TMC4_HUMAN
ID TMC4_HUMAN Reviewed; 712 AA.
AC Q7Z404; Q7Z5M3; Q8N5E4; Q8TBS7;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Transmembrane channel-like protein 4;
GN Name=TMC4;
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] (ISOFORM 2), AND VARIANT GLU-17.
RX PubMed=12812529; DOI=10.1186/1471-2164-4-24;
RA Keresztes G., Mutai H., Heller S.;
RT "TMC and EVER genes belong to a larger novel family, the TMC gene family
RT encoding transmembrane proteins.";
RL BMC Genomics 4:24-24(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=12906855; DOI=10.1016/s0888-7543(03)00154-x;
RA Kurima K., Yang Y., Sorber K., Griffith A.J.;
RT "Characterization of the transmembrane channel-like (TMC) gene family:
RT functional clues from hearing loss and epidermodysplasia verruciformis.";
RL Genomics 82:300-308(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Blood, and Colon;
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).
CC -!- FUNCTION: Probable ion channel. {ECO:0000250}.
CC -!- INTERACTION:
CC Q7Z404-3; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-23725088, EBI-12070086;
CC Q7Z404-3; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-23725088, EBI-11988865;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7Z404-2; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z404-1; Sequence=VSP_026012;
CC Name=3;
CC IsoId=Q7Z404-3; Sequence=VSP_026011, VSP_026013;
CC -!- SIMILARITY: Belongs to the TMC family. {ECO:0000305}.
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DR EMBL; AY263166; AAP78781.1; -; mRNA.
DR EMBL; AY236492; AAP69870.1; -; mRNA.
DR EMBL; AC012314; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025323; AAH25323.1; -; mRNA.
DR EMBL; BC032477; AAH32477.1; -; mRNA.
DR CCDS; CCDS12882.1; -. [Q7Z404-1]
DR CCDS; CCDS46174.1; -. [Q7Z404-2]
DR RefSeq; NP_001138775.2; NM_001145303.2.
DR RefSeq; NP_653287.2; NM_144686.3.
DR AlphaFoldDB; Q7Z404; -.
DR BioGRID; 127088; 58.
DR IntAct; Q7Z404; 3.
DR STRING; 9606.ENSP00000477627; -.
DR TCDB; 1.A.17.4.14; the calcium-dependent chloride channel (ca-clc) family.
DR GlyGen; Q7Z404; 1 site.
DR iPTMnet; Q7Z404; -.
DR PhosphoSitePlus; Q7Z404; -.
DR BioMuta; TMC4; -.
DR DMDM; 296452937; -.
DR jPOST; Q7Z404; -.
DR MassIVE; Q7Z404; -.
DR MaxQB; Q7Z404; -.
DR PaxDb; Q7Z404; -.
DR PeptideAtlas; Q7Z404; -.
DR PRIDE; Q7Z404; -.
DR ProteomicsDB; 69110; -. [Q7Z404-2]
DR ProteomicsDB; 69111; -. [Q7Z404-1]
DR ProteomicsDB; 69112; -. [Q7Z404-3]
DR DNASU; 147798; -.
DR Ensembl; ENST00000618950.4; ENSP00000478046.1; ENSG00000273722.4. [Q7Z404-2]
DR Ensembl; ENST00000621671.4; ENSP00000481629.1; ENSG00000273722.4. [Q7Z404-1]
DR GeneID; 147798; -.
DR KEGG; hsa:147798; -.
DR UCSC; uc032iss.2; human. [Q7Z404-2]
DR CTD; 147798; -.
DR DisGeNET; 147798; -.
DR GeneCards; TMC4; -.
DR HGNC; HGNC:22998; TMC4.
DR neXtProt; NX_Q7Z404; -.
DR PharmGKB; PA134874063; -.
DR eggNOG; ENOG502S3W0; Eukaryota.
DR InParanoid; Q7Z404; -.
DR OrthoDB; 1048914at2759; -.
DR PhylomeDB; Q7Z404; -.
DR TreeFam; TF313462; -.
DR PathwayCommons; Q7Z404; -.
DR SignaLink; Q7Z404; -.
DR BioGRID-ORCS; 147798; 13 hits in 1069 CRISPR screens.
DR ChiTaRS; TMC4; human.
DR GenomeRNAi; 147798; -.
DR Pharos; Q7Z404; Tdark.
DR PRO; PR:Q7Z404; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q7Z404; protein.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR GO; GO:0008381; F:mechanosensitive ion channel activity; IBA:GO_Central.
DR InterPro; IPR038900; TMC.
DR InterPro; IPR012496; TMC_dom.
DR PANTHER; PTHR23302; PTHR23302; 1.
DR Pfam; PF07810; TMC; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..712
FT /note="Transmembrane channel-like protein 4"
FT /id="PRO_0000289468"
FT TOPO_DOM 1..168
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 190..249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 250..270
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 271..348
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..369
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 370..394
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 395..415
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 416..425
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 426..446
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 447..483
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 484..504
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 505..542
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 543..565
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 566..592
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..613
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 614..654
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 655..677
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 678..712
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..418
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026011"
FT VAR_SEQ 27..32
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12812529,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_026012"
FT VAR_SEQ 419..431
FT /note="GYTRSRQIVFILL -> MKGGGGQRDVGAD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_026013"
FT VARIANT 17
FT /note="G -> E (in dbSNP:rs641738)"
FT /evidence="ECO:0000269|PubMed:12812529"
FT /id="VAR_032621"
FT VARIANT 689
FT /note="Q -> E (in dbSNP:rs36657)"
FT /id="VAR_032622"
FT CONFLICT 321
FT /note="K -> Q (in Ref. 1; AAP78781)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="S -> P (in Ref. 2; AAP69870)"
FT /evidence="ECO:0000305"
FT CONFLICT 569
FT /note="L -> V (in Ref. 1; AAP78781)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="T -> A (in Ref. 2; AAP69870)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 712 AA; 79208 MW; 9816A5014A95C9F3 CRC64;
MEENPTLESE AWGSSRGWLA PREARGAPCS SPGPSLSSVL NELPSAATLR YRDPGVLPWG
ALEEEEEDGG RSRKAFTEVT QTELQDPHPS RELPWPMQAR RAHRQRNASR DQVVYGSGTK
TDRWARLLRR SKEKTKEGLR SLQPWAWTLK RIGGQFGAGT ESYFSLLRFL LLLNVLASVL
MACMTLLPTW LGGAPPGPPG PDISSPCGSY NPHSQGLVTF ATQLFNLLSG EGYLEWSPLF
YGFYPPRPRL AVTYLCWAFA VGLICLLLIL HRSVSGLKQT LLAESEALTS YSHRVFSAWD
FGLCGDVHVR LRQRIILYEL KVELEETVVR RQAAVRTLGQ QARVWLVRVL LNLLVVALLG
AAFYGVYWAT GCTVELQEMP LVQELPLLKL GVNYLPSIFI AGVNFVLPPV FKLIAPLEGY
TRSRQIVFIL LRTVFLRLAS LVVLLFSLWN QITCGGDSEA EDCKTCGYNY KQLPCWETVL
GQEMYKLLLF DLLTVLAVAL LIQFPRKLLC GLCPGALGRL AGTQEFQVPD EVLGLIYAQT
VVWVGSFFCP LLPLLNTVKF LLLFYLKKLT LFSTCSPAAR TFRASAANFF FPLVLLLGLA
ISSVPLLYSI FLIPPSKLCG PFRGQSSIWA QIPESISSLP ETTQNFLFFL GTQAFAVPLL
LISSILMAYT VALANSYGRL ISELKRQRQT EAQNKVFLAR RAVALTSTKP AL
