Full text data of SKIV2L
SKIV2L
(DDX13, SKI2W, SKIV2, W)
[Confidence: low (only semi-automatic identification from reviews)]
Helicase SKI2W; Ski2; 3.6.4.- (Helicase-like protein; HLP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Helicase SKI2W; Ski2; 3.6.4.- (Helicase-like protein; HLP)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q15477
ID SKIV2_HUMAN Reviewed; 1246 AA.
AC Q15477; O15005; Q12902; Q15476; Q5ST66;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Helicase SKI2W;
DE Short=Ski2;
DE EC=3.6.4.-;
DE AltName: Full=Helicase-like protein;
DE Short=HLP;
GN Name=SKIV2L; Synonyms=DDX13, SKI2W, SKIV2, W;
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].
RC TISSUE=Liver;
RX PubMed=7759100; DOI=10.1016/0888-7543(95)80008-A;
RA Lee S.-G., Lee I., Park S.H., Kang C., Song K.;
RT "Identification and characterization of a human cDNA homologous to
RT yeast SKI2.";
RL Genomics 25:660-666(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS ARG-151 AND
RP LEU-214.
RX PubMed=7610041; DOI=10.1093/nar/23.12.2120;
RA Dangel A.W., Shen L., Mendoza A.R., Wu L.-C., Yu C.Y.;
RT "Human helicase gene SKI2W in the HLA class III region exhibits
RT striking structural similarities to the yeast antiviral gene SKI2 and
RT to the human gene KIAA0052: emergence of a new gene family.";
RL Nucleic Acids Res. 23:2120-2126(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-214.
RX PubMed=8812450; DOI=10.1006/geno.1996.0459;
RA Albertella M.R., Jones H., Thomson W., Olavesen M.G., Campbell R.D.;
RT "Localization of eight additional genes in the human major
RT histocompatibility complex, including the gene encoding the casein
RT kinase II beta subunit (CSNK2B).";
RL Genomics 36:240-251(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-151; LEU-214;
RP MET-917 AND VAL-1071.
RA Rowen L., Dankers C., Baskin D., Faust J., Loretz C., Ahearn M.E.,
RA Banta A., Swartzell S., Smith T.M., Spies T., Hood L.;
RT "Sequence determination of 300 kilobases of the human class III MHC
RT locus.";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP IDENTIFICATION IN THE SKI COMPLEX.
RX PubMed=16024656; DOI=10.1101/gad.1292105;
RA Zhu B., Mandal S.S., Pham A.D., Zheng Y., Erdjument-Bromage H.,
RA Batra S.K., Tempst P., Reinberg D.;
RT "The human PAF complex coordinates transcription with events
RT downstream of RNA synthesis.";
RL Genes Dev. 19:1668-1673(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, AND MASS
RP SPECTROMETRY.
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-183 AND ILE-765.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [18]
RP VARIANT THES2 GLY-341.
RX PubMed=22444670; DOI=10.1016/j.ajhg.2012.02.009;
RA Fabre A., Charroux B., Martinez-Vinson C., Roquelaure B., Odul E.,
RA Sayar E., Smith H., Colomb V., Andre N., Hugot J.P., Goulet O.,
RA Lacoste C., Sarles J., Royet J., Levy N., Badens C.;
RT "SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric
RT syndrome.";
RL Am. J. Hum. Genet. 90:689-692(2012).
CC -!- FUNCTION: Helicase; has ATPase activity. Component of the SKI
CC complex which is thought to be involved in exosome-mediated RNA
CC decay and associates with transcriptionally active genes in a
CC manner dependent on PAF1 complex (PAF1C).
CC -!- SUBUNIT: Component of the SKI complex which consists of WDR61,
CC SKIV2L and TTC37.
CC -!- SUBCELLULAR LOCATION: Nucleus (Probable). Cytoplasm (Probable).
CC -!- DISEASE: Trichohepatoenteric syndrome 2 (THES2) [MIM:614602]: A
CC syndrome characterized by intrauterine growth retardation, severe
CC diarrhea in infancy requiring total parenteral nutrition, facial
CC dysmorphism, immunodeficiency, and hair abnormalities, mostly
CC trichorrhexis nodosa. Hepatic involvement contributes to the poor
CC prognosis of affected patients. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the helicase family. SKI2 subfamily.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB52523.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; U09877; AAB52523.1; ALT_INIT; mRNA.
DR EMBL; X98378; CAA67024.1; -; Genomic_DNA.
DR EMBL; Z48796; CAA88733.1; -; mRNA.
DR EMBL; AF019413; AAB67978.1; -; Genomic_DNA.
DR EMBL; AL662849; CAI17460.1; -; Genomic_DNA.
DR EMBL; AL645922; CAQ09280.1; -; Genomic_DNA.
DR PIR; S56752; S56752.
DR RefSeq; NP_008860.4; NM_006929.4.
DR UniGene; Hs.89864; -.
DR ProteinModelPortal; Q15477; -.
DR SMR; Q15477; 280-836, 1018-1244.
DR IntAct; Q15477; 10.
DR STRING; 9606.ENSP00000394400; -.
DR PhosphoSite; Q15477; -.
DR DMDM; 3123284; -.
DR PaxDb; Q15477; -.
DR PRIDE; Q15477; -.
DR DNASU; 6499; -.
DR Ensembl; ENST00000375394; ENSP00000364543; ENSG00000204351.
DR Ensembl; ENST00000383336; ENSP00000372827; ENSG00000206353.
DR Ensembl; ENST00000412823; ENSP00000400626; ENSG00000232616.
DR Ensembl; ENST00000421789; ENSP00000399530; ENSG00000228896.
DR Ensembl; ENST00000429465; ENSP00000412310; ENSG00000223493.
DR Ensembl; ENST00000448219; ENSP00000394400; ENSG00000225737.
DR GeneID; 6499; -.
DR KEGG; hsa:6499; -.
DR UCSC; uc003nyn.1; human.
DR CTD; 6499; -.
DR GeneCards; GC06P031926; -.
DR GeneCards; GC06Pj31914; -.
DR GeneCards; GC06Pk31908; -.
DR GeneCards; GC06Pm32003; -.
DR GeneCards; GC06Pn31916; -.
DR GeneCards; GC06Po31918; -.
DR H-InvDB; HIX0005742; -.
DR H-InvDB; HIX0166115; -.
DR H-InvDB; HIX0166390; -.
DR H-InvDB; HIX0166908; -.
DR H-InvDB; HIX0167165; -.
DR H-InvDB; HIX0167404; -.
DR HGNC; HGNC:10898; SKIV2L.
DR HPA; HPA051959; -.
DR HPA; HPA054419; -.
DR MIM; 600478; gene.
DR MIM; 614602; phenotype.
DR neXtProt; NX_Q15477; -.
DR Orphanet; 84064; Syndromic diarrhea.
DR PharmGKB; PA35798; -.
DR eggNOG; COG4581; -.
DR HOGENOM; HOG000163048; -.
DR HOVERGEN; HBG060025; -.
DR InParanoid; Q15477; -.
DR KO; K12599; -.
DR OMA; KICERDM; -.
DR PhylomeDB; Q15477; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; SKIV2L; human.
DR GeneWiki; SKIV2L; -.
DR GenomeRNAi; 6499; -.
DR NextBio; 25263; -.
DR PRO; PR:Q15477; -.
DR ArrayExpress; Q15477; -.
DR Bgee; Q15477; -.
DR CleanEx; HS_SKIV2L; -.
DR Genevestigator; Q15477; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0055087; C:Ski complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004004; F:ATP-dependent RNA helicase activity; TAS:ProtInc.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR InterPro; IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
DR InterPro; IPR012961; DSH_C.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR016438; RNA_helicase_ATP-dep_SK12/DOB1.
DR InterPro; IPR025696; rRNA_proc-arch_dom.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF08148; DSHCT; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF13234; rRNA_proc-arch; 2.
DR PIRSF; PIRSF005198; Antiviral_helicase_SKI2; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 3.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Complete proteome; Cytoplasm; Disease mutation; Helicase;
KW Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; RNA-binding.
FT CHAIN 1 1246 Helicase SKI2W.
FT /FTId=PRO_0000102091.
FT DOMAIN 319 475 Helicase ATP-binding.
FT DOMAIN 585 755 Helicase C-terminal.
FT NP_BIND 332 339 ATP (Potential).
FT MOTIF 423 426 DEVH box.
FT MOD_RES 245 245 Phosphoserine.
FT MOD_RES 256 256 Phosphoserine.
FT VARIANT 151 151 Q -> R (in dbSNP:rs438999).
FT /FTId=VAR_060379.
FT VARIANT 183 183 L -> V (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035944.
FT VARIANT 214 214 M -> L (in dbSNP:rs437179).
FT /FTId=VAR_060380.
FT VARIANT 324 324 R -> W (in dbSNP:rs36038685).
FT /FTId=VAR_055888.
FT VARIANT 341 341 V -> G (in THES2; dbSNP:rs281875237).
FT /FTId=VAR_067721.
FT VARIANT 765 765 M -> I (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_035945.
FT VARIANT 887 887 D -> N (in dbSNP:rs3911893).
FT /FTId=VAR_055889.
FT VARIANT 917 917 V -> M (in dbSNP:rs106287).
FT /FTId=VAR_055890.
FT VARIANT 1071 1071 A -> V (in dbSNP:rs449643).
FT /FTId=VAR_055891.
FT VARIANT 1153 1153 G -> R (in dbSNP:rs2734329).
FT /FTId=VAR_060381.
FT VARIANT 1238 1238 V -> G (in dbSNP:rs2746400).
FT /FTId=VAR_060382.
FT CONFLICT 366 366 S -> T (in Ref. 1; AAB52523).
FT CONFLICT 623 623 H -> Q (in Ref. 2; CAA88733).
FT CONFLICT 1052 1052 L -> F (in Ref. 2; CAA88733).
SQ SEQUENCE 1246 AA; 137755 MW; 9F00097BA83A4AEC CRC64;
MMETERLVLP PPDPLDLPLR AVELGCTGHW ELLNLPGAPE SSLPHGLPPC APDLQQEAEQ
LFLSSPAWLP LHGVEHSARK WQRKTDPWSL LAVLGAPVPS DLQAQRHPTT GQILGYKEVL
LENTNLSATT SLSLRRPPGP ASQSLWGNPT QYPFWPGGMD EPTITDLNTR EEAEEEIDFE
KDLLTIPPGF KKGMDFAPKD CPTPAPGLLS LSCMLEPLDL GGGDEDENEA VGQPGGPRGD
TVSASPCSAP LARASSLEDL VLKEASTAVS TPEAPEPPSQ EQWAIPVDAT SPVGDFYRLI
PQPAFQWAFE PDVFQKQAIL HLERHDSVFV AAHTSAGKTV VAEYAIALAQ KHMTRTIYTS
PIKALSNQKF RDFRNTFGDV GLLTGDVQLH PEASCLIMTT EILRSMLYSG SDVIRDLEWV
IFDEVHYIND VERGVVWEEV LIMLPDHVSI ILLSATVPNA LEFADWIGRL KRRQIYVIST
VTRPVPLEHY LFTGNSSKTQ GELFLLLDSR GAFHTKGYYA AVEAKKERMS KHAQTFGAKQ
PTHQGGPAQD RGVYLSLLAS LRTRAQLPVV VFTFSRGRCD EQASGLTSLD LTTSSEKSEI
HLFLQRCLAR LRGSDRQLPQ VLHMSELLNR GLGVHHSGIL PILKEIVEML FSRGLVKVLF
ATETFAMGVN MPARTVVFDS MRKHDGSTFR DLLPGEYVQM AGRAGRRGLD PTGTVILLCK
GRVPEMADLH RMMMGKPSQL QSQFRLTYTM ILNLLRVDAL RVEDMMKRSF SEFPSRKDSK
AHEQALAELT KRLGALEEPD MTGQLVDLPE YYSWGEELTE TQHMIQRRIM ESVNGLKSLS
AGRVVVVKNQ EHHNALGVIL QVSSNSTSRV FTTLVLCDKP LSQDPQDRGP ATAEVPYPDD
LVGFKLFLPE GPCDHTVVKL QPGDMAAITT KVLRVNGEKI LEDFSKRQQP KFKKDPPLAA
VTTAVQELLR LAQAHPAGPP TLDPVNDLQL KDMSVVEGGL RARKLEELIQ GAQCVHSPRF
PAQYLKLRER MQIQKEMERL RFLLSDQSLL LLPEYHQRVE VLRTLGYVDE AGTVKLAGRV
ACAMSSHELL LTELMFDNAL STLRPEEIAA LLSGLVCQSP GDAGDQLPNT LKQGIERVRA
VAKRIGEVQV ACGLNQTVEE FVGELNFGLV EVVYEWARGM PFSELAGLSG TPEGLVVRCI
QRLAEMCRSL RGAARLVGEP VLGAKMETAA TLLRRDIVFA ASLYTQ
//
ID SKIV2_HUMAN Reviewed; 1246 AA.
AC Q15477; O15005; Q12902; Q15476; Q5ST66;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-NOV-2010, sequence version 3.
DT 22-JAN-2014, entry version 133.
DE RecName: Full=Helicase SKI2W;
DE Short=Ski2;
DE EC=3.6.4.-;
DE AltName: Full=Helicase-like protein;
DE Short=HLP;
GN Name=SKIV2L; Synonyms=DDX13, SKI2W, SKIV2, W;
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].
