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Protein

Programmed cell death protein 6

Gene

PDCD6

Organism
Homo sapiens (Human)
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. 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. May inhibit KDR/VEGFR2-dependent angiogenesis; the function involves inhibition of VEGF-induced phosphorylation of the Akt signaling pathway. Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway. Isoform 2 has a lower Ca2+ affinity than isoform 1. Isoform 1 and, to a lesser extent, isoform 2, can stabilize SHISA5.By similarity5 Publications

Regions

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

GO - Molecular functioni

  • binding, bridging Source: UniProtKB
  • calcium-dependent cysteine-type endopeptidase activity Source: GO_Central
  • calcium-dependent protein binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • protein anchor Source: UniProtKB
  • protein dimerization activity Source: UniProtKB

GO - Biological processi

  • activation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
  • angiogenesis Source: UniProtKB-KW
  • apoptotic signaling pathway Source: ProtInc
  • cellular response to heat Source: UniProtKB
  • intracellular protein transport Source: UniProtKB
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of TOR signaling Source: UniProtKB
  • negative regulation of vascular endothelial growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of angiogenesis Source: UniProtKB
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • positive regulation of endothelial cell migration Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • response to calcium ion Source: UniProtKB
  • vascular endothelial growth factor receptor-2 signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Angiogenesis, Apoptosis

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063438-MONOMER.

Protein family/group databases

TCDBi3.A.5.9.1. the general secretory pathway (sec) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Programmed cell death protein 6
Alternative name(s):
Apoptosis-linked gene 2 protein
Probable calcium-binding protein ALG-2
Gene namesi
Name:PDCD6
Synonyms:ALG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:8765. PDCD6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum exit site Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • nuclear membrane Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi47E → A: Loss of interaction with SEC31A and PLSCR3, and loss of localization to the endoplasmic reticulum; when associated with A-114. 2 Publications1
Mutagenesisi57W → A: Reduces the interaction with PDCD6IP and ANXA7. 1 Publication1
Mutagenesisi60F → A: Abolishes the interaction with PDCD6IP, ANXA7 and ANXA11. 1 Publication1
Mutagenesisi91Y → A: Abolishes the interaction with PDCD6IP, ANXA7 and ANXA11. 1 Publication1
Mutagenesisi95W → A: Abolishes the interaction with PDCD6IP, ANXA7 and ANXA11. 1 Publication1
Mutagenesisi114E → A: Loss of interaction with SEC31A and PLSCR3, and loss of localization to the endoplasmic reticulum; when associated with A-47. 2 Publications1
Mutagenesisi122F → A: Increases interaction with PDCD6IP and ANXA7. Impairs interaction with ANXA11. Augments stauroporine-induced cell death. 1 Publication1
Mutagenesisi122F → G: Increases interaction with PDCD6IP. Impairs interaction with ANXA11. 1 Publication1
Mutagenesisi122F → S: Increases interaction with PDCD6IP. Impairs interaction with ANAX7 and ANXA11. 1 Publication1
Mutagenesisi122F → W: Impairs interaction with ANXA11. 1 Publication1
Mutagenesisi180Y → A: Abolishes the interaction with PDCD6IP, TSG101, ANXA7 and ANXA11. 1 Publication1

Organism-specific databases

DisGeNETi10016.
OpenTargetsiENSG00000249915.
PharmGKBiPA33115.

Polymorphism and mutation databases

BioMutaiPDCD6.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000737292 – 191Programmed cell death protein 6Add BLAST190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiO75340.
MaxQBiO75340.
PaxDbiO75340.
PeptideAtlasiO75340.
PRIDEiO75340.
TopDownProteomicsiO75340-1. [O75340-1]

PTM databases

iPTMnetiO75340.
PhosphoSitePlusiO75340.

Expressioni

Gene expression databases

BgeeiENSG00000249915.
CleanExiHS_ALG2.
HS_PDCD6.
ExpressionAtlasiO75340. baseline and differential.
GenevisibleiO75340. HS.

Organism-specific databases

HPAiHPA047221.

