ID MANEA_HUMAN Reviewed; 462 AA. AC Q5SRI9; A6H8M6; Q5SRJ0; Q6MZV0; Q70JE9; Q7Z3V7; Q8WWX5; Q9H9D2; DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 11-NOV-2015, entry version 104. DE RecName: Full=Glycoprotein endo-alpha-1,2-mannosidase; DE Short=Endo-alpha mannosidase; DE Short=Endomannosidase; DE Short=hEndo; DE EC=3.2.1.130; DE AltName: Full=Mandaselin; GN Name=MANEA; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TOPOLOGY, AND RP CATALYTIC ACTIVITY. RX PubMed=15760709; DOI=10.1016/j.biochi.2004.11.004; RA Hardt B., Voelker C., Mundt S., Salska-Navarro M., Hauptmann M., RA Bause E.; RT "Human endo-alpha1,2-mannosidase is a Golgi-resident type II membrane RT protein."; RL Biochimie 87:169-179(2005). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, TISSUE SPECIFICITY, PTM, SUBCELLULAR LOCATION, AND RP TOPOLOGY. RC TISSUE=Liver; RX PubMed=15677381; DOI=10.1093/glycob/cwi045; RA Hamilton S.R., Li H., Wischnewski H., Prasad A., Kerley-Hamilton J.S., RA Mitchell T., Walling A.J., Davidson R.C., Wildt S., Gerngross T.U.; RT "Intact alpha-1,2-endomannosidase is a typical type II membrane RT protein."; RL Glycobiology 15:615-624(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Fetal kidney; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-214. RC TISSUE=Liver; RA Zeng L., Liu F., Xu X., Zhang X., Chen Z., Han Z.; RT "Novel gene expressed in human liver."; RL Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases. RN [8] RP VARIANT [LARGE SCALE ANALYSIS] CYS-331. 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., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- CATALYTIC ACTIVITY: Hydrolysis of the terminal alpha-D-glucosyl- CC (1,3)-D-mannosyl unit from the GlcMan(9)(GlcNAc)(2) CC oligosaccharide component of the glycoprotein produced in the CC Golgi membrane. {ECO:0000269|PubMed:15677381, CC ECO:0000269|PubMed:15760709}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6.2. {ECO:0000269|PubMed:15677381}; CC Temperature dependence: CC Optimum temperature is 37 degrees Celsius. CC {ECO:0000269|PubMed:15677381}; CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane CC {ECO:0000269|PubMed:15677381, ECO:0000269|PubMed:15760709}; CC Single-pass type II membrane protein {ECO:0000269|PubMed:15677381, CC ECO:0000269|PubMed:15760709}. CC -!- TISSUE SPECIFICITY: Highly expressed in the liver and kidney. CC Expressed at lower levels in muscle, pancreas, heart, placenta, CC lung and brain. {ECO:0000269|PubMed:15677381}. CC -!- PTM: Undergoes proteolytic cleavage in the C-terminal region. CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 99 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAL07306.1; Type=Frameshift; Positions=Several; Evidence={ECO:0000305}; CC Sequence=CAD97640.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI17346.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ577574; CAE12165.1; -; mRNA. DR EMBL; AY372528; AAQ75077.1; -; mRNA. DR EMBL; AK022900; BAB14298.1; -; mRNA. DR EMBL; AK291940; BAF84629.1; -; mRNA. DR EMBL; BX537398; CAD97640.1; ALT_INIT; mRNA. DR EMBL; BX640869; CAE45927.1; -; mRNA. DR EMBL; AL671884; CAI17346.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL671884; CAI17347.1; -; Genomic_DNA. DR EMBL; BC137014; AAI37015.1; -; mRNA. DR EMBL; BC137016; AAI37017.1; -; mRNA. DR EMBL; BC146671; AAI46672.1; -; mRNA. DR EMBL; BC150199; AAI50200.1; -; mRNA. DR EMBL; AY048774; AAL07306.1; ALT_FRAME; mRNA. DR CCDS; CCDS5032.1; -. DR RefSeq; NP_078917.2; NM_024641.3. DR RefSeq; XP_005267204.1; XM_005267147.2. DR UniGene; Hs.734632; -. DR UniGene; Hs.743412; -. DR ProteinModelPortal; Q5SRI9; -. DR SMR; Q5SRI9; 99-451. DR BioGrid; 122815; 25. DR STRING; 9606.ENSP00000351669; -. DR CAZy; GH99; Glycoside Hydrolase Family 99. DR PhosphoSite; Q5SRI9; -. DR BioMuta; MANEA; -. DR DMDM; 74743637; -. DR MaxQB; Q5SRI9; -. DR PaxDb; Q5SRI9; -. DR PRIDE; Q5SRI9; -. DR DNASU; 79694; -. DR Ensembl; ENST00000358812; ENSP00000351669; ENSG00000172469. DR GeneID; 79694; -. DR KEGG; hsa:79694; -. DR UCSC; uc003poo.2; human. DR CTD; 79694; -. DR GeneCards; MANEA; -. DR HGNC; HGNC:21072; MANEA. DR HPA; HPA011046; -. DR HPA; HPA011069; -. DR MIM; 612327; gene. DR neXtProt; NX_Q5SRI9; -. DR PharmGKB; PA134891001; -. DR eggNOG; ENOG410IG22; Eukaryota. DR eggNOG; ENOG410XT8Q; LUCA. DR GeneTree; ENSGT00390000016054; -. DR HOVERGEN; HBG103563; -. DR InParanoid; Q5SRI9; -. DR KO; K15538; -. DR OMA; IETHMKQ; -. DR OrthoDB; EOG7CVQ05; -. DR PhylomeDB; Q5SRI9; -. DR TreeFam; TF324051; -. DR BRENDA; 3.2.1.130; 2681. DR Reactome; R-HSA-964739; N-glycan trimming and elongation in the cis-Golgi. DR GeneWiki; MANEA; -. DR GenomeRNAi; 79694; -. DR NextBio; 68976; -. DR PRO; PR:Q5SRI9; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; Q5SRI9; -. DR CleanEx; HS_MANEA; -. DR ExpressionAtlas; Q5SRI9; baseline and differential. DR Genevisible; Q5SRI9; HS. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW. DR GO; GO:0004569; F:glycoprotein endo-alpha-1,2-mannosidase activity; IEA:UniProtKB-EC. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; TAS:Reactome. DR InterPro; IPR026071; Glyco_Hydrolase_99. DR InterPro; IPR017853; Glycoside_hydrolase_SF. DR PANTHER; PTHR13572; PTHR13572; 1. DR Pfam; PF16317; Glyco_hydro_99; 1. DR SUPFAM; SSF51445; SSF51445; 1. PE 1: Evidence at protein level; KW Complete proteome; Golgi apparatus; Hydrolase; Membrane; Polymorphism; KW Reference proteome; Signal-anchor; Transmembrane; Transmembrane helix. FT CHAIN 1 462 Glycoprotein endo-alpha-1,2-mannosidase. FT /FTId=PRO_0000282315. FT TOPO_DOM 1 8 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 9 29 Helical; Signal-anchor for type II FT membrane protein. {ECO:0000255}. FT TOPO_DOM 30 462 Lumenal. {ECO:0000255}. FT REGION 60 462 Catalytic. {ECO:0000305}. FT VARIANT 331 331 Y -> C (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036242. FT CONFLICT 129 129 E -> G (in Ref. 4; CAD97640). FT {ECO:0000305}. FT CONFLICT 237 237 N -> S (in Ref. 1; CAE12165). FT {ECO:0000305}. FT CONFLICT 344 344 F -> I (in Ref. 2; AAQ75077, 3; BAB14298 FT and 4; CAE45927). {ECO:0000305}. SQ SEQUENCE 462 AA; 53671 MW; CB593CB9B3DAA056 CRC64; MAKFRRRTCI ILALFILFIF SLMMGLKMLR PNTATFGAPF GLDLLPELHQ RTIHLGKNFD FQKSDRINSE TNTKNLKSVE ITMKPSKASE LNLDELPPLN NYLHVFYYSW YGNPQFDGKY IHWNHPVLEH WDPRIAKNYP QGRHNPPDDI GSSFYPELGS YSSRDPSVIE THMRQMRSAS IGVLALSWYP PDVNDENGEP TDNLVPTILD KAHKYNLKVT FHIEPYSNRD DQNMYKNVKY IIDKYGNHPA FYRYKTKTGN ALPMFYVYDS YITKPEKWAN LLTTSGSRSI RNSPYDGLFI ALLVEEKHKY DILQSGFDGI YTYFATNGFT YGSSHQNWAS LKLFCDKYNL IFIPSVGPGY IDTSIRPWNT QNTRNRINGK YYEIGLSAAL QTRPSLISIT SFNEWHEGTQ IEKAVPKRTS NTVYLDYRPH KPGLYLELTR KWSEKYSKER ATYALDRQLP VS //