ID   VA0D2_HUMAN             Reviewed;         350 AA.
AC   Q8N8Y2;
DT   01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=V-type proton ATPase subunit d 2;
DE            Short=V-ATPase subunit d 2;
DE   AltName: Full=Vacuolar proton pump subunit d 2;
GN   Name=ATP6V0D2;
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], AND TISSUE SPECIFICITY.
RX   PubMed=12384298; DOI=10.1016/s0378-1119(02)00884-3;
RA   Smith A.N., Borthwick K.J., Karet F.E.;
RT   "Molecular cloning and characterization of novel tissue-specific isoforms
RT   of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation
RT   in autosomal recessive distal renal tubular acidosis.";
RL   Gene 297:169-177(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=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: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase),
CC       a multisubunit enzyme composed of a peripheral complex (V1) that
CC       hydrolyzes ATP and a membrane integral complex (V0) that translocates
CC       protons. V-ATPase is responsible for acidifying and maintaining the pH
CC       of intracellular compartments and in some cell types, is targeted to
CC       the plasma membrane, where it is responsible for acidifying the
CC       extracellular environment (By similarity). May play a role in coupling
CC       of proton transport and ATP hydrolysis (By similarity). Regulator of
CC       osteoclast fusion and bone formation (By similarity).
CC       {ECO:0000250|UniProtKB:P61421, ECO:0000250|UniProtKB:Q80SY3}.
CC   -!- SUBUNIT: V-ATPase is a heteromultimeric enzyme made up of two
CC       complexes: the ATP-hydrolytic V1 complex and the proton translocation
CC       V0 complex. The V1 complex consists of three catalytic AB heterodimers
CC       that form a heterohexamer, three peripheral stalks each consisting of
CC       EG heterodimers, one central rotor including subunits D and F, and the
CC       regulatory subunits C and H. The proton translocation complex V0
CC       consists of the proton transport subunit a, a ring of proteolipid
CC       subunits c9c'', rotary subunit d, subunits e and f, and the accessory
CC       subunits ATP6AP1/Ac45 and ATP6AP2/PRR. {ECO:0000250|UniProtKB:P61421}.
CC   -!- INTERACTION:
CC       Q8N8Y2; Q03989: ARID5A; NbExp=3; IntAct=EBI-3923949, EBI-948603;
CC       Q8N8Y2; Q6IPU0: CENPP; NbExp=3; IntAct=EBI-3923949, EBI-10250303;
CC       Q8N8Y2; O43186: CRX; NbExp=3; IntAct=EBI-3923949, EBI-748171;
CC       Q8N8Y2; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-3923949, EBI-747204;
CC       Q8N8Y2; Q0VD86: INCA1; NbExp=3; IntAct=EBI-3923949, EBI-6509505;
CC       Q8N8Y2; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-3923949, EBI-16439278;
CC       Q8N8Y2; Q9BSH3: NICN1; NbExp=3; IntAct=EBI-3923949, EBI-13324229;
CC       Q8N8Y2; P26367: PAX6; NbExp=3; IntAct=EBI-3923949, EBI-747278;
CC       Q8N8Y2; Q96QT6-2: PHF12; NbExp=3; IntAct=EBI-3923949, EBI-10293106;
CC       Q8N8Y2; P01189: POMC; NbExp=3; IntAct=EBI-3923949, EBI-12219503;
CC       Q8N8Y2; Q04864-2: REL; NbExp=3; IntAct=EBI-3923949, EBI-10829018;
CC       Q8N8Y2; Q8N443: RIBC1; NbExp=3; IntAct=EBI-3923949, EBI-10265323;
CC       Q8N8Y2; Q9BVN2: RUSC1; NbExp=3; IntAct=EBI-3923949, EBI-6257312;
CC       Q8N8Y2; Q15019-3: SEPTIN2; NbExp=3; IntAct=EBI-3923949, EBI-11525407;
CC       Q8N8Y2; Q6S9Z5: ZNF474; NbExp=3; IntAct=EBI-3923949, EBI-17269964;
CC   -!- TISSUE SPECIFICITY: Kidney, osteoclast and lung.
CC       {ECO:0000269|PubMed:12384298}.
CC   -!- SIMILARITY: Belongs to the V-ATPase V0D/AC39 subunit family.
CC       {ECO:0000305}.
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DR   EMBL; AY079172; AAL87000.1; -; mRNA.
DR   EMBL; AK096027; BAC04679.1; -; mRNA.
DR   EMBL; BC065207; AAH65207.1; -; mRNA.
DR   CCDS; CCDS6241.1; -.
DR   RefSeq; NP_689778.1; NM_152565.1.
DR   AlphaFoldDB; Q8N8Y2; -.
DR   SMR; Q8N8Y2; -.
DR   BioGRID; 128858; 60.
DR   IntAct; Q8N8Y2; 31.
DR   STRING; 9606.ENSP00000285393; -.
DR   DrugBank; DB01133; Tiludronic acid.
DR   iPTMnet; Q8N8Y2; -.
DR   PhosphoSitePlus; Q8N8Y2; -.
DR   BioMuta; ATP6V0D2; -.
DR   DMDM; 74729555; -.
DR   EPD; Q8N8Y2; -.
DR   jPOST; Q8N8Y2; -.
DR   MassIVE; Q8N8Y2; -.
DR   MaxQB; Q8N8Y2; -.
DR   PaxDb; 9606-ENSP00000285393; -.
DR   PeptideAtlas; Q8N8Y2; -.
DR   ProteomicsDB; 72473; -.
DR   Pumba; Q8N8Y2; -.
DR   Antibodypedia; 25450; 147 antibodies from 24 providers.
