Full text data of SEMA7A
SEMA7A
(CD108, SEMAL)
[Confidence: high (a blood group or CD marker)]
Semaphorin-7A (CDw108; JMH blood group antigen; John-Milton-Hargen human blood group Ag; Semaphorin-K1; Sema K1; Semaphorin-L; Sema L; CD108; Flags: Precursor)
Semaphorin-7A (CDw108; JMH blood group antigen; John-Milton-Hargen human blood group Ag; Semaphorin-K1; Sema K1; Semaphorin-L; Sema L; CD108; Flags: Precursor)
hRBCD
IPI00025257
IPI00025257 Semaphorin 7A precursor Semaphorin 7A precursor membrane 1 2 3 1 4 n/a 2 1 n/a n/a 5 3 3 5 2 n/a n/a n/a 2 3 GPI- anchored to membrane n/a found at its expected molecular weight found at molecular weight
IPI00025257 Semaphorin 7A precursor Semaphorin 7A precursor membrane 1 2 3 1 4 n/a 2 1 n/a n/a 5 3 3 5 2 n/a n/a n/a 2 3 GPI- anchored to membrane n/a found at its expected molecular weight found at molecular weight
BGMUT
jmh
882 jmh SEMA7A SEMA7A SEMA7A; CDw108 reference (mRNA) reference entire coding region in cDNA JMH common 10201933 AF069493 Yamada et al. J Immunol 1999 162: 4094-4100 reference used for variant alleles of JMH antigens Blumenfeld OO, curator 2007-01-03 16:53:41.130 NA
882 jmh SEMA7A SEMA7A SEMA7A; CDw108 reference (mRNA) reference entire coding region in cDNA JMH common 10201933 AF069493 Yamada et al. J Immunol 1999 162: 4094-4100 reference used for variant alleles of JMH antigens Blumenfeld OO, curator 2007-01-03 16:53:41.130 NA
UniProt
O75326
ID SEM7A_HUMAN Reviewed; 666 AA.
AC O75326; B4DDP7; F5H1S0; Q1XE81; Q1XE82; Q1XE83; Q1XE84; Q3MIY5;
read moreDT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Semaphorin-7A;
DE AltName: Full=CDw108;
DE AltName: Full=JMH blood group antigen;
DE AltName: Full=John-Milton-Hargen human blood group Ag;
DE AltName: Full=Semaphorin-K1;
DE Short=Sema K1;
DE AltName: Full=Semaphorin-L;
DE Short=Sema L;
DE AltName: CD_antigen=CD108;
DE Flags: Precursor;
GN Name=SEMA7A; Synonyms=CD108, SEMAL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9721204; DOI=10.1006/geno.1998.5256;
RA Lange C., Liehr T., Goen M., Gebhart E., Fleckenstein B., Ensser A.;
RT "New eukaryotic semaphorins with close homology to semaphorins of DNA
RT viruses.";
RL Genomics 51:340-350(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION,
RP GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=10201933;
RA Yamada A., Kubo K., Takeshita T., Harashima N., Kawano K., Mine T.,
RA Sagawa K., Sugamura K., Itoh K.;
RT "Molecular cloning of a glycosylphosphatidylinositol-anchored molecule
RT CDw108.";
RL J. Immunol. 162:4094-4100(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=9712866; DOI=10.1074/jbc.273.35.22428;
RA Xu X., Ng S., Wu Z.-L., Nguyen D., Homburger S., Seidel-Dugan C.,
RA Ebens A., Luo Y.;
RT "Human semaphorin K1 is glycosylphosphatidylinositol-linked and
RT defines a new subfamily of viral-related semaphorins.";
RL J. Biol. Chem. 273:22428-22434(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN JOHN MILTON
RP HAGEN BLOOD GROUP SYSTEM, AND VARIANTS GLN-207; TRP-207; HIS-460 AND
RP CYS-461.
RC TISSUE=Peripheral blood;
RX PubMed=17207242; DOI=10.1111/j.1537-2995.2007.01076.x;
RA Seltsam A., Strigens S., Levene C., Yahalom V., Moulds M.,
RA Moulds J.J., Hustinx H., Weisbach V., Figueroa D., Bade-Doeding C.,
RA DeLuca D.S., Blasczyk R.;
RT "The molecular diversity of Sema7A, the semaphorin that carries the
RT JMH blood group antigens.";
RL Transfusion 47:133-146(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [GENOMIC DNA], AND VARIANT THR-115.
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain cortex;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP CHARACTERIZATION.
RX PubMed=10416131;
RA Angelisova P., Drbal K., Cerny J., Hilgert I., Horejsi V.;
RT "Characterization of the human leukocyte GPI-anchored glycoprotein
RT CDw108 and its relation to other similar molecules.";
RL Immunobiology 200:234-245(1999).
RN [10]
RP FUNCTION, INTERACTION WITH ITGB1, AND MUTAGENESIS OF ARG-267 AND
RP ASP-269.
RX PubMed=12879062; DOI=10.1038/nature01790;
RA Pasterkamp R.J., Peschon J.J., Spriggs M.K., Kolodkin A.L.;
RT "Semaphorin 7A promotes axon outgrowth through integrins and MAPKs.";
RL Nature 424:398-405(2003).
RN [11]
RP FUNCTION, AND INTERACTION WITH ITGA1 AND ITGB1.
RX PubMed=17377534; DOI=10.1038/nature05652;
RA Suzuki K., Okuno T., Yamamoto M., Pasterkamp R.J., Takegahara N.,
RA Takamatsu H., Kitao T., Takagi J., Rennert P.D., Kolodkin A.L.,
RA Kumanogoh A., Kikutani H.;
RT "Semaphorin 7A initiates T-cell-mediated inflammatory responses
RT through alpha1beta1 integrin.";
RL Nature 446:680-684(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ITGB1, INDUCTION, AND
RP TISSUE SPECIFICITY.
RX PubMed=17671519; DOI=10.1038/sj.jid.5700974;
RA Scott G.A., McClelland L.A., Fricke A.F.;
RT "Semaphorin 7a promotes spreading and dendricity in human melanocytes
RT through beta1-integrins.";
RL J. Invest. Dermatol. 128:151-161(2008).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 45-634 IN COMPLEX WITH
RP PLXNC1, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-105;
RP ASN-157; ASN-258 AND ASN-330.
RX PubMed=20727575; DOI=10.1016/j.cell.2010.07.040;
RA Liu H., Juo Z.S., Shim A.H., Focia P.J., Chen X., Garcia K.C., He X.;
RT "Structural basis of semaphorin-plexin recognition and viral mimicry
RT from Sema7A and A39R complexes with PlexinC1.";
RL Cell 142:749-761(2010).
RN [14]
RP VARIANT LEU-347.
RX PubMed=20854351; DOI=10.1111/j.1423-0410.2010.01413.x;
RA Richard M., St-Laurent J., Perreault J., Long A., St-Louis M.;
RT "A new SEMA7A variant found in Native Americans with alloantibody.";
RL Vox Sang. 100:322-326(2011).
CC -!- FUNCTION: Plays an important role in integrin-mediated signaling
CC and functions both in regulating cell migration and immune
CC responses. Promotes formation of focal adhesion complexes,
CC activation of the protein kinase PTK2/FAK1 and subsequent
CC phosphorylation of MAPK1 and MAPK3. Promotes production of
CC proinflammatory cytokines by monocytes and macrophages. Plays an
CC important role in modulating inflammation and T-cell-mediated
CC immune responses. Promotes axon growth in the embryonic olfactory
CC bulb. Promotes attachment, spreading and dendrite outgrowth in
CC melanocytes.
CC -!- SUBUNIT: Interacts with ITGA1 and ITGB1 (Probable). Interacts with
CC PLXNC1.
CC -!- INTERACTION:
CC P16333:NCK1; NbExp=2; IntAct=EBI-1753538, EBI-389883;
CC O60486:PLXNC1; NbExp=4; IntAct=EBI-1753538, EBI-2927384;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor;
CC Extracellular side. Note=Detected in a punctate pattern on the
CC cell membrane of basal and supra-basal skin keratinocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75326-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75326-2; Sequence=VSP_045349;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Detected in skin keratinocytes and on
CC endothelial cells from skin blood vessels (at protein level).
CC Expressed in fibroblasts, keratinocytes, melanocytes, placenta,
CC testis, ovary, spleen, brain, spinal chord, lung, heart, adrenal
CC gland, lymph nodes, thymus, intestine and kidney.
CC -!- INDUCTION: Up-regulated in UV-irradiated fibroblasts, but not in
CC UV-irradiated keratinocytes.
CC -!- POLYMORPHISM: Genetic variations in SEMA7A define the John Milton
CC Hagen blood group system (JMH) [MIM:614745]. Three different JMH
CC phenotypes have been identified based on the presence or absence
CC of the high-frequency JMH antigen: JMH-weak, JMH-negative, and
CC JMH-variant. The JMH-weak and -negative phenotypes can be either
CC acquired or inherited and are characterized by a reduction or
CC complete loss of JMH expression on red blood cells. Individuals
CC with the JMH-variant phenotype are usually JMH-positive and have
CC alloantibodies compatible with JMH-negative red blood cells. The
CC JMH-variant phenotype results from rare SEMA7A missense variants.
CC -!- SIMILARITY: Belongs to the semaphorin family.
CC -!- SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like)
CC domain.
CC -!- SIMILARITY: Contains 1 PSI domain.
CC -!- SIMILARITY: Contains 1 Sema domain.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=jmh";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/sema7a/";
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DR EMBL; AF030698; AAC34261.1; -; mRNA.
DR EMBL; AF030697; AAC34741.1; -; Genomic_DNA.
DR EMBL; AF069493; AAC82642.1; -; mRNA.
DR EMBL; AF071542; AAC80456.1; -; mRNA.
DR EMBL; AM180445; CAJ55398.1; -; mRNA.
DR EMBL; AM180446; CAJ55399.1; -; mRNA.
DR EMBL; AM180447; CAJ55400.1; -; mRNA.
DR EMBL; AM180448; CAJ55401.1; -; mRNA.
DR EMBL; AM180449; CAJ55402.1; -; mRNA.
DR EMBL; AM180450; CAJ55403.1; -; mRNA.
DR EMBL; AM180451; CAJ55404.1; -; mRNA.
DR EMBL; AK293280; BAG56808.1; -; mRNA.
DR EMBL; AY885237; AAW62253.1; -; Genomic_DNA.
DR EMBL; AC012435; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101643; AAI01644.1; -; mRNA.
DR EMBL; BC101647; AAI01648.1; -; mRNA.
DR RefSeq; NP_001139501.1; NM_001146029.1.
DR RefSeq; NP_001139502.1; NM_001146030.1.
DR RefSeq; NP_003603.1; NM_003612.3.
DR UniGene; Hs.24640; -.
DR PDB; 3NVQ; X-ray; 2.40 A; A/E=45-634.
DR PDBsum; 3NVQ; -.
DR ProteinModelPortal; O75326; -.
DR SMR; O75326; 46-633.
DR IntAct; O75326; 6.
DR MINT; MINT-1958248; -.
DR STRING; 9606.ENSP00000261918; -.
DR PhosphoSite; O75326; -.
DR PaxDb; O75326; -.
DR PeptideAtlas; O75326; -.
DR PRIDE; O75326; -.
DR Ensembl; ENST00000261918; ENSP00000261918; ENSG00000138623.
DR Ensembl; ENST00000543145; ENSP00000438966; ENSG00000138623.
DR GeneID; 8482; -.
DR KEGG; hsa:8482; -.
DR UCSC; uc010ull.2; human.
DR CTD; 8482; -.
DR GeneCards; GC15M074701; -.
DR HGNC; HGNC:10741; SEMA7A.
DR HPA; HPA042273; -.
DR MIM; 607961; gene+phenotype.
DR MIM; 614745; phenotype.
DR neXtProt; NX_O75326; -.
DR PharmGKB; PA35663; -.
DR eggNOG; NOG277924; -.
DR HOGENOM; HOG000154284; -.
DR HOVERGEN; HBG079171; -.
DR InParanoid; O75326; -.
DR KO; K06529; -.
DR OMA; EPMGPLK; -.
DR OrthoDB; EOG754HNX; -.
DR PhylomeDB; O75326; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; SEMA7A; human.
DR EvolutionaryTrace; O75326; -.
DR GeneWiki; SEMA7A; -.
DR GenomeRNAi; 8482; -.
DR NextBio; 31739; -.
DR PRO; PR:O75326; -.
DR ArrayExpress; O75326; -.
DR Bgee; O75326; -.
DR CleanEx; HS_SEMA7A; -.
DR Genevestigator; O75326; -.
DR GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-KW.
DR GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0004872; F:receptor activity; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR016201; Plexin-like_fold.
DR InterPro; IPR002165; Plexin_repeat.
DR InterPro; IPR001627; Semap_dom.
DR InterPro; IPR027231; Semaphorin.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR PANTHER; PTHR11036; PTHR11036; 1.
DR Pfam; PF01437; PSI; 1.
DR Pfam; PF01403; Sema; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00423; PSI; 1.
DR SMART; SM00630; Sema; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR SUPFAM; SSF103575; SSF103575; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW GPI-anchor; Immunoglobulin domain; Inflammatory response; Lipoprotein;
KW Membrane; Neurogenesis; Polymorphism; Reference proteome; Signal.
FT SIGNAL 1 44 Potential.
FT CHAIN 45 648 Semaphorin-7A.
FT /FTId=PRO_0000032347.
FT PROPEP 649 666 Removed in mature form (Potential).
FT /FTId=PRO_0000032348.
FT DOMAIN 53 490 Sema.
FT DOMAIN 544 629 Ig-like C2-type.
FT REGION 267 269 Interaction with integrins.
FT MOTIF 267 269 Cell attachment site (Potential).
FT LIPID 648 648 GPI-anchor amidated alanine (Potential).
FT CARBOHYD 105 105 N-linked (GlcNAc...).
FT CARBOHYD 157 157 N-linked (GlcNAc...).
FT CARBOHYD 258 258 N-linked (GlcNAc...).
FT CARBOHYD 330 330 N-linked (GlcNAc...).
FT CARBOHYD 602 602 N-linked (GlcNAc...) (Probable).
FT DISULFID 120 126
FT DISULFID 143 152
FT DISULFID 266 366
FT DISULFID 291 335
FT DISULFID 493 511
FT DISULFID 500 541
FT DISULFID 503 518
FT DISULFID 566 613
FT DISULFID 587 596
FT VAR_SEQ 111 124 Missing (in isoform 2).
FT /FTId=VSP_045349.
FT VARIANT 115 115 S -> T (in dbSNP:rs16968733).
FT /FTId=VAR_029282.
FT VARIANT 207 207 R -> Q (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs55637216).
FT /FTId=VAR_038836.
FT VARIANT 207 207 R -> W (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs56367230).
FT /FTId=VAR_038837.
FT VARIANT 347 347 R -> L (rare polymorphism that results in
FT JMH-variant phenotype).
FT /FTId=VAR_068679.
FT VARIANT 460 460 R -> H (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs56204206).
FT /FTId=VAR_038838.
FT VARIANT 461 461 R -> C (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs56001514).
FT /FTId=VAR_038839.
FT MUTAGEN 267 267 R->K: Abolishes ITGB1-dependent
FT enhancement of axon growth; when
FT associated with E-269.
FT MUTAGEN 269 269 D->E: Abolishes ITGB1-dependent
FT enhancement of axon growth; when
FT associated with K-267.
FT CONFLICT 545 545 K -> E (in Ref. 5; BAG56808).
FT TURN 62 64
FT STRAND 65 68
FT STRAND 77 79
FT STRAND 85 90
FT STRAND 92 99
FT STRAND 110 112
FT STRAND 129 136
FT STRAND 139 144
FT TURN 146 148
FT STRAND 151 158
FT STRAND 160 165
FT STRAND 180 183
FT STRAND 186 189
FT STRAND 204 210
FT STRAND 223 230
FT HELIX 235 237
FT STRAND 239 247
FT STRAND 257 266
FT STRAND 272 274
FT TURN 275 279
FT STRAND 285 289
FT TURN 294 296
FT STRAND 302 309
FT HELIX 316 318
FT STRAND 320 326
FT STRAND 332 338
FT HELIX 339 348
FT STRAND 368 370
FT HELIX 375 383
FT STRAND 386 389
FT STRAND 394 397
FT STRAND 401 406
FT STRAND 408 417
FT STRAND 423 431
FT STRAND 436 440
FT STRAND 451 456
FT STRAND 467 471
FT TURN 472 475
FT STRAND 476 480
FT STRAND 482 489
FT HELIX 499 505
FT STRAND 511 514
FT STRAND 517 520
FT STRAND 523 526
FT STRAND 533 535
FT TURN 537 540
FT STRAND 541 545
FT STRAND 551 556
FT STRAND 562 567
FT STRAND 573 579
FT STRAND 582 587
FT STRAND 592 602
FT STRAND 609 619
FT STRAND 621 631
SQ SEQUENCE 666 AA; 74824 MW; AD3ABE56B5EBE194 CRC64;
MTPPPPGRAA PSAPRARVPG PPARLGLPLR LRLLLLLWAA AASAQGHLRS GPRIFAVWKG
HVGQDRVDFG QTEPHTVLFH EPGSSSVWVG GRGKVYLFDF PEGKNASVRT VNIGSTKGSC
LDKRDCENYI TLLERRSEGL LACGTNARHP SCWNLVNGTV VPLGEMRGYA PFSPDENSLV
LFEGDEVYST IRKQEYNGKI PRFRRIRGES ELYTSDTVMQ NPQFIKATIV HQDQAYDDKI
YYFFREDNPD KNPEAPLNVS RVAQLCRGDQ GGESSLSVSK WNTFLKAMLV CSDAATNKNF
NRLQDVFLLP DPSGQWRDTR VYGVFSNPWN YSAVCVYSLG DIDKVFRTSS LKGYHSSLPN
PRPGKCLPDQ QPIPTETFQV ADRHPEVAQR VEPMGPLKTP LFHSKYHYQK VAVHRMQASH
GETFHVLYLT TDRGTIHKVV EPGEQEHSFA FNIMEIQPFR RAAAIQTMSL DAERRKLYVS
SQWEVSQVPL DLCEVYGGGC HGCLMSRDPY CGWDQGRCIS IYSSERSVLQ SINPAEPHKE
CPNPKPDKAP LQKVSLAPNS RYYLSCPMES RHATYSWRHK ENVEQSCEPG HQSPNCILFI
ENLTAQQYGH YFCEAQEGSY FREAQHWQLL PEDGIMAEHL LGHACALAAS LWLGVLPTLT
LGLLVH
//
ID SEM7A_HUMAN Reviewed; 666 AA.
AC O75326; B4DDP7; F5H1S0; Q1XE81; Q1XE82; Q1XE83; Q1XE84; Q3MIY5;
read moreDT 20-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 22-JAN-2014, entry version 128.
DE RecName: Full=Semaphorin-7A;
DE AltName: Full=CDw108;
DE AltName: Full=JMH blood group antigen;
DE AltName: Full=John-Milton-Hargen human blood group Ag;
DE AltName: Full=Semaphorin-K1;
DE Short=Sema K1;
DE AltName: Full=Semaphorin-L;
DE Short=Sema L;
DE AltName: CD_antigen=CD108;
DE Flags: Precursor;
GN Name=SEMA7A; Synonyms=CD108, SEMAL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=9721204; DOI=10.1006/geno.1998.5256;
RA Lange C., Liehr T., Goen M., Gebhart E., Fleckenstein B., Ensser A.;
RT "New eukaryotic semaphorins with close homology to semaphorins of DNA
RT viruses.";
RL Genomics 51:340-350(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION,
RP GLYCOSYLATION, AND TISSUE SPECIFICITY.
