Reviewed,
UniProtKB/Swiss-Prot Q15084 (PDIA6_HUMAN)
Last modified
February 9, 2010.
Version 111.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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Names and origin
| Protein names | Recommended name: Protein disulfide-isomerase A6 EC=5.3.4.1 Alternative name(s): Protein disulfide isomerase P5 Thioredoxin domain-containing protein 7 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 440 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Catalytic activity | Catalyzes the rearrangement of -S-S- bonds in proteins. |
| Subunit structure | Interacts with MICA on the surface of tumor cells, leading to MICA disulfide bond reduction which is required for its release from tumor cells. Ref.12 |
| Subcellular location | Endoplasmic reticulum lumen By similarity. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.7 Ref.10 |
| Sequence similarities | Belongs to the protein disulfide isomerase family. Contains 2 thioredoxin domains. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Endoplasmic reticulum |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Redox-active center Repeat Signal |
| Molecular function | Isomerase |
| PTM | Disulfide bond Phosphoprotein |
| Technical term | 3D-structure Complete proteome Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | cell redox homeostasis Inferred from electronic annotation. Source: InterPro protein folding Ref.1Traceable author statement. Source: ProtInc |
| Cellular component | ER-Golgi intermediate compartment Inferred from direct assay. Source: UniProtKB endoplasmic reticulum lumenInferred from electronic annotation. Source: UniProtKB-SubCell melanosomeInferred from electronic annotation. Source: UniProtKB-SubCell |
| Molecular function | protein binding Inferred from physical interaction. Source: IntAct protein disulfide isomerase activity Ref.1Traceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| IKBKE | Q14164 | 1 | EBI-1043087,EBI-307369 | |
| NME2 | P22392 | 1 | EBI-1043087,EBI-713693 | |
| TNFRSF14 | Q92956 | 1 | EBI-1043087,EBI-1056653 |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q15084-1) 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: Q15084-2) The sequence of this isoform differs from the canonical sequence as follows: 1-6: MALLVL → MRRDLREKLVWVCRPLAPVEVPANISSDFQPCSPTSPAHSLSRKSPIMYPSTTMANAP |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||||||||||||||||||||||
Molecule processing | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 19 | 19 | ||||||||||||||||||||||||||
| Chain | 20 – 440 | 421 | Protein disulfide-isomerase A6 | PRO_0000034236 | ||||||||||||||||||||||||
Regions | ||||||||||||||||||||||||||||
| Domain | 20 – 133 | 114 | Thioredoxin 1 | |||||||||||||||||||||||||
| Domain | 154 – 287 | 134 | Thioredoxin 2 | |||||||||||||||||||||||||
| Motif | 437 – 440 | 4 | Prevents secretion from ER Potential | |||||||||||||||||||||||||
| Compositional bias | 422 – 434 | 13 | Asp/Glu-rich (acidic) | |||||||||||||||||||||||||
Sites | ||||||||||||||||||||||||||||
| Active site | 55 | 1 | Nucleophile By similarity | |||||||||||||||||||||||||
| Active site | 58 | 1 | Nucleophile By similarity | |||||||||||||||||||||||||
| Active site | 190 | 1 | Nucleophile By similarity | |||||||||||||||||||||||||
| Active site | 193 | 1 | Nucleophile By similarity | |||||||||||||||||||||||||
| Site | 56 | 1 | Contributes to redox potential value By similarity | |||||||||||||||||||||||||
| Site | 57 | 1 | Contributes to redox potential value By similarity | |||||||||||||||||||||||||
| Site | 118 | 1 | Lowers pKa of C-terminal Cys of first active site By similarity | |||||||||||||||||||||||||
| Site | 191 | 1 | Contributes to redox potential value By similarity | |||||||||||||||||||||||||
| Site | 192 | 1 | Contributes to redox potential value By similarity | |||||||||||||||||||||||||
| Site | 256 | 1 | Lowers pKa of C-terminal Cys of second active site By similarity | |||||||||||||||||||||||||
Amino acid modifications | ||||||||||||||||||||||||||||
| Modified residue | 428 | 1 | Phosphoserine Ref.8 Ref.9 Ref.11 Ref.13 Ref.14 Ref.16 | |||||||||||||||||||||||||
| Disulfide bond | 55 ↔ 58 | Redox-active By similarity | ||||||||||||||||||||||||||
| Disulfide bond | 190 ↔ 193 | Redox-active By similarity | ||||||||||||||||||||||||||
Natural variations | ||||||||||||||||||||||||||||
| Alternative sequence | 1 – 6 | 6 | MALLVL → MRRDLREKLVWVCRPLAPVE VPANISSDFQPCSPTSPAHS LSRKSPIMYPSTTMANAP in isoform 2. | VSP_021803 | ||||||||||||||||||||||||
| Natural variant | 214 | 1 | K → R: dbSNP rs4807. Ref.2 Ref.4 | VAR_022152 | ||||||||||||||||||||||||
Secondary structure | ||||||||||||||||||||||||||||
Helix Strand Turn | ||||||||||||||||||||||||||||
| Helix | 169 – 173 | 5 | ||||||||||||||||||||||||||
| Turn | 174 – 176 | 3 | ||||||||||||||||||||||||||
| Beta strand | 177 – 186 | 10 | ||||||||||||||||||||||||||
| Helix | 191 – 194 | 4 | ||||||||||||||||||||||||||
| Helix | 196 – 210 | 15 | ||||||||||||||||||||||||||
| Turn | 211 – 213 | 3 | ||||||||||||||||||||||||||
| Beta strand | 214 – 221 | 8 | ||||||||||||||||||||||||||
| Turn | 222 – 224 | 3 | ||||||||||||||||||||||||||
| Helix | 227 – 232 | 6 | ||||||||||||||||||||||||||
| Beta strand | 236 – 244 | 9 | ||||||||||||||||||||||||||
| Beta strand | 247 – 252 | 6 | ||||||||||||||||||||||||||
| Helix | 258 – 272 | 15 | ||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Cloning and sequencing of the cDNA encoding human P5." Hayano T., Kikuchi M. Gene 164:377-378(1995) [PubMed: 7590364] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Placenta. |
