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Q8N138 (ORML3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 92. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ORM1-like protein 3
Gene names
Name:ORMDL3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length153 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Negative regulator of sphingolipid synthesis. May indirectly regulate endoplasmic reticulum-mediated Ca(+2) signaling. Ref.11 Ref.12

Subunit structure

Interacts with SPTLC1. Ref.12

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.1 Ref.11.

Tissue specificity

Widely expressed. Expressed in adult and fetal heart, brain, lung, liver, skeletal muscle and kidney. Expressed in adult pancreas and placenta and in fetal spleen abd thymus. Ref.1

Involvement in disease

Asthma (ASTHMA) [MIM:600807]: The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.7 Ref.8 Ref.9 Ref.10

Miscellaneous

SNPs on 17q21 locus that are associated with childhood asthma also show a consistent and strong association with transcript levels of ORMDL3, indicating that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.

Sequence similarities

Belongs to the ORM family.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseAsthma
   DomainTransmembrane
Transmembrane helix
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processceramide metabolic process

Inferred from mutant phenotype Ref.12. Source: UniProtKB

   Cellular_componentSPOTS complex

Inferred from direct assay Ref.12. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay Ref.1. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N138-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8N138-4)

The sequence of this isoform differs from the canonical sequence as follows:
     43-58: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 153153ORM1-like protein 3
PRO_0000215639

Regions

Topological domain1 – 2121Cytoplasmic Potential
Transmembrane22 – 4221Helical; Potential
Topological domain43 – 9452Lumenal Potential
Transmembrane95 – 11723Helical; Potential
Topological domain118 – 15336Cytoplasmic Potential

Natural variations

Alternative sequence43 – 5816Missing in isoform 2.
VSP_016052

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2002. Version 1.
Checksum: 3EF483CA5C03EC2E

FASTA15317,495
        10         20         30         40         50         60 
MNVGTAHSEV NPNTRVMNSR GIWLSYVLAI GLLHIVLLSI PFVSVPVVWT LTNLIHNMGM 

        70         80         90        100        110        120 
YIFLHTVKGT PFETPDQGKA RLLTHWEQMD YGVQFTASRK FLTITPIVLY FLTSFYTKYD 

       130        140        150 
QIHFVLNTVS LMSVLIPKLP QLHGVRIFGI NKY 

« Hide

Isoform 2 [UniParc].

Checksum: 63B59033E286DF75
Show »

