Q15811 (ITSN1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Intersectin-1

Alternative name(s):
SH3 domain-containing protein 1A
SH3P17

Gene names

Name:	ITSN1
Synonyms:	ITSN, SH3D1A

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	1721 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR); internalization of ITGB1 as DAB2-dependent cargo but not TFR may involve association with DAB2. Isoform 1 could be involved in brain-specific synaptic vesicle recycling. Inhibits ARHGAP31 activity toward RAC1. Ref.8 Ref.16
Subunit structure	Interacts with dynamin, CDC42, SNAP25 and SNAP23. Clusters several dynamin in a manner that is regulated by alternative splicing. Interacts with clathrin-associated proteins and other components of the endocytic machinery, such as SPIN90, EPS15, EPN1, EPN2, STON2, FCHO1, FCHO2 and DAB2. Interacts (via SH3 domains) with REPS1 and SGIP1. Interacts with ARHGAP31. Interacts with ADAM15. Ref.8 Ref.10 Ref.12 Ref.14 Ref.16 Ref.17
Subcellular location	Endomembrane system By similarity. Cell junction › synapse › synaptosome By similarity. Cell projection › lamellipodium. Membrane › clathrin-coated pit. Note: Colocalizes with SGIP1 at the plasma membrane in structures corresponding most problably to clathrin-coated pits Probable. Ref.8 Ref.12
Tissue specificity	Isoform 2 is ubiquitous in adult and fetal tissues with high expression in skeletal muscle, heart, spleen, ovary, testis and all fetal tissues tested and low expression in thymus, blood, lung, liver and pancreas. Isoform 1 is expressed almost exclusively in the brain, in all brain regions. Not expressed in the spinal cord.
Domain	SH3-3, SH3-4 and SH3-5, but not SH3-1 and SH3-2 domains, bind to dynamin By similarity. SH3-1 and SH3-4 bind to ARHGAP31. The KLERQ domain binds to SNAP-25 and SNAP-23 By similarity.
Sequence similarities	Contains 1 C2 domain. Contains 1 DH (DBL-homology) domain. Contains 2 EF-hand domains. Contains 2 EH domains. Contains 1 PH domain. Contains 5 SH3 domains.
Caution	Studies in clathrin-mediated endocytosis of ITGB1 and TFR used a siRNA mixture of ISTN1 and ISTN2, and a Dab2 mutant with impaired binding to EH domain-containing proteins EPS15 and ITSN1 suggesting a partially overlapping role of the EH domain-containing proteins (Ref.16).
Sequence caution	The sequence AAC50592.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Endocytosis
Cellular component	Cell junction Cell projection Coated pit Membrane Synapse Synaptosome
Coding sequence diversity	Alternative splicing
Domain	Coiled coil Repeat SH3 domain
Ligand	Calcium Metal-binding
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Traceable author statement. Source: Reactome negative regulation of neuron apoptotic process Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of protein kinase B signaling cascade Inferred from electronic annotation. Source: Compara regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro regulation of small GTPase mediated signal transduction Traceable author statement. Source: Reactome small GTPase mediated signal transduction Traceable author statement. Source: Reactome synaptic vesicle endocytosis Traceable author statement Ref.1. Source: ProtInc
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW coated pit Inferred from direct assay Ref.12. Source: UniProtKB cytosol Traceable author statement. Source: Reactome endocytic vesicle Inferred from electronic annotation. Source: Compara lamellipodium Inferred from electronic annotation. Source: UniProtKB-SubCell neuron projection Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay Ref.12. Source: UniProtKB synapse Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro calcium ion binding Non-traceable author statement Ref.1. Source: UniProtKB guanyl-nucleotide exchange factor activity Non-traceable author statement Ref.1. Source: UniProtKB kinase activator activity Inferred from electronic annotation. Source: Compara phospholipid binding Inferred from electronic annotation. Source: InterPro protein complex scaffold Inferred from direct assay Ref.12. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC42	P60953-1	2	EBI-602041,EBI-3625591
DISC1	Q9NRI5	3	EBI-602041,EBI-529989
Fcho2	Q3UQN2	3	EBI-602041,EBI-6094986	From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. Alternative splicing affects domains involved in protein recognition and thus may play a role in selecting specific interactions.

