CSTN2_HUMAN
ID CSTN2_HUMAN Reviewed; 955 AA.
AC Q9H4D0; B2RCW5; D3DNF4; Q3SX54; Q3ZB76; Q5UE56; Q96HZ2; Q9BSS0;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Calsyntenin-2;
DE AltName: Full=Alcadein-gamma;
DE Short=Alc-gamma;
DE Flags: Precursor;
GN Name=CLSTN2; Synonyms=CS2;
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], TISSUE SPECIFICITY, AND VARIANT ILE-366.
RC TISSUE=Fetal brain;
RX PubMed=12498782; DOI=10.1006/mcne.2002.1181;
RA Hintsch G., Zurlinden A., Meskenaite V., Steuble M., Fink-Widmer K.,
RA Kinter J., Sonderegger P.;
RT "The calsyntenins - a family of postsynaptic membrane proteins with
RT distinct neuronal expression patterns.";
RL Mol. Cell. Neurosci. 21:393-409(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ILE-366.
RX PubMed=12972431; DOI=10.1074/jbc.m306024200;
RA Araki Y., Tomita S., Yamaguchi H., Miyagi N., Sumioka A., Kirino Y.,
RA Suzuki T.;
RT "Novel cadherin-related membrane proteins, Alcadeins, enhance the X11-like
RT protein-mediated stabilization of amyloid beta-protein precursor
RT metabolism.";
RL J. Biol. Chem. 278:49448-49458(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ILE-366.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and 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 [7]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=15037614; DOI=10.1074/jbc.m401925200;
RA Araki Y., Miyagi N., Kato N., Yoshida T., Wada S., Nishimura M., Komano H.,
RA Yamamoto T., De Strooper B., Yamamoto K., Suzuki T.;
RT "Coordinated metabolism of Alcadein and amyloid beta-protein precursor
RT regulates FE65-dependent gene transactivation.";
RL J. Biol. Chem. 279:24343-24354(2004).
RN [8]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-193 AND GLN-765.
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., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May modulate calcium-mediated postsynaptic signals.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9ER65};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q9ER65}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9ER65}. Golgi
CC apparatus membrane {ECO:0000250|UniProtKB:Q9ER65}. Postsynapse
CC {ECO:0000250|UniProtKB:Q9ER65}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q9ER65}. Note=Most prominent in the postsynaptic
CC specializations of asymmetric (type I) synapses with both axodendritic
CC and axospinous localization. {ECO:0000250|UniProtKB:Q9ER65}.
CC -!- TISSUE SPECIFICITY: Restricted to the brain.
CC {ECO:0000269|PubMed:12498782}.
CC -!- DOMAIN: Binds synaptic Ca(2+) with its cytoplasmic domain.
CC {ECO:0000250}.
CC -!- PTM: Proteolytically processed under normal cellular conditions. A
CC primary zeta-cleavage generates a large extracellular (soluble) N-
CC terminal domain (sAlc) and a short C-terminal transmembrane fragment
CC (CTF1). A secondary cleavage catalyzed by gamma-secretase within the
CC transmembrane domain releases the beta-Alc-gamma chain in the
CC extracellular milieu and produces an intracellular fragment (AlcICD).
CC This processing is strongly suppressed in the tripartite complex formed
CC with APBA2 and APP, which seems to prevent the association with PSEN1
CC (By similarity). {ECO:0000250}.
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; AJ278018; CAC14924.1; -; mRNA.
DR EMBL; AY753303; AAV30553.1; -; mRNA.
DR EMBL; AK315308; BAG37712.1; -; mRNA.
DR EMBL; AC010181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC048346; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092988; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108744; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117396; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC117449; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79018.1; -; Genomic_DNA.
DR EMBL; BC004871; AAH04871.2; -; mRNA.
DR EMBL; BC007943; AAH07943.2; -; mRNA.
DR EMBL; BC103496; AAI03497.1; -; mRNA.
DR EMBL; BC103506; AAI03507.1; -; mRNA.
DR EMBL; BC104485; AAI04486.1; -; mRNA.
DR CCDS; CCDS3112.1; -.
DR RefSeq; NP_071414.2; NM_022131.2.
DR AlphaFoldDB; Q9H4D0; -.
DR SMR; Q9H4D0; -.
DR BioGRID; 122049; 21.
DR STRING; 9606.ENSP00000402460; -.
DR GlyConnect; 1061; 3 N-Linked glycans (2 sites).
DR GlyGen; Q9H4D0; 6 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q9H4D0; -.
DR PhosphoSitePlus; Q9H4D0; -.
DR BioMuta; CLSTN2; -.
DR DMDM; 296434469; -.
DR jPOST; Q9H4D0; -.
DR MassIVE; Q9H4D0; -.
DR PaxDb; Q9H4D0; -.
DR PeptideAtlas; Q9H4D0; -.
DR PRIDE; Q9H4D0; -.
DR ProteomicsDB; 80823; -.
DR Antibodypedia; 33471; 136 antibodies from 20 providers.
DR DNASU; 64084; -.
DR Ensembl; ENST00000458420.7; ENSP00000402460.2; ENSG00000158258.16.
DR GeneID; 64084; -.
DR KEGG; hsa:64084; -.
DR MANE-Select; ENST00000458420.7; ENSP00000402460.2; NM_022131.3; NP_071414.2.
DR UCSC; uc003etn.4; human.
DR CTD; 64084; -.
DR DisGeNET; 64084; -.
DR GeneCards; CLSTN2; -.
DR HGNC; HGNC:17448; CLSTN2.
DR HPA; ENSG00000158258; Group enriched (adipose tissue, brain, ovary).
DR MIM; 611323; gene.
DR neXtProt; NX_Q9H4D0; -.
DR OpenTargets; ENSG00000158258; -.
DR PharmGKB; PA38239; -.
DR VEuPathDB; HostDB:ENSG00000158258; -.
DR eggNOG; KOG1834; Eukaryota.
DR GeneTree; ENSGT00950000183086; -.
DR HOGENOM; CLU_008904_0_0_1; -.
DR InParanoid; Q9H4D0; -.
DR OMA; WQDWAKR; -.
DR OrthoDB; 302557at2759; -.
DR PhylomeDB; Q9H4D0; -.
DR TreeFam; TF315946; -.
DR PathwayCommons; Q9H4D0; -.
DR BioGRID-ORCS; 64084; 8 hits in 1070 CRISPR screens.
DR ChiTaRS; CLSTN2; human.
DR GenomeRNAi; 64084; -.
DR Pharos; Q9H4D0; Tbio.
DR PRO; PR:Q9H4D0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9H4D0; protein.
DR Bgee; ENSG00000158258; Expressed in endothelial cell and 150 other tissues.
DR Genevisible; Q9H4D0; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IBA:GO_Central.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0099061; C:integral component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0001540; F:amyloid-beta binding; IEA:InterPro.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019894; F:kinesin binding; IEA:InterPro.
DR GO; GO:0042988; F:X11-like protein binding; IEA:InterPro.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0051965; P:positive regulation of synapse assembly; IBA:GO_Central.
DR GO; GO:0050806; P:positive regulation of synaptic transmission; IBA:GO_Central.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR026914; Calsyntenin.
DR InterPro; IPR045588; CLSTN_C.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR PANTHER; PTHR14139; PTHR14139; 1.
DR Pfam; PF00028; Cadherin; 1.
DR Pfam; PF19699; CLSTN_C; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 2.
DR SUPFAM; SSF49313; SSF49313; 2.
DR SUPFAM; SSF49899; SSF49899; 1.
DR PROSITE; PS50268; CADHERIN_2; 2.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell membrane; Cell projection;
KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Membrane;
KW Reference proteome; Repeat; Signal; Synapse; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..955
FT /note="Calsyntenin-2"
FT /id="PRO_0000004023"
FT TOPO_DOM 21..831
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 832..852
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 853..955
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 44..160
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 161..280
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 887..955
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 899..928
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 56
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 716
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 729
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 193
FT /note="S -> I (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036112"
FT VARIANT 331
FT /note="I -> T (in dbSNP:rs17348572)"
FT /id="VAR_055615"
FT VARIANT 366
FT /note="V -> I (in dbSNP:rs7632885)"
FT /evidence="ECO:0000269|PubMed:12498782,
FT ECO:0000269|PubMed:12972431, ECO:0000269|Ref.5"
FT /id="VAR_039557"
FT VARIANT 765
FT /note="R -> Q (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs766718816)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036113"
FT CONFLICT 847
FT /note="V -> D (in Ref. 6; AAI03507)"
FT /evidence="ECO:0000305"
FT CONFLICT 946
FT /note="L -> P (in Ref. 6; AAI03507)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 955 AA; 107006 MW; 6059F3277F152E75 CRC64;
MLPGRLCWVP LLLALGVGSG SGGGGDSRQR RLLAAKVNKH KPWIETSYHG VITENNDTVI
LDPPLVALDK DAPVPFAGEI CAFKIHGQEL PFEAVVLNKT SGEGRLRAKS PIDCELQKEY
TFIIQAYDCG AGPHETAWKK SHKAVVHIQV KDVNEFAPTF KEPAYKAVVT EGKIYDSILQ
VEAIDEDCSP QYSQICNYEI VTTDVPFAID RNGNIRNTEK LSYDKQHQYE ILVTAYDCGQ
KPAAQDTLVQ VDVKPVCKPG WQDWTKRIEY QPGSGSMPLF PSIHLETCDG AVSSLQIVTE
LQTNYIGKGC DRETYSEKSL QKLCGASSGI IDLLPSPSAA TNWTAGLLVD SSEMIFKFDG
RQGAKVPDGI VPKNLTDQFT ITMWMKHGPS PGVRAEKETI LCNSDKTEMN RHHYALYVHN
CRLVFLLRKD FDQADTFRPA EFHWKLDQIC DKEWHYYVIN VEFPVVTLYM DGATYEPYLV
TNDWPIHPSH IAMQLTVGAC WQGGEVTKPQ FAQFFHGSLA SLTIRPGKME SQKVISCLQA
CKEGLDINSL ESLGQGIKYH FNPSQSILVM EGDDIGNINR ALQKVSYINS RQFPTAGVRR
LKVSSKVQCF GEDVCISIPE VDAYVMVLQA IEPRITLRGT DHFWRPAAQF ESARGVTLFP
DIKIVSTFAK TEAPGDVKTT DPKSEVLEEM LHNLDFCDIL VIGGDLDPRQ ECLELNHSEL
HQRHLDATNS TAGYSIYGVG SMSRYEQVLH HIRYRNWRPA SLEARRFRIK CSELNGRYTS
NEFNLEVSIL HEDQVSDKEH VNHLIVQPPF LQSVHHPESR SSIQHSSVVP SIATVVIIIS
VCMLVFVVAM GVYRVRIAHQ HFIQETEAAK ESEMDWDDSA LTITVNPMEK HEGPGHGEDE
TEGEEEEEAE EEMSSSSGSD DSEEEEEEEG MGRGRHGQNG ARQAQLEWDD STLPY