FASTA13715,689

References

« Hide 'large scale' references
[1]"ORMDL proteins are a conserved new family of endoplasmic reticulum membrane proteins."
Hjelmqvist L., Tuson M., Marfany G., Herrero E., Balcells S., Gonzalez-Duarte R.
Genome Biol. 3:RESEARCH0027.1-RESEARCH0027.13(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]"An evolutionarily conserved gene from the HER-2/Neu amplicon defines a novel gene family."
Luoh S.-W., Venkatesan N., Slamon D.J.
Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]Li H., Yu R., Shen C., Zhou G., Ke R., Lin L., Yang S.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Placenta and Testis.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain and Colon.
[7]"Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma."
Moffatt M.F., Kabesch M., Liang L., Dixon A.L., Strachan D., Heath S., Depner M., von Berg A., Bufe A., Rietschel E., Heinzmann A., Simma B., Frischer T., Willis-Owen S.A., Wong K.C., Illig T., Vogelberg C., Weiland S.K. expand/collapse author list , von Mutius E., Abecasis G.R., Farrall M., Gut I.G., Lathrop G.M., Cookson W.O.
Nature 448:470-473(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ASSOCIATION OF ORMDL3 EXPRESSION LEVELS WITH SUSCEPTIBILITY TO ASTHMA.
[8]"A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications."
Tavendale R., Macgregor D.F., Mukhopadhyay S., Palmer C.N.
J. Allergy Clin. Immunol. 121:860-863(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA.
[9]"ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry."
Sleiman P.M., Annaiah K., Imielinski M., Bradfield J.P., Kim C.E., Frackelton E.C., Glessner J.T., Eckert A.W., Otieno F.G., Santa E., Thomas K., Smith R.M., Glaberson W., Garris M., Gunnlaugsson S., Chiavacci R.M., Allen J., Spergel J. expand/collapse author list , Grundmeier R., Grunstein M.M., Magnusson M., Bisgaard H., Grant S.F., Hakonarson H.
J. Allergy Clin. Immunol. 122:1225-1227(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA.
[10]"Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma."
Wu H., Romieu I., Sienra-Monge J.J., Li H., del Rio-Navarro B.E., London S.J.
Allergy 64:629-635(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ASTHMA.
[11]"The asthma-associated ORMDL3 gene product regulates endoplasmic reticulum-mediated calcium signaling and cellular stress."
Cantero-Recasens G., Fandos C., Rubio-Moscardo F., Valverde M.A., Vicente R.
Hum. Mol. Genet. 19:111-121(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY.
[12]"Orm family proteins mediate sphingolipid homeostasis."
Breslow D.K., Collins S.R., Bodenmiller B., Aebersold R., Simons K., Shevchenko A., Ejsing C.S., Weissman J.S.
Nature 463:1048-1053(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SPTLC1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF395708 mRNA. Translation: AAM43507.1.
AF373101 mRNA. Translation: AAN76521.1.
AF373102 mRNA. Translation: AAN76522.1.
AK074811 mRNA. Translation: BAC11223.1.
AY357943 mRNA. Translation: AAQ57273.1.
AK075212 mRNA. Translation: BAC11476.1.
AK093063 mRNA. Translation: BAG52645.1.
CH471152 Genomic DNA. Translation: EAW60617.1.
BC017087 mRNA. Translation: AAH17087.1.
BC071833 mRNA. Translation: AAH71833.1.
RefSeqNP_644809.1. NM_139280.2.
XP_005257884.1. XM_005257827.2.
UniGeneHs.514151.

3D structure databases

ProteinModelPortalQ8N138.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125114. 6 interactions.
DIPDIP-48687N.
IntActQ8N138. 1 interaction.
MINTMINT-1390099.
STRING9606.ENSP00000304858.

PTM databases

PhosphoSiteQ8N138.

Polymorphism databases

DMDM74728486.

Proteomic databases

PaxDbQ8N138.
PRIDEQ8N138.

Protocols and materials databases

DNASU94103.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000304046; ENSP00000304858; ENSG00000172057. [Q8N138-1]
ENST00000394169; ENSP00000377724; ENSG00000172057. [Q8N138-1]
ENST00000579695; ENSP00000464693; ENSG00000172057. [Q8N138-1]
ENST00000584220; ENSP00000464455; ENSG00000172057. [Q8N138-4]
GeneID94103.
KEGGhsa:94103.
UCSCuc002htj.2. human. [Q8N138-1]

Organism-specific databases

CTD94103.
GeneCardsGC17M038077.
HGNCHGNC:16038. ORMDL3.
MIM600807. phenotype.
610075. gene.
neXtProtNX_Q8N138.
PharmGKBPA32821.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5081.
HOGENOMHOG000192741.
HOVERGENHBG080033.
InParanoidQ8N138.
OMAIDNGAQY.
OrthoDBEOG7N8ZX8.
PhylomeDBQ8N138.
TreeFamTF323369.

Gene expression databases

ArrayExpressQ8N138.
BgeeQ8N138.
CleanExHS_ORMDL3.
GenevestigatorQ8N138.

Family and domain databases

InterProIPR007203. ORMDL.
[Graphical view]
PANTHERPTHR12665. PTHR12665. 1 hit.
PfamPF04061. ORMDL. 1 hit.
[Graphical view]
PIRSFPIRSF018147. ORMDL. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi94103.
NextBio78379.
PROQ8N138.
SOURCESearch...

Entry information

Entry nameORML3_HUMAN
AccessionPrimary (citable) accession number: Q8N138
Secondary accession number(s): B3KS83, Q6UY83
Entry history
Integrated into UniProtKB/Swiss-Prot: November 8, 2005
Last sequence update: October 1, 2002
Last modified: April 16, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM