O75326 (SEM7A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Semaphorin-7A

Alternative name(s):
CDw108
JMH blood group antigen
John-Milton-Hargen human blood group Ag
Semaphorin-K1
Short name=Sema K1
Semaphorin-L
Short name=Sema L
CD_antigen=CD108

Gene names

Name:	SEMA7A
Synonyms:	CD108, SEMAL

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	666 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of proinflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes. Ref.8 Ref.9 Ref.10
Subunit structure	Interacts with ITGA1 and ITGB1 Probable. Interacts with PLXNC1. Ref.8 Ref.9 Ref.10 Ref.11
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor; Extracellular side. Note: Detected in a punctate pattern on the cell membrane of basal and supra-basal skin keratinocytes. Ref.2 Ref.3 Ref.10
Tissue specificity	Detected in skin keratinocytes and on endothelial cells from skin blood vessels (at protein level). Expressed in fibroblasts, keratinocytes, melanocytes, placenta, testis, ovary, spleen, brain, spinal chord, lung, heart, adrenal gland, lymph nodes, thymus, intestine and kidney. Ref.2 Ref.3 Ref.10
Induction	Up-regulated in UV-irradiated fibroblasts, but not in UV-irradiated keratinocytes. Ref.10
Sequence similarities	Belongs to the semaphorin family. Contains 1 Ig-like C2-type (immunoglobulin-like) domain. Contains 1 PSI domain. Contains 1 Sema domain.

Ontologies

Keywords
Biological process	Differentiation Inflammatory response Neurogenesis
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Immunoglobulin domain Signal
Molecular function	Developmental protein
PTM	Disulfide bond GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Traceable author statement. Source: Reactome immune response Traceable author statement. Source: ProtInc inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW integrin-mediated signaling pathway Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of axon extension Inferred from direct assay Ref.8. Source: UniProtKB positive regulation of macrophage cytokine production Inferred from sequence or structural similarity. Source: UniProtKB regulation of inflammatory response Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW external side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NCK1	P16333	2	EBI-1753538,EBI-389883
PLXNC1	O60486	4	EBI-1753538,EBI-2927384

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 44

44

Potential

Chain

45 – 648

604

Semaphorin-7A

PRO_0000032347

Propeptide

649 – 666

18

Removed in mature form Potential

PRO_0000032348

Regions

Domain

53 – 490

438

Sema

Domain

544 – 629

86

Ig-like C2-type

Region

267 – 269

3

Interaction with integrins

Motif

267 – 269

3

Cell attachment site Potential

Amino acid modifications

Lipidation

648

1

GPI-anchor amidated alanine Potential

Glycosylation

105

1

N-linked (GlcNAc...) Ref.11

Glycosylation

157

1

N-linked (GlcNAc...) Ref.11

Glycosylation

258

1

N-linked (GlcNAc...) Ref.11

Glycosylation

330

1

N-linked (GlcNAc...) Ref.11

Glycosylation

602

1

N-linked (GlcNAc...) Probable

Disulfide bond

120 ↔ 126

Ref.11

Disulfide bond

143 ↔ 152

Ref.11

Disulfide bond

266 ↔ 366

Ref.11

Disulfide bond

291 ↔ 335

Ref.11

Disulfide bond

493 ↔ 511

Ref.11

Disulfide bond

500 ↔ 541

Ref.11

Disulfide bond

503 ↔ 518

Ref.11

Disulfide bond

566 ↔ 613

Ref.11

Disulfide bond

587 ↔ 596

Ref.11

Natural variations

Natural variant

115

1

S → T. Ref.5
Corresponds to variant rs16968733 [ dbSNP | Ensembl ].

VAR_029282

Natural variant

207

1

R → Q. Ref.4
Corresponds to variant rs55637216 [ dbSNP | Ensembl ].

VAR_038836

Natural variant

207

1

R → W. Ref.4
Corresponds to variant rs56367230 [ dbSNP | Ensembl ].

VAR_038837

Natural variant

460

1

R → H. Ref.4
Corresponds to variant rs56204206 [ dbSNP | Ensembl ].

VAR_038838

Natural variant

461

1

R → C. Ref.4
Corresponds to variant rs56001514 [ dbSNP | Ensembl ].

VAR_038839

Experimental info

Mutagenesis

267

1

R → K: Abolishes ITGB1-dependent enhancement of axon growth; when associated with E-269. Ref.8

Mutagenesis

269

1

D → E: Abolishes ITGB1-dependent enhancement of axon growth; when associated with K-267. Ref.8

Secondary structure

1

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666

Helix Strand Turn

Details...

Beta strand

66 – 68

3

Beta strand

86 – 89

4

Beta strand

95 – 99

5

Beta strand

132 – 134

3

Beta strand

141 – 143

3

Turn

146 – 148

3

Beta strand

153 – 155

3

Beta strand

160 – 162

3

Beta strand

180 – 182

3

Beta strand

187 – 189

3

Beta strand

204 – 207

4

Beta strand

223 – 230

8

Helix

235 – 237

3

Beta strand

239 – 247

9

Beta strand

257 – 266

10

Turn

275 – 279

5

Beta strand

285 – 289

5

Turn

294 – 296

3

Beta strand

302 – 309

8

Helix

316 – 318

3

Beta strand

320 – 322

3

Beta strand

324 – 326

3

Beta strand

332 – 334

3

Helix

342 – 348

7

Beta strand

368 – 370

3

Helix

376 – 383

8

Beta strand

386 – 389

4

Beta strand

401 – 406

6

Beta strand

408 – 417

10

Beta strand

423 – 431

9

Beta strand

436 – 440

5

Beta strand

451 – 456

6

Beta strand

467 – 471

5

Turn

472 – 475

4

Beta strand

476 – 480

5

Beta strand

482 – 489

8

Beta strand

523 – 526

4

Beta strand

533 – 535

3

Turn

537 – 540

4

Beta strand

541 – 545

5

Beta strand

551 – 556

6

Beta strand

562 – 567

6

Beta strand

573 – 579

7

Beta strand

582 – 587

6

Beta strand

593 – 602

10

Beta strand

611 – 616

6

Beta strand

621 – 631

11

Sequences

	Sequence		Length	Mass (Da)
	O75326 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: AD3ABE56B5EBE194	FASTA	666	74,824
	10 20 30 40 50 60 MTPPPPGRAA PSAPRARVPG PPARLGLPLR LRLLLLLWAA AASAQGHLRS GPRIFAVWKG 70 80 90 100 110 120 HVGQDRVDFG QTEPHTVLFH EPGSSSVWVG GRGKVYLFDF PEGKNASVRT VNIGSTKGSC 130 140 150 160 170 180 LDKRDCENYI TLLERRSEGL LACGTNARHP SCWNLVNGTV VPLGEMRGYA PFSPDENSLV 190 200 210 220 230 240 LFEGDEVYST IRKQEYNGKI PRFRRIRGES ELYTSDTVMQ NPQFIKATIV HQDQAYDDKI 250 260 270 280 290 300 YYFFREDNPD KNPEAPLNVS RVAQLCRGDQ GGESSLSVSK WNTFLKAMLV CSDAATNKNF 310 320 330 340 350 360 NRLQDVFLLP DPSGQWRDTR VYGVFSNPWN YSAVCVYSLG DIDKVFRTSS LKGYHSSLPN 370 380 390 400 410 420 PRPGKCLPDQ QPIPTETFQV ADRHPEVAQR VEPMGPLKTP LFHSKYHYQK VAVHRMQASH 430 440 450 460 470 480 GETFHVLYLT TDRGTIHKVV EPGEQEHSFA FNIMEIQPFR RAAAIQTMSL DAERRKLYVS 490 500 510 520 530 540 SQWEVSQVPL DLCEVYGGGC HGCLMSRDPY CGWDQGRCIS IYSSERSVLQ SINPAEPHKE 550 560 570 580 590 600 CPNPKPDKAP LQKVSLAPNS RYYLSCPMES RHATYSWRHK ENVEQSCEPG HQSPNCILFI 610 620 630 640 650 660 ENLTAQQYGH YFCEAQEGSY FREAQHWQLL PEDGIMAEHL LGHACALAAS LWLGVLPTLT LGLLVH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"New eukaryotic semaphorins with close homology to semaphorins of DNA viruses." Lange C., Liehr T., Goen M., Gebhart E., Fleckenstein B., Ensser A. Genomics 51:340-350(1998) [PubMed: 9721204] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]	"Molecular cloning of a glycosylphosphatidylinositol-anchored molecule CDw108." Yamada A., Kubo K., Takeshita T., Harashima N., Kawano K., Mine T., Sagawa K., Sugamura K., Itoh K. J. Immunol. 162:4094-4100(1999) [PubMed: 10201933] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY.
[3]	"Human semaphorin K1 is glycosylphosphatidylinositol-linked and defines a new subfamily of viral-related semaphorins." Xu X., Ng S., Wu Z.-L., Nguyen D., Homburger S., Seidel-Dugan C., Ebens A., Luo Y. J. Biol. Chem. 273:22428-22434(1998) [PubMed: 9712866] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Placenta.
[4]	"The molecular diversity of Sema7A, the semaphorin that carries the JMH blood group antigens." 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. Transfusion 47:133-146(2007) [PubMed: 17207242] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLN-207; TRP-207; HIS-460 AND CYS-461. Tissue: Peripheral blood.
[5]	SeattleSNPs variation discovery resource Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-115.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain cortex.
[7]	"Characterization of the human leukocyte GPI-anchored glycoprotein CDw108 and its relation to other similar molecules." Angelisova P., Drbal K., Cerny J., Hilgert I., Horejsi V. Immunobiology 200:234-245(1999) [PubMed: 10416131] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Semaphorin 7A promotes axon outgrowth through integrins and MAPKs." Pasterkamp R.J., Peschon J.J., Spriggs M.K., Kolodkin A.L. Nature 424:398-405(2003) [PubMed: 12879062] [Abstract] Cited for: FUNCTION, INTERACTION WITH ITGB1, MUTAGENESIS OF ARG-267 AND ASP-269.
[9]	"Semaphorin 7A initiates T-cell-mediated inflammatory responses through alpha1beta1 integrin." 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. Nature 446:680-684(2007) [PubMed: 17377534] [Abstract] Cited for: FUNCTION, INTERACTION WITH ITGA1 AND ITGB1.
[10]	"Semaphorin 7a promotes spreading and dendricity in human melanocytes through beta1-integrins." Scott G.A., McClelland L.A., Fricke A.F. J. Invest. Dermatol. 128:151-161(2008) [PubMed: 17671519] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ITGB1, INDUCTION, TISSUE SPECIFICITY.
[11]	"Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1." Liu H., Juo Z.S., Shim A.H., Focia P.J., Chen X., Garcia K.C., He X. Cell 142:749-761(2010) [PubMed: 20727575] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 45-634 IN COMPLEX WITH PLXNC1, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-105; ASN-157; ASN-258 AND ASN-330.
+	Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF030698 mRNA. Translation: AAC34261.1.
AF030697 Genomic DNA. Translation: AAC34741.1.
AF069493 mRNA. Translation: AAC82642.1.
AF071542 mRNA. Translation: AAC80456.1.
AM180445 mRNA. Translation: CAJ55398.1.
AM180446 mRNA. Translation: CAJ55399.1.
AM180447 mRNA. Translation: CAJ55400.1.
AM180448 mRNA. Translation: CAJ55401.1.
AM180449 mRNA. Translation: CAJ55402.1.
AM180450 mRNA. Translation: CAJ55403.1.
AM180451 mRNA. Translation: CAJ55404.1.
AY885237 Genomic DNA. Translation: AAW62253.1.
BC101643 mRNA. Translation: AAI01644.1.
BC101647 mRNA. Translation: AAI01648.1.

