Full text data of NCLN
NCLN
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Nicalin (Nicastrin-like protein; Flags: Precursor)
Nicalin (Nicastrin-like protein; Flags: Precursor)
Comments
Isoform Q969V3-2 was detected.
Isoform Q969V3-2 was detected.
UniProt
Q969V3
ID NCLN_HUMAN Reviewed; 563 AA.
AC Q969V3; D6W613; O75252; Q6FI60; Q6ZMB7; Q8TAT7; Q96H48; Q96IS7;
read moreAC Q9BQH9; Q9BTX4; Q9NPP2;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 2.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=Nicalin;
DE AltName: Full=Nicastrin-like protein;
DE Flags: Precursor;
GN Name=NCLN;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Carcinoma;
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 [2]
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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, Kidney, and Ovary;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-563 (ISOFORM 1), AND
RP VARIANT ARG-551.
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-563 (ISOFORM 1), AND
RP VARIANT ARG-551.
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 502-563.
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH NOMO.
RX PubMed=15257293; DOI=10.1038/sj.emboj.7600307;
RA Haffner C., Frauli M., Topp S., Irmler M., Hofmann K., Regula J.T.,
RA Bally-Cuif L., Haass C.;
RT "Nicalin and its binding partner Nomo are novel Nodal signaling
RT antagonists.";
RL EMBO J. 23:3041-3050(2004).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NOMO2 AND TMEM147.
RX PubMed=20538592; DOI=10.1074/jbc.M110.132548;
RA Dettmer U., Kuhn P.H., Abou-Ajram C., Lichtenthaler S.F., Kruger M.,
RA Kremmer E., Haass C., Haffner C.;
RT "Transmembrane protein 147 (TMEM147) is a novel component of the
RT Nicalin-NOMO protein complex.";
RL J. Biol. Chem. 285:26174-26181(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: May antagonize Nodal signaling and subsequent
CC organization of axial structures during mesodermal patterning (By
CC similarity).
CC -!- SUBUNIT: Forms a complex with NOMO2 and TMEM147, resulting in a
CC stabilization of the 3 proteins, which are otherwise quickly
CC degraded by the proteasome. Due to the strong similarity between
CC NOMO1, NOMO2 and NOMO3, probably also interacts with NOMO1 and
CC NOMO3. Participates in a large protein complex, which is not
CC related to the gamma-secretase complex.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969V3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969V3-2; Sequence=VSP_013851;
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas and skeletal
CC muscle and, at lower levels, in heart.
CC -!- SIMILARITY: Belongs to the nicastrin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03076.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH25926.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAB66502.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AK172848; BAD18812.1; -; mRNA.
DR EMBL; AC005331; AAC27667.1; -; Genomic_DNA.
DR EMBL; AC011547; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69330.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69333.1; -; Genomic_DNA.
DR EMBL; BC003076; AAH03076.2; ALT_INIT; mRNA.
DR EMBL; BC007275; AAH07275.1; -; mRNA.
DR EMBL; BC008920; AAH08920.2; -; mRNA.
DR EMBL; BC010064; AAH10064.2; -; mRNA.
DR EMBL; BC013283; AAH13283.2; -; mRNA.
DR EMBL; BC019091; AAH19091.2; -; mRNA.
DR EMBL; BC025926; AAH25926.1; ALT_INIT; mRNA.
DR EMBL; AL136567; CAB66502.1; ALT_INIT; mRNA.
DR EMBL; CR533566; CAG38597.1; -; mRNA.
DR EMBL; AL365369; CAB96945.1; -; mRNA.
DR RefSeq; NP_064555.2; NM_020170.3.
DR RefSeq; XP_005259653.1; XM_005259596.1.
DR UniGene; Hs.657032; -.
DR ProteinModelPortal; Q969V3; -.
DR IntAct; Q969V3; 1.
DR MINT; MINT-3050214; -.
DR MEROPS; M28.978; -.
DR PhosphoSite; Q969V3; -.
DR DMDM; 68052797; -.
DR PaxDb; Q969V3; -.
DR PRIDE; Q969V3; -.
DR DNASU; 56926; -.
DR Ensembl; ENST00000246117; ENSP00000246117; ENSG00000125912.
DR Ensembl; ENST00000587740; ENSP00000466300; ENSG00000125912.
DR GeneID; 56926; -.
DR KEGG; hsa:56926; -.
DR UCSC; uc002lxi.3; human.
DR CTD; 56926; -.
DR GeneCards; GC19P003185; -.
DR HGNC; HGNC:26923; NCLN.
DR HPA; HPA006625; -.
DR MIM; 609156; gene.
DR neXtProt; NX_Q969V3; -.
DR PharmGKB; PA134898417; -.
DR eggNOG; NOG323516; -.
DR HOVERGEN; HBG054932; -.
DR InParanoid; Q969V3; -.
DR OMA; TEKGTPP; -.
DR OrthoDB; EOG7P2XRN; -.
DR ChiTaRS; NCLN; human.
DR GeneWiki; NCLN; -.
DR GenomeRNAi; 56926; -.
DR NextBio; 62444; -.
DR PRO; PR:Q969V3; -.
DR ArrayExpress; Q969V3; -.
DR Bgee; Q969V3; -.
DR Genevestigator; Q969V3; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0008233; F:peptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR InterPro; IPR016574; Nicalin.
DR InterPro; IPR007484; Peptidase_M28.
DR Pfam; PF04389; Peptidase_M28; 1.
DR PIRSF; PIRSF011018; Nicalin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW Glycoprotein; Membrane; Polymorphism; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 42 Potential.
FT CHAIN 43 563 Nicalin.
FT /FTId=PRO_0000019687.
FT TOPO_DOM 43 522 Lumenal (Potential).
FT TRANSMEM 523 543 Helical; (Potential).
FT TOPO_DOM 544 563 Cytoplasmic (Potential).
FT CARBOHYD 241 241 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 428 428 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 446 446 Missing (in isoform 2).
FT /FTId=VSP_013851.
FT VARIANT 214 214 E -> D (in dbSNP:rs11671067).
FT /FTId=VAR_050276.
FT VARIANT 551 551 K -> R (in dbSNP:rs2288949).
FT /FTId=VAR_022552.
FT CONFLICT 19 19 P -> L (in Ref. 6; CAG38597).
FT CONFLICT 124 124 V -> A (in Ref. 1; BAD18812).
FT CONFLICT 207 207 R -> W (in Ref. 6; CAG38597).
FT CONFLICT 387 387 H -> L (in Ref. 4; AAH03076).
SQ SEQUENCE 563 AA; 62974 MW; 5E74EDF6ABA6F44F CRC64;
MLEEAGEVLE NMLKASCLPL GFIVFLPAVL LLVAPPLPAA DAAHEFTVYR MQQYDLQGQP
YGTRNAVLNT EARTMAAEVL SRRCVLMRLL DFSYEQYQKA LRQSAGAVVI ILPRAMAAVP
QDVVRQFMEI EPEMLAMETA VPVYFAVEDE ALLSIYKQTQ AASASQGSAS AAEVLLRTAT
ANGFQMVTSG VQSKAVSDWL IASVEGRLTG LGGEDLPTIV IVAHYDAFGV APWLSLGADS
NGSGVSVLLE LARLFSRLYT YKRTHAAYNL LFFASGGGKF NYQGTKRWLE DNLDHTDSSL
LQDNVAFVLC LDTVGRGSSL HLHVSKPPRE GTLQHAFLRE LETVAAHQFP EVRFSMVHKR
INLAEDVLAW EHERFAIRRL PAFTLSHLES HRDGQRSSIM DVRSRVDSKT LTRNTRIIAE
ALTRVIYNLT EKGTPPDMPV FTEQMQIQQE QLDSVMDWLT NQPRAAQLVD KDSTFLSTLE
HHLSRYLKDV KQHHVKADKR DPEFVFYDQL KQVMNAYRVK PAVFDLLLAV GIAAYLGMAY
VAVQHFSLLY KTVQRLLVKA KTQ
//
ID NCLN_HUMAN Reviewed; 563 AA.
AC Q969V3; D6W613; O75252; Q6FI60; Q6ZMB7; Q8TAT7; Q96H48; Q96IS7;
read moreAC Q9BQH9; Q9BTX4; Q9NPP2;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 2.
DT 22-JAN-2014, entry version 101.
DE RecName: Full=Nicalin;
DE AltName: Full=Nicastrin-like protein;
DE Flags: Precursor;
GN Name=NCLN;
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Carcinoma;
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 [2]
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.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA 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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, Kidney, and Ovary;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-563 (ISOFORM 1), AND
RP VARIANT ARG-551.
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-563 (ISOFORM 1), AND
RP VARIANT ARG-551.
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 502-563.
RG The European IMAGE consortium;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH NOMO.
RX PubMed=15257293; DOI=10.1038/sj.emboj.7600307;
RA Haffner C., Frauli M., Topp S., Irmler M., Hofmann K., Regula J.T.,
RA Bally-Cuif L., Haass C.;
RT "Nicalin and its binding partner Nomo are novel Nodal signaling
RT antagonists.";
RL EMBO J. 23:3041-3050(2004).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NOMO2 AND TMEM147.