RC TISSUE=Liver;
RX PubMed=7759100; DOI=10.1016/0888-7543(95)80008-A;
RA Lee S.-G., Lee I., Park S.H., Kang C., Song K.;
RT "Identification and characterization of a human cDNA homologous to
RT yeast SKI2.";
RL Genomics 25:660-666(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANTS ARG-151 AND
RP LEU-214.
RX PubMed=7610041; DOI=10.1093/nar/23.12.2120;
RA Dangel A.W., Shen L., Mendoza A.R., Wu L.-C., Yu C.Y.;
RT "Human helicase gene SKI2W in the HLA class III region exhibits
RT striking structural similarities to the yeast antiviral gene SKI2 and
RT to the human gene KIAA0052: emergence of a new gene family.";
RL Nucleic Acids Res. 23:2120-2126(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-214.
RX PubMed=8812450; DOI=10.1006/geno.1996.0459;
RA Albertella M.R., Jones H., Thomson W., Olavesen M.G., Campbell R.D.;
RT "Localization of eight additional genes in the human major
RT histocompatibility complex, including the gene encoding the casein
RT kinase II beta subunit (CSNK2B).";
RL Genomics 36:240-251(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-151; LEU-214;
RP MET-917 AND VAL-1071.
RA Rowen L., Dankers C., Baskin D., Faust J., Loretz C., Ahearn M.E.,
RA Banta A., Swartzell S., Smith T.M., Spies T., Hood L.;
RT "Sequence determination of 300 kilobases of the human class III MHC
RT locus.";
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [6]
RP IDENTIFICATION IN THE SKI COMPLEX.
RX PubMed=16024656; DOI=10.1101/gad.1292105;
RA Zhu B., Mandal S.S., Pham A.D., Zheng Y., Erdjument-Bromage H.,
RA Batra S.K., Tempst P., Reinberg D.;
RT "The human PAF complex coordinates transcription with events
RT downstream of RNA synthesis.";
RL Genes Dev. 19:1668-1673(2005).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-245, AND MASS
RP SPECTROMETRY.
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-256, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-183 AND ILE-765.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
RN [18]
RP VARIANT THES2 GLY-341.
RX PubMed=22444670; DOI=10.1016/j.ajhg.2012.02.009;
RA Fabre A., Charroux B., Martinez-Vinson C., Roquelaure B., Odul E.,
RA Sayar E., Smith H., Colomb V., Andre N., Hugot J.P., Goulet O.,
RA Lacoste C., Sarles J., Royet J., Levy N., Badens C.;
RT "SKIV2L mutations cause syndromic diarrhea, or trichohepatoenteric
RT syndrome.";
RL Am. J. Hum. Genet. 90:689-692(2012).
CC -!- FUNCTION: Helicase; has ATPase activity. Component of the SKI
CC complex which is thought to be involved in exosome-mediated RNA
CC decay and associates with transcriptionally active genes in a
CC manner dependent on PAF1 complex (PAF1C).
CC -!- SUBUNIT: Component of the SKI complex which consists of WDR61,
CC SKIV2L and TTC37.
CC -!- SUBCELLULAR LOCATION: Nucleus (Probable). Cytoplasm (Probable).
CC -!- DISEASE: Trichohepatoenteric syndrome 2 (THES2) [MIM:614602]: A
CC syndrome characterized by intrauterine growth retardation, severe
CC diarrhea in infancy requiring total parenteral nutrition, facial
CC dysmorphism, immunodeficiency, and hair abnormalities, mostly
CC trichorrhexis nodosa. Hepatic involvement contributes to the poor
CC prognosis of affected patients. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the helicase family. SKI2 subfamily.
CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain.
CC -!- SIMILARITY: Contains 1 helicase C-terminal domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB52523.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC -----------------------------------------------------------------------
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DR EMBL; U09877; AAB52523.1; ALT_INIT; mRNA.
DR EMBL; X98378; CAA67024.1; -; Genomic_DNA.
DR EMBL; Z48796; CAA88733.1; -; mRNA.
DR EMBL; AF019413; AAB67978.1; -; Genomic_DNA.
DR EMBL; AL662849; CAI17460.1; -; Genomic_DNA.
DR EMBL; AL645922; CAQ09280.1; -; Genomic_DNA.
DR PIR; S56752; S56752.
DR RefSeq; NP_008860.4; NM_006929.4.
DR UniGene; Hs.89864; -.
DR ProteinModelPortal; Q15477; -.
DR SMR; Q15477; 280-836, 1018-1244.
DR IntAct; Q15477; 10.
DR STRING; 9606.ENSP00000394400; -.
DR PhosphoSite; Q15477; -.
DR DMDM; 3123284; -.
DR PaxDb; Q15477; -.
DR PRIDE; Q15477; -.
DR DNASU; 6499; -.
DR Ensembl; ENST00000375394; ENSP00000364543; ENSG00000204351.
DR Ensembl; ENST00000383336; ENSP00000372827; ENSG00000206353.
DR Ensembl; ENST00000412823; ENSP00000400626; ENSG00000232616.
DR Ensembl; ENST00000421789; ENSP00000399530; ENSG00000228896.
DR Ensembl; ENST00000429465; ENSP00000412310; ENSG00000223493.
DR Ensembl; ENST00000448219; ENSP00000394400; ENSG00000225737.
DR GeneID; 6499; -.
DR KEGG; hsa:6499; -.
DR UCSC; uc003nyn.1; human.
DR CTD; 6499; -.
DR GeneCards; GC06P031926; -.
DR GeneCards; GC06Pj31914; -.
DR GeneCards; GC06Pk31908; -.
DR GeneCards; GC06Pm32003; -.
DR GeneCards; GC06Pn31916; -.
DR GeneCards; GC06Po31918; -.
DR H-InvDB; HIX0005742; -.
DR H-InvDB; HIX0166115; -.
DR H-InvDB; HIX0166390; -.
DR H-InvDB; HIX0166908; -.
DR H-InvDB; HIX0167165; -.
DR H-InvDB; HIX0167404; -.
DR HGNC; HGNC:10898; SKIV2L.
DR HPA; HPA051959; -.
DR HPA; HPA054419; -.
DR MIM; 600478; gene.
DR MIM; 614602; phenotype.
DR neXtProt; NX_Q15477; -.
DR Orphanet; 84064; Syndromic diarrhea.
DR PharmGKB; PA35798; -.
DR eggNOG; COG4581; -.
DR HOGENOM; HOG000163048; -.
DR HOVERGEN; HBG060025; -.
DR InParanoid; Q15477; -.
DR KO; K12599; -.
DR OMA; KICERDM; -.
DR PhylomeDB; Q15477; -.
DR Reactome; REACT_17015; Metabolism of proteins.
DR ChiTaRS; SKIV2L; human.
DR GeneWiki; SKIV2L; -.
DR GenomeRNAi; 6499; -.
DR NextBio; 25263; -.
DR PRO; PR:Q15477; -.
DR ArrayExpress; Q15477; -.
