Full text data of RAB33B
RAB33B
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ras-related protein Rab-33B
Ras-related protein Rab-33B
hRBCD
IPI00021475
IPI00021475 Ras-related protein Rab-33B Ras-related protein Rab-33B membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 n/a n/a cytoplasmic and membrane associated n/a expected molecular weight found in band ~ 98 kDa
IPI00021475 Ras-related protein Rab-33B Ras-related protein Rab-33B membrane n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a 1 1 n/a n/a cytoplasmic and membrane associated n/a expected molecular weight found in band ~ 98 kDa
UniProt
Q9H082
ID RB33B_HUMAN Reviewed; 229 AA.
AC Q9H082; B2R987; Q4W5B0;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 114.
DE RecName: Full=Ras-related protein Rab-33B;
GN Name=RAB33B;
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 [MRNA].
RA Mao Y., Xie Y., Cheng H.;
RT "Molecular cloning and characterization of human RAB33B.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 SUBCELLULAR LOCATION.
RX PubMed=18448665; DOI=10.1091/mbc.E07-12-1231;
RA Itoh T., Fujita N., Kanno E., Yamamoto A., Yoshimori T., Fukuda M.;
RT "Golgi-resident small GTPase Rab33B interacts with Atg16L and
RT modulates autophagosome formation.";
RL Mol. Biol. Cell 19:2916-2925(2008).
RN [7]
RP FUNCTION.
RX PubMed=20163571; DOI=10.1111/j.1600-0854.2010.01051.x;
RA Starr T., Sun Y., Wilkins N., Storrie B.;
RT "Rab33b and Rab6 are functionally overlapping regulators of Golgi
RT homeostasis and trafficking.";
RL Traffic 11:626-636(2010).
RN [8]
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).
RN [9]
RP VARIANT SMC2 GLN-46.
RX PubMed=22652534; DOI=10.1136/jmedgenet-2011-100666;
RA Alshammari M.J., Al-Otaibi L., Alkuraya F.S.;
RT "Mutation in RAB33B, which encodes a regulator of retrograde Golgi
RT transport, defines a second Dyggve--Melchior--Clausen locus.";
RL J. Med. Genet. 49:455-461(2012).
RN [10]
RP VARIANT SMC2 LYS-148, AND CHARACTERIZATION OF VARIANT SMC2 LYS-148.
RX PubMed=23042644; DOI=10.1002/humu.22235;
RA Dupuis N., Lebon S., Kumar M., Drunat S., Graul-Neumann L.M.,
RA Gressens P., El Ghouzzi V.;
RT "A novel RAB33B mutation in Smith-McCort dysplasia.";
RL Hum. Mutat. 34:283-286(2013).
CC -!- FUNCTION: Protein transport. Acts, in coordination with RAB6A, to
CC regulate intra-Golgi retrograde trafficking. It is involved in
CC autophagy, acting as a modulator of autophagosome formation.
CC -!- SUBUNIT: Interacts with ATG16L; the interaction is important for
CC autophagosome formation (By similarity).
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Lipid-anchor (By
CC similarity). Golgi apparatus, cis-Golgi network.
CC -!- DISEASE: Smith-McCort dysplasia 2 (SMC2) [MIM:615222]: A rare
CC autosomal recessive osteochondrodysplasia with skeletal features
CC identical to those of Dyggve-Melchior-Clausen syndrome, but with
CC normal intelligence and no microcephaly. It is characterized by
CC short limbs and trunk with barrel-shaped chest. The radiographic
CC phenotype includes platyspondyly, generalized abnormalities of the
CC epiphyses and metaphyses, and a distinctive lacy appearance of the
CC iliac crest. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; AF350420; AAL83916.1; -; mRNA.
DR EMBL; AL136904; CAB66838.1; -; mRNA.
DR EMBL; AK313685; BAG36434.1; -; mRNA.
DR EMBL; AC114743; AAY40936.1; -; Genomic_DNA.
DR EMBL; BC111977; AAI11978.1; -; mRNA.
DR RefSeq; NP_112586.1; NM_031296.1.
DR UniGene; Hs.591679; -.
DR ProteinModelPortal; Q9H082; -.
DR SMR; Q9H082; 30-202.
DR IntAct; Q9H082; 1.
DR MINT; MINT-4723772; -.
DR STRING; 9606.ENSP00000306496; -.
DR PhosphoSite; Q9H082; -.
DR DMDM; 14916662; -.
DR PaxDb; Q9H082; -.
DR PeptideAtlas; Q9H082; -.
DR PRIDE; Q9H082; -.
DR Ensembl; ENST00000305626; ENSP00000306496; ENSG00000172007.
DR GeneID; 83452; -.
DR KEGG; hsa:83452; -.
DR UCSC; uc003ihv.3; human.
DR CTD; 83452; -.
DR GeneCards; GC04P140374; -.
DR HGNC; HGNC:16075; RAB33B.
DR HPA; HPA048367; -.
DR MIM; 605950; gene.
DR MIM; 615222; phenotype.
DR neXtProt; NX_Q9H082; -.
DR Orphanet; 178355; Smith-McCort dysplasia.
DR PharmGKB; PA34125; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; Q9H082; -.
DR KO; K07920; -.
DR OMA; PAWIEEC; -.
DR OrthoDB; EOG78PVB5; -.
DR PhylomeDB; Q9H082; -.
DR GeneWiki; RAB33B; -.
DR GenomeRNAi; 83452; -.
DR NextBio; 72374; -.
DR PRO; PR:Q9H082; -.
DR Bgee; Q9H082; -.
DR CleanEx; HS_RAB33B; -.
DR Genevestigator; Q9H082; -.
DR GO; GO:0005796; C:Golgi lumen; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:2000785; P:regulation of autophagic vacuole assembly; ISS:UniProtKB.
DR GO; GO:2000156; P:regulation of retrograde vesicle-mediated transport, Golgi to ER; IMP:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003579; Small_GTPase_Rab_type.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00175; RAB; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Autophagy; Complete proteome; Disease mutation; Dwarfism;
KW Golgi apparatus; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 229 Ras-related protein Rab-33B.
FT /FTId=PRO_0000121239.
FT NP_BIND 39 46 GTP (By similarity).
FT NP_BIND 88 92 GTP (By similarity).
FT NP_BIND 148 151 GTP (By similarity).
FT MOD_RES 229 229 Cysteine methyl ester (By similarity).
FT LIPID 227 227 S-geranylgeranyl cysteine (By
FT similarity).
FT LIPID 229 229 S-geranylgeranyl cysteine (By
FT similarity).
FT VARIANT 46 46 K -> Q (in SMC2).
FT /FTId=VAR_068854.
FT VARIANT 148 148 N -> K (in SMC2; strongly inhibits
FT protein expression and may disrupt the
FT Golgi apparatus structure).
FT /FTId=VAR_068855.
SQ SEQUENCE 229 AA; 25718 MW; 40D8B1A1D4C6CD85 CRC64;
MAEEMESSLE ASFSSSGAVS GASGFLPPAR SRIFKIIVIG DSNVGKTCLT YRFCAGRFPD
RTEATIGVDF RERAVEIDGE RIKIQLWDTA GQERFRKSMV QHYYRNVHAV VFVYDMTNMA
SFHSLPSWIE ECKQHLLAND IPRILVGNKC DLRSAIQVPT DLAQKFADTH SMPLFETSAK
NPNDNDHVEA IFMTLAHKLK SHKPLMLSQP PDNGIILKPE PKPAMTCWC
//
ID RB33B_HUMAN Reviewed; 229 AA.
AC Q9H082; B2R987; Q4W5B0;
DT 11-JUL-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAR-2001, sequence version 1.
DT 22-JAN-2014, entry version 114.
DE RecName: Full=Ras-related protein Rab-33B;
GN Name=RAB33B;
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 [MRNA].
RA Mao Y., Xie Y., Cheng H.;
RT "Molecular cloning and characterization of human RAB33B.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA Waterston R.H., Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2
RT and 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 SUBCELLULAR LOCATION.
RX PubMed=18448665; DOI=10.1091/mbc.E07-12-1231;
RA Itoh T., Fujita N., Kanno E., Yamamoto A., Yoshimori T., Fukuda M.;
RT "Golgi-resident small GTPase Rab33B interacts with Atg16L and
RT modulates autophagosome formation.";
RL Mol. Biol. Cell 19:2916-2925(2008).
RN [7]
RP FUNCTION.
RX PubMed=20163571; DOI=10.1111/j.1600-0854.2010.01051.x;
RA Starr T., Sun Y., Wilkins N., Storrie B.;
RT "Rab33b and Rab6 are functionally overlapping regulators of Golgi
RT homeostasis and trafficking.";
RL Traffic 11:626-636(2010).
RN [8]
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).
RN [9]
RP VARIANT SMC2 GLN-46.
RX PubMed=22652534; DOI=10.1136/jmedgenet-2011-100666;
RA Alshammari M.J., Al-Otaibi L., Alkuraya F.S.;
RT "Mutation in RAB33B, which encodes a regulator of retrograde Golgi
RT transport, defines a second Dyggve--Melchior--Clausen locus.";
RL J. Med. Genet. 49:455-461(2012).
RN [10]
RP VARIANT SMC2 LYS-148, AND CHARACTERIZATION OF VARIANT SMC2 LYS-148.
RX PubMed=23042644; DOI=10.1002/humu.22235;
RA Dupuis N., Lebon S., Kumar M., Drunat S., Graul-Neumann L.M.,
RA Gressens P., El Ghouzzi V.;
RT "A novel RAB33B mutation in Smith-McCort dysplasia.";
RL Hum. Mutat. 34:283-286(2013).
CC -!- FUNCTION: Protein transport. Acts, in coordination with RAB6A, to
CC regulate intra-Golgi retrograde trafficking. It is involved in
CC autophagy, acting as a modulator of autophagosome formation.
CC -!- SUBUNIT: Interacts with ATG16L; the interaction is important for
CC autophagosome formation (By similarity).
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane; Lipid-anchor (By
CC similarity). Golgi apparatus, cis-Golgi network.
CC -!- DISEASE: Smith-McCort dysplasia 2 (SMC2) [MIM:615222]: A rare
CC autosomal recessive osteochondrodysplasia with skeletal features
CC identical to those of Dyggve-Melchior-Clausen syndrome, but with
CC normal intelligence and no microcephaly. It is characterized by
CC short limbs and trunk with barrel-shaped chest. The radiographic
CC phenotype includes platyspondyly, generalized abnormalities of the
CC epiphyses and metaphyses, and a distinctive lacy appearance of the
CC iliac crest. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. Rab family.
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DR EMBL; AF350420; AAL83916.1; -; mRNA.
DR EMBL; AL136904; CAB66838.1; -; mRNA.
DR EMBL; AK313685; BAG36434.1; -; mRNA.
DR EMBL; AC114743; AAY40936.1; -; Genomic_DNA.
DR EMBL; BC111977; AAI11978.1; -; mRNA.
DR RefSeq; NP_112586.1; NM_031296.1.
DR UniGene; Hs.591679; -.
DR ProteinModelPortal; Q9H082; -.
DR SMR; Q9H082; 30-202.
DR IntAct; Q9H082; 1.
DR MINT; MINT-4723772; -.
DR STRING; 9606.ENSP00000306496; -.
DR PhosphoSite; Q9H082; -.
DR DMDM; 14916662; -.
DR PaxDb; Q9H082; -.
DR PeptideAtlas; Q9H082; -.
DR PRIDE; Q9H082; -.
DR Ensembl; ENST00000305626; ENSP00000306496; ENSG00000172007.
DR GeneID; 83452; -.
DR KEGG; hsa:83452; -.
DR UCSC; uc003ihv.3; human.
DR CTD; 83452; -.
DR GeneCards; GC04P140374; -.
DR HGNC; HGNC:16075; RAB33B.
DR HPA; HPA048367; -.
DR MIM; 605950; gene.
DR MIM; 615222; phenotype.
DR neXtProt; NX_Q9H082; -.
DR Orphanet; 178355; Smith-McCort dysplasia.
DR PharmGKB; PA34125; -.
DR eggNOG; COG1100; -.
DR HOGENOM; HOG000233968; -.
DR HOVERGEN; HBG009351; -.
DR InParanoid; Q9H082; -.
DR KO; K07920; -.
DR OMA; PAWIEEC; -.
DR OrthoDB; EOG78PVB5; -.
DR PhylomeDB; Q9H082; -.
DR GeneWiki; RAB33B; -.
DR GenomeRNAi; 83452; -.
DR NextBio; 72374; -.
DR PRO; PR:Q9H082; -.
DR Bgee; Q9H082; -.
DR CleanEx; HS_RAB33B; -.
DR Genevestigator; Q9H082; -.
DR GO; GO:0005796; C:Golgi lumen; IDA:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:2000785; P:regulation of autophagic vacuole assembly; ISS:UniProtKB.
DR GO; GO:2000156; P:regulation of retrograde vesicle-mediated transport, Golgi to ER; IMP:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR001806; Small_GTPase.
DR InterPro; IPR003579; Small_GTPase_Rab_type.
DR Pfam; PF00071; Ras; 1.
DR PRINTS; PR00449; RASTRNSFRMNG.
DR SMART; SM00175; RAB; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51419; RAB; 1.
PE 1: Evidence at protein level;
KW Autophagy; Complete proteome; Disease mutation; Dwarfism;
KW Golgi apparatus; GTP-binding; Lipoprotein; Membrane; Methylation;
KW Nucleotide-binding; Prenylation; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1 229 Ras-related protein Rab-33B.
FT /FTId=PRO_0000121239.
FT NP_BIND 39 46 GTP (By similarity).
FT NP_BIND 88 92 GTP (By similarity).
FT NP_BIND 148 151 GTP (By similarity).
FT MOD_RES 229 229 Cysteine methyl ester (By similarity).
FT LIPID 227 227 S-geranylgeranyl cysteine (By
FT similarity).
FT LIPID 229 229 S-geranylgeranyl cysteine (By
FT similarity).
FT VARIANT 46 46 K -> Q (in SMC2).
FT /FTId=VAR_068854.
FT VARIANT 148 148 N -> K (in SMC2; strongly inhibits
FT protein expression and may disrupt the
FT Golgi apparatus structure).
FT /FTId=VAR_068855.
SQ SEQUENCE 229 AA; 25718 MW; 40D8B1A1D4C6CD85 CRC64;
MAEEMESSLE ASFSSSGAVS GASGFLPPAR SRIFKIIVIG DSNVGKTCLT YRFCAGRFPD
RTEATIGVDF RERAVEIDGE RIKIQLWDTA GQERFRKSMV QHYYRNVHAV VFVYDMTNMA
SFHSLPSWIE ECKQHLLAND IPRILVGNKC DLRSAIQVPT DLAQKFADTH SMPLFETSAK
NPNDNDHVEA IFMTLAHKLK SHKPLMLSQP PDNGIILKPE PKPAMTCWC
//
MIM
605950
*RECORD*
*FIELD* NO
605950
*FIELD* TI
*605950 RAS-ASSOCIATED PROTEIN RAB33B; RAB33B
*FIELD* TX
DESCRIPTION
Small GTP-binding proteins of the RAB family, such as RAB33B, play
read moreimportant roles at defined steps of vesicular transport in protein
secretion and the endocytosis pathway (Zheng et al., 1998).
CLONING
Zheng et al. (1998) cloned and characterized mouse Rab33b, a small
GTP-binding protein closely related to RAB33A (300333), especially in
the GTP-binding domain. The Rab33b gene encodes a 229-amino acid
protein. Unlike mouse and human RAB33A, which have tissue-specific
expression, Northern blot analysis indicated that mouse Rab33b is
ubiquitously expressed. Using immunofluorescence studies, Zheng et al.
(1998) showed that Rab33b is localized to the medial Golgi cisternae,
suggesting that it may play a role in intra-Golgi transport.
GENE STRUCTURE
Zheng et al. (1998) determined that the mouse Rab33b gene contains 2
exons.
MAPPING
Gross (2013) mapped the RAB33B gene to chromosome 4q31.1 based on an
alignment of the RAB33B sequence (GenBank GENBANK AF350420) with the
genomic sequence (GRCh37).
MOLECULAR GENETICS
By exome sequencing of the proband in a consanguineous Saudi family
segregating Smith-McCort syndrome linked to chromosome 4 (SMC2; 615222),
Alshammari et al. (2012) identified a homozygous missense mutation in
the RAB33B gene (K46Q; 605950.0001). Immunoblot analysis showed severe
deficiency of RAB33B in patient cells compared with control cells, and
patient fibroblasts also displayed a marked reduction in the
immunofluorescence signal corresponding to RAB33B but comparable signal
intensity to the Golgi marker giantin (602500).
In a 22-year-old Turkish man with Smith-McCort syndrome-2, who had
previously been reported by Neumann et al. (2006), Dupuis et al. (2013)
identified a homozygous missense mutation in the RAB33B gene (N148K;
605950.0002). By Western blot analysis and immunofluorescence studies,
Dupuis et al. (2013) found marked reduction of the RAB33B protein.
*FIELD* AV
.0001
SMITH-MCCORT DYSPLASIA 2
RAB33B, LYS46GLN
By exome sequencing of the proband in a consanguineous Saudi family
segregating Smith-McCort syndrome linked to chromosome 4 (SMC2; 615222),
Alshammari et al. (2012) identified homozygosity for a c.136A-C
transversion in the RAB33B gene, resulting in a lys46-to-gln (K46Q)
substitution in the GxxxxGK [S/T] guanine nucleotide-binding domain of
the encoded GTPase. Immunoblot analysis showed severe deficiency of
RAB33B in patient cells compared with control cells, and patient
fibroblasts also displayed a marked reduction in the immunofluorescence
signal corresponding to RAB33B but comparable signal intensity to the
Golgi marker giantin (602500). The mutation fully segregated with the
disease phenotype and was absent on Sanger sequencing of 185 Saudi
controls and absent from 160 Saudi exomes.
.0002
SMITH-MCCORT DYSPLASIA 2
RAB33B, ASN148LYS
In a 22-year old Turkish man with Smith-McCort dysplasia-2 (615222), who
had previously been reported by Neumann et al. (2006), Dupuis et al.
(2013) identified a homozygous c.444T-A transversion in exon 2 of the
RAB33B gene, predicting an asn148-to-lys (N148K) substitution at a
highly conserved residue in the G-4 GTPase domain. By Western blot
analysis and immunofluorescence studies, Dupuis et al. (2013) found
marked reduction of the RAB33B protein. Both parents were heterozygous
for the mutation, which was absent in his unaffected brother and from
publicly available databases of known polymorphic variants.