RX PubMed=20538592; DOI=10.1074/jbc.M110.132548;
RA Dettmer U., Kuhn P.H., Abou-Ajram C., Lichtenthaler S.F., Kruger M.,
RA Kremmer E., Haass C., Haffner C.;
RT "Transmembrane protein 147 (TMEM147) is a novel component of the
RT Nicalin-NOMO protein complex.";
RL J. Biol. Chem. 285:26174-26181(2010).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: May antagonize Nodal signaling and subsequent
CC organization of axial structures during mesodermal patterning (By
CC similarity).
CC -!- SUBUNIT: Forms a complex with NOMO2 and TMEM147, resulting in a
CC stabilization of the 3 proteins, which are otherwise quickly
CC degraded by the proteasome. Due to the strong similarity between
CC NOMO1, NOMO2 and NOMO3, probably also interacts with NOMO1 and
CC NOMO3. Participates in a large protein complex, which is not
CC related to the gamma-secretase complex.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass
CC membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969V3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969V3-2; Sequence=VSP_013851;
CC -!- TISSUE SPECIFICITY: Highly expressed in pancreas and skeletal
CC muscle and, at lower levels, in heart.
CC -!- SIMILARITY: Belongs to the nicastrin family.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03076.2; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAH25926.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=CAB66502.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AK172848; BAD18812.1; -; mRNA.
DR EMBL; AC005331; AAC27667.1; -; Genomic_DNA.
DR EMBL; AC011547; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69330.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69333.1; -; Genomic_DNA.
DR EMBL; BC003076; AAH03076.2; ALT_INIT; mRNA.
DR EMBL; BC007275; AAH07275.1; -; mRNA.
DR EMBL; BC008920; AAH08920.2; -; mRNA.
DR EMBL; BC010064; AAH10064.2; -; mRNA.
DR EMBL; BC013283; AAH13283.2; -; mRNA.
DR EMBL; BC019091; AAH19091.2; -; mRNA.
DR EMBL; BC025926; AAH25926.1; ALT_INIT; mRNA.
DR EMBL; AL136567; CAB66502.1; ALT_INIT; mRNA.
DR EMBL; CR533566; CAG38597.1; -; mRNA.
DR EMBL; AL365369; CAB96945.1; -; mRNA.
DR RefSeq; NP_064555.2; NM_020170.3.
DR RefSeq; XP_005259653.1; XM_005259596.1.
DR UniGene; Hs.657032; -.
DR ProteinModelPortal; Q969V3; -.
DR IntAct; Q969V3; 1.
DR MINT; MINT-3050214; -.
DR MEROPS; M28.978; -.
DR PhosphoSite; Q969V3; -.
DR DMDM; 68052797; -.
DR PaxDb; Q969V3; -.
DR PRIDE; Q969V3; -.
DR DNASU; 56926; -.
DR Ensembl; ENST00000246117; ENSP00000246117; ENSG00000125912.
DR Ensembl; ENST00000587740; ENSP00000466300; ENSG00000125912.
DR GeneID; 56926; -.
DR KEGG; hsa:56926; -.
DR UCSC; uc002lxi.3; human.
DR CTD; 56926; -.
DR GeneCards; GC19P003185; -.
DR HGNC; HGNC:26923; NCLN.
DR HPA; HPA006625; -.
DR MIM; 609156; gene.
DR neXtProt; NX_Q969V3; -.
DR PharmGKB; PA134898417; -.
DR eggNOG; NOG323516; -.
DR HOVERGEN; HBG054932; -.
DR InParanoid; Q969V3; -.
DR OMA; TEKGTPP; -.
DR OrthoDB; EOG7P2XRN; -.
DR ChiTaRS; NCLN; human.
DR GeneWiki; NCLN; -.
DR GenomeRNAi; 56926; -.
DR NextBio; 62444; -.
DR PRO; PR:Q969V3; -.
DR ArrayExpress; Q969V3; -.
DR Bgee; Q969V3; -.
DR Genevestigator; Q969V3; -.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0008233; F:peptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0009966; P:regulation of signal transduction; IEA:InterPro.
DR InterPro; IPR016574; Nicalin.
DR InterPro; IPR007484; Peptidase_M28.
DR Pfam; PF04389; Peptidase_M28; 1.
DR PIRSF; PIRSF011018; Nicalin; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Endoplasmic reticulum;
KW Glycoprotein; Membrane; Polymorphism; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1 42 Potential.
FT CHAIN 43 563 Nicalin.
FT /FTId=PRO_0000019687.
FT TOPO_DOM 43 522 Lumenal (Potential).
FT TRANSMEM 523 543 Helical; (Potential).
FT TOPO_DOM 544 563 Cytoplasmic (Potential).
FT CARBOHYD 241 241 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 428 428 N-linked (GlcNAc...) (Potential).
FT VAR_SEQ 446 446 Missing (in isoform 2).
FT /FTId=VSP_013851.
FT VARIANT 214 214 E -> D (in dbSNP:rs11671067).
FT /FTId=VAR_050276.
FT VARIANT 551 551 K -> R (in dbSNP:rs2288949).
FT /FTId=VAR_022552.
FT CONFLICT 19 19 P -> L (in Ref. 6; CAG38597).
FT CONFLICT 124 124 V -> A (in Ref. 1; BAD18812).
FT CONFLICT 207 207 R -> W (in Ref. 6; CAG38597).
FT CONFLICT 387 387 H -> L (in Ref. 4; AAH03076).
SQ SEQUENCE 563 AA; 62974 MW; 5E74EDF6ABA6F44F CRC64;
MLEEAGEVLE NMLKASCLPL GFIVFLPAVL LLVAPPLPAA DAAHEFTVYR MQQYDLQGQP
YGTRNAVLNT EARTMAAEVL SRRCVLMRLL DFSYEQYQKA LRQSAGAVVI ILPRAMAAVP
QDVVRQFMEI EPEMLAMETA VPVYFAVEDE ALLSIYKQTQ AASASQGSAS AAEVLLRTAT
ANGFQMVTSG VQSKAVSDWL IASVEGRLTG LGGEDLPTIV IVAHYDAFGV APWLSLGADS
NGSGVSVLLE LARLFSRLYT YKRTHAAYNL LFFASGGGKF NYQGTKRWLE DNLDHTDSSL
LQDNVAFVLC LDTVGRGSSL HLHVSKPPRE GTLQHAFLRE LETVAAHQFP EVRFSMVHKR
INLAEDVLAW EHERFAIRRL PAFTLSHLES HRDGQRSSIM DVRSRVDSKT LTRNTRIIAE
ALTRVIYNLT EKGTPPDMPV FTEQMQIQQE QLDSVMDWLT NQPRAAQLVD KDSTFLSTLE
HHLSRYLKDV KQHHVKADKR DPEFVFYDQL KQVMNAYRVK PAVFDLLLAV GIAAYLGMAY
VAVQHFSLLY KTVQRLLVKA KTQ
//
MIM
609156
*RECORD*
*FIELD* NO
609156
*FIELD* TI
*609156 NICALIN, ZEBRAFISH, HOMOLOG OF; NCLN
*FIELD* TX
CLONING
By searching databases for sequences containing the ectodomain of the
read morenicastrin (605254) family of proteins, Haffner et al. (2004) identified
nicalin. The deduced type I transmembrane protein has a calculated
molecular mass of 63.7 kD. Nicalin contains a region similar to an
aminopeptidase domain, but it lacks amino acids necessary for catalytic
activity. Northern blot analysis detected nicalin transcripts of 4.6,
4.0, and 2.3 kb. Highest expression was in pancreas and skeletal muscle,
with somewhat lower expression in heart and very low expression in all
other tissues examined. SDS-PAGE of enriched membrane preparations of
human embryonic kidney cells and neuroblastoma cells indicated that
endogenous nicalin has an apparent molecular mass of 60 kD. Nicalin was
also detected in a 500- to 550-kD complex containing NOMO2 (609158).
Nicalin and NOMO2 cofractionated with endoplasmic reticulum membranes.
GENE FUNCTION
By coimmunoprecipitation of cotransfected cells, Haffner et al. (2004)
confirmed that NOMO2 and nicalin associated in a high molecular mass
complex and interacted directly. Ectopic expression of both proteins in
zebrafish embryos caused cyclopia, a phenotype that can arise from a
defect in mesendoderm patterning mediated by the Nodal (601265)
signaling pathway. Furthermore, Nodal- and activin (see 147290)-induced
signaling was inhibited by nicalin and NOMO2 in a cell-based reporter
assay.
Using affinity purification and coimmunoprecipitation experiments,
Dettmer et al. (2010) showed that NOMO and nicalin interacted with
TMEM147 (613585). Knockdown of each of these components by RNA
interference showed that they stabilized one another. Knockdown and
overexpression studies suggested that nicalin is the key regulator of
the complex and that it binds to NOMO prior to inclusion of TMEM147 in
the complex. Mutation analysis revealed that the transmembrane domain of
nicalin was required for interaction with TMEM147, but not NOMO.
Coprecipitation studies with zebrafish embryos revealed conservation of
the nicalin-NOMO-TMEM147 complex.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NCLN
gene to chromosome 19 (TMAP WI-15783).
*FIELD* RF
1. Dettmer, U.; Kuhn, P.-H.; Abou-Ajram, C.; Lichtenthaler, S. F.;
Kruger, M.; Kremmer, E.; Haass, C.; Haffner, C.: Transmembrane protein
147 (TMEM147) is a novel component of the nicalin-NOMO protein complex. J.
Biol. Chem. 285: 26174-26181, 2010.
2. Haffner, C.; Frauli, M.; Topp, S.; Irmler, M.; Hofmann, K.; Regula,
J. T.; Bally-Cuif, L.; Haass, C.: Nicalin and its binding partner
Nomo are novel Nodal signaling antagonists. EMBO J. 23: 3041-3050,
2004.
*FIELD* CN
Patricia A. Hartz - updated: 10/07/2010
*FIELD* CD
Patricia A. Hartz: 1/11/2005
*FIELD* ED
mgross: 10/07/2010
mgross: 1/11/2005
*RECORD*
*FIELD* NO
609156
*FIELD* TI
*609156 NICALIN, ZEBRAFISH, HOMOLOG OF; NCLN
*FIELD* TX
CLONING
By searching databases for sequences containing the ectodomain of the
read morenicastrin (605254) family of proteins, Haffner et al. (2004) identified
nicalin. The deduced type I transmembrane protein has a calculated
molecular mass of 63.7 kD. Nicalin contains a region similar to an
aminopeptidase domain, but it lacks amino acids necessary for catalytic
activity. Northern blot analysis detected nicalin transcripts of 4.6,
4.0, and 2.3 kb. Highest expression was in pancreas and skeletal muscle,
with somewhat lower expression in heart and very low expression in all
other tissues examined. SDS-PAGE of enriched membrane preparations of
human embryonic kidney cells and neuroblastoma cells indicated that
endogenous nicalin has an apparent molecular mass of 60 kD. Nicalin was
also detected in a 500- to 550-kD complex containing NOMO2 (609158).
Nicalin and NOMO2 cofractionated with endoplasmic reticulum membranes.
GENE FUNCTION
By coimmunoprecipitation of cotransfected cells, Haffner et al. (2004)
confirmed that NOMO2 and nicalin associated in a high molecular mass
complex and interacted directly. Ectopic expression of both proteins in
zebrafish embryos caused cyclopia, a phenotype that can arise from a
defect in mesendoderm patterning mediated by the Nodal (601265)
signaling pathway. Furthermore, Nodal- and activin (see 147290)-induced
signaling was inhibited by nicalin and NOMO2 in a cell-based reporter
assay.
Using affinity purification and coimmunoprecipitation experiments,
Dettmer et al. (2010) showed that NOMO and nicalin interacted with
TMEM147 (613585). Knockdown of each of these components by RNA
interference showed that they stabilized one another. Knockdown and
overexpression studies suggested that nicalin is the key regulator of
the complex and that it binds to NOMO prior to inclusion of TMEM147 in
the complex. Mutation analysis revealed that the transmembrane domain of
nicalin was required for interaction with TMEM147, but not NOMO.
Coprecipitation studies with zebrafish embryos revealed conservation of
the nicalin-NOMO-TMEM147 complex.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NCLN
gene to chromosome 19 (TMAP WI-15783).
*FIELD* RF
1. Dettmer, U.; Kuhn, P.-H.; Abou-Ajram, C.; Lichtenthaler, S. F.;
Kruger, M.; Kremmer, E.; Haass, C.; Haffner, C.: Transmembrane protein
147 (TMEM147) is a novel component of the nicalin-NOMO protein complex. J.
Biol. Chem. 285: 26174-26181, 2010.
2. Haffner, C.; Frauli, M.; Topp, S.; Irmler, M.; Hofmann, K.; Regula,
J. T.; Bally-Cuif, L.; Haass, C.: Nicalin and its binding partner
Nomo are novel Nodal signaling antagonists. EMBO J. 23: 3041-3050,
2004.
*FIELD* CN
Patricia A. Hartz - updated: 10/07/2010
*FIELD* CD
Patricia A. Hartz: 1/11/2005
*FIELD* ED
mgross: 10/07/2010
mgross: 1/11/2005