ID   MPZL2_HUMAN             Reviewed;         215 AA.
AC   O60487; A8K2R1;
DT   27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   27-MAR-2024, entry version 183.
DE   RecName: Full=Myelin protein zero-like protein 2;
DE   AltName: Full=Epithelial V-like antigen 1;
DE   Flags: Precursor;
GN   Name=MPZL2; Synonyms=EVA {ECO:0000303|PubMed:9585423}, EVA1;
GN   ORFNames=UNQ606/PRO1192;
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=Liver, and Spleen;
RX   PubMed=9585423; DOI=10.1083/jcb.141.4.1061;
RA   Guttinger M., Sutti F., Panigada M., Porcellini S., Merati B., Mariani M.,
RA   Teesalu T., Consalez G.G., Grassi F.;
RT   "Epithelial V-like antigen (EVA), a novel member of the immunoglobulin
RT   superfamily, expressed in embryonic epithelia with a potential role as
RT   homotypic adhesion molecule in thymus histogenesis.";
RL   J. Cell Biol. 141:1061-1071(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Endometrial tumor;
RA   Davenport J.W., Neale G.A.M., Goorha R.M.;
RT   "Identification of putative target genes involved in LMO2-induced
RT   leukemogenesis.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Squamous cell carcinoma;
RA   Pietas A., Petersen I., Schluens K., Petersen S.;
RT   "Human EVA1 gene which is downregulated in lung carcinoma cells.";
RL   Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=12975309; DOI=10.1101/gr.1293003;
RA   Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA   Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA   Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA   Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA   Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA   Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA   Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA   Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT   "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT   identify novel human secreted and transmembrane proteins: a bioinformatics
RT   assessment.";
RL   Genome Res. 13:2265-2270(2003).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Tongue;
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [8]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-39.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [9]
RP   INVOLVEMENT IN DFNB111, VARIANTS DFNB111 74-GLN--ASP-215 DEL; TRP-90 AND
RP   182-ARG--ASP-215 DEL, AND TISSUE SPECIFICITY.
RX   PubMed=29961571; DOI=10.1016/j.ajhg.2018.05.011;
RA   Wesdorp M., Murillo-Cuesta S., Peters T., Celaya A.M., Oonk A.,
RA   Schraders M., Oostrik J., Gomez-Rosas E., Beynon A.J., Hartel B.P.,
RA   Okkersen K., Koenen H.J.P.M., Weeda J., Lelieveld S., Voermans N.C.,
RA   Joosten I., Hoyng C.B., Lichtner P., Kunst H.P.M., Feenstra I.,
RA   de Bruijn S.E., Admiraal R.J.C., Yntema H.G., van Wijk E., Del Castillo I.,
RA   Serra P., Varela-Nieto I., Pennings R.J.E., Kremer H.;
RT   "MPZL2, encoding the epithelial junctional protein myelin protein zero-like
RT   2, is essential for hearing in man and mouse.";
RL   Am. J. Hum. Genet. 103:74-88(2018).
RN   [10]
RP   INVOLVEMENT IN DFNB111.
RX   PubMed=29982980; DOI=10.1007/s00439-018-1901-4;
RA   Bademci G., Abad C., Incesulu A., Rad A., Alper O., Kolb S.M., Cengiz F.B.,
RA   Diaz-Horta O., Silan F., Mihci E., Ocak E., Najafi M., Maroofian R.,
RA   Yilmaz E., Nur B.G., Duman D., Guo S., Sant D.W., Wang G., Monje P.V.,
RA   Haaf T., Blanton S.H., Vona B., Walz K., Tekin M.;
RT   "MPZL2 is a novel gene associated with autosomal recessive nonsyndromic
RT   moderate hearing loss.";
RL   Hum. Genet. 137:479-486(2018).
RN   [11]
RP   VARIANTS DFNB111 PHE-18 AND 74-GLN--ASP-215 DEL.
RX   PubMed=37390746; DOI=10.1016/j.ijporl.2023.111635;
RA   Li W., Guo L., Chen B., Shu Y., Li H.;
RT   "MPZL2 variant analysis with whole exome sequencing in a cohort of Chinese
RT   hearing loss patients.";
RL   Int. J. Pediatr. Otorhinolaryngol. 171:111635-111635(2023).
CC   -!- FUNCTION: Mediates homophilic cell-cell adhesion.
CC   -!- INTERACTION:
CC       O60487; Q6UWV2: MPZL3; NbExp=3; IntAct=EBI-3906725, EBI-4314854;
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass type I
CC       membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. In fetal tissues, highest
CC       expression in the inner ear. In adult tissues, highest levels in thymus
CC       and lung. {ECO:0000269|PubMed:29961571}.
CC   -!- DISEASE: Deafness, autosomal recessive, 111 (DFNB111) [MIM:618145]: A
CC       form of non-syndromic, sensorineural deafness characterized by early-
CC       onset, moderate to severe hearing loss with no vestibular involvement.
CC       Sensorineural deafness results from damage to the neural receptors of
CC       the inner ear, the nerve pathways to the brain, or the area of the
CC       brain that receives sound information. {ECO:0000269|PubMed:29961571,
CC       ECO:0000269|PubMed:29982980, ECO:0000269|PubMed:37390746}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- SIMILARITY: Belongs to the myelin P0 protein family. {ECO:0000305}.
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DR   EMBL; AF030455; AAC39762.1; -; mRNA.
DR   EMBL; AF275945; AAF87240.1; -; mRNA.
DR   EMBL; AF304447; AAG23183.1; -; mRNA.
DR   EMBL; AY359061; AAQ89420.1; -; mRNA.
DR   EMBL; AK290326; BAF83015.1; -; mRNA.
DR   EMBL; CH471065; EAW67358.1; -; Genomic_DNA.
DR   EMBL; BC017774; AAH17774.1; -; mRNA.
DR   CCDS; CCDS8393.1; -.
DR   RefSeq; NP_005788.1; NM_005797.3.
DR   RefSeq; NP_658911.1; NM_144765.2.
DR   AlphaFoldDB; O60487; -.
DR   SMR; O60487; -.
DR   BioGRID; 115500; 21.
DR   IntAct; O60487; 4.
DR   STRING; 9606.ENSP00000278937; -.
DR   GlyConnect; 1528; 11 N-Linked glycans (2 sites).
DR   GlyCosmos; O60487; 2 sites, 11 glycans.
DR   GlyGen; O60487; 5 sites, 11 N-linked glycans (2 sites), 1 O-linked glycan (3 sites).
DR   iPTMnet; O60487; -.
DR   PhosphoSitePlus; O60487; -.
DR   BioMuta; MPZL2; -.
DR   EPD; O60487; -.
DR   jPOST; O60487; -.
DR   MassIVE; O60487; -.
DR   MaxQB; O60487; -.
DR   PaxDb; 9606-ENSP00000278937; -.
DR   PeptideAtlas; O60487; -.
DR   ProteomicsDB; 49425; -.
DR   TopDownProteomics; O60487; -.
DR   Antibodypedia; 32443; 279 antibodies from 25 providers.
DR   DNASU; 10205; -.
DR   Ensembl; ENST00000278937.7; ENSP00000278937.2; ENSG00000149573.9.
DR   Ensembl; ENST00000438295.2; ENSP00000408362.2; ENSG00000149573.9.
DR   GeneID; 10205; -.
DR   KEGG; hsa:10205; -.
DR   MANE-Select; ENST00000278937.7; ENSP00000278937.2; NM_005797.4; NP_005788.1.
DR   UCSC; uc001psn.4; human.
DR   AGR; HGNC:3496; -.
DR   CTD; 10205; -.
DR   DisGeNET; 10205; -.
DR   GeneCards; MPZL2; -.
DR   HGNC; HGNC:3496; MPZL2.
DR   HPA; ENSG00000149573; Tissue enhanced (esophagus, urinary bladder).
DR   MalaCards; MPZL2; -.
DR   MIM; 604873; gene.
DR   MIM; 618145; phenotype.
DR   neXtProt; NX_O60487; -.
DR   OpenTargets; ENSG00000149573; -.