DR Bgee; Q15477; -.
DR CleanEx; HS_SKIV2L; -.
DR Genevestigator; Q15477; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0055087; C:Ski complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004004; F:ATP-dependent RNA helicase activity; TAS:ProtInc.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR InterPro; IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
DR InterPro; IPR012961; DSH_C.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR016438; RNA_helicase_ATP-dep_SK12/DOB1.
DR InterPro; IPR025696; rRNA_proc-arch_dom.
DR Pfam; PF00270; DEAD; 1.
DR Pfam; PF08148; DSHCT; 1.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF13234; rRNA_proc-arch; 2.
DR PIRSF; PIRSF005198; Antiviral_helicase_SKI2; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 3.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Complete proteome; Cytoplasm; Disease mutation; Helicase;
KW Hydrolase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; RNA-binding.
FT CHAIN 1 1246 Helicase SKI2W.
FT /FTId=PRO_0000102091.
FT DOMAIN 319 475 Helicase ATP-binding.
FT DOMAIN 585 755 Helicase C-terminal.
FT NP_BIND 332 339 ATP (Potential).
FT MOTIF 423 426 DEVH box.
FT MOD_RES 245 245 Phosphoserine.
FT MOD_RES 256 256 Phosphoserine.
FT VARIANT 151 151 Q -> R (in dbSNP:rs438999).
FT /FTId=VAR_060379.
FT VARIANT 183 183 L -> V (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035944.
FT VARIANT 214 214 M -> L (in dbSNP:rs437179).
FT /FTId=VAR_060380.
FT VARIANT 324 324 R -> W (in dbSNP:rs36038685).
FT /FTId=VAR_055888.
FT VARIANT 341 341 V -> G (in THES2; dbSNP:rs281875237).
FT /FTId=VAR_067721.
FT VARIANT 765 765 M -> I (in a colorectal cancer sample;
FT somatic mutation).
FT /FTId=VAR_035945.
FT VARIANT 887 887 D -> N (in dbSNP:rs3911893).
FT /FTId=VAR_055889.
FT VARIANT 917 917 V -> M (in dbSNP:rs106287).
FT /FTId=VAR_055890.
FT VARIANT 1071 1071 A -> V (in dbSNP:rs449643).
FT /FTId=VAR_055891.
FT VARIANT 1153 1153 G -> R (in dbSNP:rs2734329).
FT /FTId=VAR_060381.
FT VARIANT 1238 1238 V -> G (in dbSNP:rs2746400).
FT /FTId=VAR_060382.
FT CONFLICT 366 366 S -> T (in Ref. 1; AAB52523).
FT CONFLICT 623 623 H -> Q (in Ref. 2; CAA88733).
FT CONFLICT 1052 1052 L -> F (in Ref. 2; CAA88733).
SQ SEQUENCE 1246 AA; 137755 MW; 9F00097BA83A4AEC CRC64;
MMETERLVLP PPDPLDLPLR AVELGCTGHW ELLNLPGAPE SSLPHGLPPC APDLQQEAEQ
LFLSSPAWLP LHGVEHSARK WQRKTDPWSL LAVLGAPVPS DLQAQRHPTT GQILGYKEVL
LENTNLSATT SLSLRRPPGP ASQSLWGNPT QYPFWPGGMD EPTITDLNTR EEAEEEIDFE
KDLLTIPPGF KKGMDFAPKD CPTPAPGLLS LSCMLEPLDL GGGDEDENEA VGQPGGPRGD
TVSASPCSAP LARASSLEDL VLKEASTAVS TPEAPEPPSQ EQWAIPVDAT SPVGDFYRLI
PQPAFQWAFE PDVFQKQAIL HLERHDSVFV AAHTSAGKTV VAEYAIALAQ KHMTRTIYTS
PIKALSNQKF RDFRNTFGDV GLLTGDVQLH PEASCLIMTT EILRSMLYSG SDVIRDLEWV
IFDEVHYIND VERGVVWEEV LIMLPDHVSI ILLSATVPNA LEFADWIGRL KRRQIYVIST
VTRPVPLEHY LFTGNSSKTQ GELFLLLDSR GAFHTKGYYA AVEAKKERMS KHAQTFGAKQ
PTHQGGPAQD RGVYLSLLAS LRTRAQLPVV VFTFSRGRCD EQASGLTSLD LTTSSEKSEI
HLFLQRCLAR LRGSDRQLPQ VLHMSELLNR GLGVHHSGIL PILKEIVEML FSRGLVKVLF
ATETFAMGVN MPARTVVFDS MRKHDGSTFR DLLPGEYVQM AGRAGRRGLD PTGTVILLCK
GRVPEMADLH RMMMGKPSQL QSQFRLTYTM ILNLLRVDAL RVEDMMKRSF SEFPSRKDSK
AHEQALAELT KRLGALEEPD MTGQLVDLPE YYSWGEELTE TQHMIQRRIM ESVNGLKSLS
AGRVVVVKNQ EHHNALGVIL QVSSNSTSRV FTTLVLCDKP LSQDPQDRGP ATAEVPYPDD
LVGFKLFLPE GPCDHTVVKL QPGDMAAITT KVLRVNGEKI LEDFSKRQQP KFKKDPPLAA
VTTAVQELLR LAQAHPAGPP TLDPVNDLQL KDMSVVEGGL RARKLEELIQ GAQCVHSPRF
PAQYLKLRER MQIQKEMERL RFLLSDQSLL LLPEYHQRVE VLRTLGYVDE AGTVKLAGRV
ACAMSSHELL LTELMFDNAL STLRPEEIAA LLSGLVCQSP GDAGDQLPNT LKQGIERVRA
VAKRIGEVQV ACGLNQTVEE FVGELNFGLV EVVYEWARGM PFSELAGLSG TPEGLVVRCI
QRLAEMCRSL RGAARLVGEP VLGAKMETAA TLLRRDIVFA ASLYTQ
//
MIM
600478
*RECORD*
*FIELD* NO
600478
*FIELD* TI
*600478 SUPERKILLER VIRALICIDIC ACTIVITY 2, S. CEREVISIAE, HOMOLOG-LIKE; SKIV2L
;;SKI2, S. CEREVISIAE, HOMOLOG OF; SKI2;;
read moreSKI2W
*FIELD* TX
CLONING
Lee et al. (1995) identified a human cDNA with sequence homology to the
yeast nucleolar protein gene SKI2. SKI2 belongs to a group of 6 yeast
genes that repress the copy number of single- and double-stranded RNA
viruses. Lee et al. (1995) identified the cDNA by immunoscreening an
expression library with a monoclonal antibody raised against bovine
pigmented retinal cells. The antibody recognizes a 90-kD nuclear antigen
in a number of species.
Helicases are involved in DNA replication, DNA repair, recombination,
transcription, RNA splicing, and translation. Dangel et al. (1995)
cloned a putative human helicase, which they designated SKI2W, that is
located between the RD gene (154040) and a gene they called RP1 (D6S60E;
see Shen et al., 1994) in the class III region of the major
histocompatibility complex on chromosome 6. The gene occurs within an
approximately 11-kb span between RD and RP1. The cDNA was isolated from
a set of lymphocyte libraries and the predicted 1,246-amino acid protein
(137 kD) contains motifs associated with RNA helicases and has a leucine
zipper domain. The protein shares extensive similarity (39% identity) to
the yeast Ski2p gene which is involved in the inhibition of translation
of non-polyadenylated RNA and has an important role in defense against
infection by single- and double-stranded RNA viruses. The authors showed
that the recombinant SKI2W protein exhibits ATPase activity. Northern
blots indicated a 3.9-kb transcript in a variety of human transformed
lines. Dangel et al. (1995) stated that this gene was very similar in
sequence to that reported by Lee et al. (1995) and that discrepancies
between the 2 sequences were probably the result of cloning artifacts.
Inherently unstable mammalian mRNAs contain AU-rich elements (AREs)
within their 3-prime untranslated regions. In yeast, 3-prime-to-5-prime
mRNA degradation is mediated by the exosome, a multisubunit particle.
Chen et al. (2001) purified and characterized the human exosome by mass
spectrometry and found its composition to be similar to its yeast
counterpart. They identified the following protein subunits within the
human exosome: p7, which is homologous to the yeast Rrp4 protein
(602238); p8, which is homologous to the yeast Rrp42 protein (606488);
p9, which is homologous to the yeast Rrp43 protein (OIP2; 606019); p10,
which is homologous to the yeast Rrp40 protein (606489); p11, which is
homologous to the yeast Mtr3 protein (606490); p12A, which is homologous
to the yeast Rrp41 protein (606491); p12B, which is homologous to the
yeast Rrp46 protein (606492); and p13, which is homologous to the yeast
Csl4 protein (606493). They also identified 2 exosome-associated
factors, p1 (SKIV2L) and p14 (MPP6; 605500), that were not homologous to
any yeast exosome components.
GENE STRUCTURE
By genomic sequence analysis, Yang et al. (1998) determined that SKIV2L
is a polymorphic gene that spans 11 kb and contains 28 exons.
MAPPING
Lee et al. (1995) isolated genomic clones and mapped the human homolog
of SKI2 gene to 6p21 by fluorescence in situ hybridization. By genomic
sequence analysis, Yang et al. (1998) determined that the SKIV2L gene is
located 171 bp downstream from the RD gene.
GENE FUNCTION
Using a cell-free RNA decay system, Chen et al. (2001) demonstrated that
the mammalian exosome is required for rapid degradation of
ARE-containing RNAs but not for poly(A) shortening. They found that the
mammalian exosome does not recognize ARE-containing RNAs on its own. ARE
recognition required certain ARE-binding proteins that could interact
with the exosome and recruit it to unstable RNAs, thereby promoting
their rapid degradation.
MOLECULAR GENETICS
In 6 unrelated patients with typical trichohepatoenteric syndrome
(THES2; 614602) who were known to be negative for mutation in the TTC37
gene (614589), Fabre et al. (2012) sequenced the candidate gene SKIV2L
and identified homozygosity or compound heterozygosity for 8 different
mutations, respectively, in all patients (see, e.g.,
600478.0001-600478.0003). All of the unaffected parents available for
analysis were heterozygous for 1 of the mutations identified in their
child.
*FIELD* AV
.0001
TRICHOHEPATOENTERIC SYNDROME 2
SKIV2L, TRP283TER
In a French patient with trichohepatoenteric syndrome (THES2; 614602),
Fabre et al. (2012) identified compound heterozygosity for an 848G-A
transition in the SKIV2L gene, resulting in a trp283-to-ter (W283X)
substitution, and a 1022T-G transversion, resulting in a val341-to-gly
(V341G; 600478.0002) substitution.
.0002
TRICHOHEPATOENTERIC SYNDROME 2
SKIV2L, VAL341GLY
See 600478.0001 and Fabre et al. (2012).
.0003
TRICHOHEPATOENTERIC SYNDROME 2
SKIV2L, 1-BP INS, 1635A
In a North African patient with trichohepatoenteric syndrome-2 (614602),
Fabre et al. (2012) identified homozygosity for a 1-bp insertion
(1635insA) in the SKIV2L gene, causing a frameshift predicted to result
in a premature termination codon.
*FIELD* RF
1. Chen, C.-Y.; Gherzi, R.; Ong, S.-E.; Chan, E. L.; Raijmakers, R.;
Pruijn, G. J. M.; Stoecklin, G.; Moroni, C.; Mann, M.; Karin, M.:
AU binding proteins recruit the exosome to degrade ARE-containing
mRNAs. Cell 107: 451-464, 2001.
2. Dangel, A. W.; Shen, L.; Mendoza, A. R.; Wu, L.-c.; Yu, C. Y.:
Human helicase gene SKI2W in the HLA class III region exhibits striking
structural similarities to the yeast antiviral gene SKI2 and to the
human gene KIAA0052: emergence of a new gene family. Nucleic Acids
Res. 23: 2120-2126, 1995.
3. Fabre, A.; Charroux, B.; Martinez-Vinson, C.; Roquelaure, B.; Odul,
E.; Sayar, E.; Smith, H.; Colomb, V.; Andre, N.; Hugot, J.-P.; Goulet,
O.; Lacoste, C.; Sarles, J.; Royet, J.; Levy, N.; Badens, C.: SKIV2L
mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am.
J. Hum. Genet. 90: 689-692, 2012.
4. Lee, S.-G.; Lee, I.; Park, S. H.; Kang, C.; Song, K.: Identification
and characterization of a human cDNA homologous to yeast SKI2. Genomics 25:
660-666, 1995.
5. Shen, L.; Wu, L. C.; Sanlioglu, S.; Chen, R.; Mendoza, A. R.; Dangel,
A. W.; Carroll, M. C.; Zipf, W. B.; Yu, C. Y.: Structure and genetics
of the partially duplicated gene RP located immediately upstream of
the complement C4A and the C4B genes in the HLA class III region:
molecular cloning, exon-intron structure, composite retroposon, and
breakpoint of gene duplication. J. Biol. Chem. 269: 8466-8476, 1994.
6. Yang, Z.; Shen, L.; Dangel, A. W.; Wu, L.-C.; Yu, C. Y.: Four
ubiquitously expressed genes, RD (D6S45)-SKI2W (SKIV2L)-DOM3Z-RP1
(D6S60E), are present between complement component genes factor B
and C4 in the class III region of the HLA. Genomics 53: 338-347,
1998.
*FIELD* CN
Marla J. F. O'Neill - updated: 04/27/2012
Stylianos E. Antonarakis - updated: 11/26/2001
Paul J. Converse - updated: 6/6/2001
Alan F. Scott - updated: 11/7/1995
*FIELD* CD
Victor A. McKusick: 4/1/1995
*FIELD* ED
carol: 04/27/2012
mgross: 11/26/2001
mgross: 6/7/2001
terry: 6/6/2001
psherman: 5/20/1998
jamie: 2/12/1997
terry: 4/17/1996
mark: 3/25/1996
mark: 7/11/1995
mark: 4/24/1995
mark: 4/4/1995
mark: 4/1/1995
*RECORD*
*FIELD* NO
600478
*FIELD* TI
*600478 SUPERKILLER VIRALICIDIC ACTIVITY 2, S. CEREVISIAE, HOMOLOG-LIKE; SKIV2L
;;SKI2, S. CEREVISIAE, HOMOLOG OF; SKI2;;
read moreSKI2W
*FIELD* TX
CLONING
Lee et al. (1995) identified a human cDNA with sequence homology to the
yeast nucleolar protein gene SKI2. SKI2 belongs to a group of 6 yeast
genes that repress the copy number of single- and double-stranded RNA
viruses. Lee et al. (1995) identified the cDNA by immunoscreening an
expression library with a monoclonal antibody raised against bovine
pigmented retinal cells. The antibody recognizes a 90-kD nuclear antigen
in a number of species.
Helicases are involved in DNA replication, DNA repair, recombination,
transcription, RNA splicing, and translation. Dangel et al. (1995)
cloned a putative human helicase, which they designated SKI2W, that is
located between the RD gene (154040) and a gene they called RP1 (D6S60E;
see Shen et al., 1994) in the class III region of the major
histocompatibility complex on chromosome 6. The gene occurs within an
approximately 11-kb span between RD and RP1. The cDNA was isolated from
a set of lymphocyte libraries and the predicted 1,246-amino acid protein
(137 kD) contains motifs associated with RNA helicases and has a leucine
zipper domain. The protein shares extensive similarity (39% identity) to
the yeast Ski2p gene which is involved in the inhibition of translation
of non-polyadenylated RNA and has an important role in defense against
infection by single- and double-stranded RNA viruses. The authors showed
that the recombinant SKI2W protein exhibits ATPase activity. Northern
blots indicated a 3.9-kb transcript in a variety of human transformed
lines. Dangel et al. (1995) stated that this gene was very similar in
sequence to that reported by Lee et al. (1995) and that discrepancies
between the 2 sequences were probably the result of cloning artifacts.
Inherently unstable mammalian mRNAs contain AU-rich elements (AREs)
within their 3-prime untranslated regions. In yeast, 3-prime-to-5-prime
mRNA degradation is mediated by the exosome, a multisubunit particle.
Chen et al. (2001) purified and characterized the human exosome by mass
spectrometry and found its composition to be similar to its yeast
counterpart. They identified the following protein subunits within the
human exosome: p7, which is homologous to the yeast Rrp4 protein
(602238); p8, which is homologous to the yeast Rrp42 protein (606488);
p9, which is homologous to the yeast Rrp43 protein (OIP2; 606019); p10,
which is homologous to the yeast Rrp40 protein (606489); p11, which is
homologous to the yeast Mtr3 protein (606490); p12A, which is homologous
to the yeast Rrp41 protein (606491); p12B, which is homologous to the
yeast Rrp46 protein (606492); and p13, which is homologous to the yeast
Csl4 protein (606493). They also identified 2 exosome-associated
factors, p1 (SKIV2L) and p14 (MPP6; 605500), that were not homologous to
any yeast exosome components.
GENE STRUCTURE
By genomic sequence analysis, Yang et al. (1998) determined that SKIV2L
is a polymorphic gene that spans 11 kb and contains 28 exons.
MAPPING
Lee et al. (1995) isolated genomic clones and mapped the human homolog
of SKI2 gene to 6p21 by fluorescence in situ hybridization. By genomic
sequence analysis, Yang et al. (1998) determined that the SKIV2L gene is
located 171 bp downstream from the RD gene.
GENE FUNCTION
Using a cell-free RNA decay system, Chen et al. (2001) demonstrated that
the mammalian exosome is required for rapid degradation of
ARE-containing RNAs but not for poly(A) shortening. They found that the
mammalian exosome does not recognize ARE-containing RNAs on its own. ARE
recognition required certain ARE-binding proteins that could interact
with the exosome and recruit it to unstable RNAs, thereby promoting
their rapid degradation.
MOLECULAR GENETICS
In 6 unrelated patients with typical trichohepatoenteric syndrome
(THES2; 614602) who were known to be negative for mutation in the TTC37
gene (614589), Fabre et al. (2012) sequenced the candidate gene SKIV2L
and identified homozygosity or compound heterozygosity for 8 different
mutations, respectively, in all patients (see, e.g.,
600478.0001-600478.0003). All of the unaffected parents available for
analysis were heterozygous for 1 of the mutations identified in their
child.
*FIELD* AV
.0001
TRICHOHEPATOENTERIC SYNDROME 2
SKIV2L, TRP283TER
In a French patient with trichohepatoenteric syndrome (THES2; 614602),
Fabre et al. (2012) identified compound heterozygosity for an 848G-A
transition in the SKIV2L gene, resulting in a trp283-to-ter (W283X)
substitution, and a 1022T-G transversion, resulting in a val341-to-gly
(V341G; 600478.0002) substitution.
.0002
TRICHOHEPATOENTERIC SYNDROME 2
SKIV2L, VAL341GLY
See 600478.0001 and Fabre et al. (2012).
.0003
TRICHOHEPATOENTERIC SYNDROME 2
SKIV2L, 1-BP INS, 1635A
In a North African patient with trichohepatoenteric syndrome-2 (614602),
Fabre et al. (2012) identified homozygosity for a 1-bp insertion
(1635insA) in the SKIV2L gene, causing a frameshift predicted to result
in a premature termination codon.
*FIELD* RF
1. Chen, C.-Y.; Gherzi, R.; Ong, S.-E.; Chan, E. L.; Raijmakers, R.;
Pruijn, G. J. M.; Stoecklin, G.; Moroni, C.; Mann, M.; Karin, M.:
AU binding proteins recruit the exosome to degrade ARE-containing
mRNAs. Cell 107: 451-464, 2001.
2. Dangel, A. W.; Shen, L.; Mendoza, A. R.; Wu, L.-c.; Yu, C. Y.:
Human helicase gene SKI2W in the HLA class III region exhibits striking
structural similarities to the yeast antiviral gene SKI2 and to the
human gene KIAA0052: emergence of a new gene family. Nucleic Acids
Res. 23: 2120-2126, 1995.
3. Fabre, A.; Charroux, B.; Martinez-Vinson, C.; Roquelaure, B.; Odul,
E.; Sayar, E.; Smith, H.; Colomb, V.; Andre, N.; Hugot, J.-P.; Goulet,
O.; Lacoste, C.; Sarles, J.; Royet, J.; Levy, N.; Badens, C.: SKIV2L
mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am.
