TM222_HUMAN
ID TM222_HUMAN Reviewed; 208 AA.
AC Q9H0R3; D3DPL6; Q53HD8; Q5FVE9;
DT 22-AUG-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2006, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Transmembrane protein 222;
GN Name=TMEM222; Synonyms=C1orf160;
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 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 [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 18-208 (ISOFORM 1).
RC TISSUE=Lung carcinoma, and Spinal ganglion;
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 [LARGE SCALE MRNA] OF 12-208 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 24-208 (ISOFORM 1).
RC TISSUE=Cerebellum;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [7]
RP VARIANTS NEDMOSBA SER-72; 112-GLN--ARG-208 DEL; MET-148; ARG-176 AND
RP VAL-179 DEL, INVOLVEMENT IN NEDMOSBA, TISSUE SPECIFICITY, AND SUBCELLULAR
RP LOCATION.
RX PubMed=33824500; DOI=10.1038/s41436-021-01133-w;
RA Polla D.L., Farazi Fard M.A., Tabatabaei Z., Habibzadeh P., Levchenko O.A.,
RA Nikuei P., Makrythanasis P., Hussain M., von Hardenberg S., Zeinali S.,
RA Fallah M.S., Schuurs-Hoeijmakers J.H.M., Shahzad M., Fatima F., Fatima N.,
RA Kaat L.D., Bruggenwirth H.T., Fleming L.R., Condie J., Ploski R.,
RA Pollak A., Pilch J., Demina N.A., Chukhrova A.L., Sergeeva V.S.,
RA Venselaar H., Masri A.T., Hamamy H., Santoni F.A., Linda K., Ahmed Z.M.,
RA Nadif Kasri N., de Brouwer A.P.M., Bergmann A.K., Hethey S., Yavarian M.,
RA Ansar M., Riazuddin S., Riazuddin S., Silawi M., Ruggeri G., Pirozzi F.,
RA Eftekhar E., Taghipour Sheshdeh A., Bahramjahan S., Mirzaa G.M.,
RA Lavrov A.V., Antonarakis S.E., Faghihi M.A., van Bokhoven H.;
RT "Biallelic variants in TMEM222 cause a new autosomal recessive
RT neurodevelopmental disorder.";
RL Genet. Med. 23:1246-1254(2021).
CC -!- INTERACTION:
CC Q9H0R3; Q13520: AQP6; NbExp=3; IntAct=EBI-347385, EBI-13059134;
CC Q9H0R3; Q13323: BIK; NbExp=3; IntAct=EBI-347385, EBI-700794;
CC Q9H0R3; J3KQ12: BSCL2; NbExp=3; IntAct=EBI-347385, EBI-11532900;
CC Q9H0R3; P11912: CD79A; NbExp=3; IntAct=EBI-347385, EBI-7797864;
CC Q9H0R3; O00501: CLDN5; NbExp=3; IntAct=EBI-347385, EBI-18400628;
CC Q9H0R3; P58418: CLRN1; NbExp=3; IntAct=EBI-347385, EBI-17274839;
CC Q9H0R3; P21964: COMT; NbExp=3; IntAct=EBI-347385, EBI-372265;
CC Q9H0R3; Q9BUF7-2: CRB3; NbExp=3; IntAct=EBI-347385, EBI-17233035;
CC Q9H0R3; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-347385, EBI-6942903;
CC Q9H0R3; Q15125: EBP; NbExp=3; IntAct=EBI-347385, EBI-3915253;
CC Q9H0R3; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-347385, EBI-18535450;
CC Q9H0R3; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-347385, EBI-711490;
CC Q9H0R3; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-347385, EBI-781551;
CC Q9H0R3; P34910-2: EVI2B; NbExp=3; IntAct=EBI-347385, EBI-17640610;
CC Q9H0R3; Q8TBP5: FAM174A; NbExp=3; IntAct=EBI-347385, EBI-18636064;
CC Q9H0R3; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-347385, EBI-18304435;
CC Q9H0R3; P31937: HIBADH; NbExp=3; IntAct=EBI-347385, EBI-11427100;
CC Q9H0R3; Q7Z5P4: HSD17B13; NbExp=3; IntAct=EBI-347385, EBI-18053395;
CC Q9H0R3; P43628: KIR2DL3; NbExp=3; IntAct=EBI-347385, EBI-8632435;
CC Q9H0R3; Q96AG4: LRRC59; NbExp=3; IntAct=EBI-347385, EBI-358888;
CC Q9H0R3; Q68D85: NCR3LG1; NbExp=3; IntAct=EBI-347385, EBI-14061804;
CC Q9H0R3; O00623: PEX12; NbExp=3; IntAct=EBI-347385, EBI-594836;
CC Q9H0R3; O14684: PTGES; NbExp=3; IntAct=EBI-347385, EBI-11161398;
CC Q9H0R3; Q86VR2: RETREG3; NbExp=3; IntAct=EBI-347385, EBI-10192441;
CC Q9H0R3; Q6P5S7: RNASEK; NbExp=3; IntAct=EBI-347385, EBI-18397230;
CC Q9H0R3; Q14973: SLC10A1; NbExp=3; IntAct=EBI-347385, EBI-3923031;
CC Q9H0R3; Q12908: SLC10A2; NbExp=3; IntAct=EBI-347385, EBI-18114847;
CC Q9H0R3; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-347385, EBI-17280858;
CC Q9H0R3; Q16623: STX1A; NbExp=3; IntAct=EBI-347385, EBI-712466;
CC Q9H0R3; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-347385, EBI-8638294;
CC Q9H0R3; Q53FP2: TMEM35A; NbExp=3; IntAct=EBI-347385, EBI-11722971;
CC Q9H0R3; O15393-2: TMPRSS2; NbExp=3; IntAct=EBI-347385, EBI-12345267;
CC Q9H0R3; Q9Y320: TMX2; NbExp=3; IntAct=EBI-347385, EBI-6447886;
CC Q9H0R3; Q96MV8: ZDHHC15; NbExp=3; IntAct=EBI-347385, EBI-12837904;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}. Cell projection, dendrite
CC {ECO:0000269|PubMed:33824500}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H0R3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H0R3-2; Sequence=VSP_020090;
CC -!- TISSUE SPECIFICITY: Widely expressed. The highest expression is
CC observed in the brain. {ECO:0000269|PubMed:33824500}.
CC -!- DISEASE: Neurodevelopmental disorder with motor and speech delay and
CC behavioral abnormalities (NEDMOSBA) [MIM:619470]: An autosomal
CC recessive disorder characterized by global developmental delay,
CC impaired intellectual development, speech delay, delayed walking, and
CC behavioral abnormalities. Some patients develop spastic tetraplegia
CC with inability to walk independently and never gain proper speech.
CC Affected individuals may have variable additional features, including
CC poor overall growth, hypotonia, tremor, ocular anomalies, seizures, and
CC non-specific dysmorphic facial features. {ECO:0000269|PubMed:33824500}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAB66618.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; FO393419; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07764.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX07766.1; -; Genomic_DNA.
DR EMBL; BC011579; AAH11579.2; -; mRNA.
DR EMBL; BC090039; AAH90039.1; -; mRNA.
DR EMBL; AL136683; CAB66618.1; ALT_INIT; mRNA.
DR EMBL; AK222642; BAD96362.1; -; mRNA.
DR CCDS; CCDS297.2; -. [Q9H0R3-1]
DR RefSeq; NP_115501.2; NM_032125.2. [Q9H0R3-1]
DR AlphaFoldDB; Q9H0R3; -.
DR BioGRID; 123860; 52.
DR IntAct; Q9H0R3; 41.
DR STRING; 9606.ENSP00000483276; -.
DR iPTMnet; Q9H0R3; -.
DR PhosphoSitePlus; Q9H0R3; -.
DR SwissPalm; Q9H0R3; -.
DR BioMuta; TMEM222; -.
DR DMDM; 112823989; -.
DR EPD; Q9H0R3; -.
DR jPOST; Q9H0R3; -.
DR MassIVE; Q9H0R3; -.
DR MaxQB; Q9H0R3; -.
DR PaxDb; Q9H0R3; -.
DR PeptideAtlas; Q9H0R3; -.
DR PRIDE; Q9H0R3; -.
DR ProteomicsDB; 80314; -. [Q9H0R3-1]
DR ProteomicsDB; 80315; -. [Q9H0R3-2]
DR Antibodypedia; 54779; 98 antibodies from 15 providers.
DR DNASU; 84065; -.
DR Ensembl; ENST00000374076.9; ENSP00000363189.4; ENSG00000186501.15. [Q9H0R3-1]
DR Ensembl; ENST00000611517.4; ENSP00000483276.1; ENSG00000186501.15. [Q9H0R3-1]
DR GeneID; 84065; -.
DR KEGG; hsa:84065; -.
DR MANE-Select; ENST00000374076.9; ENSP00000363189.4; NM_032125.3; NP_115501.2.
DR UCSC; uc001bnr.5; human. [Q9H0R3-1]
DR CTD; 84065; -.
DR GeneCards; TMEM222; -.
DR HGNC; HGNC:25363; TMEM222.
DR HPA; ENSG00000186501; Low tissue specificity.
DR MIM; 619469; gene.
DR MIM; 619470; phenotype.
DR neXtProt; NX_Q9H0R3; -.
DR PharmGKB; PA162406598; -.
DR VEuPathDB; HostDB:ENSG00000186501; -.
DR eggNOG; KOG3150; Eukaryota.
DR GeneTree; ENSGT00390000007371; -.
DR InParanoid; Q9H0R3; -.
DR OMA; SRFPYCI; -.
DR OrthoDB; 1452247at2759; -.
DR PhylomeDB; Q9H0R3; -.
DR TreeFam; TF105899; -.
DR PathwayCommons; Q9H0R3; -.
DR SignaLink; Q9H0R3; -.
DR BioGRID-ORCS; 84065; 13 hits in 1072 CRISPR screens.
DR ChiTaRS; TMEM222; human.
DR GeneWiki; Transmembrane_protein_222; -.
DR GenomeRNAi; 84065; -.
DR Pharos; Q9H0R3; Tdark.
DR PRO; PR:Q9H0R3; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H0R3; protein.
DR Bgee; ENSG00000186501; Expressed in hypothalamus and 198 other tissues.
DR ExpressionAtlas; Q9H0R3; baseline and differential.
DR Genevisible; Q9H0R3; HS.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR InterPro; IPR008496; TMEM222/RTE1.
DR PANTHER; PTHR20921; PTHR20921; 1.
DR Pfam; PF05608; DUF778; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Disease variant; Epilepsy;
KW Intellectual disability; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..208
FT /note="Transmembrane protein 222"
FT /id="PRO_0000247963"
FT TOPO_DOM 1..55
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..76
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 77..164
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 186
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 187..207
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..96
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020090"
FT VARIANT 72
FT /note="G -> S (in NEDMOSBA)"
FT /evidence="ECO:0000269|PubMed:33824500"
FT /id="VAR_086147"
FT VARIANT 112..208
FT /note="Missing (in NEDMOSBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33824500"
FT /id="VAR_086148"
FT VARIANT 148
FT /note="V -> M (in NEDMOSBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33824500"
FT /id="VAR_086149"
FT VARIANT 176
FT /note="G -> R (in NEDMOSBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33824500"
FT /id="VAR_086150"
FT VARIANT 179
FT /note="Missing (in NEDMOSBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:33824500"
FT /id="VAR_086151"
FT CONFLICT 101
FT /note="K -> E (in Ref. 5; BAD96362)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 208 AA; 23230 MW; D1FB041F151D7BB7 CRC64;
MAEAEGSSLL LLPPPPPPPR MAEVEAPTAA ETDMKQYQGS GGVAMDVERS RFPYCVVWTP
IPVLTWFFPI IGHMGICTST GVIRDFAGPY FVSEDNMAFG KPAKYWKLDP AQVYASGPNA
WDTAVHDASE EYKHRMHNLC CDNCHSHVAL ALNLMRYNNS TNWNMVTLCF FCLLYGKYVS
VGAFVKTWLP FILLLGIILT VSLVFNLR