RX PubMed=10201933;
RA Yamada A., Kubo K., Takeshita T., Harashima N., Kawano K., Mine T.,
RA Sagawa K., Sugamura K., Itoh K.;
RT "Molecular cloning of a glycosylphosphatidylinositol-anchored molecule
RT CDw108.";
RL J. Immunol. 162:4094-4100(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Placenta;
RX PubMed=9712866; DOI=10.1074/jbc.273.35.22428;
RA Xu X., Ng S., Wu Z.-L., Nguyen D., Homburger S., Seidel-Dugan C.,
RA Ebens A., Luo Y.;
RT "Human semaphorin K1 is glycosylphosphatidylinositol-linked and
RT defines a new subfamily of viral-related semaphorins.";
RL J. Biol. Chem. 273:22428-22434(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN JOHN MILTON
RP HAGEN BLOOD GROUP SYSTEM, AND VARIANTS GLN-207; TRP-207; HIS-460 AND
RP CYS-461.
RC TISSUE=Peripheral blood;
RX PubMed=17207242; DOI=10.1111/j.1537-2995.2007.01076.x;
RA Seltsam A., Strigens S., Levene C., Yahalom V., Moulds M.,
RA Moulds J.J., Hustinx H., Weisbach V., Figueroa D., Bade-Doeding C.,
RA DeLuca D.S., Blasczyk R.;
RT "The molecular diversity of Sema7A, the semaphorin that carries the
RT JMH blood group antigens.";
RL Transfusion 47:133-146(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [GENOMIC DNA], AND VARIANT THR-115.
RG SeattleSNPs variation discovery resource;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
RA Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human
RT chromosome 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain cortex;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP CHARACTERIZATION.
RX PubMed=10416131;
RA Angelisova P., Drbal K., Cerny J., Hilgert I., Horejsi V.;
RT "Characterization of the human leukocyte GPI-anchored glycoprotein
RT CDw108 and its relation to other similar molecules.";
RL Immunobiology 200:234-245(1999).
RN [10]
RP FUNCTION, INTERACTION WITH ITGB1, AND MUTAGENESIS OF ARG-267 AND
RP ASP-269.
RX PubMed=12879062; DOI=10.1038/nature01790;
RA Pasterkamp R.J., Peschon J.J., Spriggs M.K., Kolodkin A.L.;
RT "Semaphorin 7A promotes axon outgrowth through integrins and MAPKs.";
RL Nature 424:398-405(2003).
RN [11]
RP FUNCTION, AND INTERACTION WITH ITGA1 AND ITGB1.
RX PubMed=17377534; DOI=10.1038/nature05652;
RA Suzuki K., Okuno T., Yamamoto M., Pasterkamp R.J., Takegahara N.,
RA Takamatsu H., Kitao T., Takagi J., Rennert P.D., Kolodkin A.L.,
RA Kumanogoh A., Kikutani H.;
RT "Semaphorin 7A initiates T-cell-mediated inflammatory responses
RT through alpha1beta1 integrin.";
RL Nature 446:680-684(2007).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ITGB1, INDUCTION, AND
RP TISSUE SPECIFICITY.
RX PubMed=17671519; DOI=10.1038/sj.jid.5700974;
RA Scott G.A., McClelland L.A., Fricke A.F.;
RT "Semaphorin 7a promotes spreading and dendricity in human melanocytes
RT through beta1-integrins.";
RL J. Invest. Dermatol. 128:151-161(2008).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 45-634 IN COMPLEX WITH
RP PLXNC1, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-105;
RP ASN-157; ASN-258 AND ASN-330.
RX PubMed=20727575; DOI=10.1016/j.cell.2010.07.040;
RA Liu H., Juo Z.S., Shim A.H., Focia P.J., Chen X., Garcia K.C., He X.;
RT "Structural basis of semaphorin-plexin recognition and viral mimicry
RT from Sema7A and A39R complexes with PlexinC1.";
RL Cell 142:749-761(2010).
RN [14]
RP VARIANT LEU-347.
RX PubMed=20854351; DOI=10.1111/j.1423-0410.2010.01413.x;
RA Richard M., St-Laurent J., Perreault J., Long A., St-Louis M.;
RT "A new SEMA7A variant found in Native Americans with alloantibody.";
RL Vox Sang. 100:322-326(2011).
CC -!- FUNCTION: Plays an important role in integrin-mediated signaling
CC and functions both in regulating cell migration and immune
CC responses. Promotes formation of focal adhesion complexes,
CC activation of the protein kinase PTK2/FAK1 and subsequent
CC phosphorylation of MAPK1 and MAPK3. Promotes production of
CC proinflammatory cytokines by monocytes and macrophages. Plays an
CC important role in modulating inflammation and T-cell-mediated
CC immune responses. Promotes axon growth in the embryonic olfactory
CC bulb. Promotes attachment, spreading and dendrite outgrowth in
CC melanocytes.
CC -!- SUBUNIT: Interacts with ITGA1 and ITGB1 (Probable). Interacts with
CC PLXNC1.
CC -!- INTERACTION:
CC P16333:NCK1; NbExp=2; IntAct=EBI-1753538, EBI-389883;
CC O60486:PLXNC1; NbExp=4; IntAct=EBI-1753538, EBI-2927384;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor;
CC Extracellular side. Note=Detected in a punctate pattern on the
CC cell membrane of basal and supra-basal skin keratinocytes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75326-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75326-2; Sequence=VSP_045349;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Detected in skin keratinocytes and on
CC endothelial cells from skin blood vessels (at protein level).
CC Expressed in fibroblasts, keratinocytes, melanocytes, placenta,
CC testis, ovary, spleen, brain, spinal chord, lung, heart, adrenal
CC gland, lymph nodes, thymus, intestine and kidney.
CC -!- INDUCTION: Up-regulated in UV-irradiated fibroblasts, but not in
CC UV-irradiated keratinocytes.
CC -!- POLYMORPHISM: Genetic variations in SEMA7A define the John Milton
CC Hagen blood group system (JMH) [MIM:614745]. Three different JMH
CC phenotypes have been identified based on the presence or absence
CC of the high-frequency JMH antigen: JMH-weak, JMH-negative, and
CC JMH-variant. The JMH-weak and -negative phenotypes can be either
CC acquired or inherited and are characterized by a reduction or
CC complete loss of JMH expression on red blood cells. Individuals
CC with the JMH-variant phenotype are usually JMH-positive and have
CC alloantibodies compatible with JMH-negative red blood cells. The
CC JMH-variant phenotype results from rare SEMA7A missense variants.
CC -!- SIMILARITY: Belongs to the semaphorin family.
CC -!- SIMILARITY: Contains 1 Ig-like C2-type (immunoglobulin-like)
CC domain.
CC -!- SIMILARITY: Contains 1 PSI domain.
CC -!- SIMILARITY: Contains 1 Sema domain.
CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC mutation database;
CC URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system;=jmh";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/sema7a/";
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DR EMBL; AF030698; AAC34261.1; -; mRNA.
DR EMBL; AF030697; AAC34741.1; -; Genomic_DNA.
DR EMBL; AF069493; AAC82642.1; -; mRNA.
DR EMBL; AF071542; AAC80456.1; -; mRNA.
DR EMBL; AM180445; CAJ55398.1; -; mRNA.
DR EMBL; AM180446; CAJ55399.1; -; mRNA.
DR EMBL; AM180447; CAJ55400.1; -; mRNA.
DR EMBL; AM180448; CAJ55401.1; -; mRNA.
DR EMBL; AM180449; CAJ55402.1; -; mRNA.
DR EMBL; AM180450; CAJ55403.1; -; mRNA.
DR EMBL; AM180451; CAJ55404.1; -; mRNA.
DR EMBL; AK293280; BAG56808.1; -; mRNA.
DR EMBL; AY885237; AAW62253.1; -; Genomic_DNA.
DR EMBL; AC012435; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC090826; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101643; AAI01644.1; -; mRNA.
DR EMBL; BC101647; AAI01648.1; -; mRNA.
DR RefSeq; NP_001139501.1; NM_001146029.1.
DR RefSeq; NP_001139502.1; NM_001146030.1.
DR RefSeq; NP_003603.1; NM_003612.3.
DR UniGene; Hs.24640; -.
DR PDB; 3NVQ; X-ray; 2.40 A; A/E=45-634.
DR PDBsum; 3NVQ; -.
DR ProteinModelPortal; O75326; -.
DR SMR; O75326; 46-633.
DR IntAct; O75326; 6.
DR MINT; MINT-1958248; -.
DR STRING; 9606.ENSP00000261918; -.
DR PhosphoSite; O75326; -.
DR PaxDb; O75326; -.
DR PeptideAtlas; O75326; -.
DR PRIDE; O75326; -.
DR Ensembl; ENST00000261918; ENSP00000261918; ENSG00000138623.
DR Ensembl; ENST00000543145; ENSP00000438966; ENSG00000138623.
DR GeneID; 8482; -.
DR KEGG; hsa:8482; -.
DR UCSC; uc010ull.2; human.
DR CTD; 8482; -.
DR GeneCards; GC15M074701; -.
DR HGNC; HGNC:10741; SEMA7A.
DR HPA; HPA042273; -.
DR MIM; 607961; gene+phenotype.
DR MIM; 614745; phenotype.
DR neXtProt; NX_O75326; -.
DR PharmGKB; PA35663; -.
DR eggNOG; NOG277924; -.
DR HOGENOM; HOG000154284; -.
DR HOVERGEN; HBG079171; -.
DR InParanoid; O75326; -.
DR KO; K06529; -.
DR OMA; EPMGPLK; -.
DR OrthoDB; EOG754HNX; -.
DR PhylomeDB; O75326; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; SEMA7A; human.
DR EvolutionaryTrace; O75326; -.
DR GeneWiki; SEMA7A; -.
DR GenomeRNAi; 8482; -.
DR NextBio; 31739; -.
DR PRO; PR:O75326; -.
DR ArrayExpress; O75326; -.
DR Bgee; O75326; -.
DR CleanEx; HS_SEMA7A; -.
DR Genevestigator; O75326; -.
DR GO; GO:0031225; C:anchored to membrane; IEA:UniProtKB-KW.
DR GO; GO:0009897; C:external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0004872; F:receptor activity; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; IDA:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR016201; Plexin-like_fold.
DR InterPro; IPR002165; Plexin_repeat.
DR InterPro; IPR001627; Semap_dom.
DR InterPro; IPR027231; Semaphorin.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom.
DR PANTHER; PTHR11036; PTHR11036; 1.
DR Pfam; PF01437; PSI; 1.
DR Pfam; PF01403; Sema; 1.
DR SMART; SM00409; IG; 1.
DR SMART; SM00423; PSI; 1.