| [2] | "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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT ARG-214. Tissue: Thalamus. |
| [3] | "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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Placenta. |
| [4] | "Large-scale concatenation cDNA sequencing." Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W., Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A. Genome Res. 7:353-358(1997) [PubMed: 9110174] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-440 (ISOFORM 1), VARIANT ARG-214. Tissue: Brain. |
| [5] | "Global profiling of protease cleavage sites by chemoselective labeling of protein N-termini." Xu G., Shin S.B., Jaffrey S.R. Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009) [PubMed: 19892738] [Abstract] Cited for: PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 20-38. |
| [6] | Bienvenut W.V. Submitted (OCT-2004) to UniProtKB Cited for: PROTEIN SEQUENCE OF 103-138; 195-212; 217-231; 242-289; 314-328 AND 374-386. Tissue: B-cell lymphoma. |
| [7] | "Proteomic analysis of early melanosomes: identification of novel melanosomal proteins." Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K., Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J., Hearing V.J., Hunt D.F., Appella E. J. Proteome Res. 2:69-79(2003) [PubMed: 12643545] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [8] | "Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. Tissue: Epithelium. |
| [9] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. Tissue: Epithelium. |
| [10] | "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [11] | "A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. Tissue: Epithelium. |
| [12] | "Disulphide-isomerase-enabled shedding of tumour-associated NKG2D ligands." Kaiser B.K., Yim D., Chow I.-T., Gonzalez S., Dai Z., Mann H.H., Strong R.K., Groh V., Spies T. Nature 447:482-486(2007) [PubMed: 17495932] [Abstract] Cited for: INTERACTION WITH MICA. |
| [13] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. |
| [14] | "Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed: 18318008] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. Tissue: Liver. |
| [15] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [16] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, MASS SPECTROMETRY. |
| [17] | "The solution structure of the second thioredoxin-like domain of human protein disulfide-isomerase A6." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 161-280. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | D49489 mRNA. Translation: BAA08450.1. AK127433 mRNA. Translation: BAC86977.1. BC001312 mRNA. Translation: AAH01312.1. U79278 mRNA. Translation: AAB50217.1. | ||||||||||||
| IPI | IPI00299571. IPI00644989. | ||||||||||||
| PIR | JC4369. | ||||||||||||
| RefSeq | NP_005733.1. | ||||||||||||
| UniGene | Hs.212102 | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| SMR | Q15084. Positions 20-263. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| IntAct | Q15084. 8 interactions. | ||||||||||||
| STRING | Q15084. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | Q15084. | ||||||||||||
2-D gel databases | |||||||||||||
| OGP | Q15084. | ||||||||||||
| REPRODUCTION-2DPAGE | IPI00644989. Q15084. | ||||||||||||
Proteomic databases | |||||||||||||
| PRIDE | Q15084. | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000272227; ENSP00000272227; ENSG00000143870; Homo sapiens. [Genome view] | ||||||||||||
| GeneID | 10130. | ||||||||||||
| KEGG | hsa:10130. | ||||||||||||
| UCSC | uc002rau.1. human. uc002rav.1. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 10130. | ||||||||||||
| GeneCards | GC02M010875. | ||||||||||||
| H-InvDB | HIX0001822. | ||||||||||||
| HGNC | HGNC:30168. PDIA6. | ||||||||||||
| MIM | 611099. gene. | ||||||||||||
| PharmGKB | PA134977905. | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | prNOG07147. | ||||||||||||
| HOVERGEN | Q15084. | ||||||||||||
| OMA | GRTRSDI. | ||||||||||||
| PhylomeDB | Q15084. | ||||||||||||
Enzyme and pathway databases | |||||||||||||
| BRENDA | 5.3.4.1. 247. | ||||||||||||
| Reactome | REACT_15380. Diabetes pathways. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | Q15084. | ||||||||||||
| Bgee | Q15084. | ||||||||||||
| CleanEx | HS_PDIA6. | ||||||||||||
| Genevestigator | Q15084. | ||||||||||||
| GermOnline | ENSG00000143870. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| InterPro | IPR005788. Disulphide_isomerase. IPR017936. Thioredoxin-like. IPR012336. Thioredoxin-like_fold. IPR006662. Thioredoxin-like_subdom. IPR017937. Thioredoxin_CS. IPR013766. Thioredoxin_domain. IPR012335. Thioredoxin_fold. [Graphical view] | ||||||||||||
| Gene3D | G3DSA:3.40.30.10. Thioredoxin_fold. 2 hits. | ||||||||||||
| Pfam | PF00085. Thioredoxin. 2 hits. [Graphical view] | ||||||||||||
| PRINTS | PR00421. THIOREDOXIN. | ||||||||||||
| TIGRFAMs | TIGR01126. pdi_dom. 2 hits. | ||||||||||||
| PROSITE | PS00014. ER_TARGET. 1 hit. PS00194. THIOREDOXIN_1. 2 hits. PS51352. THIOREDOXIN_2. 2 hits. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other Resources | |||||||||||||
| NextBio | 38319. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | PDIA6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q15084 Secondary accession number(s): Q6ZSH5, Q99778 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any 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
| Human chromosome 2 Human chromosome 2: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with