Isoform 1 (identifier: Q15811-1)

Also known as: Long; ITSN-l;

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: Q15811-2)

Also known as: Short; ITSN-s;

The sequence of this isoform differs from the canonical sequence as follows:
     1221-1721: Missing.

Isoform 3 (identifier: Q15811-3)

Also known as: Short 2; SH3P17;

The sequence of this isoform differs from the canonical sequence as follows:
     770-774: Missing.
     1006-1076: Missing.
     1221-1721: Missing.

Isoform 4 (identifier: Q15811-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1006-1076: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1721

1721

Intersectin-1

PRO_0000080957

Regions

Domain

21 – 109

89

EH 1

Domain

53 – 88

36

EF-hand 1

Domain

221 – 310

90

EH 2

Domain

254 – 289

36

EF-hand 2

Domain

740 – 806

67

SH3 1

Domain

913 – 971

59

SH3 2

Domain

1002 – 1060

59

SH3 3

Domain

1074 – 1138

65

SH3 4

Domain

1155 – 1214

60

SH3 5

Domain

1237 – 1423

187

DH

Domain

1462 – 1571

110

PH

Domain

1583 – 1679

97

C2

Calcium binding

66 – 77

12

1 Potential

Calcium binding

267 – 278

12

2 Potential

Region

326 – 702

377

KLERQ

Coiled coil

351 – 705

355

Potential

Amino acid modifications

Modified residue

313

1

Phosphoserine By similarity

Modified residue

315

1

Phosphoserine By similarity

Modified residue

318

1

Phosphoserine By similarity

Modified residue

902

1

Phosphoserine Ref.9

Modified residue

904

1

Phosphoserine Ref.9

Modified residue

977

1

Phosphothreonine By similarity

Modified residue

1137

1

Phosphoserine By similarity

Natural variations

Alternative sequence

770 – 774

5

Missing in isoform 3.

VSP_004293

Alternative sequence

1006 – 1076

71

Missing in isoform 3 and isoform 4.

VSP_004294

Alternative sequence

1221 – 1721

501

Missing in isoform 2 and isoform 3.

VSP_004295

Experimental info

Mutagenesis

1369

1

M → L: Decreases specificity for CDC42; when associated with I-1376. Ref.18

Mutagenesis

1376

1

L → I: Decreases specificity for CDC42; when associated with L-1369. Ref.18

Sequence conflict

114

1

A → P in AAC78610. Ref.1

Sequence conflict

114

1

A → P in AAC78611. Ref.1

Sequence conflict

1088

1

T → A in AAD53183. Ref.5

Sequence conflict

1109

1

G → R in AAD53183. Ref.5

Sequence conflict

1137

1

S → N in AAC78610. Ref.1

Sequence conflict

1137

1

S → N in AAC78611. Ref.1

Sequence conflict

1361

1

A → E in AAC78611. Ref.1

Sequence conflict

1361

1

A → E in AAC50592. Ref.4

Sequence conflict

1474

1

S → N in AAC78611. Ref.1

Sequence conflict

1474

1

S → N in AAC50592. Ref.4

Secondary structure

1

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1721

Helix Strand Turn

Details...

Turn

12 – 14

3

Helix

19 – 31

13

Beta strand

35 – 37

3

Beta strand

38 – 40

3

Helix

41 – 48

8

Helix

49 – 51

3

Helix

55 – 65

11

Beta strand

70 – 73

4

Helix

75 – 89

15

Helix

100 – 102

3

Beta strand

215 – 217

3

Helix

219 – 230

12

Beta strand

239 – 241

3

Helix

242 – 250

9

Helix

256 – 266

11

Beta strand

272 – 275

4

Helix

276 – 290

15

Helix

301 – 303

3

Turn

306 – 309

4

Beta strand

916 – 922

7

Beta strand

939 – 945

7

Beta strand

947 – 954

8

Beta strand

957 – 962

6

Helix

963 – 965

3

Beta strand

966 – 969

4

Helix

1233 – 1262

30

Helix

1264 – 1269

6

Beta strand

1271 – 1273

3

Helix

1275 – 1282

8

Helix

1285 – 1306

22

Beta strand

1308 – 1310

3

Helix

1316 – 1322

7

Helix

1323 – 1327

5

Helix

1328 – 1349

22

Helix

1351 – 1361

11

Helix

1364 – 1366

3

Helix

1371 – 1374

4

Helix

1377 – 1393

17

Helix

1403 – 1437

35

Beta strand

1451 – 1454

4

Beta strand

1456 – 1460

5

Beta strand

1463 – 1466

4

Beta strand

1472 – 1474

3

Beta strand

1479 – 1493

15

Beta strand

1511 – 1513

3

Helix

1522 – 1524

3

Beta strand

1525 – 1528

4

Beta strand

1531 – 1533

3

Beta strand

1541 – 1544

4

Beta strand

1547 – 1550

4

Helix

1556 – 1577

22

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Long) (ITSN-l) [UniParc]. Last modified October 17, 2006. Version 3. Checksum: FC4DE644D8BEA2BE	FASTA	1,721	195,422
	10 20 30 40 50 60 MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ 70 80 90 100 110 120 IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI 130 140 150 160 170 180 ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP 190 200 210 220 230 240 KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL 250 260 270 280 290 300 TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP 310 320 330 340 350 360 PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER 370 380 390 400 410 420 GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE 430 440 450 460 470 480 RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF 490 500 510 520 530 540 ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR 550 560 570 580 590 600 LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI 610 620 630 640 650 660 DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW 670 680 690 700 710 720 LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV 730 740 750 760 770 780 QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVK GEWVDESQTG 790 800 810 820 830 840 EPGWLGGELK GKTGWFPANY AEKIPENEVP APVKPVTDST SAPAPKLALR ETPAPLAVTS 850 860 870 880 890 900 SEPSTTPNNW ADFSSTWPTS TNEKPETDNW DAWAAQPSLT VPSAGQLRQR SAFTPATATG 910 920 930 940 950 960 SSPSPVLGQG EKVEGLQAQA LYPWRAKKDN HLNFNKNDVI TVLEQQDMWW FGEVQGQKGW 970 980 990 1000 1010 1020 FPKSYVKLIS GPIRKSTSMD SGSSESPASL KRVASPAAKP VVSGEEFIAM YTYESSEQGD 1030 1040 1050 1060 1070 1080 LTFQQGDVIL VTKKDGDWWT GTVGDKAGVF PSNYVRLKDS EGSGTAGKTG SLGKKPEIAQ 1090 1100 1110 1120 1130 1140 VIASYTATGP EQLTLAPGQL ILIRKKNPGG WWEGELQARG KKRQIGWFPA NYVKLLSPGT 1150 1160 1170 1180 1190 1200 SKITPTEPPK STALAAVCQV IGMYDYTAQN DDELAFNKGQ IINVLNKEDP DWWKGEVNGQ 1210 1220 1230 1240 1250 1260 VGLFPSNYVK LTTDMDPSQQ WCSDLHLLDM LTPTERKRQG YIHELIVTEE NYVNDLQLVT 1270 1280 1290 1300 1310 1320 EIFQKPLMES ELLTEKEVAM IFVNWKELIM CNIKLLKALR VRKKMSGEKM PVKMIGDILS 1330 1340 1350 1360 1370 1380 AQLPHMQPYI RFCSRQLNGA ALIQQKTDEA PDFKEFVKRL AMDPRCKGMP LSSFILKPMQ 1390 1400 1410 1420 1430 1440 RVTRYPLIIK NILENTPENH PDHSHLKHAL EKAEELCSQV NEGVREKENS DRLEWIQAHV 1450 1460 1470 1480 1490 1500 QCEGLSEQLV FNSVTNCLGP RKFLHSGKLY KAKSNKELYG FLFNDFLLLT QITKPLGSSG 1510 1520 1530 1540 1550 1560 TDKVFSPKSN LQYKMYKTPI FLNEVLVKLP TDPSGDEPIF HISHIDRVYT LRAESINERT 1570 1580 1590 1600 1610 1620 AWVQKIKAAS ELYIETEKKK REKAYLVRSQ RATGIGRLMV NVVEGIELKP CRSHGKSNPY 1630 1640 1650 1660 1670 1680 CEVTMGSQCH ITKTIQDTLN PKWNSNCQFF IRDLEQEVLC ITVFERDQFS PDDFLGRTEI 1690 1700 1710 1720 RVADIKKDQG SKGPVTKCLL LHEVPTGEIV VRLDLQLFDE P
	Isoform 2 (Short) (ITSN-s) [UniParc]. Checksum: B09FDBEF1C06F487	FASTA	1,220	137,649
	10 20 30 40 50 60 MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ 70 80 90 100 110 120 IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI 130 140 150 160 170 180 ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP 190 200 210 220 230 240 KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL 250 260 270 280 290 300 TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP 310 320 330 340 350 360 PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER 370 380 390 400 410 420 GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE 430 440 450 460 470 480 RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF 490 500 510 520 530 540 ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR 550 560 570 580 590 600 LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI 610 620 630 640 650 660 DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW 670 680 690 700 710 720 LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV 730 740 750 760 770 780 QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVK GEWVDESQTG 790 800 810 820 830 840 EPGWLGGELK GKTGWFPANY AEKIPENEVP APVKPVTDST SAPAPKLALR ETPAPLAVTS 850 860 870 880 890 900 SEPSTTPNNW ADFSSTWPTS TNEKPETDNW DAWAAQPSLT VPSAGQLRQR SAFTPATATG 910 920 930 940 950 960 SSPSPVLGQG EKVEGLQAQA LYPWRAKKDN HLNFNKNDVI TVLEQQDMWW FGEVQGQKGW 970 980 990 1000 1010 1020 FPKSYVKLIS GPIRKSTSMD SGSSESPASL KRVASPAAKP VVSGEEFIAM YTYESSEQGD 1030 1040 1050 1060 1070 1080 LTFQQGDVIL VTKKDGDWWT GTVGDKAGVF PSNYVRLKDS EGSGTAGKTG SLGKKPEIAQ 1090 1100 1110 1120 1130 1140 VIASYTATGP EQLTLAPGQL ILIRKKNPGG WWEGELQARG KKRQIGWFPA NYVKLLSPGT 1150 1160 1170 1180 1190 1200 SKITPTEPPK STALAAVCQV IGMYDYTAQN DDELAFNKGQ IINVLNKEDP DWWKGEVNGQ 1210 1220 VGLFPSNYVK LTTDMDPSQQ
	Isoform 3 (Short 2) (SH3P17) [UniParc]. Checksum: 8EEE8BE230C2F8C7	FASTA	1,144	129,416
