ID   IGS21_HUMAN             Reviewed;         467 AA.
AC   Q96ID5; Q8NBR8;
DT   21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=Immunoglobulin superfamily member 21 {ECO:0000305};
DE            Short=IgSF21 {ECO:0000305};
DE   Flags: Precursor;
GN   Name=IGSF21 {ECO:0000312|HGNC:HGNC:28246};
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 [LARGE SCALE MRNA].
RX   PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA   Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA   Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA   Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA   Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA   Isogai T.;
RT   "Signal sequence and keyword trap in silico for selection of full-length
RT   human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT   libraries.";
RL   DNA Res. 12:117-126(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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   [4]
RP   VARIANT [LARGE SCALE ANALYSIS] MET-467.
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: Involved in synaptic inhibition in the brain. Selectively
CC       regulates inhibitory presynaptic differentiation through interacting
CC       with presynaptic NRXN2. {ECO:0000250|UniProtKB:Q7TNR6}.
CC   -!- SUBUNIT: Interacts (Ig-like 1 domain) with NRXN2 (via Laminin G-like 1
CC       domain) in a trans-interaction manner. {ECO:0000250|UniProtKB:Q7TNR6}.
CC   -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC       {ECO:0000250|UniProtKB:Q7TNR6}; Lipid-anchor, GPI-anchor
CC       {ECO:0000250|UniProtKB:Q7TNR6}.
CC   -!- DOMAIN: Ig-like 1 domain is indispensable for synaptogenic activity
CC       whereas Ig-like 2 domain is secondarily responsible for the activity.
CC       {ECO:0000250|UniProtKB:Q7TNR6}.
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DR   EMBL; AK075316; BAC11542.1; -; mRNA.
DR   EMBL; AL356101; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL359738; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL365209; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL050342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC007618; AAH07618.1; -; mRNA.
DR   CCDS; CCDS184.1; -.
DR   RefSeq; NP_116269.3; NM_032880.4.
DR   AlphaFoldDB; Q96ID5; -.
DR   BioGRID; 124396; 42.
DR   IntAct; Q96ID5; 31.
DR   MINT; Q96ID5; -.
DR   STRING; 9606.ENSP00000251296; -.
DR   GlyCosmos; Q96ID5; 4 sites, No reported glycans.
DR   GlyGen; Q96ID5; 5 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q96ID5; -.
DR   PhosphoSitePlus; Q96ID5; -.
DR   BioMuta; IGSF21; -.
DR   DMDM; 74760871; -.
DR   EPD; Q96ID5; -.
DR   jPOST; Q96ID5; -.
DR   MassIVE; Q96ID5; -.
DR   MaxQB; Q96ID5; -.
DR   PaxDb; 9606-ENSP00000251296; -.
DR   PeptideAtlas; Q96ID5; -.
DR   ProteomicsDB; 76824; -.
DR   Antibodypedia; 29423; 98 antibodies from 20 providers.
DR   DNASU; 84966; -.
DR   Ensembl; ENST00000251296.4; ENSP00000251296.1; ENSG00000117154.12.
DR   GeneID; 84966; -.
DR   KEGG; hsa:84966; -.
DR   MANE-Select; ENST00000251296.4; ENSP00000251296.1; NM_032880.5; NP_116269.3.
DR   UCSC; uc001bau.3; human.
DR   AGR; HGNC:28246; -.
DR   CTD; 84966; -.
DR   DisGeNET; 84966; -.
DR   GeneCards; IGSF21; -.
DR   HGNC; HGNC:28246; IGSF21.
DR   HPA; ENSG00000117154; Tissue enriched (brain).
DR   neXtProt; NX_Q96ID5; -.
DR   OpenTargets; ENSG00000117154; -.
DR   PharmGKB; PA142671661; -.
DR   VEuPathDB; HostDB:ENSG00000117154; -.
DR   eggNOG; ENOG502QQMY; Eukaryota.
DR   GeneTree; ENSGT00390000002421; -.
DR   HOGENOM; CLU_054054_0_0_1; -.
DR   InParanoid; Q96ID5; -.
DR   OMA; YTEHPSR; -.
DR   OrthoDB; 4215545at2759; -.
DR   PhylomeDB; Q96ID5; -.
DR   TreeFam; TF331223; -.
DR   PathwayCommons; Q96ID5; -.
DR   SignaLink; Q96ID5; -.
DR   BioGRID-ORCS; 84966; 7 hits in 1139 CRISPR screens.
DR   ChiTaRS; IGSF21; human.
DR   GenomeRNAi; 84966; -.
DR   Pharos; Q96ID5; Tdark.
DR   PRO; PR:Q96ID5; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q96ID5; Protein.
DR   Bgee; ENSG00000117154; Expressed in right hemisphere of cerebellum and 118 other cell types or tissues.
DR   GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR   GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0060077; C:inhibitory synapse; ISS:UniProtKB.
DR   GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042734; C:presynaptic membrane; ISS:UniProtKB.
DR   GO; GO:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IBA:GO_Central.
DR   GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central.
DR   GO; GO:0060074; P:synapse maturation; ISS:UniProtKB.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 3.
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   PANTHER; PTHR23277:SF118; IMMUNOGLOBULIN SUPERFAMILY MEMBER 21; 1.
DR   PANTHER; PTHR23277; NECTIN-RELATED; 1.
DR   Pfam; PF07686; V-set; 1.
DR   SMART; SM00409; IG; 2.
DR   SUPFAM; SSF48726; Immunoglobulin; 3.
DR   PROSITE; PS50835; IG_LIKE; 2.
DR   Genevisible; Q96ID5; HS.
PE   2: Evidence at transcript level;
KW   Cell membrane; Disulfide bond; Glycoprotein; GPI-anchor;
KW   Immunoglobulin domain; Lipoprotein; Membrane; Postsynaptic cell membrane;
KW   Reference proteome; Repeat; Signal; Synapse.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..467
FT                   /note="Immunoglobulin superfamily member 21"
FT                   /id="PRO_0000223338"
FT   DOMAIN          25..132
FT                   /note="Ig-like 1"
FT   DOMAIN          344..429
FT                   /note="Ig-like 2"
FT   REGION          229..259
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        82
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        407
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        444
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        46..116
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT   VARIANT         245
FT                   /note="R -> H (in dbSNP:rs2355877)"
FT                   /id="VAR_056049"
FT   VARIANT         379
FT                   /note="T -> M (in dbSNP:rs12076815)"
FT                   /id="VAR_056050"
FT   VARIANT         467
FT                   /note="T -> M (in a colorectal cancer sample; somatic
FT                   mutation; dbSNP:rs766575681)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_035518"
FT   CONFLICT        369
FT                   /note="E -> G (in Ref. 1; BAC11542)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   467 AA;  51835 MW;  F62DD2C086A3EDAC CRC64;
     MRTAPSLRRC VCLLLAAILD LARGYLTVNI EPLPPVVAGD AVTLKCNFKT DGRMREIVWY
     RVTDGGTIKQ KIFTFDAMFS TNYSHMENYR KREDLVYQST VRLPEVRISD NGPYECHVGI
     YDRATREKVV LASGNIFLNV MAPPTSIEVV AADTPAPFSR YQAQNFTLVC IVSGGKPAPM
     VYFKRDGEPI DAVPLSEPPA ASSGPLQDSR PFRSLLHRDL DDTKMQKSLS LLDAENRGGR
     PYTERPSRGL TPDPNILLQP TTENIPETVV SREFPRWVHS AEPTYFLRHS RTPSSDGTVE
     VRALLTWTLN PQIDNEALFS CEVKHPALSM PMQAEVTLVA PKGPKIVMTP SRARVGDTVR
     ILVHGFQNEV FPEPMFTWTR VGSRLLDGSA EFDGKELVLE RVPAELNGSM YRCTAQNPLG
     STDTHTRLIV FENPNIPRGT EDSNGSIGPT GARLTLVLAL TVILELT
//