DR   DNASU; 245972; -.
DR   Ensembl; ENST00000285393.4; ENSP00000285393.3; ENSG00000147614.4.
DR   GeneID; 245972; -.
DR   KEGG; hsa:245972; -.
DR   MANE-Select; ENST00000285393.4; ENSP00000285393.3; NM_152565.1; NP_689778.1.
DR   UCSC; uc003ydp.2; human.
DR   AGR; HGNC:18266; -.
DR   CTD; 245972; -.
DR   DisGeNET; 245972; -.
DR   GeneCards; ATP6V0D2; -.
DR   HGNC; HGNC:18266; ATP6V0D2.
DR   HPA; ENSG00000147614; Tissue enriched (kidney).
DR   MIM; 618072; gene.
DR   neXtProt; NX_Q8N8Y2; -.
DR   OpenTargets; ENSG00000147614; -.
DR   PharmGKB; PA38516; -.
DR   VEuPathDB; HostDB:ENSG00000147614; -.
DR   eggNOG; KOG2957; Eukaryota.
DR   GeneTree; ENSGT00390000002200; -.
DR   HOGENOM; CLU_051277_0_0_1; -.
DR   InParanoid; Q8N8Y2; -.
DR   OMA; YKFCKDH; -.
DR   OrthoDB; 1211584at2759; -.
DR   PhylomeDB; Q8N8Y2; -.
DR   TreeFam; TF300857; -.
DR   BioCyc; MetaCyc:HS07458-MONOMER; -.
DR   PathwayCommons; Q8N8Y2; -.
DR   Reactome; R-HSA-1222556; ROS and RNS production in phagocytes.
DR   Reactome; R-HSA-77387; Insulin receptor recycling.
DR   Reactome; R-HSA-917977; Transferrin endocytosis and recycling.
DR   Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR   Reactome; R-HSA-983712; Ion channel transport.
DR   SignaLink; Q8N8Y2; -.
DR   BioGRID-ORCS; 245972; 17 hits in 1138 CRISPR screens.
DR   ChiTaRS; ATP6V0D2; human.
DR   GenomeRNAi; 245972; -.
DR   Pharos; Q8N8Y2; Tbio.
DR   PRO; PR:Q8N8Y2; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   RNAct; Q8N8Y2; Protein.
DR   Bgee; ENSG00000147614; Expressed in adult mammalian kidney and 107 other cell types or tissues.
DR   ExpressionAtlas; Q8N8Y2; baseline and differential.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR   GO; GO:0033181; C:plasma membrane proton-transporting V-type ATPase complex; IBA:GO_Central.
DR   GO; GO:0033179; C:proton-transporting V-type ATPase, V0 domain; IEA:InterPro.
DR   GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IDA:UniProtKB.
DR   GO; GO:0046961; F:proton-transporting ATPase activity, rotational mechanism; IEA:InterPro.
DR   GO; GO:0016241; P:regulation of macroautophagy; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0007035; P:vacuolar acidification; IBA:GO_Central.
DR   GO; GO:0007034; P:vacuolar transport; IBA:GO_Central.
DR   Gene3D; 1.10.132.50; ATP synthase (C/AC39) subunit, domain 3; 1.
DR   Gene3D; 1.20.1690.10; V-type ATP synthase subunit C domain; 2.
DR   InterPro; IPR036079; ATPase_su_c/d_sf.
DR   InterPro; IPR002843; ATPase_V0-cplx_csu/dsu.
DR   InterPro; IPR016727; ATPase_V0-cplx_dsu.
DR   InterPro; IPR044911; V-type_ATPase_su_c/d_dom_3.
DR   InterPro; IPR035067; V-type_ATPase_suC/d.
DR   PANTHER; PTHR11028:SF2; V-TYPE PROTON ATPASE SUBUNIT D 2; 1.
DR   PANTHER; PTHR11028; VACUOLAR ATP SYNTHASE SUBUNIT AC39; 1.
DR   Pfam; PF01992; vATP-synt_AC39; 1.
DR   PIRSF; PIRSF018497; V-ATP_synth_D; 1.
DR   SUPFAM; SSF103486; V-type ATP synthase subunit C; 1.
DR   Genevisible; Q8N8Y2; HS.
PE   1: Evidence at protein level;
KW   Hydrogen ion transport; Ion transport; Reference proteome; Transport.
FT   CHAIN           1..350
FT                   /note="V-type proton ATPase subunit d 2"
FT                   /id="PRO_0000285657"
FT   VARIANT         272
FT                   /note="G -> R (in dbSNP:rs10094744)"
FT                   /id="VAR_032039"
FT   VARIANT         295
FT                   /note="E -> K (in dbSNP:rs4263741)"
FT                   /id="VAR_032040"
SQ   SEQUENCE   350 AA;  40426 MW;  07658C37F2A10CB7 CRC64;
     MLEGAELYFN VDHGYLEGLV RGCKASLLTQ QDYINLVQCE TLEDLKIHLQ TTDYGNFLAN
     HTNPLTVSKI DTEMRKRLCG EFEYFRNHSL EPLSTFLTYM TCSYMIDNVI LLMNGALQKK
     SVKEILGKCH PLGRFTEMEA VNIAETPSDL FNAILIETPL APFFQDCMSE NALDELNIEL
     LRNKLYKSYL EAFYKFCKNH GDVTAEVMCP ILEFEADRRA FIITLNSFGT ELSKEDRETL
     YPTFGKLYPE GLRLLAQAED FDQMKNVADH YGVYKPLFEA VGGSGGKTLE DVFYEREVQM
     NVLAFNRQFH YGVFYAYVKL KEQEIRNIVW IAECISQRHR TKINSYIPIL
//