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Protein

Programmed cell death protein 6

Gene

Pdcd6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101 (By similarity). May mediate Ca2+-regulated signals along the death pathway. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity. May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphoprylation of the Akt signaling pathway. Isoform 2 has a lower Ca2+ affinity than isoform 1. Isoform 1 and, to a lesser extend, isoform 2, can stabilize SHISA5.By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Calcium bindingi36 – 47121Add
BLAST
Calcium bindingi73 – 84122PROSITE-ProRule annotationAdd
BLAST
Calcium bindingi103 – 114123Add
BLAST
Calcium bindingi169 – 181134Add
BLAST

GO - Molecular functioni

  1. binding, bridging Source: UniProtKB
  2. calcium-dependent cysteine-type endopeptidase activity Source: GO_Central
  3. calcium-dependent protein binding Source: UniProtKB
  4. calcium ion binding Source: UniProtKB
  5. protein anchor Source: MGI
  6. protein dimerization activity Source: UniProtKB
  7. protein homodimerization activity Source: UniProtKB

GO - Biological processi

  1. activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  2. angiogenesis Source: UniProtKB-KW
  3. apoptotic process Source: MGI
  4. cellular response to heat Source: UniProtKB
  5. intracellular protein transport Source: UniProtKB
  6. negative regulation of protein kinase B signaling Source: UniProtKB
  7. negative regulation of TOR signaling Source: UniProtKB
  8. negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  9. positive regulation of angiogenesis Source: UniProtKB
  10. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  11. positive regulation of endothelial cell migration Source: UniProtKB
  12. positive regulation of endothelial cell proliferation Source: UniProtKB
  13. proteolysis Source: GO_Central
  14. response to calcium ion Source: UniProtKB
  15. vascular endothelial growth factor receptor-2 signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Angiogenesis, Apoptosis

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Programmed cell death protein 6
Alternative name(s):
ALG-257
PMP41
Probable calcium-binding protein ALG-2
Gene namesi
Name:Pdcd6
Synonyms:Alg2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 13

Organism-specific databases

MGIiMGI:109283. Pdcd6.

Subcellular locationi

Nucleus membrane By similarity; Peripheral membrane protein By similarity. Endoplasmic reticulum membrane By similarity; Peripheral membrane protein By similarity. Nucleus By similarity. Endosome By similarity
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 (By similarity).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoplasmic vesicle Source: MGI
  3. endoplasmic reticulum Source: MGI
  4. endoplasmic reticulum exit site Source: MGI
  5. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  6. endosome Source: UniProtKB-SubCell
  7. extracellular vesicular exosome Source: MGI
  8. nuclear membrane Source: UniProtKB-SubCell
  9. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 191190Programmed cell death protein 6PRO_0000073730Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

MaxQBiP12815.
PaxDbiP12815.
PRIDEiP12815.

PTM databases

PhosphoSiteiP12815.

Expressioni

Gene expression databases

BgeeiP12815.
CleanExiMM_PDCD6.
GenevestigatoriP12815.

Interactioni

Subunit structurei

Isoform 1 and isoform 2 self-associate; probably forming homodimers. Interacts with SHISA5, PEF1, RBM22, PLSCR4, ANXA7, TSG101 and DAPK1. Interacts with PDCD6IP, SEC31A, ANXA11 (via N-terminus), PLSCR3 (via N-terminus) and MCOLN1; the interactions are calcium-dependent. Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Isoform 2 does not interact with SHISA5, PDCD6IP, TSG101, ANXA7 and ANXA11.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FASP254452EBI-309164,EBI-494743From a different organism.
SHISA5Q8N1145EBI-309164,EBI-2115556From a different organism.

Protein-protein interaction databases

BioGridi202071. 3 interactions.
IntActiP12815. 9 interactions.
MINTiMINT-217398.

Structurei

Secondary structure

1
191
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi25 – 3511Combined sources
Beta strandi41 – 433Combined sources
Helixi45 – 517Combined sources
Beta strandi55 – 584Combined sources
Helixi62 – 7211Combined sources
Beta strandi75 – 806Combined sources
Helixi82 – 10221Combined sources
Beta strandi108 – 1103Combined sources
Helixi112 – 12211Combined sources
Helixi128 – 13811Combined sources
Helixi148 – 16821Combined sources
Helixi180 – 1878Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HQVX-ray2.30A1-191[»]
ProteinModelPortaliP12815.
SMRiP12815. Positions 20-188.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP12815.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 5836EF-hand 1PROSITE-ProRule annotationAdd
BLAST
Domaini59 – 8931EF-hand 2PROSITE-ProRule annotationAdd
BLAST
Domaini90 – 12536EF-hand 3PROSITE-ProRule annotationAdd
BLAST
Domaini126 – 16136EF-hand 4PROSITE-ProRule annotationAdd
BLAST
Domaini162 – 19130EF-hand 5PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 5 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG249191.
GeneTreeiENSGT00620000087734.
HOGENOMiHOG000231984.
HOVERGENiHBG004492.
InParanoidiP12815.
OMAiRGTIYFD.
OrthoDBiEOG7RV9FM.
PhylomeDBiP12815.
TreeFamiTF314682.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF00036. EF-hand_1. 1 hit.
PF13405. EF-hand_6. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 5 hits.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P12815-1) [UniParc]FASTAAdd to basket

Also known as: ALG-2,5

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.

