FREM2_HUMAN
ID FREM2_HUMAN Reviewed; 3169 AA.
AC Q5SZK8; Q4QQG1; Q5H9N8; Q5T6Q1; Q6N057; Q6ZSB4; Q7Z305; Q7Z341;
DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 3.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=FRAS1-related extracellular matrix protein 2;
DE AltName: Full=ECM3 homolog;
DE Flags: Precursor;
GN Name=FREM2;
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 GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1817-3169 (ISOFORM 2), AND
RP VARIANT ILE-2326.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1910-3169 (ISOFORM 1), AND
RP VARIANTS CYS-2066; SER-2153 AND ILE-2326.
RC TISSUE=Fetal kidney;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1741.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [5]
RP IDENTIFICATION (ISOFORM 1), FUNCTION, INVOLVEMENT IN FRASRS2, AND VARIANT
RP FRASRS2 LYS-1972.
RX PubMed=15838507; DOI=10.1038/ng1549;
RA Jadeja S., Smyth I., Pitera J.E., Taylor M.S., van Haelst M., Bentley E.,
RA McGregor L., Hopkins J., Chalepakis G., Philip N., Perez Aytes A.,
RA Watt F.M., Darling S.M., Jackson I., Woolf A.S., Scambler P.J.;
RT "Identification of a new gene mutated in Fraser syndrome and mouse
RT myelencephalic blebs.";
RL Nat. Genet. 37:520-525(2005).
RN [6]
RP FUNCTION, INTERACTION WITH FREM1, INVOLVEMENT IN CRYPTOP, VARIANT CRYPTOP
RP TRP-2167, CHARACTERIZATION OF VARIANT CRYPTOP TRP-2167, VARIANT FRASRS2
RP TRP-2167, AND CHARACTERIZATION OF VARIANTS FRASRS2 LYS-1972 AND TRP-2167.
RX PubMed=29688405; DOI=10.1093/hmg/ddy144;
RA Yu Q., Lin B., Xie S., Gao S., Li W., Liu Y., Wang H., Huang D., Xie Z.;
RT "A homozygous mutation p.Arg2167Trp in FREM2 causes isolated
RT cryptophthalmos.";
RL Hum. Mol. Genet. 27:2357-2366(2018).
RN [7]
RP FUNCTION, INVOLVEMENT IN CRYPTOP, AND VARIANTS CRYPTOP 736-ARG--VAL-3169
RP DEL; ARG-1355--VAL-3169 DEL; TRP-1770--VAL-3169 DEL AND TRP-2167.
RX PubMed=30802441; DOI=10.1016/j.exer.2019.02.013;
RA Zhang X., Wang D., Dongye M., Zhu Y., Chen C., Wang R., Long E., Liu Z.,
RA Wu X., Lin D., Chen J., Lin Z., Wang J., Li W., Li Y., Li D., Lin H.;
RT "Loss-of-function mutations in FREM2 disrupt eye morphogenesis.";
RL Exp. Eye Res. 181:302-312(2019).
CC -!- FUNCTION: Extracellular matrix protein required for maintenance of the
CC integrity of the skin epithelium and for maintenance of renal epithelia
CC (PubMed:15838507). Required for epidermal adhesion (PubMed:15838507).
CC Involved in the development of eyelids and the anterior segment of the
CC eyeballs (PubMed:29688405, PubMed:30802441).
CC {ECO:0000269|PubMed:15838507, ECO:0000269|PubMed:29688405,
CC ECO:0000269|PubMed:30802441}.
CC -!- SUBUNIT: Interacts with FREM1. {ECO:0000269|PubMed:29688405}.
CC -!- INTERACTION:
CC Q5SZK8; Q5H8C1: FREM1; NbExp=2; IntAct=EBI-20737564, EBI-21460642;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:15838507};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5SZK8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5SZK8-2; Sequence=VSP_015035, VSP_015036;
CC -!- DOMAIN: The Calx-beta domains bind calcium with high affinity and
CC undergo a major conformational shift upon binding. {ECO:0000250}.
CC -!- DISEASE: Fraser syndrome 2 (FRASRS2) [MIM:617666]: A form of Fraser
CC syndrome, an autosomal recessive disorder characterized by
CC cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities
CC including renal agenesis or hypoplasia. Additional features include
CC abnormalities of the larynx, ear malformations, and facial
CC abnormalities. {ECO:0000269|PubMed:15838507,
CC ECO:0000269|PubMed:29688405, ECO:0000269|PubMed:30802441}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Cryptophthalmos, unilateral or bilateral, isolated (CRYPTOP)
CC [MIM:123570]: An autosomal dominant, rare condition characterized by
CC congenital eyelid malformation with an underlying malformed eye. It can
CC be bilateral or unilateral and is classified into complete (typical),
CC incomplete (atypical) and abortive (congenital symblepharon) forms. The
CC skin of patients with complete cryptophthalmos extends uninterrupted
CC from the forehead to the cheek, whereas incomplete cryptophthalmos
CC exists when there is medial eyelid fusion, but coincident intact
CC lateral structures. The symblepharon variety presents with fusion of
CC the upper eyelid skin to the superior aspect of the globe. The complete
CC variety is the most common form. {ECO:0000269|PubMed:29688405,
CC ECO:0000269|PubMed:30802441}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FRAS1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC87040.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AC017111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL354819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590007; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK127571; BAC87040.1; ALT_INIT; mRNA.
DR EMBL; BX538150; CAD98036.1; -; mRNA.
DR EMBL; BX538304; CAD98088.1; -; mRNA.
DR EMBL; BX640686; CAE45813.1; -; mRNA.
DR EMBL; CR933724; CAI46253.1; -; mRNA.
DR EMBL; BN000687; CAH56764.1; -; mRNA.
DR CCDS; CCDS31960.1; -. [Q5SZK8-1]
DR RefSeq; NP_997244.4; NM_207361.5.
DR BioGRID; 131147; 52.
DR CORUM; Q5SZK8; -.
DR IntAct; Q5SZK8; 19.
DR STRING; 9606.ENSP00000280481; -.
DR GlyGen; Q5SZK8; 7 sites.
DR iPTMnet; Q5SZK8; -.
DR PhosphoSitePlus; Q5SZK8; -.
DR BioMuta; FREM2; -.
DR DMDM; 73620903; -.
DR EPD; Q5SZK8; -.
DR jPOST; Q5SZK8; -.
DR MassIVE; Q5SZK8; -.
DR MaxQB; Q5SZK8; -.
DR PaxDb; Q5SZK8; -.
DR PeptideAtlas; Q5SZK8; -.
DR PRIDE; Q5SZK8; -.
DR ProteomicsDB; 64078; -. [Q5SZK8-1]
DR ProteomicsDB; 64079; -. [Q5SZK8-2]
DR Antibodypedia; 23253; 121 antibodies from 29 providers.
DR DNASU; 341640; -.
DR Ensembl; ENST00000280481.9; ENSP00000280481.7; ENSG00000150893.11. [Q5SZK8-1]
DR GeneID; 341640; -.
DR KEGG; hsa:341640; -.
DR MANE-Select; ENST00000280481.9; ENSP00000280481.7; NM_207361.6; NP_997244.4.
DR UCSC; uc001uwv.4; human. [Q5SZK8-1]
DR CTD; 341640; -.
DR DisGeNET; 341640; -.
DR GeneCards; FREM2; -.
DR HGNC; HGNC:25396; FREM2.
DR HPA; ENSG00000150893; Tissue enhanced (kidney, thyroid gland).
DR MalaCards; FREM2; -.
DR MIM; 123570; phenotype.
DR MIM; 608945; gene.
DR MIM; 617666; phenotype.
DR neXtProt; NX_Q5SZK8; -.
DR OpenTargets; ENSG00000150893; -.
DR Orphanet; 98949; Complete cryptophthalmia.
DR Orphanet; 2052; Fraser syndrome.
DR Orphanet; 93100; Renal agenesis, unilateral.
DR PharmGKB; PA134930862; -.
DR VEuPathDB; HostDB:ENSG00000150893; -.
DR eggNOG; KOG1306; Eukaryota.
DR eggNOG; KOG2090; Eukaryota.
DR eggNOG; KOG3597; Eukaryota.
DR GeneTree; ENSGT00940000155313; -.
DR HOGENOM; CLU_000394_0_0_1; -.
DR InParanoid; Q5SZK8; -.
DR OrthoDB; 13258at2759; -.
DR PhylomeDB; Q5SZK8; -.
DR TreeFam; TF316876; -.
DR PathwayCommons; Q5SZK8; -.
DR SignaLink; Q5SZK8; -.
DR BioGRID-ORCS; 341640; 5 hits in 1058 CRISPR screens.
DR ChiTaRS; FREM2; human.
DR GeneWiki; FREM2; -.
DR GenomeRNAi; 341640; -.
DR Pharos; Q5SZK8; Tbio.
DR PRO; PR:Q5SZK8; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q5SZK8; protein.
DR Bgee; ENSG00000150893; Expressed in adrenal tissue and 113 other tissues.
DR Genevisible; Q5SZK8; HS.
DR GO; GO:0005604; C:basement membrane; IEA:Ensembl.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0007154; P:cell communication; IEA:InterPro.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0002009; P:morphogenesis of an epithelium; IEA:Ensembl.
DR Gene3D; 2.60.40.2030; -; 5.
DR InterPro; IPR038081; CalX-like_sf.
DR InterPro; IPR003644; Calx_beta.
DR InterPro; IPR039005; CSPG_rpt.
DR InterPro; IPR045658; FRAS1-rel_N.
DR Pfam; PF03160; Calx-beta; 5.
DR Pfam; PF19309; Frem_N; 1.
DR SMART; SM00237; Calx_beta; 5.
DR SUPFAM; SSF141072; SSF141072; 5.
DR PROSITE; PS51854; CSPG; 12.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell adhesion; Cell membrane;
KW Developmental protein; Disease variant; Glycoprotein; Membrane;
KW Metal-binding; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..46
FT /evidence="ECO:0000255"
FT CHAIN 47..3169
FT /note="FRAS1-related extracellular matrix protein 2"
FT /id="PRO_0000010124"
FT TOPO_DOM 47..3113
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 3114..3134
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 3135..3169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 319..413
FT /note="CSPG 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 438..537
FT /note="CSPG 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 560..675
FT /note="CSPG 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 700..807
FT /note="CSPG 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 828..919
FT /note="CSPG 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 945..1037
FT /note="CSPG 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 1066..1168
FT /note="CSPG 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 1189..1282
FT /note="CSPG 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 1303..1399
FT /note="CSPG 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 1420..1512
FT /note="CSPG 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 1532..1621
FT /note="CSPG 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT REPEAT 1655..1752
FT /note="CSPG 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01201"
FT DOMAIN 1759..1858
FT /note="Calx-beta 1"
FT DOMAIN 1871..1982
FT /note="Calx-beta 2"
FT DOMAIN 1997..2103
FT /note="Calx-beta 3"
FT DOMAIN 2118..2220
FT /note="Calx-beta 4"
FT DOMAIN 2238..2342
FT /note="Calx-beta 5"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3036..3057
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 3141..3169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..19
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3153..3169
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1244
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1369
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1584
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1741
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT VAR_SEQ 2663..2667
FT /note="LNLVQ -> QIYNI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015035"
FT VAR_SEQ 2668..3169
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_015036"
FT VARIANT 722
FT /note="R -> K (in dbSNP:rs58363253)"
FT /id="VAR_061174"
FT VARIANT 736..3169
FT /note="Missing (in CRYPTOP)"
FT /evidence="ECO:0000269|PubMed:30802441"
FT /id="VAR_082581"
FT VARIANT 745
FT /note="P -> S (in dbSNP:rs2496423)"
FT /id="VAR_061175"
FT VARIANT 770
FT /note="V -> M (in dbSNP:rs7327915)"
FT /id="VAR_033933"
FT VARIANT 868
FT /note="L -> V (in dbSNP:rs7329939)"
FT /id="VAR_033934"
FT VARIANT 1039
FT /note="M -> K (in dbSNP:rs2496424)"
FT /id="VAR_033935"
FT VARIANT 1045
FT /note="I -> S (in dbSNP:rs17058433)"
FT /id="VAR_037569"
FT VARIANT 1070
FT /note="F -> S (in dbSNP:rs2496425)"
FT /id="VAR_033936"
FT VARIANT 1355..3169
FT /note="Missing (in CRYPTOP)"
FT /evidence="ECO:0000269|PubMed:30802441"
FT /id="VAR_082582"
FT VARIANT 1668
FT /note="R -> H (in dbSNP:rs1868463)"
FT /id="VAR_037570"
FT VARIANT 1770..3169
FT /note="Missing (in CRYPTOP)"
FT /evidence="ECO:0000269|PubMed:30802441"
FT /id="VAR_082583"
FT VARIANT 1840
FT /note="R -> W (in dbSNP:rs9603422)"
FT /id="VAR_033937"
FT VARIANT 1972
FT /note="E -> K (in FRASRS2; may impair calcium-binding in
FT the 2nd Calx-beta domain; decreases cell adhesion;
FT decreases interaction with FREM1; dbSNP:rs121434356)"
FT /evidence="ECO:0000269|PubMed:15838507,
FT ECO:0000269|PubMed:29688405"
FT /id="VAR_023201"
FT VARIANT 2066
FT /note="R -> C (in dbSNP:rs9548505)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_023202"
FT VARIANT 2153
FT /note="T -> S (in dbSNP:rs9548506)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_023203"
FT VARIANT 2167
FT /note="R -> W (in CRYPTOP and FRASRS2; decreases cell
FT adhesion; decreases interaction with FREM1;
FT dbSNP:rs114837786)"
FT /evidence="ECO:0000269|PubMed:29688405,
FT ECO:0000269|PubMed:30802441"
FT /id="VAR_082584"
FT VARIANT 2326
FT /note="T -> I (in dbSNP:rs9548509)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17974005"
FT /id="VAR_023204"
FT VARIANT 2962
FT /note="A -> V (in dbSNP:rs7996253)"
FT /id="VAR_037571"
FT CONFLICT 2030
FT /note="V -> A (in Ref. 2; CAD98088)"
FT /evidence="ECO:0000305"
FT CONFLICT 2112
FT /note="E -> K (in Ref. 3; BAC87040)"
FT /evidence="ECO:0000305"
FT CONFLICT 2116
FT /note="A -> T (in Ref. 3; BAC87040)"
FT /evidence="ECO:0000305"
FT CONFLICT 2359
FT /note="Y -> H (in Ref. 2; CAD98088)"
FT /evidence="ECO:0000305"
FT CONFLICT 2508
FT /note="L -> P (in Ref. 3; BAC87040)"
FT /evidence="ECO:0000305"
FT CONFLICT 2638
FT /note="E -> K (in Ref. 3; BAC87040)"
FT /evidence="ECO:0000305"
FT CONFLICT 2682
FT /note="F -> I (in Ref. 2; CAD98088)"
FT /evidence="ECO:0000305"
FT CONFLICT 2777
FT /note="T -> S (in Ref. 2; CAI46253)"
FT /evidence="ECO:0000305"
FT CONFLICT 2786
FT /note="E -> G (in Ref. 2; CAD98036)"
FT /evidence="ECO:0000305"
FT CONFLICT 2968
FT /note="V -> I (in Ref. 2; CAD98088/CAE45813)"
FT /evidence="ECO:0000305"
FT CONFLICT 3081
FT /note="D -> G (in Ref. 2; CAD98088)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 3169 AA; 351167 MW; A6D7AF13CCA6BC0F CRC64;
MHSAGTPGLS SRRTGNSTSF QPGPPPPPRL LLLLLLLLSL VSRVPAQPAA FGRALLSPGL
AGAAGVPAEE AIVLANRGLR VPFGREVWLD PLHDLVLQVQ PGDRCAVSVL DNDALAQRPG
RLSPKRFPCD FGPGEVRYSH LGARSPSRDR VRLQLRYDAP GGAVVLPLVL EVEVVFTQLE
VVTRNLPLVV EELLGTSNAL DARSLEFAFQ PETEECRVGI LSGLGALPRY GELLHYPQVP
GGAREGGAPE TLLMDCKAFQ ELGVRYRHTA ASRSPNRDWI PMVVELRSRG APVGSPALKR
EHFQVLVRIR GGAENTAPKP SFVAMMMMEV DQFVLTALTP DMLAAEDAES PSDLLIFNLT
SPFQPGQGYL VSTDDRSLPL SSFTQRDLRL LKIAYQPPSE DSDQERLFEL ELEVVDLEGA
ASDPFAFMVV VKPMNTMAPV VTRNTGLILY EGQSRPLTGP AGSGPQNLVI SDEDDLEAVR
LEVVAGLRHG HLVILGASSG SSAPKSFTVA ELAAGQVVYQ HDDRDGSLSD NLVLRMVDGG
GRHQVQFLFP ITLVPVDDQP PVLNANTGLT LAEGETVPIL PLSLSATDMD SDDSLLLFVL
ESPFLTTGHL LLRQTHPPHE KQELLRGLWR KEGAFYERTV TEWQQQDITE GRLFYRHSGP
HSPGPVTDQF TFRVQDNHDP PNQSGLQRFV IRIHPVDRLP PELGSGCPLR MVVQESQLTP
LRKKWLRYTD LDTDDRELRY TVTQPPTDTD ENHLPAPLGT LVLTDNPSVV VTHFTQAQIN
HHKIAYRPPG QELGVATRVA QFQFQVEDRA GNVAPGTFTL YLHPVDNQPP EILNTGFTIQ