*FIELD* RF
1. Alshammari, M. J.; Al-Otaibi, L.; Alkuraya, F. S.: Mutation in
RAB33B, which encodes a regulator of retrograde Golgi transport, defines
a second Dyggve-Melchior-Clausen locus. J. Med. Genet. 49: 455-461,
2012.
2. Dupuis, N.; Lebon, S.; Kumar, M.; Drunat, S.; Graul-Neumann, L.
M.; Gressens, P.; El Ghouzzi, V.: A novel RAB33B mutation in Smith-McCort
dysplasia. Hum. Mutat. 34: 283-286, 2013.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 5/3/2013.
4. Neumann, L. M.; El Ghouzzi, V.; Paupe, V.; Weber, H.-P.; Fastnacht,
E.; Leenen, A.; Lyding, S.; Klusmann, A.; Mayatepek, E.; Pelz, J.;
Cormier-Daire, V.: Dyggve-Melchior-Clausen syndrome and Smith-McCort
dysplasia: clinical and molecular findings in three families supporting
genetic heterogeneity in Smith-McCort dysplasia. Am. J. Med. Genet. 140A:
421-426, 2006.
5. Zheng, J. Y.; Koda, T.; Fujiwara, T.; Kishi, M.; Ikehara, Y.; Kakinuma,
M.: A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized
to the medial Golgi cisternae. J. Cell Sci. 111: 1061-1069, 1998.
*FIELD* CN
Matthew B. Gross - updated: 05/03/2013
Nara Sobreira - updated: 5/3/2013
*FIELD* CD
Yen-Pei C. Chang: 5/21/2001
*FIELD* ED
mgross: 05/03/2013
carol: 5/3/2013
wwang: 2/4/2010
alopez: 10/18/2002
mgross: 5/21/2001
*RECORD*
*FIELD* NO
605950
*FIELD* TI
*605950 RAS-ASSOCIATED PROTEIN RAB33B; RAB33B
*FIELD* TX
DESCRIPTION
Small GTP-binding proteins of the RAB family, such as RAB33B, play
read moreimportant roles at defined steps of vesicular transport in protein
secretion and the endocytosis pathway (Zheng et al., 1998).
CLONING
Zheng et al. (1998) cloned and characterized mouse Rab33b, a small
GTP-binding protein closely related to RAB33A (300333), especially in
the GTP-binding domain. The Rab33b gene encodes a 229-amino acid
protein. Unlike mouse and human RAB33A, which have tissue-specific
expression, Northern blot analysis indicated that mouse Rab33b is
ubiquitously expressed. Using immunofluorescence studies, Zheng et al.
(1998) showed that Rab33b is localized to the medial Golgi cisternae,
suggesting that it may play a role in intra-Golgi transport.
GENE STRUCTURE
Zheng et al. (1998) determined that the mouse Rab33b gene contains 2
exons.
MAPPING
Gross (2013) mapped the RAB33B gene to chromosome 4q31.1 based on an
alignment of the RAB33B sequence (GenBank GENBANK AF350420) with the
genomic sequence (GRCh37).
MOLECULAR GENETICS
By exome sequencing of the proband in a consanguineous Saudi family
segregating Smith-McCort syndrome linked to chromosome 4 (SMC2; 615222),
Alshammari et al. (2012) identified a homozygous missense mutation in
the RAB33B gene (K46Q; 605950.0001). Immunoblot analysis showed severe
deficiency of RAB33B in patient cells compared with control cells, and
patient fibroblasts also displayed a marked reduction in the
immunofluorescence signal corresponding to RAB33B but comparable signal
intensity to the Golgi marker giantin (602500).
In a 22-year-old Turkish man with Smith-McCort syndrome-2, who had
previously been reported by Neumann et al. (2006), Dupuis et al. (2013)
identified a homozygous missense mutation in the RAB33B gene (N148K;
605950.0002). By Western blot analysis and immunofluorescence studies,
Dupuis et al. (2013) found marked reduction of the RAB33B protein.
*FIELD* AV
.0001
SMITH-MCCORT DYSPLASIA 2
RAB33B, LYS46GLN
By exome sequencing of the proband in a consanguineous Saudi family
segregating Smith-McCort syndrome linked to chromosome 4 (SMC2; 615222),
Alshammari et al. (2012) identified homozygosity for a c.136A-C
transversion in the RAB33B gene, resulting in a lys46-to-gln (K46Q)
substitution in the GxxxxGK [S/T] guanine nucleotide-binding domain of
the encoded GTPase. Immunoblot analysis showed severe deficiency of
RAB33B in patient cells compared with control cells, and patient
fibroblasts also displayed a marked reduction in the immunofluorescence
signal corresponding to RAB33B but comparable signal intensity to the
Golgi marker giantin (602500). The mutation fully segregated with the
disease phenotype and was absent on Sanger sequencing of 185 Saudi
controls and absent from 160 Saudi exomes.