Interactioni

Subunit structurei

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 (PubMed:16957052, PubMed:18256029, PubMed:18940611, PubMed:20691033). Interacts with SHISA5 (PubMed:17889823). Interacts with PEF1 (PubMed:11278427, PubMed:11883899). Interacts with RBM22 (PubMed:17045351). Interacts with PLSCR4 (PubMed:18256029). Interacts with ANXA7 and TSG101 (PubMed:18256029, PubMed:20691033). Interacts with DAPK1 (PubMed:16132846). Interacts with SEC31A; the interaction is calcium-dependent (PubMed:16957052, PubMed:18256029). Interacts with ANXA11 (via N-terminus); the interaction is calcium-dependent (PubMed:11883939, PubMed:18256029, PubMed:18940611). Interacts with PLSCR3 (via N-terminus); the interaction is calcium-dependent (PubMed:18256029). Interacts with MCOLN1; the interaction is calcium-dependent (PubMed:19864416). Seems to play a role in the regulation of the distribution and function of MCOLN1 in the endosomal pathway (PubMed:19864416). Interacts with KDR (PubMed:21893193). Isoform 2 does not interact with SHISA5 (PubMed:17889823). Isoform 2 does not interact with PDCD6IP, TSG101, ANXA7 and ANXA11.By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-352915,EBI-352915
ANXA11Q5T0G83EBI-352915,EBI-10245225
DAPK1P533553EBI-352915,EBI-358616
HEBP2Q9Y5Z46EBI-352915,EBI-741593
KDRP359684EBI-352915,EBI-1005487
PDCD6IPQ8WUM45EBI-352915,EBI-310624
PEF1Q9UBV811EBI-352915,EBI-724639
PLSCR3Q9NRY69EBI-352915,EBI-750734
PTPN23Q9H3S73EBI-352915,EBI-724478
SEC31AO949796EBI-352915,EBI-1767898
VPS37CA5D8V65EBI-352915,EBI-2559305

GO - Molecular functioni

  • calcium-dependent protein binding Source: UniProtKB
  • protein anchor Source: UniProtKB
  • protein dimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi115333. 103 interactors.
DIPiDIP-33217N.
IntActiO75340. 57 interactors.
MINTiMINT-5000341.
STRINGi9606.ENSP00000264933.

Structurei

Secondary structure

1191
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi26 – 35Combined sources10
Beta strandi36 – 40Combined sources5
Beta strandi41 – 43Combined sources3
Helixi45 – 51Combined sources7
Beta strandi55 – 58Combined sources4
Helixi62 – 72Combined sources11
Beta strandi74 – 80Combined sources7
Helixi82 – 102Combined sources21
Beta strandi107 – 110Combined sources4
Helixi112 – 121Combined sources10
Helixi128 – 138Combined sources11
Beta strandi143 – 147Combined sources5
Helixi148 – 168Combined sources21
Beta strandi172 – 174Combined sources3
Helixi180 – 188Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
3WXAX-ray2.36A/B20-191[»]
ProteinModelPortaliO75340.
SMRiO75340.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75340.

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

Sequence similaritiesi

Contains 5 EF-hand domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0037. Eukaryota.
ENOG410YKQK. LUCA.
GeneTreeiENSGT00620000087734.
HOGENOMiHOG000231984.
HOVERGENiHBG004492.
InParanoidiO75340.
OMAiPMPSREF.
OrthoDBiEOG091G0ISY.
PhylomeDBiO75340.
TreeFamiTF314682.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13202. EF-hand_5. 1 hit.
PF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 5 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O75340-1) [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.

« Hide

        10         20         30         40         50
MAAYSYRPGP GAGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDTELQQ
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):21,868
Last modified:November 1, 1998 - v1
Checksum:iD0B5944CF3C696AD
GO
Isoform 2 (identifier: O75340-2) [UniParc]FASTAAdd to basket
Also known as: ALG-2(delta)GF122

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

Show »
Length:189
Mass (Da):21,664
Checksum:i8F93724C044DD93A
GO
Isoform 3 (identifier: O75340-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     70-191: Missing.