EKGHHILSET ELHVNDVDTD VAHISFTLTQ APKHGHMRVS GQILHVGGLF HLEDIKQGRV
SYAHNGDKSL TDSCSLEVSD RHHVVPITLR VNVRPVDDEV PILSHPTGTL ESYLDVLENG
ATEITANVIK GTNEETDDLM LTFLLEDPPL YGEILVNGIP AEQFTQRDIL EGSVVYTHTS
GEIGLLPKAD SFNLSLSDMS QEWRIGGNTI QGVTIWVTIL PVDSQAPEIF VGEQLIVMEG
DKSVITSVHI SAEDVDSLND DILCTIVIQP TSGYVENISP APGSEKSRAG IAISAFNLKD
LRQGHINYVQ SVHKGVEPVE DRFVFRCSDG INFSERQFFP IVIIPTNDEQ PEMFMREFMV
MEGMSLVIDT PILNAADADV PLDDLTFTIT QFPTHGHIMN QLINGTVLVE SFTLDQIIES
SSIIYEHDDS ETQEDSFVIK LTDGKHSVEK TVLIIVIPVD DETPRMTINN GLEIEIGDTK
IINNKILMAT DLDSEDKSLV YIIRYGPGHG LLQRRKPTGA FENITLGMNF TQDEVDRNLI
QYVHLGQEGI RDLIKFDVTD GINPLIDRYF YVSIGSIDIV FPDVISKGVS LKEGGKVTLT
TDLLSTSDLN SPDENLVFTI TRAPMRGHLE CTDQPGVSIT SFTQLQLAGN KIYYIHTADD
EVKMDSFEFQ VTDGRNPVFR TFRISISDVD NKKPVVTIHK LVVSESENKL ITPFELTVED
RDTPDKLLKF TITQVPIHGH LLFNNTRPVM VFTKQDLNEN LISYKHDGTE SSEDSFSFTV
TDGTHTDFYV FPDTVFETRR PQVMKIQVLA VDNSVPQIAV NKGASTLRTL ATGHLGFMIT
SKILKVEDRD SLHISLRFIV TEAPQHGYLL NLDKGNHSIT QFTQADIDDM KICYVLREGA
NATSDMFYFA VEDGGGNKLT YQNFRLNWAW ISFEKEYYLV NEDSKFLDVV LKRRGYLGET
SFISIGTRDR TAEKDKDFKG KAQKQVQFNP GQTRATWRVR ILSDGEHEQS ETFQVVLSEP
VLAALEFPTV ATVEIVDPGD EPTVFIPQSK YSVEEDVGEL FIPIRRSGDV SQELMVVCYT
QQGTATGTVP TSVLSYSDYI SRPEDHTSVV RFDKDEREKL CRIVIIDDSL YEEEETFHVL
LSMPMGGRIG SEFPGAQVTI VPDKDDEPIF YFGDVEYSVD ESAGYVEVQV WRTGTDLSKS
SSVTVRSRKT DPPSADAGTD YVGISRNLDF APGVNMQPVR VVILDDLGQP ALEGIEKFEL
VLRMPMNAAL GEPSKATVSI NDSVSDLPKM QFKERIYTGS ESDGQIVTMI HRTGDVQYRS
SVRCYTRQGS AQVMMDFEER PNTDTSIITF LPGETEKPCI LELMDDVLYE EVEELRLVLG
TPQSNSPFGA AVGEQNETLI RIRDDADKTV IKFGETKFSV TEPKEPGESV VIRIPVIRQG
DTSKVSIVRV HTKDGSATSG EDYHPVSEEI EFKEGETQHV VEIEVTFDGV REMREAFTVH
LKPDENMIAE MQLTKAIVYI EEMSSMADVT FPSVPQIVSL LMYDDTSKAK ESAEPMSGYP
VICITACNPK YSDYDKTGSI CASENINDTL TRYRWLISAP AGPDGVTSPM REVDFDTFFT
SSKMVTLDSI YFQPGSRVQC AARAVNTNGD EGLELMSPIV TISREEGLCQ PRVPGVVGAE
PFSAKLRYTG PEDADYTNLI KLTVTMPHID GMLPVISTRE LSNFELTLSP DGTRVGNHKC
SNLLDYTEVK THYGFLTDAT KNPEIIGETY PYQYSLSIRG STTLRFYRNL NLEACLWEFV
SYYDMSELLA DCGGTIGTDG QVLNLVQSYV TLRVPLYVSY VFHSPVGVGG WQHFDLKSEL
RLTFVYDTAI LWNDGIGSPP EAELQGSLYP TSMRIGDEGR LAVHFKTEAQ FHGLFVLSHP
ASFTSSVIMS ADHPGLTFSL RLIRSEPTYN QPVQQWSFVS DFAVRDYSGT YTVKLVPCTA
PSHQEYRLPV TCNPREPVTF DLDIRFQQVS DPVAAEFSLN TQMYLLSKKS LWLSDGSMGF
GQESDVAFAE GDIIYGRVMV DPVQNLGDSF YCSIEKVFLC TGADGYVPKY SPMNAEYGCL
ADSPSLLYRF KIVDKAQPET QATSFGNVLF NAKLAVDDPE AILLVNQPGS DGFKVDSTPL
FQVALGREWY IHTIYTVRSK DNANRGIGKR SVEYHSLVSQ GKPQSTTKSR KKREIRSTPS
LAWEIGAENS RGTNIQHIAL DRTKRQIPHG RAPPDGILPW ELNSPSSAVS LVTVVGGTTV
GLLTICLTVI AVLMCRGKES FRGKDAPKGS SSSEPMVPPQ SHHNDSSEV
