Reviewed, UniProtKB/Swiss-Prot Q15084 (PDIA6_HUMAN)

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

Name:	PDIA6
Synonyms:	TXNDC7

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.1 Traceable author statement. Source: ProtInc
Cellular component	ER-Golgi intermediate compartment Inferred from direct assay. Source: UniProtKB endoplasmic reticulum lumen Inferred from electronic annotation. Source: UniProtKB-SubCell melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein binding Inferred from physical interaction. Source: IntAct protein disulfide isomerase activity Ref.1 Traceable 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

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

440

Helix Strand Turn

Details...

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

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 06895409F0265D7C	FASTA	440	48,121
	10 20 30 40 50 60 MALLVLGLVS CTFFLAVNGL YSSSDDVIEL TPSNFNREVI QSDSLWLVEF YAPWCGHCQR 70 80 90 100 110 120 LTPEWKKAAT ALKDVVKVGA VDADKHHSLG GQYGVQGFPT IKIFGSNKNR PEDYQGGRTG 130 140 150 160 170 180 EAIVDAALSA LRQLVKDRLG GRSGGYSSGK QGRSDSSSKK DVIELTDDSF DKNVLDSEDV 190 200 210 220 230 240 WMVEFYAPWC GHCKNLEPEW AAAASEVKEQ TKGKVKLAAV DATVNQVLAS RYGIRGFPTI 250 260 270 280 290 300 KIFQKGESPV DYDGGRTRSD IVSRALDLFS DNAPPPELLE IINEDIAKRT CEEHQLCVVA 310 320 330 340 350 360 VLPHILDTGA AGRNSYLEVL LKLADKYKKK MWGWLWTEAG AQSELETALG IGGFGYPAMA 370 380 390 400 410 420 AINARKMKFA LLKGSFSEQG INEFLRELSF GRGSTAPVGG GAFPTIVERE PWDGRDGELP 430 440 VEDDIDLSDV ELDDLGKDEL
	Isoform 2. Checksum: 987BB19EC01F116C	FASTA	492	53,901
	10 20 30 40 50 60 MRRDLREKLV WVCRPLAPVE VPANISSDFQ PCSPTSPAHS LSRKSPIMYP STTMANAPGL 70 80 90 100 110 120 VSCTFFLAVN GLYSSSDDVI ELTPSNFNRE VIQSDSLWLV EFYAPWCGHC QRLTPEWKKA 130 140 150 160 170 180 ATALKDVVKV GAVDADKHHS LGGQYGVQGF PTIKIFGSNK NRPEDYQGGR TGEAIVDAAL 190 200 210 220 230 240 SALRQLVKDR LGGRSGGYSS GKQGRSDSSS KKDVIELTDD SFDKNVLDSE DVWMVEFYAP 250 260 270 280 290 300 WCGHCKNLEP EWAAAASEVK EQTKGKVKLA AVDATVNQVL ASRYGIRGFP TIKIFQKGES 310 320 330 340 350 360 PVDYDGGRTR SDIVSRALDL FSDNAPPPEL LEIINEDIAK RTCEEHQLCV VAVLPHILDT 370 380 390 400 410 420 GAAGRNSYLE VLLKLADKYK KKMWGWLWTE AGAQSELETA LGIGGFGYPA MAAINARKMK 430 440 450 460 470 480 FALLKGSFSE QGINEFLREL SFGRGSTAPV GGGAFPTIVE REPWDGRDGE LPVEDDIDLS 490 DVELDDLGKD EL

References

	« Hide 'large scale' referencesShow '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. , 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: 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

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1X5D	NMR	-	A	161-280	[»]

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

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	February 9, 2010
This is version 111 of the entry and version 1 of the sequence. [Complete 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.