J. Hum. Genet. 90: 689-692, 2012.
4. Lee, S.-G.; Lee, I.; Park, S. H.; Kang, C.; Song, K.: Identification
and characterization of a human cDNA homologous to yeast SKI2. Genomics 25:
660-666, 1995.
5. Shen, L.; Wu, L. C.; Sanlioglu, S.; Chen, R.; Mendoza, A. R.; Dangel,
A. W.; Carroll, M. C.; Zipf, W. B.; Yu, C. Y.: Structure and genetics
of the partially duplicated gene RP located immediately upstream of
the complement C4A and the C4B genes in the HLA class III region:
molecular cloning, exon-intron structure, composite retroposon, and
breakpoint of gene duplication. J. Biol. Chem. 269: 8466-8476, 1994.
6. Yang, Z.; Shen, L.; Dangel, A. W.; Wu, L.-C.; Yu, C. Y.: Four
ubiquitously expressed genes, RD (D6S45)-SKI2W (SKIV2L)-DOM3Z-RP1
(D6S60E), are present between complement component genes factor B
and C4 in the class III region of the HLA. Genomics 53: 338-347,
1998.
*FIELD* CN
Marla J. F. O'Neill - updated: 04/27/2012
Stylianos E. Antonarakis - updated: 11/26/2001
Paul J. Converse - updated: 6/6/2001
Alan F. Scott - updated: 11/7/1995
*FIELD* CD
Victor A. McKusick: 4/1/1995
*FIELD* ED
carol: 04/27/2012
mgross: 11/26/2001
mgross: 6/7/2001
terry: 6/6/2001
psherman: 5/20/1998
jamie: 2/12/1997
terry: 4/17/1996
mark: 3/25/1996
mark: 7/11/1995
mark: 4/24/1995
mark: 4/4/1995
mark: 4/1/1995
MIM
614602
*RECORD*
*FIELD* NO
614602
*FIELD* TI
#614602 TRICHOHEPATOENTERIC SYNDROME 2; THES2
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moretrichohepatoenteric syndrome-2 (THES2) is caused by homozygous or
compound heterozygous mutation in the SKIV2L gene (600478) on chromosome
6p21.3.
DESCRIPTION
Trichohepatoenteric syndrome (THES) is a rare and severe disease
characterized by intrauterine growth retardation, facial dysmorphism,
hair abnormalities, intractable diarrhea, and immunodeficiency (summary
by Fabre et al., 2012).
- Genetic Heterogeneity of Trichohepatoenteric Syndrome
For a discussion of genetic heterogeneity of trichohepatoenteric
syndrome, see THES1 (222470).
CLINICAL FEATURES
Egritas et al. (2009) reported a 4.5-year-old Turkish girl who was small
for gestational age at preterm birth (32 weeks) and developed
intractable mucoid and occasionally bloody diarrhea within the first 3
months of life. Examination revealed low hairline, poorly pigmented
woolly hair, facial dysmorphism including square forehead, prominent
cheeks, and a broad nasal root, and hepatomegaly. Microscopic hair
examination showed trichorrhexis nodosa. Laboratory evaluation revealed
hypochromic microcytic anemia compatible with iron deficiency, but liver
enzymes were normal and stool examination was unremarkable, as were
metabolic, glycosylation, chromosomal, and viral studies. Liver biopsy
showed nonspecific mild chronic hepatitis; upper and lower
gastrointestinal endoscopy was normal; and duodenal biopsy specimens
showed normal villous patterns, whereas colonic mucosal biopsies showed
cryptitis, cryptic abscesses, and polymorphonuclear and mononuclear
infiltration in the lamina propria, consistent with a diagnosis of
diffuse mild colitis with active-chronic inflammation. Egritas et al.
(2009) considered this patient to represent a case of THES. She had a
brother with cryptogenic liver disease who had no history of chronic
diarrhea, facial dysmorphism, or hair abnormalities. Their parents were
nonconsanguineous.
Fabre et al. (2012) studied 6 unrelated children with typical
trichohepatoenteric syndrome who were known to be negative for mutation
in the TTC37 gene (614589), including the Turkish girl originally
reported by Egritas et al. (2009). All 6 patients presented with severe
and intractable diarrhea that occurred between 1 and 12 weeks after
birth, hair abnormalities involving sparse, fragile, and uncombable
hair, and trichorrhexis nodosa, and facial dysmorphism characterized by
hypertelorism, broad flat nasal bridge, and prominent forehead. All
children received parenteral nutrition, but the amount of time varied
between individuals and ranged from a few weeks to several years.
Immunodeficiency was mostly due to low immunoglobulin levels and to the
absence of an immune response to vaccines. Fabre et al. (2012) noted
that the clinical presentation in these 6 patients was indistinguishable
from that of THES patients with mutation in TTC37 (see 222470).
MAPPING
In a consanguineous family with trichohepatoenteric syndrome, Fabre et
al. (2012) performed linkage analysis in which the TTC37 interval was
excluded, revealing instead a region of homozygosity on chromosome
6p24.3-p21.2.
MOLECULAR GENETICS
In 6 unrelated patients with typical trichohepatoenteric syndrome, Fabre
et al. (2012) sequenced the candidate gene SKIV2L (600478) and
identified homozygosity or compound heterozygosity for 8 different
mutations, respectively, in all patients (see, e.g.,
600478.0001-600478.0003). All of the unaffected parents available for
analysis were heterozygous for 1 of the mutations identified in their
child.
*FIELD* RF
1. Egritas, O.; Dalgic, B.; Onder, M.: Tricho-hepato-enteric syndrome
presenting with mild colitis. Europ. J. Pediat. 168: 933-935, 2009.
2. Fabre, A.; Charroux, B.; Martinez-Vinson, C.; Roquelaure, B.; Odul,
E.; Sayar, E.; Smith, H.; Colomb, V.; Andre, N.; Hugot, J.-P.; Goulet,
O.; Lacoste, C.; Sarles, J.; Royet, J.; Levy, N.; Badens, C.: SKIV2L
mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am.
