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Programmed cell death protein 6



Rattus norvegicus (Rat)
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli


Calcium sensor that plays a key role in processes such as endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal biogenesis or membrane repair (By similarity). Acts as an adapter that bridges unrelated proteins or stabilizes weak protein-protein complexes in response to calcium: calcium-binding triggers exposure of apolar surface, promoting interaction with different sets of proteins thanks to 3 different hydrophobic pockets, leading to translocation to membranes (By similarity). Involved in ER-Golgi transport (PubMed:27276012). Regulates ER-Golgi transport by promoting the association between PDCD6IP and TSG101, thereby bridging together the ESCRT-III and ESCRT-I complexes (By similarity). Together with PEF1, acts as calcium-dependent adapter for the BCR(KLHL12) complex, a complex involved in ER-Golgi transport by regulating the size of COPII coats (By similarity). In response to cytosolic calcium increase, the heterodimer formed with PEF1 interacts with, and bridges together the BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting monoubiquitination of SEC31 and subsequent collagen export, which is required for neural crest specification (By similarity). Involved in the regulation of the distribution and function of MCOLN1 in the endosomal pathway (By similarity). Promotes localization and polymerization of TFG at endoplasmic reticulum exit site (By similarity). Required for T-cell receptor-, Fas-, and glucocorticoid-induced apoptosis (By similarity). May mediate Ca2+-regulated signals along the death pathway: interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (By similarity). Its role in apoptosis may however be indirect, as suggested by knockout experiments (By similarity). May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphorylation of the Akt signaling pathway (By similarity).By similarity1 Publication
Isoform 2: Has a lower Ca2+ affinity than isoform 1 (By similarity).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi36Calcium 1By similarity1
Metal bindingi38Calcium 1By similarity1
Metal bindingi40Calcium 1By similarity1
Metal bindingi42Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi47Calcium 1By similarity1
Metal bindingi103Calcium 2By similarity1
Metal bindingi105Calcium 2By similarity1
Metal bindingi107Calcium 2By similarity1
Metal bindingi109Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi114Calcium 2By similarity1
Metal bindingi169MagnesiumBy similarity1
Metal bindingi171MagnesiumBy similarity1
Metal bindingi173MagnesiumBy similarity1
Metal bindingi175Magnesium; via carbonyl oxygenBy similarity1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi36 – 471By similarityAdd BLAST12
Calcium bindingi73 – 842PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi103 – 1143By similarityAdd BLAST12
Calcium bindingi169 – 1814By similarityAdd BLAST13

GO - Molecular functioni

GO - Biological processi


Biological processAngiogenesis, Apoptosis
LigandCalcium, Magnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Programmed cell death protein 6
Alternative name(s):
Apoptosis-linked gene 2 protein homologBy similarity
Short name:
ALG-2By similarity
Gene namesi
Synonyms:Alg2By similarity
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi1311239. Pdcd6.

Subcellular locationi

  • Endoplasmic reticulum membrane 1 Publication; Peripheral membrane protein By similarity
  • Cytoplasmic vesicleCOPII-coated vesicle membrane By similarity
  • Cytoplasm By similarity
  • Nucleus By similarity
  • Endosome By similarity

  • Note: Interaction with RBM22 induces relocalization from the cytoplasm to the nucleus (By similarity). Translocated from the cytoplasm to the nucleus after heat shock cell treatment (By similarity). Accumulates in cytoplasmic vesicle-like organelles after heat shock treatment, which may represent stress granules (By similarity). In response to calcium increase, relocates from cytolasm to COPII vesicle coat (By similarity). Localizes to endoplasmic reticulum exit site (ERES) (PubMed:27276012).By similarity1 Publication

GO - Cellular componenti

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00004396422 – 191Programmed cell death protein 6By similarityAdd BLAST190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1