DR SMART; SM00630; Sema; 1.
DR SUPFAM; SSF101912; SSF101912; 1.
DR SUPFAM; SSF103575; SSF103575; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS51004; SEMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW GPI-anchor; Immunoglobulin domain; Inflammatory response; Lipoprotein;
KW Membrane; Neurogenesis; Polymorphism; Reference proteome; Signal.
FT SIGNAL 1 44 Potential.
FT CHAIN 45 648 Semaphorin-7A.
FT /FTId=PRO_0000032347.
FT PROPEP 649 666 Removed in mature form (Potential).
FT /FTId=PRO_0000032348.
FT DOMAIN 53 490 Sema.
FT DOMAIN 544 629 Ig-like C2-type.
FT REGION 267 269 Interaction with integrins.
FT MOTIF 267 269 Cell attachment site (Potential).
FT LIPID 648 648 GPI-anchor amidated alanine (Potential).
FT CARBOHYD 105 105 N-linked (GlcNAc...).
FT CARBOHYD 157 157 N-linked (GlcNAc...).
FT CARBOHYD 258 258 N-linked (GlcNAc...).
FT CARBOHYD 330 330 N-linked (GlcNAc...).
FT CARBOHYD 602 602 N-linked (GlcNAc...) (Probable).
FT DISULFID 120 126
FT DISULFID 143 152
FT DISULFID 266 366
FT DISULFID 291 335
FT DISULFID 493 511
FT DISULFID 500 541
FT DISULFID 503 518
FT DISULFID 566 613
FT DISULFID 587 596
FT VAR_SEQ 111 124 Missing (in isoform 2).
FT /FTId=VSP_045349.
FT VARIANT 115 115 S -> T (in dbSNP:rs16968733).
FT /FTId=VAR_029282.
FT VARIANT 207 207 R -> Q (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs55637216).
FT /FTId=VAR_038836.
FT VARIANT 207 207 R -> W (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs56367230).
FT /FTId=VAR_038837.
FT VARIANT 347 347 R -> L (rare polymorphism that results in
FT JMH-variant phenotype).
FT /FTId=VAR_068679.
FT VARIANT 460 460 R -> H (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs56204206).
FT /FTId=VAR_038838.
FT VARIANT 461 461 R -> C (rare polymorphism that results in
FT JMH-variant phenotype; dbSNP:rs56001514).
FT /FTId=VAR_038839.
FT MUTAGEN 267 267 R->K: Abolishes ITGB1-dependent
FT enhancement of axon growth; when
FT associated with E-269.
FT MUTAGEN 269 269 D->E: Abolishes ITGB1-dependent
FT enhancement of axon growth; when
FT associated with K-267.
FT CONFLICT 545 545 K -> E (in Ref. 5; BAG56808).
FT TURN 62 64
FT STRAND 65 68
FT STRAND 77 79
FT STRAND 85 90
FT STRAND 92 99
FT STRAND 110 112
FT STRAND 129 136
FT STRAND 139 144
FT TURN 146 148
FT STRAND 151 158
FT STRAND 160 165
FT STRAND 180 183
FT STRAND 186 189
FT STRAND 204 210
FT STRAND 223 230
FT HELIX 235 237
FT STRAND 239 247
FT STRAND 257 266
FT STRAND 272 274
FT TURN 275 279
FT STRAND 285 289
FT TURN 294 296
FT STRAND 302 309
FT HELIX 316 318
FT STRAND 320 326
FT STRAND 332 338
FT HELIX 339 348
FT STRAND 368 370
FT HELIX 375 383
FT STRAND 386 389
FT STRAND 394 397
FT STRAND 401 406
FT STRAND 408 417
FT STRAND 423 431
FT STRAND 436 440
FT STRAND 451 456
FT STRAND 467 471
FT TURN 472 475
FT STRAND 476 480
FT STRAND 482 489
FT HELIX 499 505
FT STRAND 511 514
FT STRAND 517 520
FT STRAND 523 526
FT STRAND 533 535
FT TURN 537 540
FT STRAND 541 545
FT STRAND 551 556
FT STRAND 562 567
FT STRAND 573 579
FT STRAND 582 587
FT STRAND 592 602
FT STRAND 609 619
FT STRAND 621 631
SQ SEQUENCE 666 AA; 74824 MW; AD3ABE56B5EBE194 CRC64;
MTPPPPGRAA PSAPRARVPG PPARLGLPLR LRLLLLLWAA AASAQGHLRS GPRIFAVWKG
HVGQDRVDFG QTEPHTVLFH EPGSSSVWVG GRGKVYLFDF PEGKNASVRT VNIGSTKGSC
LDKRDCENYI TLLERRSEGL LACGTNARHP SCWNLVNGTV VPLGEMRGYA PFSPDENSLV
LFEGDEVYST IRKQEYNGKI PRFRRIRGES ELYTSDTVMQ NPQFIKATIV HQDQAYDDKI
YYFFREDNPD KNPEAPLNVS RVAQLCRGDQ GGESSLSVSK WNTFLKAMLV CSDAATNKNF
NRLQDVFLLP DPSGQWRDTR VYGVFSNPWN YSAVCVYSLG DIDKVFRTSS LKGYHSSLPN
PRPGKCLPDQ QPIPTETFQV ADRHPEVAQR VEPMGPLKTP LFHSKYHYQK VAVHRMQASH
GETFHVLYLT TDRGTIHKVV EPGEQEHSFA FNIMEIQPFR RAAAIQTMSL DAERRKLYVS
SQWEVSQVPL DLCEVYGGGC HGCLMSRDPY CGWDQGRCIS IYSSERSVLQ SINPAEPHKE
CPNPKPDKAP LQKVSLAPNS RYYLSCPMES RHATYSWRHK ENVEQSCEPG HQSPNCILFI
ENLTAQQYGH YFCEAQEGSY FREAQHWQLL PEDGIMAEHL LGHACALAAS LWLGVLPTLT
LGLLVH
//
MIM
607961
*RECORD*
*FIELD* NO
607961
*FIELD* TI
*607961 SEMAPHORIN 7A; SEMA7A
;;SEMAPHORIN L; SEMAL;;
SEMAPHORIN K1; SEMAK1;;
CDW108
read more*FIELD* TX
DESCRIPTION
SEMA7A is an 80-kD membrane-bound semaphorin that associates with cell
surfaces via a glycosylphosphatidylinositol (GPI) linkage. It is
preferentially expressed on activated lymphocytes and erythrocytes.
SEMA7A carries the John Milton Hagen (JMH) blood group antigens (see
614745) (summary by Yamada et al., 1999).
CLONING
By PCR using primers designed from alcelaphine herpesvirus-1 (AHV) sema,
followed by 5-prime and 3-prime RACE, Lange et al. (1998) cloned
full-length SEMA7A, which they designated SEMAL, from a placenta cDNA
library. The deduced 666-amino acid protein has a calculated molecular
mass of about 75 kD, and the unglycosylated protein has a calculated
molecular mass of about 70 kD following signal peptide cleavage. SEMA7A
contains a 44-amino acid N-terminal signal sequence, a semaphorin domain
of about 500 amino acids, an immunoglobulin-like motif, and a C-terminal
hydrophobic domain that lacks a significant intracellular tail. The
semaphorin domain has several conserved cysteine residues and an RGD
motif. SEMA7A also contains 5 N-glycosylation sites and several
myristoylation sites. Northern blot analysis detected a 3.2-kb
transcript expressed predominantly in spleen, thymus, testis, and ovary.
Little or no expression was detected in prostate, small intestine,
colon, and peripheral blood leukocytes. RNA dot blot analysis detected
expression in placenta, spleen, and gonadal tissue, but not in neuronal
or muscular tissue.
By searching an EST database using AHV sema as probe, Xu et al. (1998)
identified SEMA7A, which they designated SEMAK1. SEMA7A shares about 50%
amino acid identity with AHV sema and less than 30% identity with other
semaphorins. Northern blot analysis of adult mouse tissues detected a
4.4-kb Sema7a transcript expressed at high levels in brain, spinal cord,
lung, and testis. In situ hybridization detected weak but dynamic
expression of Sema7a in spinal cord, cerebellum, and cortex during
embryonic development. In adult mice, Sema7a was expressed in several
brain structures and cell layers.
By PCR using primers based on the N-terminal amino acid sequence of
SEMA7A, followed by screening a leukemic T-cell line cDNA library and a
placenta cDNA library, Yamada et al. (1999) cloned SEMA7A, which they
called CDW108. Northern blot analysis detected a 3.5-kb transcript
expressed at highest levels in placenta, testis, and spleen, with low
levels in brain and thymus. Yamada et al. (1999) detected 5
differentially glycosylated forms of SEMA7A by SDS-PAGE of a transfected
esophageal cancer cell line. The largest protein had an apparent
molecular mass of about 80 kD. Treatment with peptide-N-glycosidase
revealed a deglycosylated protein with an apparent molecular mass of
about 65 kD.
Sato and Takahashi (1998) cloned mouse Sema7a. They noted that the
immunoglobulin-like domain of the deduced 664-amino acid protein is of
the C2 type. Human and mouse SEMA7A share 89.5% identity. Northern blot
analysis of rat tissues detected highest expression in the nervous
system, and expression in the cerebellum and brain stem increased during
development. Moderate expression was detected in thymus and spleen.
GENE STRUCTURE
Lange et al. (1998) determined that the SEMA7A gene contains at least 13
exons and spans about 9 kb.
Seltsam et al. (2007) stated that the SEMA7A gene contains 14 exons.
MAPPING
By FISH, Lange et al. (1998) mapped the SEMA7A gene to chromosome
15q22.2-q23. Using radiation hybrid analysis, Yamada et al. (1999)
mapped the SEMA7A gene to chromosome 15q23-q24.
Lange et al. (1998) mapped the mouse Sema7a gene to chromosome 9A3.3-B.
GENE FUNCTION
Xu et al. (1998) demonstrated that SEMA7A is a GPI-anchored membrane
protein. SEMA7A was expressed on the cell surface of transfected COS-7
cells, and treatment with phospholipase C (see 600220) released the
protein from the cell surface. A soluble mutant of SEMA7A bound to
macrophage and mast cell lines, but it did not bind to COS-7 cells
expressing neuropilin-1 (602069) or neuropilin-2 (602070), receptors for
several secreted semaphorins. Xu et al. (1998) concluded that these
macrophage and mast cell lines contain a specific receptor for SEMA7A.
Pasterkamp et al. (2003) showed that semaphorin 7A, a membrane-anchored
member of the semaphorin family of guidance proteins known for its
immunomodulatory effects, can also mediate neuronal functions.
Pasterkamp et al. (2003) showed that unlike many other semaphorins,
which act as repulsive guidance cues, SEMA7A enhances central and
peripheral axon growth and is required for proper axon tract formation
during embryonic development. Unexpectedly, SEMA7A enhancement of axon
outgrowth requires integrin receptors and activation of MAPK signaling
pathways. Pasterkamp et al. (2003) concluded that their findings defined
a theretofore unknown biologic function for semaphorins, identified an
unexpected role for integrins and integrin-dependent intracellular
signaling in mediating semaphorin responses, and provided a framework
for understanding and interfering with SEMA7A function in both immune
and nervous systems. Pasterkamp et al. (2003) showed that
SEMA7A-mediated axon growth is plexin C1 (604259)-independent.
Suzuki et al. (2007) demonstrated that SEMA7A, which is expressed on
activated T cells, stimulates cytokine production in monocytes and
macrophages through alpha-1-beta-1 integrin (192968, 135630) (also known
as very late antigen-1) as a component of the immunologic synapse, and
is critical for the effector phase of the inflammatory immune response.
Sema7A-null mice are defective in cell-mediated immune responses such as
contact hypersensitivity and experimental autoimmune encephalomyelitis.
Although antigen-specific and cytokine-producing effector T cells could
develop and migrate into antigen-challenged sites in Sema7a-null mice,
Sema7a-null T cells failed to induce contact hypersensitivity even when
directly injected into the antigen-challenged sites. Thus, Suzuki et al.
(2007) concluded that the interaction between SEMA7A and alpha-1-beta-1
integrin is crucial at the site of inflammation.
MOLECULAR GENETICS
- Association with Bone Mineral Density
Koh et al. (2006) genotyped 5 polymorphisms of the SEMA7A gene in 560
postmenopausal Korean women and measured bone mineral density (BMD; see
601884) of the lumbar spine and proximal femur. The SEMA7A polymorphisms
15775C-G (dbSNP rs2072649) and 22331A-G (dbSNP rs741761) were associated
with a low BMD of the femoral neck and lumbar spine (p = 0.02 and 0.04,
respectively) in a recessive model. A haplotype based on the 5 SNPs,
so-called ht4, was associated with risk of vertebral fracture (OR = 1.87
and 1.93, p = 0.03 and 0.02, in dominant and codominant models,
respectively). Koh et al. (2006) suggested that variations in SEMA7A may
play a role in decreased BMD and risk of vertebral fracture.
- John Milton Hagen Blood Group System: JMH-Variant Phenotype
In 5 unrelated individuals with JMH-variant phenotype (see 614745) from
5 different countries, Seltsam et al. (2007) identified 4 missense
mutations in the SEMA7A gene (607961.0001-607961.0004). These mutations
were not detected in genomic DNA from 100 randomly selected individuals
from Northern Germany. All 4 missense mutations occurred in the
semaphorin domain of SEMA7A.
ANIMAL MODEL
Czopik et al. (2006) found that T cells from immunized Sema7a -/- mice
had increased proliferative responses to antigen that were not
attributable to Sema7a deficiency on macrophages or dendritic cells.
Sema7a -/- mice were prone to die at the onset of experimental
autoimmune encephalomyelitis (EAE) and had higher clinical EAE scores
compared with wildtype littermates. Delayed-type hypersensitivity
responses were also enhanced in Sema7a -/- mice. Czopik et al. (2006)
concluded that SEMA7A plays an important T cell-intrinsic inhibitory
role and is essential in limiting T cell-mediated autoimmunity.
*FIELD* AV
.0001
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG207GLN
In 2 unrelated individuals with JMH-negative phenotype (see 614745) from
Germany and Canada, Seltsam et al. (2007) identified a 620G-A transition
in exon 6 of the SEMA7A gene, resulting in an arg207-to-gln (R207Q)
substitution in the semaphorin domain of the protein.
.0002
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG207TRP
In a Japanese individual with JMH-negative phenotype (see 614745),
Seltsam et al. (2007) identified a 619C-T transition in exon 6 of the
SEMA7A gene, resulting in an arg207-to-trp (R207W) substitution in the
semaphorin domain of the protein.
.0003
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG460HIS
In an individual with JMH-negative phenotype (see 614745) from the U.S.,
Seltsam et al. (2007) identified a 1379G-A transition in exon 11 of the
SEMA7A gene, resulting in an arg460-to-his (R460H) substitution in the
semaphorin domain of the protein.
.0004
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG461CYS
In a Polish individual with JMH-negative phenotype (see 614745), Seltsam
et al. (2007) identified a 1381C-T transition in exon 11 of the SEMA7A
gene, resulting in an arg461-to-cys (R461C) substitution in the
semaphorin domain of the protein.
.0005
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG347LEU
In 4 young Native American women with JMH-negative phenotype (see
614745) from a reservation northwest of Quebec City, Canada, Richard et
al. (2011) identified a 1040G-T transversion in exon 9 of the SEMA7A
gene, resulting in an arg347-to-leu (R347L) substitution in the
semaphorin domain. At least 2 of the women were JHM-positive and their
alloantibody was compatible with most JHM-negative red blood cells
tested; the other 2 women were not tested. Soluble forms of wildtype and
R347L variant SEMA7A proteins were produced in vitro and demonstrated a
specific alloantibody reaction with wildtype recombinant SEMA7A, but not
with the R347L variant form.
*FIELD* RF
1. Czopik, A. K.; Bynoe, M. S.; Palm, N.; Raine, C. S.; Medzhitov,
R.: Semaphorin 7A is a negative regulator of T cell responses. Immunity 24:
591-600, 2006.
2. Koh, J.-M.; Oh, B.; Lee, J. Y.; Lee, J.-K.; Kimm, K.; Kim, G. S.;
Park, B. L.; Cheong, H. S.; Shin, H. D.; Hong, J. M.; Kim, T.-H.;
Park, E. K.; Kim, S.-Y.: Association study of semaphorin 7a (sema7a)
polymorphisms with bone mineral density and fracture risk in postmenopausal
Korean women. J. Hum. Genet. 51: 112-117, 2006.
3. Lange, C.; Liehr, T.; Goen, M.; Gebhart, E.; Fleckenstein, B.;
Ensser, A.: New eukaryotic semaphorins with close homology to semaphorins
of DNA viruses. Genomics 51: 340-350, 1998.
4. Pasterkamp, R. J.; Peschon, J. J.; Spriggs, M. K.; Kolodkin, A.
L.: Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature 424:
398-405, 2003.
5. Richard, M.; St-Laurent, J.; Perreault, J.; Long, A.; St-Louis,
M.: A new SEMA7A variant found in Native Americans with alloantibody. Vox
Sang. 100: 322-326, 2011.
6. Sato, Y.; Takahashi, H.: Molecular cloning and expression of murine
homologue of semaphorin K1 gene. Biochim. Biophys. Acta 1443: 419-422,
1998.
7. Seltsam, A.; Strigens, S.; Levene, C.; Yahalom, V.; Moulds, M.;
Moulds, J. J.; Hustinx, H.; Weisbach, V.; Figueroa, D.; Bade-Doeding,
C.; DeLuca, D. S.; Blasczyk, R.: The molecular diversity of Sema7A,
the semaphorin that carries the JMH blood group antigens. Transfusion 47:
133-146, 2007.
8. Suzuki, K.; Okuno, T.; Yamamoto, M.; Pasterkamp, R. J.; Takegahara,
N.; Takamatsu, H.; Kitao, T.; Takagi, J.; Rennert, P. D.; Kolodkin,
A. L.; Kumanogoh, A.; Kikutani, H.: Semaphorin 7A initiates T-cell-mediated
inflammatory responses through alpha-1-beta-1 integrin. Nature 446:
680-684, 2007.
9. Xu, X.; Ng, S.; Wu, Z.-L.; Nguyen, D.; Homburger, S.; Seidel-Dugan,
C.; Ebens, A.; Luo, Y.: Human semaphorin K1 is glycosylphosphatidylinositol-linked
and defines a new subfamily of viral-related semaphorins. J. Biol.
Chem. 273: 22428-22434, 1998.
10. Yamada, A.; Kubo, K.; Takeshita, T.; Harashima, N.; Kawano, K.;
Mine, T.; Sagawa, K.; Sugamura, K.; Itoh, K.: Molecular cloning of
a glycosylphosphatidylinositol-anchored molecule CDw108. J. Immun. 162:
4094-4100, 1999.
*FIELD* CN
Matthew B. Gross - updated: 07/27/2012
Ada Hamosh - updated: 4/27/2007
Paul J. Converse - updated: 1/5/2007
Marla J. F. O'Neill - updated: 4/6/2006
Ada Hamosh - updated: 8/5/2003
*FIELD* CD
Patricia A. Hartz: 7/21/2003
*FIELD* ED
mgross: 07/27/2012
carol: 5/20/2010
alopez: 5/10/2007
terry: 4/27/2007
mgross: 1/5/2007
wwang: 4/10/2006
terry: 4/6/2006
joanna: 11/5/2004
terry: 7/19/2004
alopez: 8/6/2003
terry: 8/5/2003
mgross: 7/21/2003
*RECORD*
*FIELD* NO
607961
*FIELD* TI
*607961 SEMAPHORIN 7A; SEMA7A
;;SEMAPHORIN L; SEMAL;;
SEMAPHORIN K1; SEMAK1;;
CDW108
read more*FIELD* TX
DESCRIPTION
SEMA7A is an 80-kD membrane-bound semaphorin that associates with cell
surfaces via a glycosylphosphatidylinositol (GPI) linkage. It is
preferentially expressed on activated lymphocytes and erythrocytes.
SEMA7A carries the John Milton Hagen (JMH) blood group antigens (see
614745) (summary by Yamada et al., 1999).
