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O75340 (PDCD6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Programmed cell death protein 6
Alternative name(s):
Apoptosis-linked gene 2 protein
Probable calcium-binding protein ALG-2
Gene names
Name:PDCD6
Synonyms:ALG2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length191 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. May mediate Ca2+-regulated signals along the death pathway By similarity. Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity. Ref.11 Ref.15

Subunit structure

Self-associates By similarity. Homodimer. Interacts with PEF1. Interacts with RBM22. Interacts with PLSCR4, ANXA7 and TSG101. Interacts with SEC31A, PDCD6IP, and the N-termini of ANXA11 and PLSCR3 in a calcium-dependent manner. Interacts with DAPK1. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.18

Subcellular location

Nucleus membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Nucleus. Note: Interaction with RBM22 induces relocalization from the cytoplasm to the nucleus. Translocated from the cytoplasm to the nucleus after heat shock cell treatment. Accumulates in cytoplasmic vesicle-like organelles after heat shock treatment, which may represent stress granules. Ref.13 Ref.17

Sequence similarities

Contains 5 EF-hand domains.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O75340-1)

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: O75340-2)

The sequence of this isoform differs from the canonical sequence as follows:
     121-122: Missing.
Isoform 3 (identifier: O75340-3)

The sequence of this isoform differs from the canonical sequence as follows:
     70-191: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 191191Programmed cell death protein 6
PRO_0000073729

Regions

Domain23 – 5836EF-hand 1
Domain59 – 8931EF-hand 2
Domain90 – 12536EF-hand 3
Domain126 – 16136EF-hand 4
Domain162 – 19130EF-hand 5
Calcium binding36 – 47121
Calcium binding73 – 84122 Potential
Calcium binding103 – 114123
Calcium binding169 – 181134

Natural variations

Alternative sequence70 – 191122Missing in isoform 3.
VSP_045542
Alternative sequence121 – 1222Missing in isoform 2.
VSP_045113
Natural variant1231G → C in a breast cancer sample; somatic mutation. Ref.19
VAR_035459

Experimental info

Mutagenesis471E → A: Loss of interaction with SEC31A and PLSCR3, and loss of localization to the endoplasmic reticulum; when associated with A-114. Ref.13 Ref.14
Mutagenesis571W → A: Reduces the interaction with PDCD6IP and ANXA7. Ref.14
Mutagenesis601F → A: Abolishes the interaction with PDCD6IP, ANXA7 and ANXA11. Ref.14
Mutagenesis911Y → A: Abolishes the interaction with PDCD6IP, ANXA7 and ANXA11. Ref.14
Mutagenesis951W → A: Abolishes the interaction with PDCD6IP, ANXA7 and ANXA11. Ref.14
Mutagenesis1141E → A: Loss of interaction with SEC31A and PLSCR3, and loss of localization to the endoplasmic reticulum; when associated with A-47. Ref.13 Ref.14
Mutagenesis1801Y → A: Abolishes the interaction with PDCD6IP, TSG101, ANXA7 and ANXA11. Ref.14

Secondary structure

............................ 191
Helix Strand Turn

Details...

Sequences

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

Last modified November 1, 1998. Version 1.
Checksum: D0B5944CF3C696AD

FASTA19121,868
        10         20         30         40         50         60 
MAAYSYRPGP GAGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDTELQQ ALSNGTWTPF 

        70         80         90        100        110        120 
NPVTVRSIIS MFDRENKAGV NFSEFTGVWK YITDWQNVFR TYDRDNSGMI DKNELKQALS 

       130        140        150        160        170        180 
GFGYRLSDQF HDILIRKFDR QGRGQIAFDD FIQGCIVLQR LTDIFRRYDT DQDGWIQVSY 

       190 
EQYLSMVFSI V 

« Hide

Isoform 2 [UniParc].

Checksum: 8F93724C044DD93A
Show »

FASTA18921,664
Isoform 3 [UniParc].

Checksum: 8410709B76C52B47
Show »