.0002
SMITH-MCCORT DYSPLASIA 2
RAB33B, ASN148LYS
In a 22-year old Turkish man with Smith-McCort dysplasia-2 (615222), who
had previously been reported by Neumann et al. (2006), Dupuis et al.
(2013) identified a homozygous c.444T-A transversion in exon 2 of the
RAB33B gene, predicting an asn148-to-lys (N148K) substitution at a
highly conserved residue in the G-4 GTPase domain. By Western blot
analysis and immunofluorescence studies, Dupuis et al. (2013) found
marked reduction of the RAB33B protein. Both parents were heterozygous
for the mutation, which was absent in his unaffected brother and from
publicly available databases of known polymorphic variants.
*FIELD* RF
1. Alshammari, M. J.; Al-Otaibi, L.; Alkuraya, F. S.: Mutation in
RAB33B, which encodes a regulator of retrograde Golgi transport, defines
a second Dyggve-Melchior-Clausen locus. J. Med. Genet. 49: 455-461,
2012.
2. Dupuis, N.; Lebon, S.; Kumar, M.; Drunat, S.; Graul-Neumann, L.
M.; Gressens, P.; El Ghouzzi, V.: A novel RAB33B mutation in Smith-McCort
dysplasia. Hum. Mutat. 34: 283-286, 2013.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 5/3/2013.
4. Neumann, L. M.; El Ghouzzi, V.; Paupe, V.; Weber, H.-P.; Fastnacht,
E.; Leenen, A.; Lyding, S.; Klusmann, A.; Mayatepek, E.; Pelz, J.;
Cormier-Daire, V.: Dyggve-Melchior-Clausen syndrome and Smith-McCort
dysplasia: clinical and molecular findings in three families supporting
genetic heterogeneity in Smith-McCort dysplasia. Am. J. Med. Genet. 140A:
421-426, 2006.
5. Zheng, J. Y.; Koda, T.; Fujiwara, T.; Kishi, M.; Ikehara, Y.; Kakinuma,
M.: A novel Rab GTPase, Rab33B, is ubiquitously expressed and localized
to the medial Golgi cisternae. J. Cell Sci. 111: 1061-1069, 1998.
*FIELD* CN
Matthew B. Gross - updated: 05/03/2013
Nara Sobreira - updated: 5/3/2013
*FIELD* CD
Yen-Pei C. Chang: 5/21/2001
*FIELD* ED
mgross: 05/03/2013
carol: 5/3/2013
wwang: 2/4/2010
alopez: 10/18/2002
mgross: 5/21/2001
MIM
615222
*RECORD*
*FIELD* NO
615222
*FIELD* TI
#615222 SMITH-MCCORT DYSPLASIA 2; SMC2
*FIELD* TX
A number sign (#) is used with this entry because Smith-McCort
read moredysplasia-2 (SMC2) is caused by homozygous mutation in the RAB33B gene
(605950) on chromosome 18p11.
DESCRIPTION
Smith-McCort dysplasia is a rare autosomal recessive
osteochondrodysplasia characterized by short trunk dwarfism with a
barrel-shaped chest, rhizomelic limb shortening, and specific radiologic
features including marked platyspondyly with double-humped end-plates,
kyphoscoliosis, metaphyseal irregularities, laterally displaced capital
femoral epiphyses, and small pelvis with a lace-like appearance of iliac
crests. These clinical and radiologic features are also common to
Dyggve-Melchior-Clausen syndrome (DMC; 223800), which is distinguished
from SMC by the additional feature of mental retardation (summary by
Dupuis et al., 2013).
For a discussion of genetic heterogeneity of Smith-McCort dysplasia, see
SMC1 (607326).
CLINICAL FEATURES
Alshammari et al. (2012) reported a consanguineous Saudi family in which
4 sibs and 2 first cousins had Dyggve-Melchior-Clausen syndrome and
normal intelligence (Smith-McCort dysplasia). All were short and had
variable degrees of progressive pectus carinatum deformity, limitation
of joint mobility, and lumbar lordosis. The index patient had
significant short stature and no gross craniofacial dysmorphism. He had
a short neck, significant pectus carinatum, exaggerated lumbar lordosis,
and limitation of elbow extension and interphalangeal joint flexion with
difficulty making a fist. There was genu valgus and no evidence of
organomegaly.
