PACC1_HUMAN
ID PACC1_HUMAN Reviewed; 350 AA.
AC Q9H813; B7Z4D6; Q6IA87; Q9NV85;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Proton-activated chloride channel {ECO:0000303|PubMed:31023925};
DE Short=PAC {ECO:0000303|PubMed:31023925};
DE Short=hPAC {ECO:0000303|PubMed:31023925};
DE AltName: Full=Acid-sensitive outwardly-rectifying anion channel {ECO:0000303|PubMed:31318332};
DE Short=ASOR {ECO:0000303|PubMed:31318332};
DE AltName: Full=Proton-activated outwardly rectifying anion channel {ECO:0000303|PubMed:31318332};
DE Short=PAORAC {ECO:0000303|PubMed:31318332};
DE AltName: Full=Transmembrane protein 206 {ECO:0000305};
DE Short=hTMEM206 {ECO:0000303|PubMed:31318332};
GN Name=PACC1 {ECO:0000312|HGNC:HGNC:25593};
GN Synonyms=C1orf75 {ECO:0000312|HGNC:HGNC:25593},
GN TMEM206 {ECO:0000312|HGNC:HGNC:25593};
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] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, Retinoblastoma, and Teratocarcinoma;
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 MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-155 AND ASN-162.
RC TISSUE=Leukemic T-cell;
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-9, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, AND GLYCOSYLATION.
RX PubMed=31318332; DOI=10.7554/elife.49187;
RA Ullrich F., Blin S., Lazarow K., Daubitz T., von Kries J.P., Jentsch T.J.;
RT "Identification of TMEM206 proteins as pore of PAORAC/ASOR acid-sensitive
RT chloride channels.";
RL Elife 8:0-0(2019).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF ILE-307.
RX PubMed=31023925; DOI=10.1126/science.aav9739;
RA Yang J., Chen J., Del Carmen Vitery M., Osei-Owusu J., Chu J., Yu H.,
RA Sun S., Qiu Z.;
RT "PAC, an evolutionarily conserved membrane protein, is a proton-activated
RT chloride channel.";
RL Science 364:395-399(2019).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] ASN-336.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Proton-activated chloride channel that mediates import of
CC chloride ion in response to extracellular acidic pH (PubMed:31023925,
CC PubMed:31318332). Involved in acidosis-induced cell death by mediating
CC chloride influx and subsequent cell swelling (PubMed:31023925,
CC PubMed:31318332). {ECO:0000269|PubMed:31023925,
CC ECO:0000269|PubMed:31318332}.
CC -!- INTERACTION:
CC Q9H813; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-4319734, EBI-12019274;
CC Q9H813; Q9Y342: PLLP; NbExp=3; IntAct=EBI-4319734, EBI-3919291;
CC Q9H813; Q04941: PLP2; NbExp=5; IntAct=EBI-4319734, EBI-608347;
CC Q9H813; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-4319734, EBI-8652744;
CC Q9H813; Q9BVK8: TMEM147; NbExp=4; IntAct=EBI-4319734, EBI-348587;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31023925,
CC ECO:0000269|PubMed:31318332}; Multi-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H813-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H813-2; Sequence=VSP_042887;
CC -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in brain.
CC {ECO:0000269|PubMed:31023925}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:31318332}.
CC -!- SIMILARITY: Belongs to the proton-activated chloride channel family.
CC {ECO:0000305}.
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DR EMBL; AK001736; BAA91870.1; -; mRNA.
DR EMBL; AK024066; BAB14810.1; -; mRNA.
DR EMBL; AK297200; BAH12522.1; -; mRNA.
DR EMBL; CR457268; CAG33549.1; -; mRNA.
DR EMBL; AC092803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL360091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006320; AAH06320.1; -; mRNA.
DR CCDS; CCDS1504.1; -. [Q9H813-1]
DR CCDS; CCDS55687.1; -. [Q9H813-2]
DR RefSeq; NP_001185791.1; NM_001198862.1. [Q9H813-2]
DR RefSeq; NP_060722.2; NM_018252.2. [Q9H813-1]
DR PDB; 7JNA; EM; 3.60 A; A/B/C=1-350.
DR PDB; 7JNC; EM; 3.73 A; A/B/C=1-350.
DR PDB; 7SQF; EM; 3.10 A; A/B/C=1-350.
DR PDB; 7SQG; EM; 2.60 A; A/B/C=1-350.
DR PDB; 7SQH; EM; 2.50 A; A/B/C=1-350.
DR PDBsum; 7JNA; -.
DR PDBsum; 7JNC; -.
DR PDBsum; 7SQF; -.
DR PDBsum; 7SQG; -.
DR PDBsum; 7SQH; -.
DR AlphaFoldDB; Q9H813; -.
DR SMR; Q9H813; -.
DR BioGRID; 120539; 119.
DR IntAct; Q9H813; 94.
DR STRING; 9606.ENSP00000438863; -.
DR TCDB; 1.A.114.1.1; the proton-activated chloride channel (pacc) family.
DR GlyGen; Q9H813; 3 sites.
DR iPTMnet; Q9H813; -.
DR PhosphoSitePlus; Q9H813; -.
DR SwissPalm; Q9H813; -.
DR BioMuta; TMEM206; -.
DR DMDM; 74752717; -.
DR EPD; Q9H813; -.
DR jPOST; Q9H813; -.
DR MassIVE; Q9H813; -.
DR MaxQB; Q9H813; -.
DR PaxDb; Q9H813; -.
DR PeptideAtlas; Q9H813; -.
DR PRIDE; Q9H813; -.
DR ProteomicsDB; 81166; -. [Q9H813-1]
DR ProteomicsDB; 81167; -. [Q9H813-2]
DR Antibodypedia; 47113; 29 antibodies from 12 providers.
DR DNASU; 55248; -.
DR Ensembl; ENST00000261455.9; ENSP00000261455.4; ENSG00000065600.13. [Q9H813-1]
DR Ensembl; ENST00000535273.2; ENSP00000438863.1; ENSG00000065600.13. [Q9H813-2]
DR GeneID; 55248; -.
DR KEGG; hsa:55248; -.
DR MANE-Select; ENST00000261455.9; ENSP00000261455.4; NM_018252.3; NP_060722.2.
DR UCSC; uc001hjc.5; human. [Q9H813-1]
DR CTD; 55248; -.
DR DisGeNET; 55248; -.
DR GeneCards; PACC1; -.
DR HGNC; HGNC:25593; PACC1.
DR HPA; ENSG00000065600; Tissue enhanced (brain).
DR MIM; 618427; gene.
DR neXtProt; NX_Q9H813; -.
DR OpenTargets; ENSG00000065600; -.
DR PharmGKB; PA162406386; -.
DR VEuPathDB; HostDB:ENSG00000065600; -.
DR eggNOG; ENOG502QS5H; Eukaryota.
DR GeneTree; ENSGT00390000017528; -.
DR HOGENOM; CLU_068069_0_0_1; -.
DR InParanoid; Q9H813; -.
DR OMA; ITYMLFA; -.
DR OrthoDB; 829411at2759; -.
DR PhylomeDB; Q9H813; -.
DR TreeFam; TF333307; -.
DR PathwayCommons; Q9H813; -.
DR SignaLink; Q9H813; -.
DR BioGRID-ORCS; 55248; 8 hits in 1082 CRISPR screens.
DR ChiTaRS; TMEM206; human.
DR GenomeRNAi; 55248; -.
DR Pharos; Q9H813; Tdark.
DR PRO; PR:Q9H813; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H813; protein.
DR Bgee; ENSG00000065600; Expressed in C1 segment of cervical spinal cord and 156 other tissues.
DR Genevisible; Q9H813; HS.
DR GO; GO:0009986; C:cell surface; HDA:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0061797; F:pH-gated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IDA:UniProtKB.
DR InterPro; IPR029366; TMEM206.
DR PANTHER; PTHR16087; PTHR16087; 1.
DR Pfam; PF15122; TMEM206; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Chloride;
KW Chloride channel; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..350
FT /note="Proton-activated chloride channel"
FT /id="PRO_0000279471"
FT TOPO_DOM 1..64
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:31023925,
FT ECO:0000305|PubMed:31318332"
FT TRANSMEM 65..85
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 86..301
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 319..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:31023925,
FT ECO:0000305|PubMed:31318332"
FT MOD_RES 9
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 10
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9D771"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9D771"
FT MOD_RES 24
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66H28"
FT CARBOHYD 155
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 162
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT VAR_SEQ 12
FT /note="E -> EAVRPALPSSKPCLLTSPAVLVKLLSSSASTSRPPNLGHLWQPSSSV
FT PLHRAASLAKVRQFQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042887"
FT VARIANT 336
FT /note="K -> N (in a breast cancer sample; somatic mutation;
FT dbSNP:rs1034429230)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035847"
FT MUTAGEN 307
FT /note="I->A: Reduced I(-) permeability."
FT /evidence="ECO:0000269|PubMed:31023925"
FT CONFLICT 11..12
FT /note="QE -> RV (in Ref. 2; CAG33549)"
FT /evidence="ECO:0000305"
FT CONFLICT 23
FT /note="N -> S (in Ref. 1; BAA91870)"
FT /evidence="ECO:0000305"
FT CONFLICT 47
FT /note="D -> G (in Ref. 2; CAG33549)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="Y -> C (in Ref. 1; BAA91870)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 350 AA; 40043 MW; 5F68ACA21DDD0674 CRC64;
MIRQERSTSY QELSEELVQV VENSELADEQ DKETVRVQGP GILPGLDSES ASSSIRFSKA
CLKNVFSVLL IFIYLLLMAV AVFLVYRTIT DFREKLKHPV MSVSYKEVDR YDAPGIALYP
GQAQLLSCKH HYEVIPPLTS PGQPGDMNCT TQRINYTDPF SNQTVKSALI VQGPREVKKR
ELVFLQFRLN KSSEDFSAID YLLFSSFQEF LQSPNRVGFM QACESAYSSW KFSGGFRTWV
KMSLVKTKEE DGREAVEFRQ ETSVVNYIDQ RPAAKKSAQL FFVVFEWKDP FIQKVQDIVT
ANPWNTIALL CGAFLALFKA AEFAKLSIKW MIKIRKRYLK RRGQATSHIS