CLONING
By PCR using primers designed from alcelaphine herpesvirus-1 (AHV) sema,
followed by 5-prime and 3-prime RACE, Lange et al. (1998) cloned
full-length SEMA7A, which they designated SEMAL, from a placenta cDNA
library. The deduced 666-amino acid protein has a calculated molecular
mass of about 75 kD, and the unglycosylated protein has a calculated
molecular mass of about 70 kD following signal peptide cleavage. SEMA7A
contains a 44-amino acid N-terminal signal sequence, a semaphorin domain
of about 500 amino acids, an immunoglobulin-like motif, and a C-terminal
hydrophobic domain that lacks a significant intracellular tail. The
semaphorin domain has several conserved cysteine residues and an RGD
motif. SEMA7A also contains 5 N-glycosylation sites and several
myristoylation sites. Northern blot analysis detected a 3.2-kb
transcript expressed predominantly in spleen, thymus, testis, and ovary.
Little or no expression was detected in prostate, small intestine,
colon, and peripheral blood leukocytes. RNA dot blot analysis detected
expression in placenta, spleen, and gonadal tissue, but not in neuronal
or muscular tissue.
By searching an EST database using AHV sema as probe, Xu et al. (1998)
identified SEMA7A, which they designated SEMAK1. SEMA7A shares about 50%
amino acid identity with AHV sema and less than 30% identity with other
semaphorins. Northern blot analysis of adult mouse tissues detected a
4.4-kb Sema7a transcript expressed at high levels in brain, spinal cord,
lung, and testis. In situ hybridization detected weak but dynamic
expression of Sema7a in spinal cord, cerebellum, and cortex during
embryonic development. In adult mice, Sema7a was expressed in several
brain structures and cell layers.
By PCR using primers based on the N-terminal amino acid sequence of
SEMA7A, followed by screening a leukemic T-cell line cDNA library and a
placenta cDNA library, Yamada et al. (1999) cloned SEMA7A, which they
called CDW108. Northern blot analysis detected a 3.5-kb transcript
expressed at highest levels in placenta, testis, and spleen, with low
levels in brain and thymus. Yamada et al. (1999) detected 5
differentially glycosylated forms of SEMA7A by SDS-PAGE of a transfected
esophageal cancer cell line. The largest protein had an apparent
molecular mass of about 80 kD. Treatment with peptide-N-glycosidase
revealed a deglycosylated protein with an apparent molecular mass of
about 65 kD.
Sato and Takahashi (1998) cloned mouse Sema7a. They noted that the
immunoglobulin-like domain of the deduced 664-amino acid protein is of
the C2 type. Human and mouse SEMA7A share 89.5% identity. Northern blot
analysis of rat tissues detected highest expression in the nervous
system, and expression in the cerebellum and brain stem increased during
development. Moderate expression was detected in thymus and spleen.
GENE STRUCTURE
Lange et al. (1998) determined that the SEMA7A gene contains at least 13
exons and spans about 9 kb.
Seltsam et al. (2007) stated that the SEMA7A gene contains 14 exons.
MAPPING
By FISH, Lange et al. (1998) mapped the SEMA7A gene to chromosome
15q22.2-q23. Using radiation hybrid analysis, Yamada et al. (1999)
mapped the SEMA7A gene to chromosome 15q23-q24.
Lange et al. (1998) mapped the mouse Sema7a gene to chromosome 9A3.3-B.
GENE FUNCTION
Xu et al. (1998) demonstrated that SEMA7A is a GPI-anchored membrane
protein. SEMA7A was expressed on the cell surface of transfected COS-7
cells, and treatment with phospholipase C (see 600220) released the
protein from the cell surface. A soluble mutant of SEMA7A bound to
macrophage and mast cell lines, but it did not bind to COS-7 cells
expressing neuropilin-1 (602069) or neuropilin-2 (602070), receptors for
several secreted semaphorins. Xu et al. (1998) concluded that these
macrophage and mast cell lines contain a specific receptor for SEMA7A.
Pasterkamp et al. (2003) showed that semaphorin 7A, a membrane-anchored
member of the semaphorin family of guidance proteins known for its
immunomodulatory effects, can also mediate neuronal functions.
Pasterkamp et al. (2003) showed that unlike many other semaphorins,
which act as repulsive guidance cues, SEMA7A enhances central and
peripheral axon growth and is required for proper axon tract formation
during embryonic development. Unexpectedly, SEMA7A enhancement of axon
outgrowth requires integrin receptors and activation of MAPK signaling
pathways. Pasterkamp et al. (2003) concluded that their findings defined
a theretofore unknown biologic function for semaphorins, identified an
unexpected role for integrins and integrin-dependent intracellular
signaling in mediating semaphorin responses, and provided a framework
for understanding and interfering with SEMA7A function in both immune
and nervous systems. Pasterkamp et al. (2003) showed that
SEMA7A-mediated axon growth is plexin C1 (604259)-independent.
Suzuki et al. (2007) demonstrated that SEMA7A, which is expressed on
activated T cells, stimulates cytokine production in monocytes and
macrophages through alpha-1-beta-1 integrin (192968, 135630) (also known
as very late antigen-1) as a component of the immunologic synapse, and
is critical for the effector phase of the inflammatory immune response.
Sema7A-null mice are defective in cell-mediated immune responses such as
contact hypersensitivity and experimental autoimmune encephalomyelitis.
Although antigen-specific and cytokine-producing effector T cells could
develop and migrate into antigen-challenged sites in Sema7a-null mice,
Sema7a-null T cells failed to induce contact hypersensitivity even when
directly injected into the antigen-challenged sites. Thus, Suzuki et al.
(2007) concluded that the interaction between SEMA7A and alpha-1-beta-1
integrin is crucial at the site of inflammation.
MOLECULAR GENETICS
- Association with Bone Mineral Density
Koh et al. (2006) genotyped 5 polymorphisms of the SEMA7A gene in 560
postmenopausal Korean women and measured bone mineral density (BMD; see
601884) of the lumbar spine and proximal femur. The SEMA7A polymorphisms
15775C-G (dbSNP rs2072649) and 22331A-G (dbSNP rs741761) were associated
with a low BMD of the femoral neck and lumbar spine (p = 0.02 and 0.04,
respectively) in a recessive model. A haplotype based on the 5 SNPs,
so-called ht4, was associated with risk of vertebral fracture (OR = 1.87
and 1.93, p = 0.03 and 0.02, in dominant and codominant models,
respectively). Koh et al. (2006) suggested that variations in SEMA7A may
play a role in decreased BMD and risk of vertebral fracture.
- John Milton Hagen Blood Group System: JMH-Variant Phenotype
In 5 unrelated individuals with JMH-variant phenotype (see 614745) from
5 different countries, Seltsam et al. (2007) identified 4 missense
mutations in the SEMA7A gene (607961.0001-607961.0004). These mutations
were not detected in genomic DNA from 100 randomly selected individuals
from Northern Germany. All 4 missense mutations occurred in the
semaphorin domain of SEMA7A.
ANIMAL MODEL
Czopik et al. (2006) found that T cells from immunized Sema7a -/- mice
had increased proliferative responses to antigen that were not
attributable to Sema7a deficiency on macrophages or dendritic cells.
Sema7a -/- mice were prone to die at the onset of experimental
autoimmune encephalomyelitis (EAE) and had higher clinical EAE scores
compared with wildtype littermates. Delayed-type hypersensitivity
responses were also enhanced in Sema7a -/- mice. Czopik et al. (2006)
concluded that SEMA7A plays an important T cell-intrinsic inhibitory
role and is essential in limiting T cell-mediated autoimmunity.
*FIELD* AV
.0001
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG207GLN
In 2 unrelated individuals with JMH-negative phenotype (see 614745) from
Germany and Canada, Seltsam et al. (2007) identified a 620G-A transition
in exon 6 of the SEMA7A gene, resulting in an arg207-to-gln (R207Q)
substitution in the semaphorin domain of the protein.
.0002
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG207TRP
In a Japanese individual with JMH-negative phenotype (see 614745),
Seltsam et al. (2007) identified a 619C-T transition in exon 6 of the
SEMA7A gene, resulting in an arg207-to-trp (R207W) substitution in the
semaphorin domain of the protein.
.0003
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG460HIS
In an individual with JMH-negative phenotype (see 614745) from the U.S.,
Seltsam et al. (2007) identified a 1379G-A transition in exon 11 of the
SEMA7A gene, resulting in an arg460-to-his (R460H) substitution in the
semaphorin domain of the protein.
.0004
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG461CYS
In a Polish individual with JMH-negative phenotype (see 614745), Seltsam
et al. (2007) identified a 1381C-T transition in exon 11 of the SEMA7A
gene, resulting in an arg461-to-cys (R461C) substitution in the
semaphorin domain of the protein.
.0005
JOHN MILTON HAGEN BLOOD GROUP SYSTEM, JMH-VARIANT PHENOTYPE
SEMA7A, ARG347LEU
In 4 young Native American women with JMH-negative phenotype (see
614745) from a reservation northwest of Quebec City, Canada, Richard et
al. (2011) identified a 1040G-T transversion in exon 9 of the SEMA7A
gene, resulting in an arg347-to-leu (R347L) substitution in the
semaphorin domain. At least 2 of the women were JHM-positive and their
alloantibody was compatible with most JHM-negative red blood cells
tested; the other 2 women were not tested. Soluble forms of wildtype and
R347L variant SEMA7A proteins were produced in vitro and demonstrated a
specific alloantibody reaction with wildtype recombinant SEMA7A, but not
with the R347L variant form.
*FIELD* RF
1. Czopik, A. K.; Bynoe, M. S.; Palm, N.; Raine, C. S.; Medzhitov,
R.: Semaphorin 7A is a negative regulator of T cell responses. Immunity 24:
591-600, 2006.
2. Koh, J.-M.; Oh, B.; Lee, J. Y.; Lee, J.-K.; Kimm, K.; Kim, G. S.;
Park, B. L.; Cheong, H. S.; Shin, H. D.; Hong, J. M.; Kim, T.-H.;
Park, E. K.; Kim, S.-Y.: Association study of semaphorin 7a (sema7a)
polymorphisms with bone mineral density and fracture risk in postmenopausal
Korean women. J. Hum. Genet. 51: 112-117, 2006.
