PDCD6_RAT
ID PDCD6_RAT Reviewed; 191 AA.
AC G3V7W1; B5DEP1;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Programmed cell death protein 6;
DE AltName: Full=Apoptosis-linked gene 2 protein homolog {ECO:0000250|UniProtKB:P12815};
DE Short=ALG-2 {ECO:0000250|UniProtKB:P12815};
GN Name=Pdcd6 {ECO:0000312|RGD:1311239};
GN Synonyms=Alg2 {ECO:0000250|UniProtKB:P12815};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pituitary {ECO:0000312|EMBL:AAI68744.1};
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27276012; DOI=10.1371/journal.pone.0157227;
RA Rayl M., Truitt M., Held A., Sargeant J., Thorsen K., Hay J.C.;
RT "Penta-EF-Hand protein peflin is a negative regulator of ER-to-Golgi
RT transport.";
RL PLoS ONE 11:E0157227-E0157227(2016).
CC -!- FUNCTION: Calcium sensor that plays a key role in processes such as
CC endoplasmic reticulum (ER)-Golgi vesicular transport, endosomal
CC biogenesis or membrane repair (By similarity). Acts as an adapter that
CC bridges unrelated proteins or stabilizes weak protein-protein complexes
CC in response to calcium: calcium-binding triggers exposure of apolar
CC surface, promoting interaction with different sets of proteins thanks
CC to 3 different hydrophobic pockets, leading to translocation to
CC membranes (By similarity). Involved in ER-Golgi transport
CC (PubMed:27276012). Regulates ER-Golgi transport by promoting the
CC association between PDCD6IP and TSG101, thereby bridging together the
CC ESCRT-III and ESCRT-I complexes (By similarity). Together with PEF1,
CC acts as calcium-dependent adapter for the BCR(KLHL12) complex, a
CC complex involved in ER-Golgi transport by regulating the size of COPII
CC coats (By similarity). In response to cytosolic calcium increase, the
CC heterodimer formed with PEF1 interacts with, and bridges together the
CC BCR(KLHL12) complex and SEC31 (SEC31A or SEC31B), promoting
CC monoubiquitination of SEC31 and subsequent collagen export, which is
CC required for neural crest specification (By similarity). Involved in
CC the regulation of the distribution and function of MCOLN1 in the
CC endosomal pathway (By similarity). Promotes localization and
CC polymerization of TFG at endoplasmic reticulum exit site (By
CC similarity). Required for T-cell receptor-, Fas-, and glucocorticoid-
CC induced apoptosis (By similarity). May mediate Ca(2+)-regulated signals
CC along the death pathway: interaction with DAPK1 can accelerate
CC apoptotic cell death by increasing caspase-3 activity (By similarity).
CC Its role in apoptosis may however be indirect, as suggested by knockout
CC experiments (By similarity). May inhibit KDR/VEGFR2-dependent
CC angiogenesis; the function involves inhibition of VEGF-induced
CC phosphorylation of the Akt signaling pathway (By similarity).
CC {ECO:0000250|UniProtKB:O75340, ECO:0000250|UniProtKB:P12815,
CC ECO:0000269|PubMed:27276012}.
CC -!- FUNCTION: [Isoform 2]: Has a lower Ca(2+) affinity than isoform 1 (By
CC similarity). {ECO:0000250|UniProtKB:P12815}.
CC -!- SUBUNIT: Homodimer and heterodimer; heterodimerizes (via the EF-hand 5)
CC with PEF1 (By similarity). Isoform 1 and isoform 2 self-associate;
CC probably forming homodimers. Interacts with CPNE4 (via VWFA domain) (By
CC similarity). Interacts with PDCD6IP; the interaction is calcium-
CC dependent. Interacts with RBM22. Interacts with PLSCR4. Interacts with
CC ANXA7 and TSG101. Interacts with DAPK1. Interacts with SEC31A; the
CC interaction is calcium-dependent and promotes monoubiquitination of
CC SEC31A. Interacts with ANXA11 (via N-terminus); the interaction is
CC calcium-dependent. Interacts with PLSCR3 (via N-terminus); the
CC interaction is calcium-dependent. Interacts with MCOLN1; the
CC interaction is calcium-dependent. Interacts with KDR; the interaction
CC is calcium-dependent. Interacts with HEBP2; the interaction is calcium-
CC dependent. Interacts with TFG. Isoform 1: Interacts with SHISA5,
CC leading to stabilize it. Isoform 2: Does not interact with SHISA5.
CC Isoform 2: Does not interact with PDCD6IP, TSG101, ANXA7 and ANXA11 (By
CC similarity). {ECO:0000250|UniProtKB:O75340,
CC ECO:0000250|UniProtKB:P12815}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:27276012}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O75340}. Cytoplasmic vesicle, COPII-coated
CC vesicle membrane {ECO:0000250|UniProtKB:O75340}. Cytoplasm
CC {ECO:0000250|UniProtKB:O75340}. Nucleus {ECO:0000250|UniProtKB:O75340}.
CC Endosome {ECO:0000250|UniProtKB:O75340}. Note=Interaction with RBM22
CC induces relocalization from the cytoplasm to the nucleus (By
CC similarity). Translocated from the cytoplasm to the nucleus after heat
CC shock cell treatment (By similarity). Accumulates in cytoplasmic
CC vesicle-like organelles after heat shock treatment, which may represent
CC stress granules (By similarity). In response to calcium increase,
CC relocates from cytoplasm to COPII vesicle coat (By similarity).
CC Localizes to endoplasmic reticulum exit site (ERES) (PubMed:27276012).
CC {ECO:0000250|UniProtKB:O75340, ECO:0000269|PubMed:27276012}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=G3V7W1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=G3V7W1-2; Sequence=VSP_058894;
CC -!- DOMAIN: Interacts with different set of proteins thanks to 3 different
CC hydrophobic pockets. Hydrophobic pockets 1 and 2, which mediate
CC interaction with PDCD6IP, are largely formed by residues from EF-hand 3
CC (EF3) to 5 (EF5), as well as by Tyr-180 (EF5) of a dimerizing molecule
CC (Pocket 1) and from EF-hand (EF2) to 4 (EF4) (Pocket 2). Hydrophobic
CC pocket 3, which mediates interaction with SEC31A, is mainly formed by
CC residues from EF-hand 1 (EF1) to 3 (EF3).
CC {ECO:0000250|UniProtKB:O75340}.
CC -!- DOMAIN: EF-hand 1 (EF1) and 3 (EF3) are the high-affinity calcium-
CC binding sites, while EF-hand 5 (EF5) binds calcium with low-affinity. A
CC one-residue insertion in the EF5-binding loop prevents the glutamyl
CC residue at the C-terminal end of the loop from serving as the canonical
CC bidentate calcium ligand (By similarity). EF5 acts as a high-affinity
CC magnesium-binding domain instead (By similarity). Magnesium, may affect
CC dimerization (By similarity). EF5 may bind either calcium or magnesium
CC depending on the context (By similarity).
CC {ECO:0000250|UniProtKB:O75340, ECO:0000250|UniProtKB:P12815}.
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DR EMBL; AC094217; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474002; EDL87681.1; -; Genomic_DNA.
DR EMBL; BC168744; AAI68744.1; -; mRNA.
DR RefSeq; NP_001100922.1; NM_001107452.1. [G3V7W1-1]
DR RefSeq; XP_006227846.1; XM_006227784.3. [G3V7W1-2]
DR AlphaFoldDB; G3V7W1; -.
DR SMR; G3V7W1; -.
DR STRING; 10116.ENSRNOP00000019735; -.
DR jPOST; G3V7W1; -.
DR PaxDb; G3V7W1; -.
DR PRIDE; G3V7W1; -.
DR Ensembl; ENSRNOT00000019735; ENSRNOP00000019735; ENSRNOG00000014485. [G3V7W1-1]
DR GeneID; 308061; -.
DR KEGG; rno:308061; -.
DR CTD; 10016; -.
DR RGD; 1311239; Pdcd6.
DR eggNOG; KOG0037; Eukaryota.
DR GeneTree; ENSGT00940000160982; -.
DR HOGENOM; CLU_051357_1_1_1; -.
DR InParanoid; G3V7W1; -.
DR OMA; SREFLWD; -.
DR OrthoDB; 1330600at2759; -.
DR TreeFam; TF314682; -.
DR PRO; PR:G3V7W1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Proteomes; UP000234681; Chromosome 1.
DR Bgee; ENSRNOG00000014485; Expressed in jejunum and 20 other tissues.
DR GO; GO:0030127; C:COPII vesicle coat; ISS:UniProtKB.
DR GO; GO:0031463; C:Cul3-RING ubiquitin ligase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0070971; C:endoplasmic reticulum exit site; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:RGD.
DR GO; GO:0043495; F:protein-membrane adaptor activity; ISO:RGD.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISS:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0034605; P:cellular response to heat; ISO:RGD.
DR GO; GO:0048208; P:COPII vesicle coating; ISS:UniProtKB.
DR GO; GO:0006888; P:endoplasmic reticulum to Golgi vesicle-mediated transport; ISS:UniProtKB.
DR GO; GO:0006886; P:intracellular protein transport; ISO:RGD.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0014032; P:neural crest cell development; ISS:UniProtKB.
DR GO; GO:0014029; P:neural crest formation; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; ISO:RGD.
DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; ISO:RGD.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR Pfam; PF13202; EF-hand_5; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 5.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 3.
PE 2: Evidence at transcript level;
KW Acetylation; Alternative splicing; Angiogenesis; Apoptosis; Calcium;
KW Cytoplasm; Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Magnesium;
KW Membrane; Metal-binding; Nucleus; Reference proteome; Repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O75340"
FT CHAIN 2..191
FT /note="Programmed cell death protein 6"
FT /evidence="ECO:0000250|UniProtKB:P12815"
FT /id="PRO_0000439642"
FT DOMAIN 23..58
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 59..89
FT /note="EF-hand 2"
FT /evidence="ECO:0000305"
FT DOMAIN 90..125
FT /note="EF-hand 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 126..161
FT /note="EF-hand 4"
FT /evidence="ECO:0000305"
FT DOMAIN 162..191
FT /note="EF-hand 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 36
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 38
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12815"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 103
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 105
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 107
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 109
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P12815,
FT ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 169
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P12815"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P12815"
FT BINDING 173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P12815"
FT BINDING 175
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P12815"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O75340"
FT VAR_SEQ 121..122
FT /note="Missing (in isoform 2)"
FT /id="VSP_058894"
SQ SEQUENCE 191 AA; 21905 MW; BA20307D09A69124 CRC64;
MAAYSYRPGP GAGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDNELQQ ALSNGTWTPF
NPVTVRSIIS MFDRENKAGV NFSEFTGVWK YITDWQNVFR TYDRDNSGMI DKHELKQALS
GFGYRLSDQF HDILIRKFDR QGRGQIAFDD FIQGCIVLQR LTDIFRRYDT DQDGWIQVSY
EQYLSMVFSI V