MAPPING
By linkage analysis in a consanguineous Saudi family segregating
Smith-McCort syndrome in which mutation in the DYM gene (607461) had
been excluded, Alshammari et al. (2012) found linkage of the disorder to
a 19-Mb region on chromosome 4 between SNPs dbSNP rs6844366 and dbSNP
rs2215748 (maximum lod of 3.25).
MOLECULAR GENETICS
By exome sequencing of the proband in a consanguineous Saudi family
segregating Smith-McCort syndrome linked to chromosome 4, Alshammari et
al. (2012) identified a homozygous missense mutation in the RAB33B gene
(K46Q; 605950.0001). Immunoblot analysis showed severe deficiency of
RAB33B in patient cells compared with control cells, and patient
fibroblasts also displayed a marked reduction in the immunofluorescence
signal corresponding to RAB33B but comparable signal intensity to the
Golgi marker giantin (602500).
In a Turkish patient with Smith-McCort syndrome in whom Neumann et al.
(2006) had found no mutation in the DYM gene (607461), Dupuis et al.
(2013) identified a homozygous missense mutation in the RAB33B gene
(N148K; 605950.0002). By Western blot analysis and immunofluorescence
studies, Dupuis et al. (2013) found marked reduction of the RAB33B
protein.
*FIELD* RF
1. Alshammari, M. J.; Al-Otaibi, L.; Alkuraya, F. S.: Mutation in
RAB33B, which encodes a regulator of retrograde Golgi transport, defines
a second Dyggve-Melchior-Clausen locus. J. Med. Genet. 49: 455-461,
2012.
2. Dupuis, N.; Lebon, S.; Kumar, M.; Drunat, S.; Graul-Neumann, L.
M.; Gressens, P.; El Ghouzzi, V.: A novel RAB33B mutation in Smith-McCort
dysplasia. Hum. Mutat. 34: 283-286, 2013.
3. Neumann, L. M.; El Ghouzzi, V.; Paupe, V.; Weber, H.-P.; Fastnacht,
E.; Leenen, A.; Lyding, S.; Klusmann, A.; Mayatepek, E.; Pelz, J.;
Cormier-Daire, V.: Dyggve-Melchior-Clausen syndrome and Smith-McCort
dysplasia: clinical and molecular findings in three families supporting
genetic heterogeneity in Smith-McCort dysplasia. Am. J. Med. Genet. 140A:
421-426, 2006.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Weight];
Low weight
HEAD AND NECK:
[Neck];
Short neck
CHEST:
[External features];
Short trunk;
Barrel-shaped chest;
[Ribs, sternum, clavicles, and scapulae];
Pectus carinatum
SKELETAL:
[Spine];
Exaggerated lordosis;
Platyspondyly;
Posterior double humps of vertebral body;
Irregular surface of iliac spine;
Odontoid hypoplasia, mild;
[Limbs];
Elevated shoulder joints;
Limited extension of elbow joints;
Genu valgum;
Flattened femoral heads;
Broad femoral neck, mild;
Reduced trochanter and femur head distance ratio;
Irregular shallow acetabular roofs;
Metaphyseal irregularity of the upper tibia;
Flattened epiphysis of the lower tibia;
Flattened humeral head;
[Hands];
Short metacarpal bones;
Broad metacarpal bones;
Short phalanges;
Broad phalanges;
Broad interphalangeal joints;
[Feet];
Flat feet;
Prominent heels;
Short metatarsal bones;
Broad metatarsal bones;
Short phalanges;
Broad phalanges
MOLECULAR BASIS:
Caused by mutation in the Ras-associated protein RAB33B gene (RAB33B,
605950.0001)
*FIELD* CD
Nara Sobreira: 5/3/2013
*FIELD* ED
joanna: 05/03/2013
joanna: 5/3/2013
*FIELD* CD
Nara Sobreira: 5/3/2013
*FIELD* ED
carol: 05/03/2013
carol: 5/3/2013
*RECORD*
*FIELD* NO
615222
*FIELD* TI
#615222 SMITH-MCCORT DYSPLASIA 2; SMC2
*FIELD* TX
A number sign (#) is used with this entry because Smith-McCort
read moredysplasia-2 (SMC2) is caused by homozygous mutation in the RAB33B gene
(605950) on chromosome 18p11.
DESCRIPTION
Smith-McCort dysplasia is a rare autosomal recessive
osteochondrodysplasia characterized by short trunk dwarfism with a
barrel-shaped chest, rhizomelic limb shortening, and specific radiologic
features including marked platyspondyly with double-humped end-plates,
kyphoscoliosis, metaphyseal irregularities, laterally displaced capital
femoral epiphyses, and small pelvis with a lace-like appearance of iliac
crests. These clinical and radiologic features are also common to
Dyggve-Melchior-Clausen syndrome (DMC; 223800), which is distinguished
from SMC by the additional feature of mental retardation (summary by
Dupuis et al., 2013).