3. Lange, C.; Liehr, T.; Goen, M.; Gebhart, E.; Fleckenstein, B.;
Ensser, A.: New eukaryotic semaphorins with close homology to semaphorins
of DNA viruses. Genomics 51: 340-350, 1998.
4. Pasterkamp, R. J.; Peschon, J. J.; Spriggs, M. K.; Kolodkin, A.
L.: Semaphorin 7A promotes axon outgrowth through integrins and MAPKs. Nature 424:
398-405, 2003.
5. Richard, M.; St-Laurent, J.; Perreault, J.; Long, A.; St-Louis,
M.: A new SEMA7A variant found in Native Americans with alloantibody. Vox
Sang. 100: 322-326, 2011.
6. Sato, Y.; Takahashi, H.: Molecular cloning and expression of murine
homologue of semaphorin K1 gene. Biochim. Biophys. Acta 1443: 419-422,
1998.
7. Seltsam, A.; Strigens, S.; Levene, C.; Yahalom, V.; Moulds, M.;
Moulds, J. J.; Hustinx, H.; Weisbach, V.; Figueroa, D.; Bade-Doeding,
C.; DeLuca, D. S.; Blasczyk, R.: The molecular diversity of Sema7A,
the semaphorin that carries the JMH blood group antigens. Transfusion 47:
133-146, 2007.
8. Suzuki, K.; Okuno, T.; Yamamoto, M.; Pasterkamp, R. J.; Takegahara,
N.; Takamatsu, H.; Kitao, T.; Takagi, J.; Rennert, P. D.; Kolodkin,
A. L.; Kumanogoh, A.; Kikutani, H.: Semaphorin 7A initiates T-cell-mediated
inflammatory responses through alpha-1-beta-1 integrin. Nature 446:
680-684, 2007.
9. Xu, X.; Ng, S.; Wu, Z.-L.; Nguyen, D.; Homburger, S.; Seidel-Dugan,
C.; Ebens, A.; Luo, Y.: Human semaphorin K1 is glycosylphosphatidylinositol-linked
and defines a new subfamily of viral-related semaphorins. J. Biol.
Chem. 273: 22428-22434, 1998.
10. Yamada, A.; Kubo, K.; Takeshita, T.; Harashima, N.; Kawano, K.;
Mine, T.; Sagawa, K.; Sugamura, K.; Itoh, K.: Molecular cloning of
a glycosylphosphatidylinositol-anchored molecule CDw108. J. Immun. 162:
4094-4100, 1999.
*FIELD* CN
Matthew B. Gross - updated: 07/27/2012
Ada Hamosh - updated: 4/27/2007
Paul J. Converse - updated: 1/5/2007
Marla J. F. O'Neill - updated: 4/6/2006
Ada Hamosh - updated: 8/5/2003
*FIELD* CD
Patricia A. Hartz: 7/21/2003
*FIELD* ED
mgross: 07/27/2012
carol: 5/20/2010
alopez: 5/10/2007
terry: 4/27/2007
mgross: 1/5/2007
wwang: 4/10/2006
terry: 4/6/2006
joanna: 11/5/2004
terry: 7/19/2004
alopez: 8/6/2003
terry: 8/5/2003
mgross: 7/21/2003
MIM
614745
*RECORD*
*FIELD* NO
614745
*FIELD* TI
#614745 BLOOD GROUP, JOHN MILTON HAGEN SYSTEM
;;JOHN MILTON HAGEN BLOOD GROUP SYSTEM;;
read moreJMH BLOOD GROUP SYSTEM
*FIELD* TX
A number sign (#) is used with this entry because the John Milton Hagen
(JMH) blood group system is based, at least partly, on variation in the
gene encoding semaphorin-7A (SEMA7A; 607961) on chromosome 15q22.2-q23.
DESCRIPTION
JMH blood group antigens are carried by SEMA7A, a membrane-associated
protein that plays important roles in the nervous system and immune
responses. Three different JMH phenotypes have been identified based on
the presence or absence of the high-frequency JMH (or JMH1) antigen:
JMH-weak, JMH-negative, and JMH-variant. The JMH-weak and -negative
phenotypes can be either acquired or inherited and are characterized by
a reduction or complete loss of JMH expression on red blood cells
(RBCs), often with concomitant occurrence of JMH antibodies. Acquired
JMH-weak or -negative phenotypes are typically found in elderly persons
and can be transient. The JMH antibodies present in the acquired
phenotypes have autoimmune characteristics and are clinically
irrelevant. The inherited JMH-negative phenotype has been found in only
1 family. Mechanisms underlying the JMH-weak and -negative phenotypes
have yet to be identified. Individuals with the JMH-variant phenotype
are usually JMH-positive and have alloantibodies compatible with
JMH-negative RBCs. The JMH-variant phenotype results from rare missense
mutations in the SEMA7A gene (summary by Seltsam et al. (2007) and
Richard et al. (2011)).
CLINICAL FEATURES
Seltsam et al. (2007) identified 3 different RBC phenotypes with unusual
JMH expression in 33 of 44 individuals with abnormal JMH blood groups
and their family members. Eleven individuals had a JMH-variant phenotype
lacking single JMH epitopes, 18 individuals had a JMH-negative
phenotype, and 4 individuals had a JMH-weak phenotype. In most cases,
these JMH phenotypes were associated with the presence of JMH or
JMH-like antibodies in serum. The 11 remaining individuals, who were
family members of individuals with JMH-variant or JMH-negative
phenotypes, had normal JHM blood groups.
- JMH-Variant Phenotype
Seltsam et al. (2007) identified 5 propositi with JMH-variant phenotype
from Canada, Germany, Japan, Poland, and the U.S. The JMH-variant
phenotype was also present in 6 of 14 family members of the propositi.
Determination of variant JMH status was based on variably positive or
negative reactions of RBCs with anti-JMH serum samples. JMH-like
antibodies were only present in the serum of the propositi, which
reacted positive with all but JMH-negative RBCs, the propositus's own
RBCs, and RBCs of compatible JMH-positive sibs.
- JMH-Negative Phenotype
Seltsam et al. (2007) identified 18 individuals with JMH-negative
phenotype from Canada, Germany, Israel, Sweden, Switzerland, and the
U.S. The ages of the RBH-negative individuals, as far as known, ranged
from 54 to 82 years. The JMH-negative phenotype was identified by
negative reaction of the individuals' RBCs with JMH antisera from
immunized patients. In addition, no JMH antigen was detected on the
surface of JMH-negative RBCs by flow cytometric and immunoblot analyses.
JMH antibodies were detected in 14 of the JMH-negative individuals. Four
JMH-negative individuals belonged to an apparently healthy family in
which the JMH-negative phenotype had been detected in 3 generations. The
other JMH-negative individuals were unrelated and information about
inheritance was not available. However, in 2 of these individuals, who
were apparently healthy, JMH-negative status had remained stable over
decades, excluding the transient JMH-negative phenotype. RT-PCR analysis
of total mRNA from peripheral blood cells of JMH-negative individuals
revealed normal expression of SEMA7A. Peripheral B lymphocytes from
JMH-negative individuals could be stimulated to express normal levels of
SEMA7A, and reticulocytes from JMH-negative individuals exhibited normal
expression of SEMA7A. RBCs of JMH-negative individuals showed normal
expression of other GPI-linked membrane proteins, excluding deficient
biosynthesis of the GPI anchor as the basis for loss of SEMA7A on RBCs.
Seltsam et al. (2007) concluded that the JMH-negative phenotype results
from an autoimmune-related and/or RBC lineage-specific
posttranscriptional or posttranslational mechanism.
- JMH-Weak Phenotype
Seltsam et al. (2007) identified 4 individuals with RBH-weak phenotype.
RBCs from these individuals exhibited weak reactions with JMH
antibodies, and JMH antibodies were present in serum samples. In 2
individuals, RBCs produced a weakly positive direct antiglobulin test.
Three of the JMH-weak individuals were over 50 years of age, and the
fourth was a 32-year-old pregnant woman. The pregnant woman displayed
variable SEMA7A expression during pregnancy, and her baby was born
without any symptoms of hemolytic disease of the fetus or newborn.
INHERITANCE
- JMH-Variant Phenotype
By family studies, including extended genomic sequencing, Seltsam et al.
(2007) found that the JMH-variant phenotype was inherited in an
autosomal recessive fashion in 5 families.
- JMH-Negative Phenotype
Seltsam et al. (2007) noted that the JMH-negative phenotype, which is
typically acquired rather than inherited, was present in 3 generations
of an apparently healthy family. They confirmed this finding and
concluded that autosomal dominant inheritance was likely.
MAPPING
The SEMA7A gene, which encodes the protein carrying the JHM antigens,
was mapped to chromosome 15q22.2-q23 by Lange et al. (1998).
MOLECULAR GENETICS
- JMH-Variant Phenotype
In 5 unrelated individuals with JMH-variant phenotype from 5 different
countries, Seltsam et al. (2007) identified 4 missense mutations in the
SEMA7A gene (607961.0001-607961.0004). These mutations were not detected
in genomic DNA from 100 randomly selected individuals from Northern
Germany. All 4 missense mutations occurred in the semaphorin domain of
SEMA7A. Studies with JMH-variant RBCs and transfectants expressing
membrane-anchored recombinant SEMA7A proteins showed that the variant
SEMA7A proteins were of normal length and were expressed at levels equal
to those of the wildtype protein. In inhibition studies with soluble
recombinant wildtype and variant SEMA7A proteins, JMH-like
alloantibodies of JMH-variant individuals did not react with the related
recombinant variant SEMA7A protein, but they did react with the wildtype
and unrelated variant SEMA7A proteins, indicating that expression of
variant JMH antigen is based on the absence of certain SEMA7A epitopes.
Serologic compatibility testing of JMH-variant blood samples confirmed
these results.
In 4 young Native American women with JMH-negative phenotype from a
reservation northwest of Quebec City, Canada, Richard et al. (2011)
identified a novel missense mutation in the SEMA7A gene (607961.0005).
At least 2 of the women were JHM-positive and their alloantibody was
compatible with most JHM-negative RBCs tested; the other 2 women were
not tested. Soluble forms of wildtype and R347L variant SEMA7A proteins
were produced in vitro and demonstrated a specific alloantibody reaction
with wildtype recombinant SEMA7A, but not with the R347L variant form.
