt; NX_Q7RTS9; -.
DR   OpenTargets; ENSG00000141627; -.
DR   Orphanet; 239; Dyggve-Melchior-Clausen disease.
DR   Orphanet; 178355; Smith-McCort dysplasia.
DR   PharmGKB; PA134879547; -.
DR   VEuPathDB; HostDB:ENSG00000141627; -.
DR   eggNOG; KOG2225; Eukaryota.
DR   GeneTree; ENSGT00390000008772; -.
DR   HOGENOM; CLU_013309_2_0_1; -.
DR   InParanoid; Q7RTS9; -.
DR   OrthoDB; 10297at2759; -.
DR   PhylomeDB; Q7RTS9; -.
DR   TreeFam; TF314870; -.
DR   PathwayCommons; Q7RTS9; -.
DR   SignaLink; Q7RTS9; -.
DR   BioGRID-ORCS; 54808; 17 hits in 1164 CRISPR screens.
DR   ChiTaRS; DYM; human.
DR   GeneWiki; DYM; -.
DR   GenomeRNAi; 54808; -.
DR   Pharos; Q7RTS9; Tbio.
DR   PRO; PR:Q7RTS9; -.
DR   Proteomes; UP000005640; Chromosome 18.
DR   RNAct; Q7RTS9; Protein.
DR   Bgee; ENSG00000141627; Expressed in bone marrow cell and 180 other cell types or tissues.
DR   ExpressionAtlas; Q7RTS9; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR   GO; GO:0060348; P:bone development; IMP:UniProtKB.
DR   GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR   InterPro; IPR019142; Dymeclin.
DR   PANTHER; PTHR12895; DYMECLIN; 1.
DR   PANTHER; PTHR12895:SF9; DYMECLIN; 1.
DR   Pfam; PF09742; Dymeclin; 1.
DR   Genevisible; Q7RTS9; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cytoplasm; Disease variant; Dwarfism;
KW   Golgi apparatus; Lipoprotein; Membrane; Myristate; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:25255805"
FT   CHAIN           2..669
FT                   /note="Dymeclin"
FT                   /id="PRO_0000086883"
FT   LIPID           2
FT                   /note="N-myristoyl glycine"
FT                   /evidence="ECO:0000269|PubMed:25255805,
FT                   ECO:0000305|PubMed:18996921"
FT   VAR_SEQ         65
FT                   /note="V -> A (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036442"
FT   VAR_SEQ         66..255
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_036443"
FT   VARIANT         87
FT                   /note="E -> K (in SMC1; does not affect protein
FT                   localization; dbSNP:rs120074164)"
FT                   /evidence="ECO:0000269|PubMed:12491225,
FT                   ECO:0000269|PubMed:18996921"
FT                   /id="VAR_022740"
FT   VARIANT         469
FT                   /note="N -> Y (in DMC; results in protein mis-localization
FT                   and aggregation; dbSNP:rs120074163)"
FT                   /evidence="ECO:0000269|PubMed:12491225,
FT                   ECO:0000269|PubMed:18996921"
FT                   /id="VAR_054499"
FT   VARIANT         542
FT                   /note="C -> R (in SMC1; dbSNP:rs120074165)"
FT                   /evidence="ECO:0000269|PubMed:19005420"
FT                   /id="VAR_065293"
FT   MUTAGEN         2
FT                   /note="G->A: Does not affect protein localization to Golgi
FT                   apparatus. Prevents myristoylation in vitro."
FT                   /evidence="ECO:0000269|PubMed:18996921"
FT   CONFLICT        66
FT                   /note="E -> K (in Ref. 2; BAC11088)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        249
FT                   /note="L -> P (in Ref. 2; BAC11088)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        381
FT                   /note="E -> G (in Ref. 3; BAF83992)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        408
FT                   /note="D -> Y (in Ref. 4; AAH64394)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        453
FT                   /note="R -> K (in Ref. 3; BAF83992)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        537
FT                   /note="E -> G (in Ref. 3; BAF83992)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   669 AA;  75935 MW;  7C8A216A09DBE43F CRC64;
     MGSNSSRIGD LPKNEYLKKL SGTESISEND PFWNQLLSFS FPAPTSSSEL KLLEEATISV
     CRSLVENNPR TGNLGALIKV FLSRTKELKL SAECQNHIFI WQTHNALFII CCLLKVFICQ
     MSEEELQLHF TYEEKSPGNY SSDSEDLLEE LLCCLMQLIT DIPLLDITYE ISVEAISTMV
     VFLSCQLFHK EVLRQSISHK YLMRGPCLPY TSKLVKTLLY NFIRQEKPPP PGAHVFPQQS
     DGGGLLYGLA SGVATGLWTV FTLGGVGSKA AASPELSSPL ANQSLLLLLV LANLTDASDA
     PNPYRQAIMS FKNTQDSSPF PSSIPHAFQI NFNSLYTALC EQQTSDQATL LLYTLLHQNS
     NIRTYMLART DMENLVLPIL EILYHVEERN SHHVYMALII LLILTEDDGF NRSIHEVILK
     NITWYSERVL TEISLGSLLI LVVIRTIQYN MTRTRDKYLH TNCLAALANM SAQFRSLHQY
     AAQRIISLFS LLSKKHNKVL EQATQSLRGS LSSNDVPLPD YAQDLNVIEE VIRMMLEIIN
     SCLTNSLHHN PNLVYALLYK RDLFEQFRTH PSFQDIMQNI DLVISFFSSR LLQAGAELSV
     ERVLEIIKQG VVALPKDRLK KFPELKFKYV EEEQPEEFFI PYVWSLVYNS AVGLYWNPQD
     IQLFTMDSD
//