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P12815 (PDCD6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. 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·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Programmed cell death protein 6
Alternative name(s):
ALG-257
PMP41
Probable calcium-binding protein ALG-2
Gene names
Name:Pdcd6
Synonyms:Alg2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length191 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7

Subunit structure

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. Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

Nucleus membrane; Peripheral membrane protein By similarity. Endoplasmic reticulum membrane; 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.

Sequence similarities

Contains 5 EF-hand domains.

Sequence caution

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

Ontologies

Keywords
   Biological processAngiogenesis
Apoptosis
   Cellular componentEndoplasmic reticulum
Endosome
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandCalcium
Metal-binding
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of cysteine-type endopeptidase activity involved in apoptotic process

Inferred from direct assay PubMed 14561754. Source: MGI

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from direct assay Ref.1. Source: MGI

cellular response to heat

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular protein transport

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of TOR signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein kinase B signaling

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

proteolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to calcium ion

Inferred from direct assay PubMed 17214967. Source: UniProtKB

vascular endothelial growth factor receptor-2 signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 17214967. Source: UniProtKB

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionbinding, bridging

Inferred from sequence or structural similarity. Source: UniProtKB

calcium ion binding

Inferred from mutant phenotype PubMed 17214967. Source: UniProtKB

calcium-dependent cysteine-type endopeptidase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

calcium-dependent protein binding

Inferred from physical interaction PubMed 17214967. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 11606059Ref.7. Source: IntAct

protein dimerization activity

Inferred from physical interaction Ref.5. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.5. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FASP254452EBI-309164,EBI-494743From a different organism.
SHISA5Q8N1145EBI-309164,EBI-2115556From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P12815-1)

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.
Isoform 2 (identifier: P12815-2)

Also known as: ALG-2,1;

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed By similarity
Chain2 – 191190Programmed cell death protein 6
PRO_0000073730

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

Amino acid modifications

Modified residue21N-acetylalanine By similarity

Natural variations

Alternative sequence121 – 1222Missing in isoform 2.
VSP_047715

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (ALG-2,5) [UniParc].

Last modified November 1, 1997. Version 2.
Checksum: 2704E984BF7F6F40

FASTA19121,867
        10         20         30         40         50         60 
MAAYSYRPGP GGGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDNELQQ 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 (ALG-2,1) [UniParc].

Checksum: 725B3EF5FDA06A72
Show »

FASTA18921,663

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS26642.1. [P12815-1]
RefSeqNP_035181.1. NM_011051.3. [P12815-1]
XP_006517219.1. XM_006517156.1. [P12815-2]
UniGeneMm.24254.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1HQVX-ray2.30A1-191[»]
ProteinModelPortalP12815.
SMRP12815. Positions 20-188.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202071. 3 interactions.
IntActP12815. 9 interactions.
MINTMINT-217398.

PTM databases

PhosphoSiteP12815.

Proteomic databases

MaxQBP12815.
PaxDbP12815.
PRIDEP12815.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022060; ENSMUSP00000022060; ENSMUSG00000021576. [P12815-1]
GeneID18570.
KEGGmmu:18570.
UCSCuc007rey.2. mouse. [P12815-1]

Organism-specific databases

CTD10016.
MGIMGI:109283. Pdcd6.

Phylogenomic databases

eggNOGNOG249191.
GeneTreeENSGT00620000087734.
HOGENOMHOG000231984.
HOVERGENHBG004492.
InParanoidP12815.
OMAFLWNIFQ.
OrthoDBEOG7RV9FM.
PhylomeDBP12815.
TreeFamTF314682.

Gene expression databases

BgeeP12815.
CleanExMM_PDCD6.
GenevestigatorP12815.

Family and domain databases

Gene3D1.10.238.10. 1 hit.
InterProIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamPF00036. EF-hand_1. 1 hit.
PF13405. EF-hand_6. 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

EvolutionaryTraceP12815.
NextBio294404.
PROP12815.
SOURCESearch...

Entry information

Entry namePDCD6_MOUSE
AccessionPrimary (citable) accession number: P12815
Secondary accession number(s): Q545I0, Q61145
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1997
Last modified: July 9, 2014
This is version 135 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot