TMM64_HUMAN
ID TMM64_HUMAN Reviewed; 380 AA.
AC Q6YI46; B4DUC0; F5GXM4; Q2HIZ7; Q8N3G6;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Transmembrane protein 64;
GN Name=TMEM64;
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 [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 66-380 (ISOFORM 1).
RC TISSUE=Testis;
RA Ding P., Jin C., Han W., Wang L., Song Q., Zhang Y., Ma D.;
RL Submitted (SEP-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 99-380 (ISOFORM 1).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
CC -!- FUNCTION: Positively regulates TNFSF11-induced osteoclast
CC differentiation. Acts as a regulator of TNFSF11-mediated Ca(2+)
CC signaling pathways via its interaction with SERCA2 which is critical
CC for the TNFSF11-induced CREB1 activation and mitochondrial ROS
CC generation necessary for proper osteoclast generation. Association
CC between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking
CC for activation of NFATC1 and production of mitochondrial ROS, thereby
CC triggering Ca (2+) signaling cascades that promote osteoclast
CC differentiation and activation. Negatively regulates osteoblast
CC differentiation and positively regulates adipocyte differentiation via
CC modulation of the canonical Wnt signaling pathway. Mediates the switch
CC in lineage commitment to osteogenesis rather than to adipogenesis in
CC mesenchymal stem cells by negatively regulating the expression,
CC activity and nuclear localization of CTNNB1.
CC {ECO:0000250|UniProtKB:Q3U145}.
CC -!- SUBUNIT: Interacts with ATP2A2. {ECO:0000250|UniProtKB:Q3U145}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q3U145}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6YI46-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6YI46-2; Sequence=VSP_025441, VSP_025442;
CC Name=3;
CC IsoId=Q6YI46-3; Sequence=VSP_044998, VSP_044999;
CC Name=4;
CC IsoId=Q6YI46-4; Sequence=VSP_044999;
CC -!- DOMAIN: The VTT domain was previously called the SNARE-assoc domain. As
CC there is no evidence that this domain associates with SNARE proteins,
CC it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain.
CC {ECO:0000250|UniProtKB:P36164}.
CC -!- SIMILARITY: Belongs to the TVP38/TMEM64 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAN05737.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=CAD39028.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK300583; BAG62282.1; -; mRNA.
DR EMBL; AB015752; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC106038; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113828; AAI13829.1; -; mRNA.
DR EMBL; AY147881; AAN05737.1; ALT_INIT; mRNA.
DR EMBL; AL834364; CAD39028.2; ALT_INIT; mRNA.
DR CCDS; CCDS34920.2; -. [Q6YI46-1]
DR CCDS; CCDS55260.1; -. [Q6YI46-4]
DR RefSeq; NP_001008495.2; NM_001008495.3. [Q6YI46-1]
DR RefSeq; NP_001139745.1; NM_001146273.1. [Q6YI46-4]
DR AlphaFoldDB; Q6YI46; -.
DR SMR; Q6YI46; -.
DR BioGRID; 127978; 6.
DR STRING; 9606.ENSP00000414786; -.
DR TCDB; 9.B.27.5.1; the death effector domain a (deda) family.
DR iPTMnet; Q6YI46; -.
DR PhosphoSitePlus; Q6YI46; -.
DR BioMuta; TMEM64; -.
DR DMDM; 147736782; -.
DR EPD; Q6YI46; -.
DR jPOST; Q6YI46; -.
DR MassIVE; Q6YI46; -.
DR MaxQB; Q6YI46; -.
DR PaxDb; Q6YI46; -.
DR PeptideAtlas; Q6YI46; -.
DR PRIDE; Q6YI46; -.
DR ProteomicsDB; 24468; -.
DR ProteomicsDB; 67851; -. [Q6YI46-1]
DR ProteomicsDB; 67852; -. [Q6YI46-2]
DR Antibodypedia; 77108; 32 antibodies from 8 providers.
DR DNASU; 169200; -.