- JMH-Negative Phenotype
Seltsam et al. (2007) found that JMH-negative individuals lacked
phenotypically relevant mutations in the coding region or promoter of
the SEMA7A gene. They concluded that the JMH-negative phenotype does not
result from variation in the SEMA7A gene.
- JMH-Weak Phenotype
Seltsam et al. (2007) found that JMH-weak individuals lacked
phenotypically relevant mutations in the SEMA7A gene. They concluded
that the JMH-weak phenotype does not result from variation in the SEMA7A
gene.
*FIELD* RF
1. Lange, C.; Liehr, T.; Goen, M.; Gebhart, E.; Fleckenstein, B.;
Ensser, A.: New eukaryotic semaphorins with close homology to semaphorins
of DNA viruses. Genomics 51: 340-350, 1998.
2. Richard, M.; St-Laurent, J.; Perreault, J.; Long, A.; St-Louis,
M.: A new SEMA7A variant found in Native Americans with alloantibody. Vox
Sang. 100: 322-326, 2011.
3. Seltsam, A.; Strigens, S.; Levene, C.; Yahalom, V.; Moulds, M.;
Moulds, J. J.; Hustinx, H.; Weisbach, V.; Figueroa, D.; Bade-Doeding,
C.; DeLuca, D. S.; Blasczyk, R.: The molecular diversity of Sema7A,
the semaphorin that carries the JMH blood group antigens. Transfusion 47:
133-146, 2007.
*FIELD* CD
Matthew B. Gross: 7/26/2012
*FIELD* ED
mgross: 07/27/2012
*RECORD*
*FIELD* NO
614745
*FIELD* TI
#614745 BLOOD GROUP, JOHN MILTON HAGEN SYSTEM
;;JOHN MILTON HAGEN BLOOD GROUP SYSTEM;;
read moreJMH BLOOD GROUP SYSTEM
*FIELD* TX
A number sign (#) is used with this entry because the John Milton Hagen
(JMH) blood group system is based, at least partly, on variation in the
gene encoding semaphorin-7A (SEMA7A; 607961) on chromosome 15q22.2-q23.
DESCRIPTION
JMH blood group antigens are carried by SEMA7A, a membrane-associated
protein that plays important roles in the nervous system and immune
responses. Three different JMH phenotypes have been identified based on
the presence or absence of the high-frequency JMH (or JMH1) antigen:
JMH-weak, JMH-negative, and JMH-variant. The JMH-weak and -negative
phenotypes can be either acquired or inherited and are characterized by
a reduction or complete loss of JMH expression on red blood cells
(RBCs), often with concomitant occurrence of JMH antibodies. Acquired
JMH-weak or -negative phenotypes are typically found in elderly persons
and can be transient. The JMH antibodies present in the acquired
phenotypes have autoimmune characteristics and are clinically
irrelevant. The inherited JMH-negative phenotype has been found in only
1 family. Mechanisms underlying the JMH-weak and -negative phenotypes
have yet to be identified. Individuals with the JMH-variant phenotype
are usually JMH-positive and have alloantibodies compatible with
JMH-negative RBCs. The JMH-variant phenotype results from rare missense
mutations in the SEMA7A gene (summary by Seltsam et al. (2007) and
Richard et al. (2011)).
CLINICAL FEATURES
Seltsam et al. (2007) identified 3 different RBC phenotypes with unusual
JMH expression in 33 of 44 individuals with abnormal JMH blood groups
and their family members. Eleven individuals had a JMH-variant phenotype
lacking single JMH epitopes, 18 individuals had a JMH-negative
phenotype, and 4 individuals had a JMH-weak phenotype. In most cases,
these JMH phenotypes were associated with the presence of JMH or
JMH-like antibodies in serum. The 11 remaining individuals, who were
family members of individuals with JMH-variant or JMH-negative
phenotypes, had normal JHM blood groups.
- JMH-Variant Phenotype
Seltsam et al. (2007) identified 5 propositi with JMH-variant phenotype
from Canada, Germany, Japan, Poland, and the U.S. The JMH-variant
phenotype was also present in 6 of 14 family members of the propositi.
Determination of variant JMH status was based on variably positive or
negative reactions of RBCs with anti-JMH serum samples. JMH-like
antibodies were only present in the serum of the propositi, which
reacted positive with all but JMH-negative RBCs, the propositus's own
RBCs, and RBCs of compatible JMH-positive sibs.
- JMH-Negative Phenotype
Seltsam et al. (2007) identified 18 individuals with JMH-negative
phenotype from Canada, Germany, Israel, Sweden, Switzerland, and the
U.S. The ages of the RBH-negative individuals, as far as known, ranged
from 54 to 82 years. The JMH-negative phenotype was identified by
negative reaction of the individuals' RBCs with JMH antisera from
immunized patients. In addition, no JMH antigen was detected on the
surface of JMH-negative RBCs by flow cytometric and immunoblot analyses.
JMH antibodies were detected in 14 of the JMH-negative individuals. Four
JMH-negative individuals belonged to an apparently healthy family in
which the JMH-negative phenotype had been detected in 3 generations. The
other JMH-negative individuals were unrelated and information about
inheritance was not available. However, in 2 of these individuals, who
were apparently healthy, JMH-negative status had remained stable over
decades, excluding the transient JMH-negative phenotype. RT-PCR analysis
of total mRNA from peripheral blood cells of JMH-negative individuals
revealed normal expression of SEMA7A. Peripheral B lymphocytes from
JMH-negative individuals could be stimulated to express normal levels of
SEMA7A, and reticulocytes from JMH-negative individuals exhibited normal
expression of SEMA7A. RBCs of JMH-negative individuals showed normal
expression of other GPI-linked membrane proteins, excluding deficient
biosynthesis of the GPI anchor as the basis for loss of SEMA7A on RBCs.
Seltsam et al. (2007) concluded that the JMH-negative phenotype results
from an autoimmune-related and/or RBC lineage-specific
posttranscriptional or posttranslational mechanism.
- JMH-Weak Phenotype
Seltsam et al. (2007) identified 4 individuals with RBH-weak phenotype.
RBCs from these individuals exhibited weak reactions with JMH
antibodies, and JMH antibodies were present in serum samples. In 2
individuals, RBCs produced a weakly positive direct antiglobulin test.
Three of the JMH-weak individuals were over 50 years of age, and the
fourth was a 32-year-old pregnant woman. The pregnant woman displayed
variable SEMA7A expression during pregnancy, and her baby was born
without any symptoms of hemolytic disease of the fetus or newborn.
INHERITANCE
- JMH-Variant Phenotype
By family studies, including extended genomic sequencing, Seltsam et al.
(2007) found that the JMH-variant phenotype was inherited in an
autosomal recessive fashion in 5 families.
- JMH-Negative Phenotype
Seltsam et al. (2007) noted that the JMH-negative phenotype, which is
typically acquired rather than inherited, was present in 3 generations
of an apparently healthy family. They confirmed this finding and
concluded that autosomal dominant inheritance was likely.
MAPPING
The SEMA7A gene, which encodes the protein carrying the JHM antigens,
was mapped to chromosome 15q22.2-q23 by Lange et al. (1998).
MOLECULAR GENETICS
- JMH-Variant Phenotype
In 5 unrelated individuals with JMH-variant phenotype from 5 different
countries, Seltsam et al. (2007) identified 4 missense mutations in the
SEMA7A gene (607961.0001-607961.0004). These mutations were not detected
in genomic DNA from 100 randomly selected individuals from Northern
Germany. All 4 missense mutations occurred in the semaphorin domain of
SEMA7A. Studies with JMH-variant RBCs and transfectants expressing
membrane-anchored recombinant SEMA7A proteins showed that the variant
SEMA7A proteins were of normal length and were expressed at levels equal
to those of the wildtype protein. In inhibition studies with soluble
recombinant wildtype and variant SEMA7A proteins, JMH-like
alloantibodies of JMH-variant individuals did not react with the related
recombinant variant SEMA7A protein, but they did react with the wildtype
and unrelated variant SEMA7A proteins, indicating that expression of
variant JMH antigen is based on the absence of certain SEMA7A epitopes.
Serologic compatibility testing of JMH-variant blood samples confirmed
these results.
In 4 young Native American women with JMH-negative phenotype from a
reservation northwest of Quebec City, Canada, Richard et al. (2011)
identified a novel missense mutation in the SEMA7A gene (607961.0005).
At least 2 of the women were JHM-positive and their alloantibody was
compatible with most JHM-negative RBCs tested; the other 2 women were
not tested. Soluble forms of wildtype and R347L variant SEMA7A proteins
were produced in vitro and demonstrated a specific alloantibody reaction
with wildtype recombinant SEMA7A, but not with the R347L variant form.
- JMH-Negative Phenotype
Seltsam et al. (2007) found that JMH-negative individuals lacked
phenotypically relevant mutations in the coding region or promoter of
the SEMA7A gene. They concluded that the JMH-negative phenotype does not
result from variation in the SEMA7A gene.
- JMH-Weak Phenotype
Seltsam et al. (2007) found that JMH-weak individuals lacked
phenotypically relevant mutations in the SEMA7A gene. They concluded
that the JMH-weak phenotype does not result from variation in the SEMA7A
gene.
*FIELD* RF
1. Lange, C.; Liehr, T.; Goen, M.; Gebhart, E.; Fleckenstein, B.;
Ensser, A.: New eukaryotic semaphorins with close homology to semaphorins
of DNA viruses. Genomics 51: 340-350, 1998.
2. Richard, M.; St-Laurent, J.; Perreault, J.; Long, A.; St-Louis,
M.: A new SEMA7A variant found in Native Americans with alloantibody. Vox
Sang. 100: 322-326, 2011.
3. Seltsam, A.; Strigens, S.; Levene, C.; Yahalom, V.; Moulds, M.;
Moulds, J. J.; Hustinx, H.; Weisbach, V.; Figueroa, D.; Bade-Doeding,
C.; DeLuca, D. S.; Blasczyk, R.: The molecular diversity of Sema7A,
the semaphorin that carries the JMH blood group antigens. Transfusion 47:
133-146, 2007.
*FIELD* CD
Matthew B. Gross: 7/26/2012
*FIELD* ED
mgross: 07/27/2012