Keywords - PTMi


Proteomic databases



Gene expression databases



Subunit structurei

Homodimer and heterodimer; heterodimerizes (via the EF-hand 5) with PEF1 (By similarity). Isoform 1 and isoform 2 self-associate; probably forming homodimers. Interacts with CPNE4 (via VWFA domain) (By similarity). Interacts with PDCD6IP; the interaction is calcium-dependent. Interacts with RBM22. Interacts with PLSCR4. Interacts with ANXA7 and TSG101. Interacts with DAPK1. Interacts with SEC31A; the interaction is calcium-dependent and promotes monoubiquitination of SEC31A. Interacts with ANXA11 (via N-terminus); the interaction is calcium-dependent. Interacts with PLSCR3 (via N-terminus); the interaction is calcium-dependent. Interacts with MCOLN1; the interaction is calcium-dependent. Interacts with KDR; the interaction is calcium-dependent. Interacts with HEBP2; the interaction is calcium-dependent. Interacts with TFG. Isoform 1: Interacts with SHISA5, leading to stabilize it. Isoform 2: Does not interact with SHISA5. Isoform 2: Does not interact with PDCD6IP, TSG101, ANXA7 and ANXA11 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini23 – 58EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini59 – 89EF-hand 2PROSITE-ProRule annotationAdd BLAST31
Domaini90 – 125EF-hand 3PROSITE-ProRule annotationAdd BLAST36
Domaini126 – 161EF-hand 4PROSITE-ProRule annotationAdd BLAST36
Domaini162 – 191EF-hand 5PROSITE-ProRule annotationAdd BLAST30


Interacts with different set of proteins thanks to 3 different hydrophobic pockets. Hydrophobic pockets 1 and 2, which mediate interaction with PDCD6IP, are largely formed by residues from EF-hand 3 (EF3) to 5 (EF5), as well as by Tyr-180 (EF5) of a dimerizing molecule (Pocket 1) and from EF-hand (EF2) to 4 (EF4) (Pocket 2). Hydrophobic pocket 3, which mediates interaction with SEC31A, is mainly formed by residues from EF-hand 1 (EF1) to 3 (EF3).By similarity
EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium-binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity. A one-residue insertion in the EF5-binding loop prevents the glutamyl residue at the C-terminal end of the loop from serving as the canonical bidentate calcium ligand (By similarity). EF5 acts as a high-affinity magnesium-binding domain instead (By similarity). Magnesium, may affect dimerization (By similarity). EF5 may bind either calcium or magnesium depending on the context (By similarity).By similarity

Keywords - Domaini


Phylogenomic databases

eggNOGiKOG0037. Eukaryota.

Family and domain databases

CDDicd00051. EFh. 1 hit.
InterProiView protein in InterPro
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
PfamiView protein in Pfam
PF13202. EF-hand_5. 1 hit.
PF13499. EF-hand_7. 1 hit.
SMARTiView protein in SMART
SM00054. EFh. 5 hits.
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiView protein in PROSITE
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.

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: G3V7W1-1) [UniParc]FASTAAdd to basket

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.

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        10         20         30         40         50
60 70 80 90 100
110 120 130 140 150
160 170 180 190
Mass (Da):21,905
Last modified:November 16, 2011 - v1
Isoform 2 (identifier: G3V7W1-2) [UniParc]FASTAAdd to basket

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

Show »
Mass (Da):21,700

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_058894121 – 122Missing in isoform 2. 2

Sequence databases

Select the link destinations:
Links Updated
AC094217 Genomic DNA. No translation available.
CH474002 Genomic DNA. Translation: EDL87681.1.
BC168744 mRNA. Translation: AAI68744.1.
RefSeqiNP_001100922.1. NM_001107452.1. [G3V7W1-1]
XP_006227846.1. XM_006227784.3. [G3V7W1-2]

Genome annotation databases

EnsembliENSRNOT00000019735; ENSRNOP00000019735; ENSRNOG00000014485. [G3V7W1-1]

Keywords - Coding sequence diversityi

Alternative splicing

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 one 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.

Entry informationi

Entry nameiPDCD6_RAT
AccessioniPrimary (citable) accession number: G3V7W1
Secondary accession number(s): B5DEP1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2017
Last sequence update: November 16, 2011
Last modified: June 7, 2017
This is version 44 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome