DRAM2_HUMAN
ID DRAM2_HUMAN Reviewed; 266 AA.
AC Q6UX65; B3SUG9; Q4VWF6; Q86VD3; Q8NBQ4;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=DNA damage-regulated autophagy modulator protein 2;
DE AltName: Full=Transmembrane protein 77;
GN Name=DRAM2; Synonyms=TMEM77; ORFNames=PSEC0031, UNQ154/PRO180;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Xu J., Xie Y., Mao Y.;
RT "Identification of a novel human putative transmembrane protein that is up-
RT regulated in hepatoma.";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Seo Y.-J., Kim K., Park J.;
RT "Cloning of DRAM-like protein.";
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Eye;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 100-266.
RC TISSUE=Teratocarcinoma;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=19895784; DOI=10.1016/j.bbrc.2009.10.149;
RA Park S.M., Kim K., Lee E.J., Kim B.K., Lee T.J., Seo T., Jang I.S.,
RA Lee S.H., Kim S., Lee J.H., Park J.;
RT "Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell
RT death.";
RL Biochem. Biophys. Res. Commun. 390:1340-1344(2009).
RN [9]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19556885; DOI=10.4161/cc.8.14.9050;
RA O'Prey J., Skommer J., Wilkinson S., Ryan K.M.;
RT "Analysis of DRAM-related proteins reveals evolutionarily conserved and
RT divergent roles in the control of autophagy.";
RL Cell Cycle 8:2260-2265(2009).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, INVOLVEMENT IN CORD21, AND VARIANTS CORD21
RP ALA-22 DEL; HIS-27; ASN-44; 73-VAL--TYR-75 DEL AND LEU-121.
RX PubMed=25983245; DOI=10.1016/j.ajhg.2015.04.006;
RG UK Inherited Retinal Disease Consortium;
RA El-Asrag M.E., Sergouniotis P.I., McKibbin M., Plagnol V., Sheridan E.,
RA Waseem N., Abdelhamed Z., McKeefry D., Van Schil K., Poulter J.A.,
RA Johnson C.A., Carr I.M., Leroy B.P., De Baere E., Inglehearn C.F.,
RA Webster A.R., Toomes C., Ali M.;
RT "Biallelic mutations in the autophagy regulator DRAM2 cause retinal
RT dystrophy with early macular involvement.";
RL Am. J. Hum. Genet. 96:948-954(2015).
CC -!- FUNCTION: Plays a role in the initiation of autophagy. In the retina,
CC might be involved in the process of photoreceptor cells renewal and
CC recycling to preserve visual function. Induces apoptotic cell death
CC when coexpressed with DRAM1. {ECO:0000269|PubMed:19895784,
CC ECO:0000269|PubMed:25983245}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:19556885,
CC ECO:0000269|PubMed:19895784}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19556885, ECO:0000269|PubMed:19895784}.
CC Photoreceptor inner segment {ECO:0000250|UniProtKB:Q9CR48}. Apical cell
CC membrane {ECO:0000250|UniProtKB:Q9CR48}. Note=Localized to
CC photoreceptor inner segments and to the apical surface of retinal
CC pigment epithelial cells. {ECO:0000250|UniProtKB:Q9CR48}.
CC -!- TISSUE SPECIFICITY: Expression is down-regulated in ovarian tumors (at
CC protein level). Widely expressed with highest levels in placenta and
CC heart. Expressed in the retina. Not detected in brain or thymus.
CC {ECO:0000269|PubMed:19556885, ECO:0000269|PubMed:19895784,
CC ECO:0000269|PubMed:25983245}.
CC -!- INDUCTION: Not induced by p53/TP53 or TP73/p73.
CC {ECO:0000269|PubMed:19556885}.
CC -!- DISEASE: Cone-rod dystrophy 21 (CORD21) [MIM:616502]: A form of cone-
CC rod dystrophy, an inherited retinal dystrophy characterized by retinal
CC pigment deposits visible on fundus examination, predominantly in the
CC macular region, and initial loss of cone photoreceptors followed by rod
CC degeneration. This leads to decreased visual acuity and sensitivity in
CC the central visual field, followed by loss of peripheral vision. Severe
CC loss of vision occurs earlier than in retinitis pigmentosa, due to cone
CC photoreceptors degenerating at a higher rate than rod photoreceptors.
CC {ECO:0000269|PubMed:25983245}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DRAM/TMEM150 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC11562.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY336747; AAR02410.1; -; mRNA.
DR EMBL; EF710624; ABR27678.1; -; mRNA.
DR EMBL; AY358492; AAQ88856.1; -; mRNA.
DR EMBL; AL355816; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56464.1; -; Genomic_DNA.
DR EMBL; BC047025; AAH47025.3; -; mRNA.
DR EMBL; BC091509; AAH91509.1; -; mRNA.
DR EMBL; AK075350; BAC11562.1; ALT_INIT; mRNA.
DR CCDS; CCDS30801.1; -.
DR RefSeq; NP_848549.3; NM_178454.4.
DR RefSeq; XP_005270526.1; XM_005270469.2.
DR RefSeq; XP_005270527.1; XM_005270470.1.
DR RefSeq; XP_011539009.1; XM_011540707.1.
DR RefSeq; XP_011539010.1; XM_011540708.1.
DR AlphaFoldDB; Q6UX65; -.
DR BioGRID; 126108; 5.
DR IntAct; Q6UX65; 5.
DR STRING; 9606.ENSP00000286692; -.
DR TCDB; 8.A.113.1.9; the tentonin or tmem150 (tmem150) family.
DR iPTMnet; Q6UX65; -.
DR PhosphoSitePlus; Q6UX65; -.
DR SwissPalm; Q6UX65; -.
DR BioMuta; DRAM2; -.
DR DMDM; 74749415; -.
DR EPD; Q6UX65; -.
DR jPOST; Q6UX65; -.
DR MassIVE; Q6UX65; -.
DR MaxQB; Q6UX65; -.
DR PaxDb; Q6UX65; -.
DR PeptideAtlas; Q6UX65; -.
DR PRIDE; Q6UX65; -.
DR ProteomicsDB; 67568; -.
DR Antibodypedia; 20104; 78 antibodies from 19 providers.
DR DNASU; 128338; -.
DR Ensembl; ENST00000286692.8; ENSP00000286692.4; ENSG00000156171.15.
DR Ensembl; ENST00000484310.6; ENSP00000503400.1; ENSG00000156171.15.
DR Ensembl; ENST00000539140.6; ENSP00000437718.1; ENSG00000156171.15.
DR GeneID; 128338; -.
DR KEGG; hsa:128338; -.
DR MANE-Select; ENST00000484310.6; ENSP00000503400.1; NM_001349884.2; NP_001336813.1.
DR UCSC; uc001ead.5; human.
DR CTD; 128338; -.
DR DisGeNET; 128338; -.
DR GeneCards; DRAM2; -.
DR HGNC; HGNC:28769; DRAM2.
DR HPA; ENSG00000156171; Low tissue specificity.
DR MalaCards; DRAM2; -.
DR MIM; 613360; gene.
DR MIM; 616502; phenotype.
DR neXtProt; NX_Q6UX65; -.
DR OpenTargets; ENSG00000156171; -.
DR Orphanet; 1872; Cone rod dystrophy.
DR PharmGKB; PA165751270; -.
DR VEuPathDB; HostDB:ENSG00000156171; -.
DR eggNOG; KOG4320; Eukaryota.
DR GeneTree; ENSGT01030000234578; -.
DR HOGENOM; CLU_059992_2_2_1; -.
DR InParanoid; Q6UX65; -.
DR OMA; IYMLVQT; -.
DR OrthoDB; 1199230at2759; -.
DR PhylomeDB; Q6UX65; -.
DR TreeFam; TF314508; -.
DR PathwayCommons; Q6UX65; -.
DR SignaLink; Q6UX65; -.
DR SIGNOR; Q6UX65; -.
DR BioGRID-ORCS; 128338; 13 hits in 1075 CRISPR screens.
DR ChiTaRS; DRAM2; human.
DR GenomeRNAi; 128338; -.
DR Pharos; Q6UX65; Tbio.
DR PRO; PR:Q6UX65; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q6UX65; protein.
DR Bgee; ENSG00000156171; Expressed in monocyte and 180 other tissues.
DR ExpressionAtlas; Q6UX65; baseline and differential.
DR Genevisible; Q6UX65; HS.
DR GO; GO:0016324; C:apical plasma membrane; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0001917; C:photoreceptor inner segment; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0007601; P:visual perception; IMP:UniProtKB.
DR InterPro; IPR032990; DRAM2.
DR InterPro; IPR019402; Frag1/DRAM/Sfk1.
DR PANTHER; PTHR21324:SF10; PTHR21324:SF10; 1.
DR Pfam; PF10277; Frag1; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Autophagy; Cell membrane; Cone-rod dystrophy; Disease variant;
KW Lysosome; Membrane; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..266
FT /note="DNA damage-regulated autophagy modulator protein 2"
FT /id="PRO_0000254102"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 118..138
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 207..227
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VARIANT 22
FT /note="Missing (in CORD21)"
FT /evidence="ECO:0000269|PubMed:25983245"
FT /id="VAR_075073"
FT VARIANT 27
FT /note="Y -> H (in CORD21; dbSNP:rs786205662)"
FT /evidence="ECO:0000269|PubMed:25983245"
FT /id="VAR_075074"
FT VARIANT 44
FT /note="S -> N (in CORD21; dbSNP:rs786205665)"
FT /evidence="ECO:0000269|PubMed:25983245"
FT /id="VAR_075075"
FT VARIANT 73..75
FT /note="Missing (in CORD21)"
FT /evidence="ECO:0000269|PubMed:25983245"
FT /id="VAR_075076"
FT VARIANT 121
FT /note="H -> L (in CORD21; dbSNP:rs786205664)"
FT /evidence="ECO:0000269|PubMed:25983245"
FT /id="VAR_075077"
FT CONFLICT 221
FT /note="G -> V (in Ref. 1; AAR02410)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 266 AA; 29766 MW; 4F91D5C212D458E5 CRC64;
MWWFQQGLSF LPSALVIWTS AAFIFSYITA VTLHHIDPAL PYISDTGTVA PEKCLFGAML
NIAAVLCIAT IYVRYKQVHA LSPEENVIIK LNKAGLVLGI LSCLGLSIVA NFQKTTLFAA
HVSGAVLTFG MGSLYMFVQT ILSYQMQPKI HGKQVFWIRL LLVIWCGVSA LSMLTCSSVL
HSGNFGTDLE QKLHWNPEDK GYVLHMITTA AEWSMSFSFF GFFLTYIRDF QKISLRVEAN
LHGLTLYDTA PCPINNERTR LLSRDI