J. Hum. Genet. 90: 689-692, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Decreased height;
[Weight];
Low birth weight;
[Other];
Failure to thrive;
Intrauterine growth retardation (IUGR)
HEAD AND NECK:
[Face];
Prominent forehead;
Square forehead;
Prominent cheeks;
[Eyes];
Hypertelorism;
[Nose];
Flat, broad nose
CARDIOVASCULAR:
[Heart];
Cardiac abnormalities
ABDOMEN:
[Liver];
Hepatomegaly;
Hepatitis, chronic, nonspecific;
Cirrhosis;
Iron deposition (in some patients);
[Gastrointestinal];
Diarrhea, severe and intractable;
Villous atrophy;
Colitis
SKIN, NAILS, HAIR:
[Hair];
Thin, sparse hair;
Uncombable hair;
Brittle hair;
Woolly hair;
Poorly pigmented hair;
Trichorrhexis nodosa
IMMUNOLOGY:
Immune deficiency
PRENATAL MANIFESTATIONS:
Intrauterine growth retardation
LABORATORY ABNORMALITIES:
Decreased serum iron (in some patients)
MISCELLANEOUS:
Onset in the first few months of life Patients may need lifelong total
parenteral nutrition
MOLECULAR BASIS:
Caused by mutation in the superkiller viralicidic activity 2-like,
S. cerevisiae homolog gene (SKIV2L, 600478.0001)
*FIELD* CD
Marla J. F. O'Neill: 5/1/2012
*FIELD* ED
joanna: 05/01/2012
*FIELD* CD
Marla J. F. O'Neill: 4/27/2012
*FIELD* ED
carol: 04/27/2012
carol: 4/27/2012
*RECORD*
*FIELD* NO
614602
*FIELD* TI
#614602 TRICHOHEPATOENTERIC SYNDROME 2; THES2
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
read moretrichohepatoenteric syndrome-2 (THES2) is caused by homozygous or
compound heterozygous mutation in the SKIV2L gene (600478) on chromosome
6p21.3.
DESCRIPTION
Trichohepatoenteric syndrome (THES) is a rare and severe disease
characterized by intrauterine growth retardation, facial dysmorphism,
hair abnormalities, intractable diarrhea, and immunodeficiency (summary
by Fabre et al., 2012).
- Genetic Heterogeneity of Trichohepatoenteric Syndrome
For a discussion of genetic heterogeneity of trichohepatoenteric
syndrome, see THES1 (222470).
CLINICAL FEATURES
Egritas et al. (2009) reported a 4.5-year-old Turkish girl who was small
for gestational age at preterm birth (32 weeks) and developed
intractable mucoid and occasionally bloody diarrhea within the first 3
months of life. Examination revealed low hairline, poorly pigmented
woolly hair, facial dysmorphism including square forehead, prominent
cheeks, and a broad nasal root, and hepatomegaly. Microscopic hair
examination showed trichorrhexis nodosa. Laboratory evaluation revealed
hypochromic microcytic anemia compatible with iron deficiency, but liver
enzymes were normal and stool examination was unremarkable, as were
metabolic, glycosylation, chromosomal, and viral studies. Liver biopsy
showed nonspecific mild chronic hepatitis; upper and lower
gastrointestinal endoscopy was normal; and duodenal biopsy specimens
showed normal villous patterns, whereas colonic mucosal biopsies showed
cryptitis, cryptic abscesses, and polymorphonuclear and mononuclear
infiltration in the lamina propria, consistent with a diagnosis of
diffuse mild colitis with active-chronic inflammation. Egritas et al.
(2009) considered this patient to represent a case of THES. She had a
brother with cryptogenic liver disease who had no history of chronic
diarrhea, facial dysmorphism, or hair abnormalities. Their parents were
nonconsanguineous.
Fabre et al. (2012) studied 6 unrelated children with typical
trichohepatoenteric syndrome who were known to be negative for mutation
in the TTC37 gene (614589), including the Turkish girl originally
reported by Egritas et al. (2009). All 6 patients presented with severe
and intractable diarrhea that occurred between 1 and 12 weeks after
birth, hair abnormalities involving sparse, fragile, and uncombable
hair, and trichorrhexis nodosa, and facial dysmorphism characterized by
hypertelorism, broad flat nasal bridge, and prominent forehead. All
children received parenteral nutrition, but the amount of time varied
between individuals and ranged from a few weeks to several years.
Immunodeficiency was mostly due to low immunoglobulin levels and to the
absence of an immune response to vaccines. Fabre et al. (2012) noted
that the clinical presentation in these 6 patients was indistinguishable
from that of THES patients with mutation in TTC37 (see 222470).
MAPPING
In a consanguineous family with trichohepatoenteric syndrome, Fabre et
al. (2012) performed linkage analysis in which the TTC37 interval was
excluded, revealing instead a region of homozygosity on chromosome
6p24.3-p21.2.
MOLECULAR GENETICS
In 6 unrelated patients with typical trichohepatoenteric syndrome, Fabre
et al. (2012) sequenced the candidate gene SKIV2L (600478) and
identified homozygosity or compound heterozygosity for 8 different
mutations, respectively, in all patients (see, e.g.,
600478.0001-600478.0003). All of the unaffected parents available for
analysis were heterozygous for 1 of the mutations identified in their
child.
*FIELD* RF
1. Egritas, O.; Dalgic, B.; Onder, M.: Tricho-hepato-enteric syndrome
presenting with mild colitis. Europ. J. Pediat. 168: 933-935, 2009.
2. Fabre, A.; Charroux, B.; Martinez-Vinson, C.; Roquelaure, B.; Odul,
E.; Sayar, E.; Smith, H.; Colomb, V.; Andre, N.; Hugot, J.-P.; Goulet,
O.; Lacoste, C.; Sarles, J.; Royet, J.; Levy, N.; Badens, C.: SKIV2L
mutations cause syndromic diarrhea, or trichohepatoenteric syndrome. Am.
J. Hum. Genet. 90: 689-692, 2012.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Decreased height;
[Weight];
Low birth weight;
[Other];
Failure to thrive;
Intrauterine growth retardation (IUGR)
HEAD AND NECK:
[Face];
Prominent forehead;
Square forehead;
Prominent cheeks;
[Eyes];
Hypertelorism;
[Nose];
Flat, broad nose
CARDIOVASCULAR:
[Heart];
Cardiac abnormalities
ABDOMEN:
[Liver];
Hepatomegaly;
Hepatitis, chronic, nonspecific;
Cirrhosis;
Iron deposition (in some patients);
[Gastrointestinal];
Diarrhea, severe and intractable;
Villous atrophy;
Colitis
SKIN, NAILS, HAIR:
[Hair];
Thin, sparse hair;
Uncombable hair;
Brittle hair;
Woolly hair;
Poorly pigmented hair;
Trichorrhexis nodosa
IMMUNOLOGY:
Immune deficiency
PRENATAL MANIFESTATIONS:
Intrauterine growth retardation
LABORATORY ABNORMALITIES:
Decreased serum iron (in some patients)
MISCELLANEOUS:
Onset in the first few months of life Patients may need lifelong total
parenteral nutrition
MOLECULAR BASIS:
Caused by mutation in the superkiller viralicidic activity 2-like,
S. cerevisiae homolog gene (SKIV2L, 600478.0001)
*FIELD* CD
Marla J. F. O'Neill: 5/1/2012
*FIELD* ED
joanna: 05/01/2012
*FIELD* CD
Marla J. F. O'Neill: 4/27/2012
*FIELD* ED
carol: 04/27/2012
carol: 4/27/2012