DR   Orphanet; 90636; Rare autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR   PharmGKB; PA162396145; -.
DR   VEuPathDB; HostDB:ENSG00000149573; -.
DR   eggNOG; ENOG502RYWU; Eukaryota.
DR   GeneTree; ENSGT01030000234556; -.
DR   HOGENOM; CLU_090350_0_0_1; -.
DR   InParanoid; O60487; -.
DR   OMA; FHEQPYP; -.
DR   OrthoDB; 4225254at2759; -.
DR   PhylomeDB; O60487; -.
DR   TreeFam; TF331728; -.
DR   PathwayCommons; O60487; -.
DR   SignaLink; O60487; -.
DR   BioGRID-ORCS; 10205; 13 hits in 1158 CRISPR screens.
DR   ChiTaRS; MPZL2; human.
DR   GenomeRNAi; 10205; -.
DR   Pharos; O60487; Tbio.
DR   PRO; PR:O60487; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; O60487; Protein.
DR   Bgee; ENSG00000149573; Expressed in gingival epithelium and 162 other cell types or tissues.
DR   ExpressionAtlas; O60487; baseline and differential.
DR   GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR   GO; GO:0098609; P:cell-cell adhesion; IBA:GO_Central.
DR   GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; TAS:ProtInc.
DR   CDD; cd05880; IgV_EVA1; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   InterPro; IPR007110; Ig-like_dom.
DR   InterPro; IPR036179; Ig-like_dom_sf.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR003599; Ig_sub.
DR   InterPro; IPR013106; Ig_V-set.
DR   InterPro; IPR029863; MPZL2_Ig-like_dom.
DR   InterPro; IPR000920; Myelin_P0-rel.
DR   PANTHER; PTHR13869; MYELIN P0 RELATED; 1.
DR   PANTHER; PTHR13869:SF21; MYELIN PROTEIN ZERO-LIKE PROTEIN 2; 1.
DR   Pfam; PF07686; V-set; 1.
DR   PRINTS; PR00213; MYELINP0.
DR   SMART; SM00409; IG; 1.
DR   SMART; SM00406; IGv; 1.
DR   SUPFAM; SSF48726; Immunoglobulin; 1.
DR   PROSITE; PS50835; IG_LIKE; 1.
DR   Genevisible; O60487; HS.
PE   1: Evidence at protein level;
KW   Cell adhesion; Deafness; Disease variant; Disulfide bond; Glycoprotein;
KW   Immunoglobulin domain; Membrane; Non-syndromic deafness;
KW   Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..215
FT                   /note="Myelin protein zero-like protein 2"
FT                   /id="PRO_0000014756"
FT   TOPO_DOM        27..154
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        155..175
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        176..215
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          27..141
FT                   /note="Ig-like V-type"
FT   CARBOHYD        39
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        118
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        47..123
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VARIANT         18
FT                   /note="L -> F (in DFNB111; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:37390746"
FT                   /id="VAR_088675"
FT   VARIANT         74..215
FT                   /note="Missing (in DFNB111; pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:29961571,
FT                   ECO:0000269|PubMed:37390746"
FT                   /id="VAR_081571"
FT   VARIANT         90
FT                   /note="R -> W (in DFNB111; uncertain significance;
FT                   dbSNP:rs187493775)"
FT                   /evidence="ECO:0000269|PubMed:29961571"
FT                   /id="VAR_081572"
FT   VARIANT         182..215
FT                   /note="Missing (in DFNB111; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:29961571"
FT                   /id="VAR_081573"
SQ   SEQUENCE   215 AA;  24484 MW;  9D19EBA798B5815A CRC64;
     MYGKSSTRAV LLLLGIQLTA LWPIAAVEIY TSRVLEAVNG TDARLKCTFS SFAPVGDALT
     VTWNFRPLDG GPEQFVFYYH IDPFQPMSGR FKDRVSWDGN PERYDASILL WKLQFDDNGT
     YTCQVKNPPD VDGVIGEIRL SVVHTVRFSE IHFLALAIGS ACALMIIIVI VVVLFQHYRK
     KRWAERAHKV VEIKSKEEER LNQEKKVSVY LEDTD
//