Note: No experimental confirmation available.
Show »
Length:69
Mass (Da):7,349
Checksum:i8410709B76C52B47
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035459123G → C in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04554270 – 191Missing in isoform 3. 1 PublicationAdd BLAST122
Alternative sequenceiVSP_045113121 – 122Missing in isoform 2. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3854.1. [O75340-1]
CCDS58940.1. [O75340-2]
CCDS58941.1. [O75340-3]
RefSeqiNP_001254485.1. NM_001267556.1. [O75340-2]
NP_001254486.1. NM_001267557.1.
NP_001254487.1. NM_001267558.1.
NP_001254488.1. NM_001267559.1. [O75340-3]
NP_037364.1. NM_013232.3. [O75340-1]
UniGeneiHs.50823.

Genome annotation databases

EnsembliENST00000264933; ENSP00000264933; ENSG00000249915. [O75340-1]
ENST00000505221; ENSP00000422085; ENSG00000249915. [O75340-3]
ENST00000507528; ENSP00000423815; ENSG00000249915. [O75340-2]
GeneIDi10016.
KEGGihsa:10016.
UCSCiuc003jat.1. human. [O75340-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3854.1. [O75340-1]
CCDS58940.1. [O75340-2]
CCDS58941.1. [O75340-3]
RefSeqiNP_001254485.1. NM_001267556.1. [O75340-2]
NP_001254486.1. NM_001267557.1.
NP_001254487.1. NM_001267558.1.
NP_001254488.1. NM_001267559.1. [O75340-3]
NP_037364.1. NM_013232.3. [O75340-1]
UniGeneiHs.50823.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
3WXAX-ray2.36A/B20-191[»]
ProteinModelPortaliO75340.
SMRiO75340.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115333. 103 interactors.
DIPiDIP-33217N.
IntActiO75340. 57 interactors.
MINTiMINT-5000341.
STRINGi9606.ENSP00000264933.

Protein family/group databases

TCDBi3.A.5.9.1. the general secretory pathway (sec) family.

PTM databases

iPTMnetiO75340.
PhosphoSitePlusiO75340.

Polymorphism and mutation databases

BioMutaiPDCD6.

Proteomic databases

EPDiO75340.
MaxQBiO75340.
PaxDbiO75340.
PeptideAtlasiO75340.
PRIDEiO75340.
TopDownProteomicsiO75340-1. [O75340-1]

Protocols and materials databases

DNASUi10016.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264933; ENSP00000264933; ENSG00000249915. [O75340-1]
ENST00000505221; ENSP00000422085; ENSG00000249915. [O75340-3]
ENST00000507528; ENSP00000423815; ENSG00000249915. [O75340-2]
GeneIDi10016.
KEGGihsa:10016.
UCSCiuc003jat.1. human. [O75340-1]

Organism-specific databases

CTDi10016.
DisGeNETi10016.
GeneCardsiPDCD6.
HGNCiHGNC:8765. PDCD6.
HPAiHPA047221.
MIMi601057. gene.
neXtProtiNX_O75340.
OpenTargetsiENSG00000249915.
PharmGKBiPA33115.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0037. Eukaryota.
ENOG410YKQK. LUCA.
GeneTreeiENSGT00620000087734.
HOGENOMiHOG000231984.
HOVERGENiHBG004492.
InParanoidiO75340.
OMAiPMPSREF.
OrthoDBiEOG091G0ISY.
PhylomeDBiO75340.
TreeFamiTF314682.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000063438-MONOMER.

Miscellaneous databases

ChiTaRSiPDCD6. human.
EvolutionaryTraceiO75340.
GeneWikiiPDCD6.
GenomeRNAii10016.
PROiO75340.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000249915.
CleanExiHS_ALG2.
HS_PDCD6.
ExpressionAtlasiO75340. baseline and differential.
GenevisibleiO75340. HS.

Family and domain databases

CDDicd00051. EFh. 1 hit.
Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
[Graphical view]
PfamiPF13202. EF-hand_5. 1 hit.
PF13499. EF-hand_7. 1 hit.
[Graphical view]
SMARTiSM00054. EFh. 5 hits.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
PROSITEiPS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPDCD6_HUMAN
AccessioniPrimary (citable) accession number: O75340
Secondary accession number(s): B2RD16
, E7ESR3, Q2YDC2, Q5TZS0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: November 1, 1998
Last modified: November 30, 2016
This is version 161 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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.