« Hide

        10         20         30         40         50
MAAYSYRPGP GGGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDNELQQ
60 70 80 90 100
ALSNGTWTPF NPVTVRSIIS MFDRENKAGV NFSEFTGVWK YITDWQNVFR
110 120 130 140 150
TYDRDNSGMI DKNELKQALS GFGYRLSDQF HDILIRKFDR QGRGQIAFDD
160 170 180 190
FIQGCIVLQR LTDIFRRYDT DQDGWIQVSY EQYLSMVFSI V
Length:191
Mass (Da):21,867
Last modified:November 1, 1997 - v2
Checksum:i2704E984BF7F6F40
GO
Isoform 2 (identifier: P12815-2) [UniParc]FASTAAdd to basket

Also known as: ALG-2,1

The sequence of this isoform differs from the canonical sequence as follows:
     121-122: Missing.

Show »
Length:189
Mass (Da):21,663
Checksum:i725B3EF5FDA06A72
GO

Sequence cautioni

The sequence CAA33064.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei121 – 1222Missing in isoform 2. CuratedVSP_047715

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U49112 mRNA. Translation: AAB38108.1.
AK008610 mRNA. Translation: BAB25775.1.
AK028223 mRNA. Translation: BAC25823.1.
AK150335 mRNA. Translation: BAE29477.1.
BC040079 mRNA. Translation: AAH40079.1.
X14938 mRNA. Translation: CAA33064.1. Different initiation.
CCDSiCCDS26642.1. [P12815-1]
RefSeqiNP_035181.1. NM_011051.3. [P12815-1]
XP_006517219.1. XM_006517156.1. [P12815-2]
UniGeneiMm.24254.

Genome annotation databases

EnsembliENSMUST00000022060; ENSMUSP00000022060; ENSMUSG00000021576. [P12815-1]
GeneIDi18570.
KEGGimmu:18570.
UCSCiuc007rey.2. mouse. [P12815-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U49112 mRNA. Translation: AAB38108.1.
AK008610 mRNA. Translation: BAB25775.1.
AK028223 mRNA. Translation: BAC25823.1.
AK150335 mRNA. Translation: BAE29477.1.
BC040079 mRNA. Translation: AAH40079.1.
X14938 mRNA. Translation: CAA33064.1. Different initiation.
CCDSiCCDS26642.1. [P12815-1]
RefSeqiNP_035181.1. NM_011051.3. [P12815-1]
XP_006517219.1. XM_006517156.1. [P12815-2]
UniGeneiMm.24254.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1HQVX-ray2.30A1-191[»]
ProteinModelPortaliP12815.
SMRiP12815. Positions 20-188.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202071. 3 interactions.
IntActiP12815. 9 interactions.
MINTiMINT-217398.

PTM databases

PhosphoSiteiP12815.

Proteomic databases

MaxQBiP12815.
PaxDbiP12815.
PRIDEiP12815.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000022060; ENSMUSP00000022060; ENSMUSG00000021576. [P12815-1]
GeneIDi18570.
KEGGimmu:18570.
UCSCiuc007rey.2. mouse. [P12815-1]

Organism-specific databases

CTDi10016.
MGIiMGI:109283. Pdcd6.

Phylogenomic databases

eggNOGiNOG249191.
GeneTreeiENSGT00620000087734.
HOGENOMiHOG000231984.
HOVERGENiHBG004492.
InParanoidiP12815.
OMAiRGTIYFD.
OrthoDBiEOG7RV9FM.
PhylomeDBiP12815.
TreeFamiTF314682.

Miscellaneous databases

EvolutionaryTraceiP12815.
NextBioi294404.
PROiP12815.
SOURCEiSearch...

Gene expression databases

BgeeiP12815.
CleanExiMM_PDCD6.
GenevestigatoriP12815.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF00036. EF-hand_1. 1 hit.
PF13405. EF-hand_6. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 5 hits.
[Graphical view]
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3."
    Vito P., Lacana E., D'Adamio L.
    Science 271:521-525(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6J.
    Tissue: Bone marrow and Small intestine.
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Mammary gland.
  4. "A partial cDNA for a novel protein which has a typical E-F hand structure."
    Kageyama H., Shimizu M., Hiwasa T., Sakiyama S.
    Biochim. Biophys. Acta 1008:255-257(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 44-181.
    Strain: BALB/c.
    Tissue: Fibroblast.
  5. "Alix, a novel mouse protein undergoing calcium-dependent interaction with the apoptotsis-linked-gene 2 (ALG-2) protein."
    Missotten M., Nichols A., Rieger K., Sadoul R.
    Cell Death Differ. 6:124-129(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: SELF-ASSOCIATION, INTERACTION WITH PDCD6IP.
  6. "Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+) affinities and target recognition."
    Tarabykina S., Moller A.L., Durussel I., Cox J., Berchtold M.W.
    J. Biol. Chem. 275:10514-10518(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION, SELF-ASSOCIATION, INTERACTION WITH PDCD6IP.
  7. "The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-inducible gene product localized at the endoplasmic reticulum membrane."
    Draeby I., Woods Y.L., la Cour J.M., Mollerup J., Bourdon J.C., Berchtold M.W.
    Arch. Biochem. Biophys. 467:87-94(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH WITH SHISA5.
  8. "Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins."
    Jia J., Tarabykina S., Hansen C., Berchtold M., Cygler M.
    Structure 9:267-275(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALCIUM, SUBUNIT, INTERACTION WITH PDCD6IP.

Entry informationi

Entry nameiPDCD6_MOUSE
AccessioniPrimary (citable) accession number: P12815
Secondary accession number(s): Q545I0, Q61145
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1997
Last modified: March 4, 2015
This is version 141 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.