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Protein

Transmembrane protein 64

Gene

TMEM64

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

Positively regulates TNFSF11-induced osteoclast differentiation. Acts as a regulator of TNFSF11-mediated Ca2+ signaling pathways via its interaction with SERCA2 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation. Negatively regulates osteoblast differentiation and positively regulates adipocyte differentiation via modulation of the canonical Wnt signaling pathway. Mediates the switch in lineage commitment to osteogenesis rather than to adipogenesis in mesenchymal stem cells by negatively regulating the expression, activity and nuclear localization of CTNNB1.By similarity

GO - Biological processi

Complete GO annotation...

Protein family/group databases

TCDBi9.B.27.5.1. the deda or ydjx-z (deda) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protein 64
Gene namesi
Name:TMEM64
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:25441. TMEM64.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei50 – 7021HelicalSequence analysisAdd
BLAST
Transmembranei84 – 10421HelicalSequence analysisAdd
BLAST
Transmembranei120 – 14021HelicalSequence analysisAdd
BLAST
Transmembranei160 – 18021HelicalSequence analysisAdd
BLAST
Transmembranei188 – 20821HelicalSequence analysisAdd
BLAST
Transmembranei308 – 32821HelicalSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142670777.

Polymorphism and mutation databases

BioMutaiTMEM64.
DMDMi147736782.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 380380Transmembrane protein 64PRO_0000287342Add
BLAST

Proteomic databases

MaxQBiQ6YI46.
PaxDbiQ6YI46.
PeptideAtlasiQ6YI46.
PRIDEiQ6YI46.

PTM databases

iPTMnetiQ6YI46.
PhosphoSiteiQ6YI46.

Expressioni

Gene expression databases

BgeeiENSG00000180694.
CleanExiHS_TMEM64.
ExpressionAtlasiQ6YI46. baseline and differential.
GenevisibleiQ6YI46. HS.

Organism-specific databases

HPAiCAB034221.

Interactioni

Subunit structurei

Interacts with ATP2A2.By similarity

Protein-protein interaction databases

BioGridi127978. 1 interaction.
STRINGi9606.ENSP00000414786.

Structurei

3D structure databases

ProteinModelPortaliQ6YI46.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the TVP38/TMEM64 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3140. Eukaryota.
COG0398. LUCA.
GeneTreeiENSGT00390000007813.
HOGENOMiHOG000065765.
HOVERGENiHBG103402.
InParanoidiQ6YI46.
OMAiGMGLMMV.
OrthoDBiEOG091G0E5P.
PhylomeDBiQ6YI46.
TreeFamiTF323931.

Family and domain databases

InterProiIPR032816. SNARE_assoc.
IPR015414. TMEM64/TMEM41.
[Graphical view]
PANTHERiPTHR12677. PTHR12677. 1 hit.
PfamiPF09335. SNARE_assoc. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6YI46-1) [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
MRSPGGILLQ ALPRLLQHAA LPGLAELPAR WALPRGAGGD GPADRLPRGG
60 70 80 90 100
GASAAAAAAA ASGALLGAYL ERHGPPEASE LPEPGGALAG GPGSGGGGVV
110 120 130 140 150
VGVAEVRNWR CCCLGSTCWC RSLVLVCVLA ALCFASLALV RRYLHHLLLW
160 170 180 190 200
VESLDSLLGV LLFVVGFIVV SFPCGWGYIV LNVAAGYLYG FVLGMGLMMV
210 220 230 240 250
GVLIGTFIAH VVCKRLLTAW VAARIQSSEK LSAVIRVVEG GSGLKVVALA
260 270 280 290 300
RLTPIPFGLQ NAVFSITDLS LPNYLMASSV GLLPTQLLNS YLGTTLRTME
310 320 330 340 350
DVIAEQSVSG YFVFCLQIII SIGLMFYVVH RAQVELNAAI VACEMELKSS
360 370 380
LVKGNQPNTS GSSFYNKRTL TFSGGGINVV
Length:380
Mass (Da):39,665
Last modified:May 15, 2007 - v2
Checksum:i4A57C0802C9265C2
GO
Isoform 2 (identifier: Q6YI46-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-261: Missing.
     262-265: AVFS → MPPR

Show »
Length:119
Mass (Da):12,953
Checksum:i9216DAA8BE2F3376
GO
Isoform 3 (identifier: Q6YI46-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-194: Missing.
     266-317: Missing.

Note: No experimental confirmation available.
Show »
Length:134
Mass (Da):14,250
Checksum:iF3D8BEB5D6047F95
GO
Isoform 4 (identifier: Q6YI46-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     266-317: Missing.

Note: No experimental confirmation available.
Show »
Length:328
Mass (Da):33,968
Checksum:i5B56F4566F0F118F
GO

Sequence cautioni

The sequence AAN05737 differs from that shown. Reason: Erroneous initiation. Curated
The sequence CAD39028 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti66 – 661L → S in AAN05737 (Ref. 4) Curated
Sequence conflicti333 – 3331Q → L in BAG62282 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 261261Missing in isoform 2. 1 PublicationVSP_025441Add
BLAST
Alternative sequencei1 – 194194Missing in isoform 3. 1 PublicationVSP_044998Add
BLAST
Alternative sequencei262 – 2654AVFS → MPPR in isoform 2. 1 PublicationVSP_025442
Alternative sequencei266 – 31752Missing in isoform 3 and isoform 4. 1 PublicationVSP_044999Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK300583 mRNA. Translation: BAG62282.1.
AB015752 Genomic DNA. No translation available.
AC093329 Genomic DNA. No translation available.
AC106038 Genomic DNA. No translation available.
BC113828 mRNA. Translation: AAI13829.1.
AY147881 mRNA. Translation: AAN05737.1. Different initiation.
AL834364 mRNA. Translation: CAD39028.2. Different initiation.
CCDSiCCDS34920.2. [Q6YI46-1]
CCDS55260.1. [Q6YI46-4]
RefSeqiNP_001008495.2. NM_001008495.3. [Q6YI46-1]
NP_001139745.1. NM_001146273.1. [Q6YI46-4]
UniGeneiHs.567759.
Hs.737401.

Genome annotation databases

EnsembliENST00000418210; ENSP00000411951; ENSG00000180694. [Q6YI46-4]
ENST00000458549; ENSP00000414786; ENSG00000180694. [Q6YI46-1]
ENST00000519519; ENSP00000429832; ENSG00000180694. [Q6YI46-2]
GeneIDi169200.
KEGGihsa:169200.
UCSCiuc003yen.3. human. [Q6YI46-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK300583 mRNA. Translation: BAG62282.1.
AB015752 Genomic DNA. No translation available.
AC093329 Genomic DNA. No translation available.
AC106038 Genomic DNA. No translation available.
BC113828 mRNA. Translation: AAI13829.1.
AY147881 mRNA. Translation: AAN05737.1. Different initiation.
AL834364 mRNA. Translation: CAD39028.2. Different initiation.
CCDSiCCDS34920.2. [Q6YI46-1]
CCDS55260.1. [Q6YI46-4]
RefSeqiNP_001008495.2. NM_001008495.3. [Q6YI46-1]
NP_001139745.1. NM_001146273.1. [Q6YI46-4]
UniGeneiHs.567759.
Hs.737401.

3D structure databases

ProteinModelPortaliQ6YI46.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127978. 1 interaction.
STRINGi9606.ENSP00000414786.

Protein family/group databases

TCDBi9.B.27.5.1. the deda or ydjx-z (deda) family.

PTM databases

iPTMnetiQ6YI46.
PhosphoSiteiQ6YI46.

Polymorphism and mutation databases

BioMutaiTMEM64.
DMDMi147736782.

Proteomic databases

MaxQBiQ6YI46.
PaxDbiQ6YI46.
PeptideAtlasiQ6YI46.
PRIDEiQ6YI46.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000418210; ENSP00000411951; ENSG00000180694. [Q6YI46-4]
ENST00000458549; ENSP00000414786; ENSG00000180694. [Q6YI46-1]
ENST00000519519; ENSP00000429832; ENSG00000180694. [Q6YI46-2]
GeneIDi169200.
KEGGihsa:169200.
UCSCiuc003yen.3. human. [Q6YI46-1]

Organism-specific databases

CTDi169200.
GeneCardsiTMEM64.
H-InvDBHIX0007640.
HGNCiHGNC:25441. TMEM64.
HPAiCAB034221.
neXtProtiNX_Q6YI46.
PharmGKBiPA142670777.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3140. Eukaryota.
COG0398. LUCA.
GeneTreeiENSGT00390000007813.
HOGENOMiHOG000065765.
HOVERGENiHBG103402.
InParanoidiQ6YI46.
OMAiGMGLMMV.
OrthoDBiEOG091G0E5P.
PhylomeDBiQ6YI46.
TreeFamiTF323931.

Miscellaneous databases

ChiTaRSiTMEM64. human.
GenomeRNAii169200.
PROiQ6YI46.

Gene expression databases

BgeeiENSG00000180694.
CleanExiHS_TMEM64.
ExpressionAtlasiQ6YI46. baseline and differential.
GenevisibleiQ6YI46. HS.

Family and domain databases

InterProiIPR032816. SNARE_assoc.
IPR015414. TMEM64/TMEM41.
[Graphical view]
PANTHERiPTHR12677. PTHR12677. 1 hit.
PfamiPF09335. SNARE_assoc. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTMM64_HUMAN
AccessioniPrimary (citable) accession number: Q6YI46
Secondary accession number(s): B4DUC0
, F5GXM4, Q2HIZ7, Q8N3G6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 15, 2007
Last sequence update: May 15, 2007
Last modified: September 7, 2016
This is version 95 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. 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.