FASTA697,349

References

« Hide 'large scale' references
[1]Ganjei J.K., D'Adamio L.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]Urcelay E., Ibarreta D., Parrilla R., Ayuso M.S.
Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[3]"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: Cerebellum.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]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].
[7]"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] (ISOFORMS 1; 2 AND 3).
Tissue: Colon, Ovary and Placenta.
[8]"Peflin and ALG-2, members of the penta-EF-hand protein family, form a heterodimer that dissociates in a Ca2+-dependent manner."
Kitaura Y., Matsumoto S., Satoh H., Hitomi K., Maki M.
J. Biol. Chem. 276:14053-14058(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PEF1.
[9]"Both ALG-2 and peflin, penta-EF-hand (PEF) proteins, are stabilized by dimerization through their fifth EF-hand regions."
Kitaura Y., Satoh H., Takahashi H., Shibata H., Maki M.
Arch. Biochem. Biophys. 399:12-18(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PEF1.
[10]"ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner."
Satoh H., Shibata H., Nakano Y., Kitaura Y., Maki M.
Biochem. Biophys. Res. Commun. 291:1166-1172(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ANXA11.
[11]"Programmed cell death 6 (PDCD6) protein interacts with death-associated protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3 dependent pathway."
Lee J.H., Rho S.B., Chun T.
Biotechnol. Lett. 27:1011-1015(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH DAPK1.
[12]"Nuclear translocation of the calcium-binding protein ALG-2 induced by the RNA-binding protein RBM22."
Montaville P., Dai Y., Cheung C.Y., Giller K., Becker S., Michalak M., Webb S.E., Miller A.L., Krebs J.
Biochim. Biophys. Acta 1763:1335-1343(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RBM22.
[13]"The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A."
Yamasaki A., Tani K., Yamamoto A., Kitamura N., Komada M.
Mol. Biol. Cell 17:4876-4887(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SEC31A AND PDCD6IP, MUTAGENESIS OF GLU-47 AND GLU-114, SUBCELLULAR LOCATION.
[14]"Identification of Alix-type and non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants."
Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T., Maki M.
J. Biol. Chem. 283:9623-9632(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PLSCR3; PLSCR4; PDCD6IP; ANXA7; ANXA11; SEC31A AND TSG101, MUTAGENESIS OF GLU-47; TRP-57; PHE-60; TYR-91; TRP-95; GLU-114 AND TYR-180.
[15]"Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101."
Okumura M., Ichioka F., Kobayashi R., Suzuki H., Yoshida H., Shibata H., Maki M.
Biochem. Biophys. Res. Commun. 386:237-241(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"Stress induced subcellular distribution of ALG-2, RBM22 and hSlu7."
Janowicz A., Michalak M., Krebs J.
Biochim. Biophys. Acta 1813:1045-1049(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[18]"Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism."
Suzuki H., Kawasaki M., Inuzuka T., Okumura M., Kakiuchi T., Shibata H., Wakatsuki S., Maki M.
Structure 16:1562-1573(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 24-191 IN COMPLEXES WITH CALCIUM; ZINC AND PDCD6IP, SUBUNIT, INTERACTION WITH PDCD6IP.
[19]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] CYS-123.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF035606 mRNA. Translation: AAC27697.1.
U58773 mRNA. Translation: AAF14336.1.
AK315370 mRNA. Translation: BAG37763.1.
BT020072 mRNA. Translation: AAV38875.1.
AC010442 Genomic DNA. No translation available.
AC021087 Genomic DNA. No translation available.
AC118458 Genomic DNA. No translation available.
CH471235 Genomic DNA. Translation: EAW50991.1.
BC012384 mRNA. Translation: AAH12384.1.
BC106706 mRNA. Translation: AAI06707.1.
BC110291 mRNA. Translation: AAI10292.1.
CB991882 mRNA. No translation available.
IPIIPI00025277.
IPI00967847.
RefSeqNP_001254485.1. NM_001267556.1.
NP_001254486.1. NM_001267557.1.
NP_001254487.1. NM_001267558.1.
NP_001254488.1. NM_001267559.1.
NP_037364.1. NM_013232.3.
UniGeneHs.50823.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZN8X-ray2.70A2-191[»]
2ZN9X-ray2.40A/B20-191[»]
2ZNDX-ray1.70A20-191[»]
2ZNEX-ray2.20A/B24-191[»]
2ZRSX-ray3.10A/B/C/D/E/F/G/H24-191[»]
2ZRTX-ray3.30A/B/C/D/E/F/G/H24-191[»]
3AAJX-ray2.40A/B24-191[»]
3AAKX-ray2.70A20-191[»]
ProteinModelPortalO75340.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-33217N.
IntActO75340. 26 interactions.
MINTMINT-5000341.
STRING9606.ENSP00000323816.

PTM databases

PhosphoSiteO75340.

Proteomic databases

PRIDEO75340.

Protocols and materials databases

DNASU10016.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264933; ENSP00000264933; ENSG00000249915.
ENST00000505221; ENSP00000422085; ENSG00000249915.
ENST00000507528; ENSP00000423815; ENSG00000249915.
GeneID10016.
KEGGhsa:10016.
UCSCuc003jat.1. human.

Organism-specific databases

CTD10016.
GeneCardsGC05P000258.
HGNCHGNC:8765. PDCD6.
MIM601057. gene.
neXtProtNX_O75340.
PharmGKBPA33115.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHOG000231984.
HOVERGENHBG004492.
OMANGWITIN.
OrthoDBEOG4H464S.

Gene expression databases

ArrayExpressO75340.
BgeeO75340.
CleanExHS_ALG2.
HS_PDCD6.
GenevestigatorO75340.
GermOnlineENSG00000063438. Homo sapiens.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamPF13499. EF_hand_5. 1 hit.
[Graphical view]
SMARTSM00054. EFh. 5 hits.
[Graphical view]
PROSITEPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPDCD6. human.
EvolutionaryTraceO75340.
GenomeRNAi10016.
NextBio37841.
SOURCESearch...

Entry information

Entry namePDCD6_HUMAN
AccessionPrimary (citable) accession number: O75340
Secondary accession number(s): B2RD16 expand/collapse secondary AC list , E7ESR3, Q2YDC2, Q5TZS0
Entry history
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1998
Last modified: May 1, 2013
This is version 124 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

Human chromosome 5

Human chromosome 5: 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