PDCD6_MOUSE
ID PDCD6_MOUSE Reviewed; 191 AA.
AC P12815; Q545I0; Q61145;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Programmed cell death protein 6;
DE AltName: Full=ALG-257;
DE AltName: Full=Apoptosis-linked gene 2 protein {ECO:0000303|PubMed:8560270};
DE Short=ALG-2 {ECO:0000303|PubMed:8560270};
DE AltName: Full=PMP41;
GN Name=Pdcd6; Synonyms=Alg2 {ECO:0000303|PubMed:8560270};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION.
RX PubMed=8560270; DOI=10.1126/science.271.5248.521;
RA Vito P., Lacana E., D'Adamio L.;
RT "Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's
RT disease gene ALG-3.";
RL Science 271:521-525(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Small intestine;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 44-181.
RC STRAIN=BALB/cJ; TISSUE=Fibroblast;
RX PubMed=2736249; DOI=10.1016/0167-4781(80)90018-4;
RA Kageyama H., Shimizu M., Hiwasa T., Sakiyama S.;
RT "A partial cDNA for a novel protein which has a typical E-F hand
RT structure.";
RL Biochim. Biophys. Acta 1008:255-257(1989).
RN [5]
RP SELF-ASSOCIATION, AND INTERACTION WITH PDCD6IP.
RX PubMed=10200558; DOI=10.1038/sj.cdd.4400456;
RA Missotten M., Nichols A., Rieger K., Sadoul R.;
RT "Alix, a novel mouse protein undergoing calcium-dependent interaction with
RT the apoptosis-linked-gene 2 (ALG-2) protein.";
RL Cell Death Differ. 6:124-129(1999).
RN [6]
RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORMS 1 AND 2),
RP SELF-ASSOCIATION, AND INTERACTION WITH PDCD6IP.
RX PubMed=10744743; DOI=10.1074/jbc.275.14.10514;
RA Tarabykina S., Moller A.L., Durussel I., Cox J., Berchtold M.W.;
RT "Two forms of the apoptosis-linked protein ALG-2 with different Ca(2+)
RT affinities and target recognition.";
RL J. Biol. Chem. 275:10514-10518(2000).
RN [7]
RP INTERACTION WITH CPNE4.
RX PubMed=12522145; DOI=10.1074/jbc.m212632200;
RA Tomsig J.L., Snyder S.L., Creutz C.E.;
RT "Identification of targets for calcium signaling through the copine family
RT of proteins. Characterization of a coiled-coil copine-binding motif.";
RL J. Biol. Chem. 278:10048-10054(2003).
RN [8]
RP INTERACTION WITH SHISA5.
RX PubMed=17889823; DOI=10.1016/j.abb.2007.07.028;
RA Draeby I., Woods Y.L., la Cour J.M., Mollerup J., Bourdon J.C.,
RA Berchtold M.W.;
RT "The calcium binding protein ALG-2 binds and stabilizes Scotin, a p53-
RT inducible gene product localized at the endoplasmic reticulum membrane.";
RL Arch. Biochem. Biophys. 467:87-94(2007).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12024023; DOI=10.1128/mcb.22.12.4094-4100.2002;
RA Jang I.K., Hu R., Lacana E., D'Adamio L., Gu H.;
RT "Apoptosis-linked gene 2-deficient mice exhibit normal T-cell development
RT and function.";
RL Mol. Cell. Biol. 22:4094-4100(2002).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH CALCIUM, SUBUNIT,
RP INTERACTION WITH PDCD6IP, DOMAIN, AND FUNCTION.
RX PubMed=11525164; DOI=10.1016/s0969-2126(01)00585-8;
RA Jia J., Tarabykina S., Hansen C., Berchtold M., Cygler M.;
RT "Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced
RT changes in penta-EF-hand proteins.";
RL Structure 9:267-275(2001).
RN [12] {ECO:0007744|PDB:5JJG}
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 24-191 IN COMPLEX WITH MAGNESIUM,
RP SUBUNIT, DOMAIN, MAGNESIUM-BINDING, MUTAGENESIS OF ASP-169, AND FUNCTION.
RX PubMed=27541325; DOI=10.1021/acs.biochem.6b00596;
RA Tanner J.J., Frey B.B., Pemberton T., Henzl M.T.;
RT "EF5 is the high-affinity Mg(2+) site in ALG-2.";
RL Biochemistry 55:5128-5141(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 (PubMed:10744743, PubMed:11525164,
CC PubMed:27541325). Acts as an adapter that bridges unrelated proteins or
CC stabilizes weak protein-protein complexes in response to calcium:
CC calcium-binding triggers exposure of apolar surface, promoting
CC interaction with different sets of proteins thanks to 3 different
CC hydrophobic pockets, leading to translocation to membranes
CC (PubMed:10744743, PubMed:11525164, PubMed:27541325). Involved in ER-
CC Golgi transport by promoting the association between PDCD6IP and
CC TSG101, thereby bridging together the ESCRT-III and ESCRT-I complexes
CC (PubMed:10744743, PubMed:11525164, PubMed:27541325). Together with
CC PEF1, 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 (PubMed:8560270). May mediate Ca(2+)-regulated
CC signals 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 (PubMed:12024023). 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:0000269|PubMed:10744743,
CC ECO:0000269|PubMed:11525164, ECO:0000269|PubMed:12024023,
CC ECO:0000269|PubMed:27541325, ECO:0000305|PubMed:12024023}.
CC -!- FUNCTION: [Isoform 2]: Has a lower Ca(2+) affinity than isoform 1
CC (PubMed:10744743). {ECO:0000269|PubMed:10744743}.
CC -!- SUBUNIT: Homodimer and heterodimer; heterodimerizes (via the EF-hand 5)
CC with PEF1 (PubMed:10200558, PubMed:11525164, PubMed:27541325). Isoform
CC 1 and isoform 2 self-associate; probably forming homodimers (By
CC similarity). Interacts with CPNE4 (via VWFA domain) (PubMed:12522145).
CC Interacts with PDCD6IP; the interaction is calcium-dependent
CC (PubMed:10200558, PubMed:10744743, PubMed:11525164). Interacts with
CC RBM22 (By similarity). Interacts with PLSCR4 (By similarity). Interacts
CC with ANXA7 and TSG101 (By similarity). Interacts with DAPK1 (By
CC similarity). Interacts with SEC31A; the interaction is calcium-
CC dependent and promotes monoubiquitination of SEC31A (By similarity).
CC Interacts with ANXA11 (via N-terminus); the interaction is calcium-
CC dependent (By similarity). Interacts with PLSCR3 (via N-terminus); the
CC interaction is calcium-dependent (By similarity). Interacts with
CC MCOLN1; the interaction is calcium-dependent (By similarity). Interacts
CC with KDR; the interaction is calcium-dependent (By similarity).
CC Interacts with HEBP2; the interaction is calcium-dependent (By
CC similarity). Interacts with TFG (By similarity). Isoform 1: Interacts
CC with SHISA5, leading to stabilize it (PubMed:17889823). Isoform 2: Does
CC not interact with SHISA5 (PubMed:17889823). Isoform 2: Does not
CC interact with PDCD6IP, TSG101, ANXA7 and ANXA11 (PubMed:10744743).
CC {ECO:0000250|UniProtKB:O75340, ECO:0000269|PubMed:10200558,
CC ECO:0000269|PubMed:10744743, ECO:0000269|PubMed:11525164,
CC ECO:0000269|PubMed:12522145, ECO:0000269|PubMed:17889823,
CC ECO:0000269|PubMed:27541325}.
CC -!- INTERACTION:
CC P12815; P25445: FAS; Xeno; NbExp=2; IntAct=EBI-309164, EBI-494743;
CC P12815; Q8N114: SHISA5; Xeno; NbExp=5; IntAct=EBI-309164, EBI-2115556;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O75340}; 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. Translocated
CC from the cytoplasm to the nucleus after heat shock cell treatment.
CC Accumulates in cytoplasmic vesicle-like organelles after heat shock
CC treatment, which may represent stress granules. In response to calcium
CC increase, relocates from cytoplasm to COPII vesicle coat. Localizes to
CC endoplasmic reticulum exit site (ERES). {ECO:0000250|UniProtKB:O75340}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=ALG-2,5;
CC IsoId=P12815-1; Sequence=Displayed;
CC Name=2; Synonyms=ALG-2,1;
CC IsoId=P12815-2; Sequence=VSP_047715;
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
CC (PubMed:11525164). A one-residue insertion in the EF5-binding loop
CC prevents the glutamyl residue at the C-terminal end of the loop from
CC serving as the canonical bidentate calcium ligand (PubMed:11525164).
CC EF5 acts as a high-affinity magnesium-binding domain instead
CC (PubMed:27541325). Magnesium, may affect dimerization
CC (PubMed:27541325). EF5 may bind either calcium or magnesium depending
CC on the context. {ECO:0000269|PubMed:11525164,
CC ECO:0000269|PubMed:27541325, ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:12024023). Mice
CC develop normally and display no obvious immune defect
CC (PubMed:12024023). T-cells retain susceptibility to apoptotic stimuli
CC (PubMed:12024023). {ECO:0000269|PubMed:12024023}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA33064.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U49112; AAB38108.1; -; mRNA.
DR EMBL; AK008610; BAB25775.1; -; mRNA.
DR EMBL; AK028223; BAC25823.1; -; mRNA.
DR EMBL; AK150335; BAE29477.1; -; mRNA.
DR EMBL; BC040079; AAH40079.1; -; mRNA.
DR EMBL; X14938; CAA33064.1; ALT_INIT; mRNA.
DR CCDS; CCDS26642.1; -. [P12815-1]
DR CCDS; CCDS88484.1; -. [P12815-2]
DR RefSeq; NP_035181.1; NM_011051.3. [P12815-1]
DR RefSeq; XP_006517219.1; XM_006517156.1.
DR PDB; 1HQV; X-ray; 2.30 A; A=1-191.
DR PDB; 5JJG; X-ray; 1.72 A; A=24-191.
DR PDBsum; 1HQV; -.
DR PDBsum; 5JJG; -.
DR AlphaFoldDB; P12815; -.
DR SMR; P12815; -.
DR BioGRID; 202071; 21.
DR ELM; P12815; -.
DR IntAct; P12815; 10.
DR MINT; P12815; -.
DR STRING; 10090.ENSMUSP00000022060; -.
DR PhosphoSitePlus; P12815; -.
DR EPD; P12815; -.
DR jPOST; P12815; -.
DR MaxQB; P12815; -.
DR PaxDb; P12815; -.
DR PeptideAtlas; P12815; -.
DR PRIDE; P12815; -.
DR ProteomicsDB; 288013; -. [P12815-1]
DR ProteomicsDB; 288014; -. [P12815-2]
DR Antibodypedia; 36748; 327 antibodies from 34 providers.
DR DNASU; 18570; -.
DR Ensembl; ENSMUST00000022060; ENSMUSP00000022060; ENSMUSG00000021576. [P12815-1]
DR Ensembl; ENSMUST00000222759; ENSMUSP00000152458; ENSMUSG00000021576. [P12815-2]
DR GeneID; 18570; -.
DR KEGG; mmu:18570; -.
DR UCSC; uc007rey.2; mouse. [P12815-1]
DR CTD; 10016; -.
DR MGI; MGI:109283; Pdcd6.
DR VEuPathDB; HostDB:ENSMUSG00000021576; -.
DR eggNOG; KOG0037; Eukaryota.
DR GeneTree; ENSGT00940000160982; -.
DR HOGENOM; CLU_051357_1_1_1; -.
DR InParanoid; P12815; -.
DR OMA; SREFLWD; -.
DR OrthoDB; 1330600at2759; -.
DR PhylomeDB; P12815; -.
DR TreeFam; TF314682; -.
DR BioGRID-ORCS; 18570; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Pdcd6; mouse.
DR EvolutionaryTrace; P12815; -.
DR PRO; PR:P12815; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P12815; protein.
DR Bgee; ENSMUSG00000021576; Expressed in small intestine Peyer's patch and 255 other tissues.
DR Genevisible; P12815; MM.
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; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IMP:UniProtKB.
DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISS:UniProtKB.
DR GO; GO:0043495; F:protein-membrane adaptor activity; ISO:MGI.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:MGI.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0034605; P:cellular response to heat; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISS:UniProtKB.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:1902527; P:positive regulation of protein monoubiquitination; ISS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; ISS:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Angiogenesis; Apoptosis;
KW Calcium; Cytoplasm; Cytoplasmic vesicle; Endoplasmic reticulum; Endosome;
KW Magnesium; 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 /id="PRO_0000073730"
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:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 38
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:11525164,
FT ECO:0007744|PDB:1HQV"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 103
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 105
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 107
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 109
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:11525164, ECO:0007744|PDB:1HQV"
FT BINDING 169
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:27541325,
FT ECO:0007744|PDB:1HQV, ECO:0007744|PDB:5JJG"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:27541325,
FT ECO:0007744|PDB:1HQV, ECO:0007744|PDB:5JJG"
FT BINDING 173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:27541325,
FT ECO:0007744|PDB:1HQV, ECO:0007744|PDB:5JJG"
FT BINDING 175
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:27541325,
FT ECO:0007744|PDB:1HQV, ECO:0007744|PDB:5JJG"
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 /evidence="ECO:0000305"
FT /id="VSP_047715"
FT MUTAGEN 169
FT /note="D->A: Abolishes magnesium and calcium-binding to the
FT EF-hand 5 domain (EF5)."
FT /evidence="ECO:0000269|PubMed:27541325"
FT HELIX 25..35
FT /evidence="ECO:0007829|PDB:5JJG"
FT STRAND 41..43
FT /evidence="ECO:0007829|PDB:1HQV"
FT HELIX 45..51
FT /evidence="ECO:0007829|PDB:5JJG"
FT STRAND 55..58
FT /evidence="ECO:0007829|PDB:5JJG"
FT HELIX 62..72
FT /evidence="ECO:0007829|PDB:5JJG"
FT STRAND 74..80
FT /evidence="ECO:0007829|PDB:5JJG"
FT HELIX 82..102
FT /evidence="ECO:0007829|PDB:5JJG"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:5JJG"
FT HELIX 112..121
FT /evidence="ECO:0007829|PDB:5JJG"
FT HELIX 128..138
FT /evidence="ECO:0007829|PDB:5JJG"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:5JJG"
FT HELIX 148..168
FT /evidence="ECO:0007829|PDB:5JJG"
FT HELIX 180..190
FT /evidence="ECO:0007829|PDB:5JJG"
SQ SEQUENCE 191 AA; 21867 MW; 2704E984BF7F6F40 CRC64;
MAAYSYRPGP GGGPGPAAGA ALPDQSFLWN VFQRVDKDRS GVISDNELQQ ALSNGTWTPF
NPVTVRSIIS MFDRENKAGV NFSEFTGVWK YITDWQNVFR TYDRDNSGMI DKNELKQALS
GFGYRLSDQF HDILIRKFDR QGRGQIAFDD FIQGCIVLQR LTDIFRRYDT DQDGWIQVSY
EQYLSMVFSI V
