TM199_HUMAN
ID TM199_HUMAN Reviewed; 208 AA.
AC Q8N511;
DT 31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Transmembrane protein 199 {ECO:0000303|PubMed:26833330};
GN Name=TMEM199 {ECO:0000303|PubMed:26833330, ECO:0000312|HGNC:HGNC:18085};
GN Synonyms=C17orf32 {ECO:0000312|HGNC:HGNC:18085};
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].
RC TISSUE=Gastric adenocarcinoma;
RA Zhang D.L., Ding P.G., Ling L.J., Chen R.-S., Ma D.-L.;
RT "In silico cloning of C17orf32, a novel human gene and verification of its
RT coding region by RT-PCR.";
RL Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 29:543-549(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [6]
RP SUBCELLULAR LOCATION, FUNCTION, VARIANTS CDG2P GLY-7; PRO-14 AND PRO-31,
RP AND INVOLVEMENT IN CDG2P.
RX PubMed=26833330; DOI=10.1016/j.ajhg.2015.12.011;
RA Jansen J.C., Timal S., van Scherpenzeel M., Michelakakis H., Vicogne D.,
RA Ashikov A., Moraitou M., Hoischen A., Huijben K., Steenbergen G.,
RA van den Boogert M.A., Porta F., Calvo P.L., Mavrikou M., Cenacchi G.,
RA van den Bogaart G., Salomon J., Holleboom A.G., Rodenburg R.J.,
RA Drenth J.P., Huynen M.A., Wevers R.A., Morava E., Foulquier F.,
RA Veltman J.A., Lefeber D.J.;
RT "TMEM199 deficiency is a disorder of Golgi homeostasis characterized by
RT elevated aminotransferases, alkaline phosphatase, and cholesterol and
RT abnormal glycosylation.";
RL Am. J. Hum. Genet. 98:322-330(2016).
RN [7]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=28296633; DOI=10.7554/elife.22693;
RA Miles A.L., Burr S.P., Grice G.L., Nathan J.A.;
RT "The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115,
RT control HIF1alpha prolyl hydroxylation by regulating cellular iron
RT levels.";
RL Elife 6:E22693-E22693(2017).
CC -!- FUNCTION: Accessory component of the proton-transporting vacuolar (V)-
CC ATPase protein pump involved in intracellular iron homeostasis. In
CC aerobic conditions, required for intracellular iron homeostasis, thus
CC triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and
CC leading to HIF1A hydroxylation and subsequent proteasomal degradation.
CC Necessary for endolysosomal acidification and lysosomal degradation
CC (PubMed:28296633). May be involved in Golgi homeostasis
CC (PubMed:26833330). {ECO:0000269|PubMed:26833330,
CC ECO:0000269|PubMed:28296633}.
CC -!- SUBUNIT: Accessory component of the multisubunit proton-transporting
CC vacuolar (V)-ATPase protein pump. {ECO:0000269|PubMed:28296633}.
CC -!- INTERACTION:
CC Q8N511; Q13520: AQP6; NbExp=3; IntAct=EBI-10265825, EBI-13059134;
CC Q8N511; Q13323: BIK; NbExp=3; IntAct=EBI-10265825, EBI-700794;
CC Q8N511; Q9UGN4: CD300A; NbExp=3; IntAct=EBI-10265825, EBI-10320732;
CC Q8N511; Q15125: EBP; NbExp=3; IntAct=EBI-10265825, EBI-3915253;
CC Q8N511; Q9GZR5: ELOVL4; NbExp=3; IntAct=EBI-10265825, EBI-18535450;
CC Q8N511; O75477: ERLIN1; NbExp=3; IntAct=EBI-10265825, EBI-359299;
CC Q8N511; P38484: IFNGR2; NbExp=3; IntAct=EBI-10265825, EBI-3905457;
CC Q8N511; Q8N5M9: JAGN1; NbExp=3; IntAct=EBI-10265825, EBI-10266796;
CC Q8N511; Q8N6L0: KASH5; NbExp=3; IntAct=EBI-10265825, EBI-749265;
CC Q8N511; Q9H6H4: REEP4; NbExp=3; IntAct=EBI-10265825, EBI-7545592;
CC Q8N511; Q96EP9: SLC10A4; NbExp=3; IntAct=EBI-10265825, EBI-17456472;
CC Q8N511; Q16623: STX1A; NbExp=3; IntAct=EBI-10265825, EBI-712466;
CC Q8N511; Q12846: STX4; NbExp=3; IntAct=EBI-10265825, EBI-744942;
CC Q8N511; Q9NPL8: TIMMDC1; NbExp=3; IntAct=EBI-10265825, EBI-6268651;
CC Q8N511; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-10265825, EBI-8638294;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle, COPI-coated vesicle membrane
CC {ECO:0000269|PubMed:26833330}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum-Golgi intermediate compartment
CC membrane {ECO:0000269|PubMed:26833330}; Multi-pass membrane protein
CC {ECO:0000255}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:28296633}; Multi-pass membrane protein
CC {ECO:0000255}. Note=Partial colocalization with GOLGB1.
CC {ECO:0000269|PubMed:26833330}.
CC -!- DISEASE: Congenital disorder of glycosylation 2P (CDG2P) [MIM:616829]:
CC A form of congenital disorder of glycosylation, a genetically
CC heterogeneous group of autosomal recessive, multisystem disorders
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. CDG2P is characterized by mild
CC metabolic dysfunction, primarily affecting the liver. Psychomotor
CC development is normal. {ECO:0000269|PubMed:26833330}. Note=The disease
CC is caused by variants affecting the gene represented in this entry.
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DR EMBL; AY074907; AAO12163.1; -; mRNA.
DR EMBL; AC002094; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF573651; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC033113; AAH33113.1; -; mRNA.
DR CCDS; CCDS11228.1; -.
DR RefSeq; NP_689677.1; NM_152464.2.
DR AlphaFoldDB; Q8N511; -.
DR BioGRID; 127028; 144.
DR IntAct; Q8N511; 48.
DR MINT; Q8N511; -.
DR STRING; 9606.ENSP00000292114; -.
DR TCDB; 9.B.206.1.1; the tmem199 (tmem199) family.
DR iPTMnet; Q8N511; -.
DR PhosphoSitePlus; Q8N511; -.
DR BioMuta; TMEM199; -.
DR DMDM; 51701337; -.
DR EPD; Q8N511; -.
DR jPOST; Q8N511; -.
DR MassIVE; Q8N511; -.
DR MaxQB; Q8N511; -.
DR PaxDb; Q8N511; -.
DR PeptideAtlas; Q8N511; -.
DR PRIDE; Q8N511; -.
DR ProteomicsDB; 71994; -.
DR Antibodypedia; 34886; 41 antibodies from 20 providers.
DR DNASU; 147007; -.
DR Ensembl; ENST00000292114.8; ENSP00000292114.3; ENSG00000244045.13.
DR GeneID; 147007; -.
DR KEGG; hsa:147007; -.
DR MANE-Select; ENST00000292114.8; ENSP00000292114.3; NM_152464.3; NP_689677.1.
DR UCSC; uc002hba.4; human.
DR CTD; 147007; -.
DR DisGeNET; 147007; -.
DR GeneCards; TMEM199; -.
DR HGNC; HGNC:18085; TMEM199.
DR HPA; ENSG00000244045; Low tissue specificity.
DR MalaCards; TMEM199; -.
DR MIM; 616815; gene.
DR MIM; 616829; phenotype.
DR neXtProt; NX_Q8N511; -.
DR OpenTargets; ENSG00000244045; -.
DR Orphanet; 466703; TMEM199-CDG.
DR PharmGKB; PA162406348; -.
DR VEuPathDB; HostDB:ENSG00000244045; -.
DR eggNOG; ENOG502RXKD; Eukaryota.
DR GeneTree; ENSGT00390000014591; -.
DR HOGENOM; CLU_114590_0_0_1; -.
DR InParanoid; Q8N511; -.
DR OMA; DFGQQVR; -.
DR OrthoDB; 1216090at2759; -.
DR PhylomeDB; Q8N511; -.
DR TreeFam; TF314610; -.
DR PathwayCommons; Q8N511; -.
DR SignaLink; Q8N511; -.
DR BioGRID-ORCS; 147007; 497 hits in 1093 CRISPR screens.
DR ChiTaRS; TMEM199; human.
DR GenomeRNAi; 147007; -.
DR Pharos; Q8N511; Tbio.
DR PRO; PR:Q8N511; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q8N511; protein.
DR Bgee; ENSG00000244045; Expressed in monocyte and 126 other tissues.
DR ExpressionAtlas; Q8N511; baseline and differential.
DR Genevisible; Q8N511; HS.
DR GO; GO:0030663; C:COPI-coated vesicle membrane; IDA:UniProtKB.
DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IEA:GOC.
DR GO; GO:0016471; C:vacuolar proton-transporting V-type ATPase complex; IDA:UniProtKB.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:UniProtKB.
DR GO; GO:0036295; P:cellular response to increased oxygen levels; IMP:UniProtKB.
DR GO; GO:0007042; P:lysosomal lumen acidification; IMP:UniProtKB.
DR GO; GO:1905146; P:lysosomal protein catabolic process; IMP:UniProtKB.
DR GO; GO:0070072; P:vacuolar proton-transporting V-type ATPase complex assembly; IEA:InterPro.
DR InterPro; IPR021013; ATPase_Vma12.
DR PANTHER; PTHR31394; PTHR31394; 1.
DR Pfam; PF11712; Vma12; 1.
PE 1: Evidence at protein level;
KW Acetylation; Congenital disorder of glycosylation; Cytoplasmic vesicle;
KW Disease variant; Endoplasmic reticulum; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..208
FT /note="Transmembrane protein 199"
FT /id="PRO_0000079298"
FT TRANSMEM 146..166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 179..199
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT VARIANT 7
FT /note="A -> G (in CDG2P; dbSNP:rs369488804)"
FT /evidence="ECO:0000269|PubMed:26833330"
FT /id="VAR_075770"
FT VARIANT 14
FT /note="A -> P (in CDG2P; dbSNP:rs869025586)"
FT /evidence="ECO:0000269|PubMed:26833330"
FT /id="VAR_075771"
FT VARIANT 31
FT /note="R -> P (in CDG2P; dbSNP:rs782531869)"
FT /evidence="ECO:0000269|PubMed:26833330"
FT /id="VAR_075772"
FT VARIANT 158
FT /note="V -> I (in dbSNP:rs12572)"
FT /id="VAR_033749"
FT VARIANT 166
FT /note="L -> V (in dbSNP:rs36106147)"
FT /id="VAR_033750"
SQ SEQUENCE 208 AA; 23130 MW; 498FCA8F39D361C0 CRC64;
MASSLLAGER LVRALGPGGE LEPERLPRKL RAELEAALGK KHKGGDSSSG PQRLVSFRLI
RDLHQHLRER DSKLYLHELL EGSEIYLPEV VKPPRNPELV ARLEKIKIQL ANEEYKRITR
NVTCQDTRHG GTLSDLGKQV RSLKALVITI FNFIVTVVAA FVCTYLGSQY IFTEMASRVL
AALIVASVVG LAELYVMVRA MEGELGEL
