O94813 (SLIT2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Slit homolog 2 protein
Short name=Slit-2

Cleaved into the following 2 chains:

1. Slit homolog 2 protein N-product
2. Slit homolog 2 protein C-product

Gene names

Name:	SLIT2
Synonyms:	SLIL3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1529 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	Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth-stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal chord midline post-crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration. Ref.3 Ref.6 Ref.7 Ref.8 Ref.10 Ref.11
Subunit structure	Interacts with GREM1 By similarity. Homodimer. Binds ROBO1 and ROBO2 with high affinity. Ref.3 Ref.10 Ref.15
Subcellular location	Secreted. Note: The C-terminal cleavage protein is more diffusible than the larger N-terminal protein that is more tightly cell associated. Ref.3
Tissue specificity	Fetal lung and kidney, and adult spinal cord. Weak expression in adult adrenal gland, thyroid, trachea and other tissues examined. Ref.1 Ref.2
Domain	The leucine-rich repeat domain is sufficient for guiding both axon projection and neuronal migration, in vitro. Ref.9
Sequence similarities	Contains 1 CTCK (C-terminal cystine knot-like) domain. Contains 7 EGF-like domains. Contains 1 laminin G-like domain. Contains 20 LRR (leucine-rich) repeats. Contains 4 LRRCT domains. Contains 4 LRRNT domains.

Ontologies

Keywords
Biological process	Chemotaxis Differentiation Neurogenesis
Cellular component	Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Leucine-rich repeat Repeat Signal
Ligand	Heparin-binding
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Roundabout signaling pathway Inferred from mutant phenotype PubMed 18829537. Source: BHF-UCL apoptotic process involved in luteolysis Inferred from expression pattern PubMed 18566128. Source: UniProtKB axon extension involved in axon guidance Inferred from direct assay PubMed 16840550. Source: UniProtKB branching morphogenesis of an epithelial tube Inferred from direct assay PubMed 18345009. Source: UniProtKB cell migration involved in sprouting angiogenesis Inferred from mutant phenotype PubMed 19351956. Source: BHF-UCL cell-cell adhesion Inferred from electronic annotation. Source: Compara cellular response to heparin Inferred from direct assay PubMed 17062560. Source: UniProtKB cellular response to hormone stimulus Inferred from expression pattern PubMed 18566128. Source: UniProtKB chemorepulsion involved in postnatal olfactory bulb interneuron migration Inferred from direct assay PubMed 15207848. Source: UniProtKB corticospinal neuron axon guidance through spinal cord Inferred from mutant phenotype Ref.6. Source: BHF-UCL dorsal/ventral axon guidance Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara induction of negative chemotaxis Inferred from direct assay PubMed 10197527. Source: UniProtKB mammary duct terminal end bud growth Inferred from electronic annotation. Source: Compara metanephros development Inferred from electronic annotation. Source: Compara motor neuron axon guidance Inferred from direct assay Ref.3. Source: UniProtKB negative regulation of actin filament polymerization Inferred from direct assay PubMed 19759280. Source: UniProtKB negative regulation of cell growth Inferred from mutant phenotype PubMed 18829537. Source: BHF-UCL negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of cellular response to growth factor stimulus Inferred from direct assay PubMed 16439689. Source: BHF-UCL negative regulation of chemokine-mediated signaling pathway Inferred from mutant phenotype PubMed 18829537. Source: BHF-UCL negative regulation of endothelial cell migration Inferred from direct assay PubMed 18345009. Source: UniProtKB negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of lamellipodium assembly Inferred from direct assay PubMed 16439689. Source: UniProtKB negative regulation of monocyte chemotaxis Inferred from sequence or structural similarity. Source: BHF-UCL negative regulation of mononuclear cell migration Inferred from direct assay PubMed 16439689. Source: BHF-UCL negative regulation of neutrophil chemotaxis Inferred from direct assay PubMed 19759280. Source: UniProtKB negative regulation of protein phosphorylation Inferred from direct assay PubMed 18345009. Source: UniProtKB negative regulation of retinal ganglion cell axon guidance Inferred from direct assay PubMed 17062560. Source: UniProtKB negative regulation of small GTPase mediated signal transduction Inferred from direct assay PubMed 16439689. Source: UniProtKB negative regulation of smooth muscle cell chemotaxis Inferred from direct assay PubMed 16439689. Source: BHF-UCL negative regulation of vascular permeability Inferred from direct assay PubMed 18345009. Source: UniProtKB positive regulation of apoptotic process Inferred from mutant phenotype PubMed 18566128. Source: UniProtKB positive regulation of axonogenesis Traceable author statement PubMed 10197527. Source: UniProtKB response to cortisol stimulus Inferred from expression pattern PubMed 18566128. Source: UniProtKB retinal ganglion cell axon guidance Inferred from direct assay Ref.7Ref.15. Source: UniProtKB ureteric bud development Inferred from mutant phenotype PubMed 15130495. Source: UniProtKB
Cellular_component	cell surface Inferred from direct assay Ref.3. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 18566128. Source: UniProtKB extracellular space Inferred from direct assay PubMed 16439689PubMed 19005219Ref.3. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	GTPase inhibitor activity Inferred from direct assay PubMed 16439689PubMed 19759280. Source: UniProtKB calcium ion binding Non-traceable author statement Ref.1. Source: UniProtKB chemorepellent activity Inferred from electronic annotation. Source: Compara heparin binding Inferred from direct assay PubMed 17062560. Source: UniProtKB laminin-1 binding Inferred from direct assay Ref.3. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.15. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O94813-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O94813-2)

The sequence of this isoform differs from the canonical sequence as follows:
     258-258: S → SDEEE
     480-487: Missing.

Isoform 3 (identifier: O94813-3)

The sequence of this isoform differs from the canonical sequence as follows:
     480-487: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 1529

1499

Slit homolog 2 protein

PRO_0000007725

Chain

31 – 1121

1091

Slit homolog 2 protein N-product Ref.3

PRO_0000007726

Chain

1122 – 1529

408

Slit homolog 2 protein C-product Ref.3

PRO_0000007727

Regions

Domain

31 – 55

25

LRRNT

Repeat

56 – 77

22

LRR 1

Repeat

80 – 101

22

LRR 2

Repeat

104 – 125

22

LRR 3

Repeat

128 – 149

22

LRR 4

Repeat

152 – 173

22

LRR 5

Repeat

176 – 197

22

LRR 6

Domain

209 – 259

51

LRRCT 1

Domain

264 – 300

37

LRRNT 2

Repeat

301 – 322

22

LRR 7

Repeat

325 – 346

22

LRR 8

Repeat

349 – 370

22

LRR 9

Repeat

373 – 394

22

LRR 10

Repeat

397 – 418

22

LRR 11

Domain

430 – 480

51

LRRCT 2

Domain

497 – 533

37

LRRNT 3

Repeat

534 – 555

22

LRR 12

Repeat

559 – 580

22

LRR 13

Repeat

583 – 604

22

LRR 14

Repeat

607 – 628

22

LRR 15

Repeat

631 – 652

22

LRR 16

Domain

664 – 714

51

LRRCT 3

Domain

718 – 754

37

LRRNT 4

Repeat

755 – 777

23

LRR 17

Repeat

778 – 799

22

LRR 18

Repeat

802 – 823

22

LRR 19

Repeat

826 – 847

22

LRR 20

Domain

859 – 909

51

LRRCT 4

Domain

918 – 955

38

EGF-like 1

Domain

957 – 996

40

EGF-like 2

Domain

998 – 1034

37

EGF-like 3; calcium-binding Potential

Domain

1036 – 1074

39

EGF-like 4

Domain

1076 – 1112

37

EGF-like 5; calcium-binding Potential

Domain

1121 – 1157

37

EGF-like 6

Domain

1160 – 1333

174

Laminin G-like

Domain

1332 – 1368

37

EGF-like 7

Domain

1453 – 1528

76

CTCK

Sites

Site

1121 – 1122

2

Cleavage Ref.3

Amino acid modifications

Glycosylation

66

1

N-linked (GlcNAc...) Potential

Glycosylation

186

1

N-linked (GlcNAc...) Potential

Glycosylation

564

1

N-linked (GlcNAc...) Potential

Glycosylation

623

1

N-linked (GlcNAc...)

Glycosylation

794

1

N-linked (GlcNAc...) Potential

Glycosylation

799

1

N-linked (GlcNAc...) Potential

Glycosylation

1009

1

N-linked (GlcNAc...) Potential

Glycosylation

1010

1

N-linked (GlcNAc...) Potential

Glycosylation

1019

1

N-linked (GlcNAc...) Potential

Glycosylation

1183

1

N-linked (GlcNAc...) Potential

Glycosylation

1266

1

N-linked (GlcNAc...) Potential

Glycosylation

1300

1

N-linked (GlcNAc...) Potential

Disulfide bond

277 ↔ 286

Ref.13 Ref.14 Ref.15

Disulfide bond

434 ↔ 457

Ref.13 Ref.14 Ref.15

Disulfide bond

436 ↔ 478

Ref.13 Ref.14 Ref.15

Disulfide bond

506 ↔ 512

Ref.13 Ref.14 Ref.15

Disulfide bond

510 ↔ 519

Ref.13 Ref.14 Ref.15

Disulfide bond

668 ↔ 691

Ref.13 Ref.14 Ref.15

Disulfide bond

670 ↔ 712

Ref.13 Ref.14 Ref.15

Disulfide bond

727 ↔ 733

Ref.13 Ref.14 Ref.15

Disulfide bond

731 ↔ 740

Ref.13 Ref.14 Ref.15

Disulfide bond

863 ↔ 886

Ref.13 Ref.14 Ref.15

Disulfide bond

865 ↔ 907

Ref.13 Ref.14 Ref.15

Disulfide bond

922 ↔ 933

By similarity

Disulfide bond

927 ↔ 943

By similarity

Disulfide bond

945 ↔ 954

By similarity

Disulfide bond

961 ↔ 972

By similarity

Disulfide bond

966 ↔ 984

By similarity

Disulfide bond

986 ↔ 995

By similarity

Disulfide bond

1002 ↔ 1013

By similarity

Disulfide bond

1007 ↔ 1022

By similarity

Disulfide bond

1024 ↔ 1033

By similarity

Disulfide bond

1040 ↔ 1053

By similarity

Disulfide bond

1047 ↔ 1062

By similarity

Disulfide bond

1064 ↔ 1073

By similarity

Disulfide bond

1080 ↔ 1091

By similarity

Disulfide bond

1085 ↔ 1100

By similarity

Disulfide bond

1102 ↔ 1111

By similarity

Disulfide bond

1125 ↔ 1136

By similarity

Disulfide bond

1130 ↔ 1145

By similarity

Disulfide bond

1147 ↔ 1156

By similarity

Disulfide bond

1307 ↔ 1333

By similarity

Disulfide bond

1336 ↔ 1346

By similarity

Disulfide bond

1341 ↔ 1356

By similarity

Disulfide bond

1358 ↔ 1367

By similarity

Disulfide bond

1375 ↔ 1385

By similarity

Disulfide bond

1380 ↔ 1395

By similarity

Disulfide bond

1397 ↔ 1406

By similarity

Disulfide bond

1416 ↔ 1426

By similarity

Disulfide bond

1421 ↔ 1436

By similarity

Disulfide bond

1438 ↔ 1447

By similarity

Disulfide bond

1453 ↔ 1492

By similarity

Disulfide bond

1471 ↔ 1506

By similarity

Disulfide bond

1482 ↔ 1522

By similarity

Disulfide bond

1486 ↔ 1524

By similarity

Natural variations

Alternative sequence

258

1

S → SDEEE in isoform 2.

VSP_050035

Alternative sequence

480 – 487

8

Missing in isoform 2 and isoform 3.

VSP_050036

Natural variant

636

1

S → P. Ref.1

VAR_018098

Natural variant

1277

1

S → F. Ref.1

VAR_018099

Experimental info

Sequence conflict

226

1

Q → K in AAD25539. Ref.2

Sequence conflict

607 – 610

4

SLKT → KPQN in AAD04309. Ref.3

Sequence conflict

634

1

L → M in AAD04309. Ref.3

Secondary structure

1

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1529

Helix Strand Turn

Details...

Beta strand

277 – 280

4

Beta strand

283 – 285

3

Beta strand

304 – 306

3

Turn

317 – 322

6

Beta strand

328 – 330

3

Turn

341 – 346

6

Beta strand

352 – 354

3

Turn

365 – 370

6

Beta strand

376 – 378

3

Turn

389 – 394

6

Beta strand

400 – 402

3

Turn

413 – 418

6

Beta strand

424 – 426

3

Helix

436 – 438

3

Helix

439 – 447

9

Beta strand

456 – 460

5

Helix

461 – 463

3

Helix

468 – 470

3

Helix

473 – 475

3

Beta strand

511 – 513

3

Beta strand

516 – 518

3

Beta strand

536 – 539

4

Helix

554 – 556

3

Beta strand

562 – 564

3

Turn

575 – 580

6

Beta strand

586 – 588

3

Helix

599 – 602

4

Beta strand

610 – 612

3

Beta strand

633 – 636

4

Turn

647 – 652

6

Beta strand

658 – 660

3

Helix

670 – 672

3

Helix

673 – 681

9

Beta strand

690 – 694

5

Helix

695 – 697

3

Helix

702 – 704

3

Helix

707 – 709

3

Beta strand

732 – 734

3

Beta strand

737 – 739

3

Beta strand

758 – 760

3

Helix

771 – 775

5

Beta strand

781 – 783

3

Turn

794 – 799

6

Beta strand

805 – 807

3

Turn

818 – 823

6

Beta strand

829 – 831

3

Turn

842 – 847

6

Beta strand

853 – 855

3

Helix

865 – 867

3

Helix

868 – 876

9

Beta strand

885 – 889

5

Helix

890 – 892

3

Turn

897 – 899

3

Helix

902 – 904

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 5D19CC5E7FD461BA	FASTA	1,529	169,870
	10 20 30 40 50 60 MRGVGWQMLS LSLGLVLAIL NKVAPQACPA QCSCSGSTVD CHGLALRSVP RNIPRNTERL 70 80 90 100 110 120 DLNGNNITRI TKTDFAGLRH LRVLQLMENK ISTIERGAFQ DLKELERLRL NRNHLQLFPE 130 140 150 160 170 180 LLFLGTAKLY RLDLSENQIQ AIPRKAFRGA VDIKNLQLDY NQISCIEDGA FRALRDLEVL 190 200 210 220 230 240 TLNNNNITRL SVASFNHMPK LRTFRLHSNN LYCDCHLAWL SDWLRQRPRV GLYTQCMGPS 250 260 270 280 290 300 HLRGHNVAEV QKREFVCSGH QSFMAPSCSV LHCPAACTCS NNIVDCRGKG LTEIPTNLPE 310 320 330 340 350 360 TITEIRLEQN TIKVIPPGAF SPYKKLRRID LSNNQISELA PDAFQGLRSL NSLVLYGNKI 370 380 390 400 410 420 TELPKSLFEG LFSLQLLLLN ANKINCLRVD AFQDLHNLNL LSLYDNKLQT IAKGTFSPLR 430 440 450 460 470 480 AIQTMHLAQN PFICDCHLKW LADYLHTNPI ETSGARCTSP RRLANKRIGQ IKSKKFRCSA 490 500 510 520 530 540 KEQYFIPGTE DYRSKLSGDC FADLACPEKC RCEGTTVDCS NQKLNKIPEH IPQYTAELRL 550 560 570 580 590 600 NNNEFTVLEA TGIFKKLPQL RKINFSNNKI TDIEEGAFEG ASGVNEILLT SNRLENVQHK 610 620 630 640 650 660 MFKGLESLKT LMLRSNRITC VGNDSFIGLS SVRLLSLYDN QITTVAPGAF DTLHSLSTLN 670 680 690 700 710 720 LLANPFNCNC YLAWLGEWLR KKRIVTGNPR CQKPYFLKEI PIQDVAIQDF TCDDGNDDNS 730 740 750 760 770 780 CSPLSRCPTE CTCLDTVVRC SNKGLKVLPK GIPRDVTELY LDGNQFTLVP KELSNYKHLT 790 800 810 820 830 840 LIDLSNNRIS TLSNQSFSNM TQLLTLILSY NRLRCIPPRT FDGLKSLRLL SLHGNDISVV 850 860 870 880 890 900 PEGAFNDLSA LSHLAIGANP LYCDCNMQWL SDWVKSEYKE PGIARCAGPG EMADKLLLTT 910 920 930 940 950 960 PSKKFTCQGP VDVNILAKCN PCLSNPCKND GTCNSDPVDF YRCTCPYGFK GQDCDVPIHA 970 980 990 1000 1010 1020 CISNPCKHGG TCHLKEGEED GFWCICADGF EGENCEVNVD DCEDNDCENN STCVDGINNY 1030 1040 1050 1060 1070 1080 TCLCPPEYTG ELCEEKLDFC AQDLNPCQHD SKCILTPKGF KCDCTPGYVG EHCDIDFDDC 1090 1100 1110 1120 1130 1140 QDNKCKNGAH CTDAVNGYTC ICPEGYSGLF CEFSPPMVLP RTSPCDNFDC QNGAQCIVRI 1150 1160 1170 1180 1190 1200 NEPICQCLPG YQGEKCEKLV SVNFINKESY LQIPSAKVRP QTNITLQIAT DEDSGILLYK 1210 1220 1230 1240 1250 1260 GDKDHIAVEL YRGRVRASYD TGSHPASAIY SVETINDGNF HIVELLALDQ SLSLSVDGGN 1270 1280 1290 1300 1310 1320 PKIITNLSKQ STLNFDSPLY VGGMPGKSNV ASLRQAPGQN GTSFHGCIRN LYINSELQDF 1330 1340 1350 1360 1370 1380 QKVPMQTGIL PGCEPCHKKV CAHGTCQPSS QAGFTCECQE GWMGPLCDQR TNDPCLGNKC 1390 1400 1410 1420 1430 1440 VHGTCLPINA FSYSCKCLEG HGGVLCDEEE DLFNPCQAIK CKHGKCRLSG LGQPYCECSS 1450 1460 1470 1480 1490 1500 GYTGDSCDRE ISCRGERIRD YYQKQQGYAA CQTTKKVSRL ECRGGCAGGQ CCGPLRSKRR 1510 1520 KYSFECTDGS SFVDEVEKVV KCGCTRCVS
	Isoform 2 [UniParc]. Checksum: 56DE2356BB2E5CAD	FASTA	1,525	169,395
	10 20 30 40 50 60 MRGVGWQMLS LSLGLVLAIL NKVAPQACPA QCSCSGSTVD CHGLALRSVP RNIPRNTERL 70 80 90 100 110 120 DLNGNNITRI TKTDFAGLRH LRVLQLMENK ISTIERGAFQ DLKELERLRL NRNHLQLFPE 130 140 150 160 170 180 LLFLGTAKLY RLDLSENQIQ AIPRKAFRGA VDIKNLQLDY NQISCIEDGA FRALRDLEVL 190 200 210 220 230 240 TLNNNNITRL SVASFNHMPK LRTFRLHSNN LYCDCHLAWL SDWLRQRPRV GLYTQCMGPS 250 260 270 280 290 300 HLRGHNVAEV QKREFVCSDE EEGHQSFMAP SCSVLHCPAA CTCSNNIVDC RGKGLTEIPT 310 320 330 340 350 360 NLPETITEIR LEQNTIKVIP PGAFSPYKKL RRIDLSNNQI SELAPDAFQG LRSLNSLVLY 370 380 390 400 410 420 GNKITELPKS LFEGLFSLQL LLLNANKINC LRVDAFQDLH NLNLLSLYDN KLQTIAKGTF 430 440 450 460 470 480 SPLRAIQTMH LAQNPFICDC HLKWLADYLH TNPIETSGAR CTSPRRLANK RIGQIKSKKF 490 500 510 520 530 540 RCSGTEDYRS KLSGDCFADL ACPEKCRCEG TTVDCSNQKL NKIPEHIPQY TAELRLNNNE 550 560 570 580 590 600 FTVLEATGIF KKLPQLRKIN FSNNKITDIE EGAFEGASGV NEILLTSNRL ENVQHKMFKG 610 620 630 640 650 660 LESLKTLMLR SNRITCVGND SFIGLSSVRL LSLYDNQITT VAPGAFDTLH SLSTLNLLAN 670 680 690 700 710 720 PFNCNCYLAW LGEWLRKKRI VTGNPRCQKP YFLKEIPIQD VAIQDFTCDD GNDDNSCSPL 730 740 750 760 770 780 SRCPTECTCL DTVVRCSNKG LKVLPKGIPR DVTELYLDGN QFTLVPKELS NYKHLTLIDL 790 800 810 820 830 840 SNNRISTLSN QSFSNMTQLL TLILSYNRLR CIPPRTFDGL KSLRLLSLHG NDISVVPEGA 850 860 870 880 890 900 FNDLSALSHL AIGANPLYCD CNMQWLSDWV KSEYKEPGIA RCAGPGEMAD KLLLTTPSKK 910 920 930 940 950 960 FTCQGPVDVN ILAKCNPCLS NPCKNDGTCN SDPVDFYRCT CPYGFKGQDC DVPIHACISN 970 980 990 1000 1010 1020 PCKHGGTCHL KEGEEDGFWC ICADGFEGEN CEVNVDDCED NDCENNSTCV DGINNYTCLC 1030 1040 1050 1060 1070 1080 PPEYTGELCE EKLDFCAQDL NPCQHDSKCI LTPKGFKCDC TPGYVGEHCD IDFDDCQDNK 1090 1100 1110 1120 1130 1140 CKNGAHCTDA VNGYTCICPE GYSGLFCEFS PPMVLPRTSP CDNFDCQNGA QCIVRINEPI 1150 1160 1170 1180 1190 1200 CQCLPGYQGE KCEKLVSVNF INKESYLQIP SAKVRPQTNI TLQIATDEDS GILLYKGDKD 1210 1220 1230 1240 1250 1260 HIAVELYRGR VRASYDTGSH PASAIYSVET INDGNFHIVE LLALDQSLSL SVDGGNPKII 1270 1280 1290 1300 1310 1320 TNLSKQSTLN FDSPLYVGGM PGKSNVASLR QAPGQNGTSF HGCIRNLYIN SELQDFQKVP 1330 1340 1350 1360 1370 1380 MQTGILPGCE PCHKKVCAHG TCQPSSQAGF TCECQEGWMG PLCDQRTNDP CLGNKCVHGT 1390 1400 1410 1420 1430 1440 CLPINAFSYS CKCLEGHGGV LCDEEEDLFN PCQAIKCKHG KCRLSGLGQP YCECSSGYTG 1450 1460 1470 1480 1490 1500 DSCDREISCR GERIRDYYQK QQGYAACQTT KKVSRLECRG GCAGGQCCGP LRSKRRKYSF 1510 1520 ECTDGSSFVD EVEKVVKCGC TRCVS
	Isoform 3 [UniParc]. Checksum: 7620F3C96DD4E534	FASTA	1,521	168,893
	10 20 30 40 50 60 MRGVGWQMLS LSLGLVLAIL NKVAPQACPA QCSCSGSTVD CHGLALRSVP RNIPRNTERL 70 80 90 100 110 120 DLNGNNITRI TKTDFAGLRH LRVLQLMENK ISTIERGAFQ DLKELERLRL NRNHLQLFPE 130 140 150 160 170 180 LLFLGTAKLY RLDLSENQIQ AIPRKAFRGA VDIKNLQLDY NQISCIEDGA FRALRDLEVL 190 200 210 220 230 240 TLNNNNITRL SVASFNHMPK LRTFRLHSNN LYCDCHLAWL SDWLRQRPRV GLYTQCMGPS 250 260 270 280 290 300 HLRGHNVAEV QKREFVCSGH QSFMAPSCSV LHCPAACTCS NNIVDCRGKG LTEIPTNLPE 310 320 330 340 350 360 TITEIRLEQN TIKVIPPGAF SPYKKLRRID LSNNQISELA PDAFQGLRSL NSLVLYGNKI 370 380 390 400 410 420 TELPKSLFEG LFSLQLLLLN ANKINCLRVD AFQDLHNLNL LSLYDNKLQT IAKGTFSPLR 430 440 450 460 470 480 AIQTMHLAQN PFICDCHLKW LADYLHTNPI ETSGARCTSP RRLANKRIGQ IKSKKFRCSG 490 500 510 520 530 540 TEDYRSKLSG DCFADLACPE KCRCEGTTVD CSNQKLNKIP EHIPQYTAEL RLNNNEFTVL 550 560 570 580 590 600 EATGIFKKLP QLRKINFSNN KITDIEEGAF EGASGVNEIL LTSNRLENVQ HKMFKGLESL 610 620 630 640 650 660 KTLMLRSNRI TCVGNDSFIG LSSVRLLSLY DNQITTVAPG AFDTLHSLST LNLLANPFNC 670 680 690 700 710 720 NCYLAWLGEW LRKKRIVTGN PRCQKPYFLK EIPIQDVAIQ DFTCDDGNDD NSCSPLSRCP 730 740 750 760 770 780 TECTCLDTVV RCSNKGLKVL PKGIPRDVTE LYLDGNQFTL VPKELSNYKH LTLIDLSNNR 790 800 810 820 830 840 ISTLSNQSFS NMTQLLTLIL SYNRLRCIPP RTFDGLKSLR LLSLHGNDIS VVPEGAFNDL 850 860 870 880 890 900 SALSHLAIGA NPLYCDCNMQ WLSDWVKSEY KEPGIARCAG PGEMADKLLL TTPSKKFTCQ 910 920 930 940 950 960 GPVDVNILAK CNPCLSNPCK NDGTCNSDPV DFYRCTCPYG FKGQDCDVPI HACISNPCKH 970 980 990 1000 1010 1020 GGTCHLKEGE EDGFWCICAD GFEGENCEVN VDDCEDNDCE NNSTCVDGIN NYTCLCPPEY 1030 1040 1050 1060 1070 1080 TGELCEEKLD FCAQDLNPCQ HDSKCILTPK GFKCDCTPGY VGEHCDIDFD DCQDNKCKNG 1090 1100 1110 1120 1130 1140 AHCTDAVNGY TCICPEGYSG LFCEFSPPMV LPRTSPCDNF DCQNGAQCIV RINEPICQCL 1150 1160 1170 1180 1190 1200 PGYQGEKCEK LVSVNFINKE SYLQIPSAKV RPQTNITLQI ATDEDSGILL YKGDKDHIAV 1210 1220 1230 1240 1250 1260 ELYRGRVRAS YDTGSHPASA IYSVETINDG NFHIVELLAL DQSLSLSVDG GNPKIITNLS 1270 1280 1290 1300 1310 1320 KQSTLNFDSP LYVGGMPGKS NVASLRQAPG QNGTSFHGCI RNLYINSELQ DFQKVPMQTG 1330 1340 1350 1360 1370 1380 ILPGCEPCHK KVCAHGTCQP SSQAGFTCEC QEGWMGPLCD QRTNDPCLGN KCVHGTCLPI 1390 1400 1410 1420 1430 1440 NAFSYSCKCL EGHGGVLCDE EEDLFNPCQA IKCKHGKCRL SGLGQPYCEC SSGYTGDSCD 1450 1460 1470 1480 1490 1500 REISCRGERI RDYYQKQQGY AACQTTKKVS RLECRGGCAG GQCCGPLRSK RRKYSFECTD 1510 1520 GSSFVDEVEK VVKCGCTRCV S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expressions of three mammalian homologues of Drosophila slit suggest possible roles for Slit in the formation and maintenance of the nervous system." Itoh A., Miyabayashi T., Ohno M., Sakano S. Brain Res. Mol. Brain Res. 62:175-186(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, VARIANTS PRO-636 AND PHE-1277. Tissue: Fetal lung.
[2]	"Distinct but overlapping expression patterns of two vertebrate slit homologs implies functional roles in CNS development and organogenesis." Holmes G.P., Negus K., Burridge L., Raman S., Algar E., Yamada T., Little M.H. Mech. Dev. 79:57-72(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY. Tissue: Fetal brain and Fetal kidney.
[3]	"Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance." Brose K., Bland K.S., Wang K.H., Arnott D., Henzel W., Goodman C.S., Tessier-Lavigne M., Kidd T. Cell 96:795-806(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1122-1129, FUNCTION, INTERACTION WITH ROBO1 AND ROBO2, SUBCELLULAR LOCATION. Tissue: Fetal brain.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
[6]	"Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord." Zou Y., Stoeckli E., Chen H., Tessier-Lavigne M. Cell 102:363-375(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Slit2 is a repellent for retinal ganglion cell axons." Niclou S.P., Jia L., Raper J.A. J. Neurosci. 20:4962-4974(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors." Wu J.Y., Feng L., Park H.T., Havlioglu N., Wen L., Tang H., Bacon K.B., Jiang Z.H., Zhang X.C., Rao Y. Nature 410:948-952(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons." Chen J.H., Wen L., Dupuis S., Wu J.Y., Rao Y. J. Neurosci. 21:1548-1556(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN.
[10]	"Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance." Nguyen-Ba-Charvet K.T., Brose K., Ma L., Wang K.H., Marillat V., Sotelo C., Tessier-Lavigne M., Chedotal A. J. Neurosci. 21:4281-4289(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ROBO1 AND ROBO2.
[11]	"Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex." Stein E., Tessier-Lavigne M. Science 291:1928-1938(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes." Wong K., Park H.T., Wu J.Y., Rao Y. Curr. Opin. Genet. Dev. 12:583-591(2002) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[13]	"Production of Slit2 LRR domains in mammalian cells for structural studies and the structure of human Slit2 domain 3." Morlot C., Hemrika W., Romijn R.A., Gros P., Cusack S., McCarthy A.A. Acta Crystallogr. D 63:961-968(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 504-716, DISULFIDE BONDS.
[14]	"Structural insights into the Slit-Robo complex." Morlot C., Thielens N.M., Ravelli R.B., Hemrika W., Romijn R.A., Gros P., Cusack S., McCarthy A.A. Proc. Natl. Acad. Sci. U.S.A. 104:14923-14928(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 271-480 IN COMPLEX WITH ROBO1, DISULFIDE BONDS.
[15]	"Structure and functional relevance of the Slit2 homodimerization domain." Seiradake E., von Philipsborn A.C., Henry M., Fritz M., Lortat-Jacob H., Jamin M., Hemrika W., Bastmeyer M., Cusack S., McCarthy A.A. EMBO Rep. 10:736-741(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 726-907, SUBUNIT, DISULFIDE BONDS, HEPARIN-BINDING.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB017168 mRNA. Translation: BAA35185.1.
AF055585 mRNA. Translation: AAD04309.1.
AF133270 mRNA. Translation: AAD25539.1.
CH471069 Genomic DNA. Translation: EAW92793.1.
BC117190 mRNA. Translation: AAI17191.1.
BC143978 mRNA. Translation: AAI43979.1.