IPI

IPI00025257.

RefSeq

NP_001139501.1. NM_001146029.1.
NP_001139502.1. NM_001146030.1.
NP_003603.1. NM_003612.3.

UniGene

Hs.24640.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3NVQ	X-ray	2.40	A/E	45-634	[»]

ProteinModelPortal

O75326.

SMR

O75326. Positions 46-633.

ModBase

Search...

Protein-protein interaction databases

IntAct

O75326. 7 interactions.

MINT

MINT-1958248.

STRING

O75326.

Proteomic databases

PeptideAtlas

O75326.

PRIDE

O75326.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261918; ENSP00000261918; ENSG00000138623.

GeneID

8482.

KEGG

hsa:8482.

UCSC

uc002axv.1. human.

Organism-specific databases

CTD

8482.

GeneCards

GC15M074701.

H-InvDB

HIX0012429.

HGNC

HGNC:10741. SEMA7A.

HPA

HPA042273.

MIM

607961. gene+phenotype.

neXtProt

NX_O75326.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG17208.

GeneTree

ENSGT00390000013125.

HOGENOM

HBG127219.

HOVERGEN

HBG079171.

InParanoid

O75326.

OMA

CILFIEN.

OrthoDB

EOG4N30ND.

PhylomeDB

O75326.

Enzyme and pathway databases

Reactome

REACT_111045. Developmental Biology.

Gene expression databases

ArrayExpress

O75326.

Bgee

O75326.

CleanEx

HS_SEMA7A.

Genevestigator

O75326.

GermOnline

ENSG00000138623. Homo sapiens.

Family and domain databases

InterPro

IPR007110. Ig-like.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR003659. Plexin-like.
IPR016201. Plexin-like_fold.
IPR002165. Plexin_repeat.
IPR001627. Semaphorin/CD100_Ag.
IPR015943. WD40/YVTN_repeat-like_dom.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.130.10.10. WD40/YVTN_repeat-like. 1 hit.

KO

K06529.

Pfam

PF01437. PSI. 1 hit.
PF01403. Sema. 1 hit.
[Graphical view]

SMART

SM00409. IG. 1 hit.
SM00423. PSI. 1 hit.
SM00630. Sema. 1 hit.
[Graphical view]

SUPFAM

SSF103575. Plexin-like_fold. 1 hit.
SSF101912. Sema. 1 hit.

PROSITE

PS50835. IG_LIKE. 1 hit.
PS51004. SEMA. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

31739.

SOURCE

Search...

Entry information

Entry name

SEM7A_HUMAN

Accession

Primary (citable) accession number: O75326
Secondary accession number(s): Q1XE81 , Q1XE82, Q1XE83, Q1XE84, Q3MIY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 20, 2001
Last sequence update:	November 1, 1998
Last modified:	January 25, 2012
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.