DR Ensembl; ENST00000418210.2; ENSP00000411951.2; ENSG00000180694.14. [Q6YI46-4]
DR Ensembl; ENST00000458549.7; ENSP00000414786.2; ENSG00000180694.14. [Q6YI46-1]
DR Ensembl; ENST00000519519.5; ENSP00000429832.1; ENSG00000180694.14. [Q6YI46-2]
DR GeneID; 169200; -.
DR KEGG; hsa:169200; -.
DR MANE-Select; ENST00000458549.7; ENSP00000414786.2; NM_001008495.4; NP_001008495.2.
DR UCSC; uc003yen.3; human. [Q6YI46-1]
DR CTD; 169200; -.
DR DisGeNET; 169200; -.
DR GeneCards; TMEM64; -.
DR HGNC; HGNC:25441; TMEM64.
DR HPA; ENSG00000180694; Tissue enhanced (epididymis).
DR neXtProt; NX_Q6YI46; -.
DR OpenTargets; ENSG00000180694; -.
DR PharmGKB; PA142670777; -.
DR VEuPathDB; HostDB:ENSG00000180694; -.
DR eggNOG; KOG3140; Eukaryota.
DR GeneTree; ENSGT00390000007813; -.
DR HOGENOM; CLU_069147_0_0_1; -.
DR InParanoid; Q6YI46; -.
DR OMA; LMVYIVQ; -.
DR OrthoDB; 1327131at2759; -.
DR PhylomeDB; Q6YI46; -.
DR TreeFam; TF323931; -.
DR PathwayCommons; Q6YI46; -.
DR BioGRID-ORCS; 169200; 19 hits in 1080 CRISPR screens.
DR ChiTaRS; TMEM64; human.
DR GenomeRNAi; 169200; -.
DR Pharos; Q6YI46; Tdark.
DR PRO; PR:Q6YI46; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q6YI46; protein.
DR Bgee; ENSG00000180694; Expressed in corpus epididymis and 193 other tissues.
DR ExpressionAtlas; Q6YI46; baseline and differential.
DR Genevisible; Q6YI46; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl.
DR GO; GO:0045780; P:positive regulation of bone resorption; IBA:GO_Central.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IBA:GO_Central.
DR GO; GO:0043462; P:regulation of ATP-dependent activity; IEA:Ensembl.
DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR InterPro; IPR032816; SNARE_assoc.
DR Pfam; PF09335; SNARE_assoc; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..380
FT /note="Transmembrane protein 64"
FT /id="PRO_0000287342"
FT TRANSMEM 50..70
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 120..140
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 186..296
FT /note="VTT domain"
FT /evidence="ECO:0000250|UniProtKB:P36164"
FT VAR_SEQ 1..261
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025441"
FT VAR_SEQ 1..194
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044998"
FT VAR_SEQ 262..265
FT /note="AVFS -> MPPR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025442"
FT VAR_SEQ 266..317
FT /note="Missing (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044999"
FT CONFLICT 66
FT /note="L -> S (in Ref. 4; AAN05737)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="Q -> L (in Ref. 1; BAG62282)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 380 AA; 39665 MW; 4A57C0802C9265C2 CRC64;
MRSPGGILLQ ALPRLLQHAA LPGLAELPAR WALPRGAGGD GPADRLPRGG GASAAAAAAA
ASGALLGAYL ERHGPPEASE LPEPGGALAG GPGSGGGGVV VGVAEVRNWR CCCLGSTCWC
RSLVLVCVLA ALCFASLALV RRYLHHLLLW VESLDSLLGV LLFVVGFIVV SFPCGWGYIV
LNVAAGYLYG FVLGMGLMMV GVLIGTFIAH VVCKRLLTAW VAARIQSSEK LSAVIRVVEG
GSGLKVVALA RLTPIPFGLQ NAVFSITDLS LPNYLMASSV GLLPTQLLNS YLGTTLRTME
DVIAEQSVSG YFVFCLQIII SIGLMFYVVH RAQVELNAAI VACEMELKSS LVKGNQPNTS
GSSFYNKRTL TFSGGGINVV
