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Protein

Nicalin

Gene

NCLN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning.By similarity

GO - Biological processi

  • protein destabilization Source: UniProtKB
  • regulation of protein complex assembly Source: UniProtKB
  • regulation of signal transduction Source: GO_Central
Complete GO annotation...

Protein family/group databases

MEROPSiM28.978.

Names & Taxonomyi

Protein namesi
Recommended name:
Nicalin
Alternative name(s):
Nicastrin-like protein
Gene namesi
Name:NCLN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:26923. NCLN.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini43 – 522480LumenalSequence analysisAdd
BLAST
Transmembranei523 – 54321HelicalSequence analysisAdd
BLAST
Topological domaini544 – 56320CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134898417.

Polymorphism and mutation databases

BioMutaiNCLN.
DMDMi68052797.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4242Sequence analysisAdd
BLAST
Chaini43 – 563521NicalinPRO_0000019687Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi241 – 2411N-linked (GlcNAc...)Sequence analysis
Glycosylationi428 – 4281N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ969V3.
MaxQBiQ969V3.
PaxDbiQ969V3.
PRIDEiQ969V3.

PTM databases

iPTMnetiQ969V3.
PhosphoSiteiQ969V3.
SwissPalmiQ969V3.

Expressioni

Tissue specificityi

Highly expressed in pancreas and skeletal muscle and, at lower levels, in heart.1 Publication

Gene expression databases

BgeeiQ969V3.
ExpressionAtlasiQ969V3. baseline and differential.
GenevisibleiQ969V3. HS.

Organism-specific databases

HPAiHPA006625.

Interactioni

Subunit structurei

Forms a complex with NOMO2 and TMEM147, resulting in a stabilization of the 3 proteins, which are otherwise quickly degraded by the proteasome. Due to the strong similarity between NOMO1, NOMO2 and NOMO3, probably also interacts with NOMO1 and NOMO3. Participates in a large protein complex, which is not related to the gamma-secretase complex.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP5-9P263713EBI-10281480,EBI-3958099

Protein-protein interaction databases

BioGridi121253. 24 interactions.
IntActiQ969V3. 11 interactions.
MINTiMINT-3050214.
STRINGi9606.ENSP00000246117.

Structurei

3D structure databases

ProteinModelPortaliQ969V3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the nicastrin family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2526. Eukaryota.
ENOG410XQZK. LUCA.
GeneTreeiENSGT00500000044945.
HOVERGENiHBG054932.
InParanoidiQ969V3.
OMAiDVRQHHV.
OrthoDBiEOG7P2XRN.
PhylomeDBiQ969V3.
TreeFamiTF105849.

Family and domain databases

InterProiIPR016574. Nicalin.
IPR007484. Peptidase_M28.
[Graphical view]
PfamiPF04389. Peptidase_M28. 1 hit.
[Graphical view]
PIRSFiPIRSF011018. Nicalin. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969V3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLEEAGEVLE NMLKASCLPL GFIVFLPAVL LLVAPPLPAA DAAHEFTVYR
60 70 80 90 100
MQQYDLQGQP YGTRNAVLNT EARTMAAEVL SRRCVLMRLL DFSYEQYQKA
110 120 130 140 150
LRQSAGAVVI ILPRAMAAVP QDVVRQFMEI EPEMLAMETA VPVYFAVEDE
160 170 180 190 200
ALLSIYKQTQ AASASQGSAS AAEVLLRTAT ANGFQMVTSG VQSKAVSDWL
210 220 230 240 250
IASVEGRLTG LGGEDLPTIV IVAHYDAFGV APWLSLGADS NGSGVSVLLE
260 270 280 290 300
LARLFSRLYT YKRTHAAYNL LFFASGGGKF NYQGTKRWLE DNLDHTDSSL
310 320 330 340 350
LQDNVAFVLC LDTVGRGSSL HLHVSKPPRE GTLQHAFLRE LETVAAHQFP
360 370 380 390 400
EVRFSMVHKR INLAEDVLAW EHERFAIRRL PAFTLSHLES HRDGQRSSIM
410 420 430 440 450
DVRSRVDSKT LTRNTRIIAE ALTRVIYNLT EKGTPPDMPV FTEQMQIQQE
460 470 480 490 500
QLDSVMDWLT NQPRAAQLVD KDSTFLSTLE HHLSRYLKDV KQHHVKADKR
510 520 530 540 550
DPEFVFYDQL KQVMNAYRVK PAVFDLLLAV GIAAYLGMAY VAVQHFSLLY
560
KTVQRLLVKA KTQ
Length:563
Mass (Da):62,974
Last modified:October 25, 2004 - v2
Checksum:i5E74EDF6ABA6F44F
GO
Isoform 2 (identifier: Q969V3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     446-446: Missing.

Show »
Length:562
Mass (Da):62,846
Checksum:iC66C473B8BF9DA6D
GO

Sequence cautioni

The sequence AAH03076.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH25926.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB66502.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191P → L in CAG38597 (Ref. 6) Curated
Sequence conflicti124 – 1241V → A in BAD18812 (PubMed:14702039).Curated
Sequence conflicti207 – 2071R → W in CAG38597 (Ref. 6) Curated
Sequence conflicti387 – 3871H → L in AAH03076 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti214 – 2141E → D.
Corresponds to variant rs11671067 [ dbSNP | Ensembl ].
VAR_050276
Natural varianti551 – 5511K → R.2 Publications
Corresponds to variant rs2288949 [ dbSNP | Ensembl ].
VAR_022552

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei446 – 4461Missing in isoform 2. 1 PublicationVSP_013851

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK172848 mRNA. Translation: BAD18812.1.
AC005331 Genomic DNA. Translation: AAC27667.1.
AC011547 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69330.1.
CH471139 Genomic DNA. Translation: EAW69333.1.
BC003076 mRNA. Translation: AAH03076.2. Different initiation.
BC007275 mRNA. Translation: AAH07275.1.
BC008920 mRNA. Translation: AAH08920.2.
BC010064 mRNA. Translation: AAH10064.2.
BC013283 mRNA. Translation: AAH13283.2.
BC019091 mRNA. Translation: AAH19091.2.
BC025926 mRNA. Translation: AAH25926.1. Different initiation.
AL136567 mRNA. Translation: CAB66502.1. Different initiation.
CR533566 mRNA. Translation: CAG38597.1.
AL365369 mRNA. Translation: CAB96945.1.
CCDSiCCDS32869.1. [Q969V3-1]
RefSeqiNP_064555.2. NM_020170.3. [Q969V3-1]
UniGeneiHs.657032.

Genome annotation databases

EnsembliENST00000246117; ENSP00000246117; ENSG00000125912. [Q969V3-1]
GeneIDi56926.
KEGGihsa:56926.
UCSCiuc002lxi.4. human. [Q969V3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK172848 mRNA. Translation: BAD18812.1.
AC005331 Genomic DNA. Translation: AAC27667.1.
AC011547 Genomic DNA. No translation available.
CH471139 Genomic DNA. Translation: EAW69330.1.
CH471139 Genomic DNA. Translation: EAW69333.1.
BC003076 mRNA. Translation: AAH03076.2. Different initiation.
BC007275 mRNA. Translation: AAH07275.1.
BC008920 mRNA. Translation: AAH08920.2.
BC010064 mRNA. Translation: AAH10064.2.
BC013283 mRNA. Translation: AAH13283.2.
BC019091 mRNA. Translation: AAH19091.2.
BC025926 mRNA. Translation: AAH25926.1. Different initiation.
AL136567 mRNA. Translation: CAB66502.1. Different initiation.
CR533566 mRNA. Translation: CAG38597.1.
AL365369 mRNA. Translation: CAB96945.1.
CCDSiCCDS32869.1. [Q969V3-1]
RefSeqiNP_064555.2. NM_020170.3. [Q969V3-1]
UniGeneiHs.657032.

3D structure databases

ProteinModelPortaliQ969V3.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121253. 24 interactions.
IntActiQ969V3. 11 interactions.
MINTiMINT-3050214.
STRINGi9606.ENSP00000246117.

Protein family/group databases

MEROPSiM28.978.

PTM databases

iPTMnetiQ969V3.
PhosphoSiteiQ969V3.
SwissPalmiQ969V3.

Polymorphism and mutation databases

BioMutaiNCLN.
DMDMi68052797.

Proteomic databases

EPDiQ969V3.
MaxQBiQ969V3.
PaxDbiQ969V3.
PRIDEiQ969V3.

Protocols and materials databases

DNASUi56926.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246117; ENSP00000246117; ENSG00000125912. [Q969V3-1]
GeneIDi56926.
KEGGihsa:56926.
UCSCiuc002lxi.4. human. [Q969V3-1]

Organism-specific databases

CTDi56926.
GeneCardsiNCLN.
HGNCiHGNC:26923. NCLN.
HPAiHPA006625.
MIMi609156. gene.
neXtProtiNX_Q969V3.
PharmGKBiPA134898417.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2526. Eukaryota.
ENOG410XQZK. LUCA.
GeneTreeiENSGT00500000044945.
HOVERGENiHBG054932.
InParanoidiQ969V3.
OMAiDVRQHHV.
OrthoDBiEOG7P2XRN.
PhylomeDBiQ969V3.
TreeFamiTF105849.

Miscellaneous databases

ChiTaRSiNCLN. human.
GeneWikiiNCLN.
GenomeRNAii56926.
PROiQ969V3.
SOURCEiSearch...

Gene expression databases

BgeeiQ969V3.
ExpressionAtlasiQ969V3. baseline and differential.
GenevisibleiQ969V3. HS.

Family and domain databases

InterProiIPR016574. Nicalin.
IPR007484. Peptidase_M28.
[Graphical view]
PfamiPF04389. Peptidase_M28. 1 hit.
[Graphical view]
PIRSFiPIRSF011018. Nicalin. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Carcinoma.
  2. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Brain, Kidney and Ovary.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-563 (ISOFORM 1), VARIANT ARG-551.
  6. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 12-563 (ISOFORM 1), VARIANT ARG-551.
  7. The European IMAGE consortium
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 502-563.
  8. "Nicalin and its binding partner Nomo are novel Nodal signaling antagonists."
    Haffner C., Frauli M., Topp S., Irmler M., Hofmann K., Regula J.T., Bally-Cuif L., Haass C.
    EMBO J. 23:3041-3050(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH NOMO.
  9. "Transmembrane protein 147 (TMEM147) is a novel component of the Nicalin-NOMO protein complex."
    Dettmer U., Kuhn P.H., Abou-Ajram C., Lichtenthaler S.F., Kruger M., Kremmer E., Haass C., Haffner C.
    J. Biol. Chem. 285:26174-26181(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH NOMO2 AND TMEM147.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiNCLN_HUMAN
AccessioniPrimary (citable) accession number: Q969V3
Secondary accession number(s): D6W613
, O75252, Q6FI60, Q6ZMB7, Q8TAT7, Q96H48, Q96IS7, Q9BQH9, Q9BTX4, Q9NPP2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 21, 2005
Last sequence update: October 25, 2004
Last modified: June 8, 2016
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.