IPI

IPI00006288.
IPI00220114.
IPI00335003.

RefSeq

NP_004778.1. NM_004787.1.

UniGene

Hs.29802.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2V70	X-ray	3.01	A/B/C/D	504-714	[»]
2V9S	X-ray	2.00	A/B/C/D	271-480	[»]
2V9T	X-ray	1.70	B	271-480	[»]
2WFH	X-ray	1.80	A/B	726-907	[»]

ProteinModelPortal

O94813.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-38198N.

IntAct

O94813. 6 interactions.

MINT

MINT-6768470.

STRING

9606.ENSP00000273739.

PTM databases

PhosphoSite

O94813.

Proteomic databases

PaxDb

O94813.

PRIDE

O94813.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000503823; ENSP00000427548; ENSG00000145147.
ENST00000503837; ENSP00000422261; ENSG00000145147.
ENST00000504154; ENSP00000422591; ENSG00000145147.

GeneID

9353.

KEGG

hsa:9353.

UCSC

uc003gpr.1. human.
uc003gps.1. human.

Organism-specific databases

CTD

9353.

GeneCards

GC04P020254.

HGNC

HGNC:11086. SLIT2.

HPA

CAB007590.
HPA019511.
HPA023088.

MIM

603746. gene.

neXtProt

NX_O94813.

PharmGKB

PA35939.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4886.

HOGENOM

HOG000116120.

HOVERGEN

HBG057959.

InParanoid

O94813.

KO

K06839.

PhylomeDB

O94813.

Enzyme and pathway databases

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.

Reactome

REACT_111045. Developmental Biology.
REACT_96538. Developmental Biology.

Gene expression databases

ArrayExpress

O94813.

Bgee

O94813.

CleanEx

HS_SLIT2.

Genevestigator

O94813.

GermOnline

ENSG00000145147. Homo sapiens.

Family and domain databases

Gene3D

2.60.120.200. 1 hit.

InterPro

IPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000483. Cys-rich_flank_reg_C.
IPR006207. Cys_knot_C.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR003645. Fol_N.
IPR001791. Laminin_G.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRR-contain_N.
[Graphical view]

Pfam

PF00008. EGF. 6 hits.
PF02210. Laminin_G_2. 1 hit.
PF00560. LRR_1. 1 hit.
PF01463. LRRCT. 4 hits.
PF01462. LRRNT. 4 hits.
[Graphical view]

SMART

SM00041. CT. 1 hit.
SM00181. EGF. 7 hits.
SM00179. EGF_CA. 2 hits.
SM00274. FOLN. 3 hits.
SM00282. LamG. 1 hit.
SM00369. LRR_TYP. 8 hits.
SM00082. LRRCT. 4 hits.
SM00013. LRRNT. 4 hits.
[Graphical view]

SUPFAM

SSF49899. ConA_like_lec_gl. 1 hit.

PROSITE

PS00010. ASX_HYDROXYL. 2 hits.
PS01185. CTCK_1. 1 hit.
PS01225. CTCK_2. 1 hit.
PS00022. EGF_1. 9 hits.
PS01186. EGF_2. 7 hits.
PS50026. EGF_3. 9 hits.
PS01187. EGF_CA. 2 hits.
PS50025. LAM_G_DOMAIN. 1 hit.
PS51450. LRR. 20 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O94813.

GenomeRNAi

9353.

NextBio

35025.

SOURCE

Search...

Entry information

Entry name

SLIT2_HUMAN

Accession

Primary (citable) accession number: O94813
Secondary accession number(s): B7ZLR5 , O95710, Q17RU3, Q9Y5Q7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2003
Last sequence update:	May 1, 1999
Last modified:	May 29, 2013
This is version 136 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.