For a discussion of genetic heterogeneity of Smith-McCort dysplasia, see
SMC1 (607326).
CLINICAL FEATURES
Alshammari et al. (2012) reported a consanguineous Saudi family in which
4 sibs and 2 first cousins had Dyggve-Melchior-Clausen syndrome and
normal intelligence (Smith-McCort dysplasia). All were short and had
variable degrees of progressive pectus carinatum deformity, limitation
of joint mobility, and lumbar lordosis. The index patient had
significant short stature and no gross craniofacial dysmorphism. He had
a short neck, significant pectus carinatum, exaggerated lumbar lordosis,
and limitation of elbow extension and interphalangeal joint flexion with
difficulty making a fist. There was genu valgus and no evidence of
organomegaly.
MAPPING
By linkage analysis in a consanguineous Saudi family segregating
Smith-McCort syndrome in which mutation in the DYM gene (607461) had
been excluded, Alshammari et al. (2012) found linkage of the disorder to
a 19-Mb region on chromosome 4 between SNPs dbSNP rs6844366 and dbSNP
rs2215748 (maximum lod of 3.25).
MOLECULAR GENETICS
By exome sequencing of the proband in a consanguineous Saudi family
segregating Smith-McCort syndrome linked to chromosome 4, Alshammari et
al. (2012) identified a homozygous missense mutation in the RAB33B gene
(K46Q; 605950.0001). Immunoblot analysis showed severe deficiency of
RAB33B in patient cells compared with control cells, and patient
fibroblasts also displayed a marked reduction in the immunofluorescence
signal corresponding to RAB33B but comparable signal intensity to the
Golgi marker giantin (602500).
In a Turkish patient with Smith-McCort syndrome in whom Neumann et al.
(2006) had found no mutation in the DYM gene (607461), Dupuis et al.
(2013) identified a homozygous missense mutation in the RAB33B gene
(N148K; 605950.0002). By Western blot analysis and immunofluorescence
studies, Dupuis et al. (2013) found marked reduction of the RAB33B
protein.
*FIELD* RF
1. Alshammari, M. J.; Al-Otaibi, L.; Alkuraya, F. S.: Mutation in
RAB33B, which encodes a regulator of retrograde Golgi transport, defines
a second Dyggve-Melchior-Clausen locus. J. Med. Genet. 49: 455-461,
2012.
2. Dupuis, N.; Lebon, S.; Kumar, M.; Drunat, S.; Graul-Neumann, L.
M.; Gressens, P.; El Ghouzzi, V.: A novel RAB33B mutation in Smith-McCort
dysplasia. Hum. Mutat. 34: 283-286, 2013.
3. Neumann, L. M.; El Ghouzzi, V.; Paupe, V.; Weber, H.-P.; Fastnacht,
E.; Leenen, A.; Lyding, S.; Klusmann, A.; Mayatepek, E.; Pelz, J.;
Cormier-Daire, V.: Dyggve-Melchior-Clausen syndrome and Smith-McCort
dysplasia: clinical and molecular findings in three families supporting
genetic heterogeneity in Smith-McCort dysplasia. Am. J. Med. Genet. 140A:
421-426, 2006.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature;
[Weight];
Low weight
HEAD AND NECK:
[Neck];
Short neck
CHEST:
[External features];
Short trunk;
Barrel-shaped chest;
[Ribs, sternum, clavicles, and scapulae];
Pectus carinatum
SKELETAL:
[Spine];
Exaggerated lordosis;
Platyspondyly;
Posterior double humps of vertebral body;
Irregular surface of iliac spine;
Odontoid hypoplasia, mild;
[Limbs];
Elevated shoulder joints;
Limited extension of elbow joints;
Genu valgum;
Flattened femoral heads;
Broad femoral neck, mild;
Reduced trochanter and femur head distance ratio;
Irregular shallow acetabular roofs;
Metaphyseal irregularity of the upper tibia;
Flattened epiphysis of the lower tibia;
Flattened humeral head;
[Hands];
Short metacarpal bones;
Broad metacarpal bones;
Short phalanges;
Broad phalanges;
Broad interphalangeal joints;
[Feet];
Flat feet;
Prominent heels;
Short metatarsal bones;
Broad metatarsal bones;
Short phalanges;
Broad phalanges
MOLECULAR BASIS:
Caused by mutation in the Ras-associated protein RAB33B gene (RAB33B,
605950.0001)
*FIELD* CD
Nara Sobreira: 5/3/2013
*FIELD* ED
joanna: 05/03/2013
joanna: 5/3/2013
*FIELD* CD
Nara Sobreira: 5/3/2013
*FIELD* ED
carol: 05/03/2013
carol: 5/3/2013