	10 20 30 40 50 60 MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ 70 80 90 100 110 120 IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI 130 140 150 160 170 180 ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP 190 200 210 220 230 240 KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL 250 260 270 280 290 300 TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP 310 320 330 340 350 360 PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER 370 380 390 400 410 420 GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE 430 440 450 460 470 480 RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF 490 500 510 520 530 540 ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR 550 560 570 580 590 600 LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI 610 620 630 640 650 660 DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW 670 680 690 700 710 720 LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV 730 740 750 760 770 780 QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVD ESQTGEPGWL 790 800 810 820 830 840 GGELKGKTGW FPANYAEKIP ENEVPAPVKP VTDSTSAPAP KLALRETPAP LAVTSSEPST 850 860 870 880 890 900 TPNNWADFSS TWPTSTNEKP ETDNWDAWAA QPSLTVPSAG QLRQRSAFTP ATATGSSPSP 910 920 930 940 950 960 VLGQGEKVEG LQAQALYPWR AKKDNHLNFN KNDVITVLEQ QDMWWFGEVQ GQKGWFPKSY 970 980 990 1000 1010 1020 VKLISGPIRK STSMDSGSSE SPASLKRVAS PAAKPVVSGE EIAQVIASYT ATGPEQLTLA 1030 1040 1050 1060 1070 1080 PGQLILIRKK NPGGWWEGEL QARGKKRQIG WFPANYVKLL SPGTSKITPT EPPKSTALAA 1090 1100 1110 1120 1130 1140 VCQVIGMYDY TAQNDDELAF NKGQIINVLN KEDPDWWKGE VNGQVGLFPS NYVKLTTDMD PSQQ
	Isoform 4 [UniParc]. Checksum: 584F3A7AD02E4434	FASTA	1,650	187,788
	10 20 30 40 50 60 MAQFPTPFGG SLDIWAITVE ERAKHDQQFH SLKPISGFIT GDQARNFFFQ SGLPQPVLAQ 70 80 90 100 110 120 IWALADMNND GRMDQVEFSI AMKLIKLKLQ GYQLPSALPP VMKQQPVAIS SAPAFGMGGI 130 140 150 160 170 180 ASMPPLTAVA PVPMGSIPVV GMSPTLVSSV PTAAVPPLAN GAPPVIQPLP AFAHPAATLP 190 200 210 220 230 240 KSSSFSRSGP GSQLNTKLQK AQSFDVASVP PVAEWAVPQS SRLKYRQLFN SHDKTMSGHL 250 260 270 280 290 300 TGPQARTILM QSSLPQAQLA SIWNLSDIDQ DGKLTAEEFI LAMHLIDVAM SGQPLPPVLP 310 320 330 340 350 360 PEYIPPSFRR VRSGSGISVI SSTSVDQRLP EEPVLEDEQQ QLEKKLPVTF EDKKRENFER 370 380 390 400 410 420 GNLELEKRRQ ALLEQQRKEQ ERLAQLERAE QERKERERQE QERKRQLELE KQLEKQRELE 430 440 450 460 470 480 RQREEERRKE IERREAAKRE LERQRQLEWE RNRRQELLNQ RNKEQEDIVV LKAKKKTLEF 490 500 510 520 530 540 ELEALNDKKH QLEGKLQDIR CRLTTQRQEI ESTNKSRELR IAEITHLQQQ LQESQQMLGR 550 560 570 580 590 600 LIPEKQILND QLKQVQQNSL HRDSLVTLKR ALEAKELARQ HLRDQLDEVE KETRSKLQEI 610 620 630 640 650 660 DIFNNQLKEL REIHNKQQLQ KQKSMEAERL KQKEQERKII ELEKQKEEAQ RRAQERDKQW 670 680 690 700 710 720 LEHVQQEDEH QRPRKLHEEE KLKREESVKK KDGEEKGKQE AQDKLGRLFH QHQEPAKPAV 730 740 750 760 770 780 QAPWSTAEKG PLTISAQENV KVVYYRALYP FESRSHDEIT IQPGDIVMVK GEWVDESQTG 790 800 810 820 830 840 EPGWLGGELK GKTGWFPANY AEKIPENEVP APVKPVTDST SAPAPKLALR ETPAPLAVTS 850 860 870 880 890 900 SEPSTTPNNW ADFSSTWPTS TNEKPETDNW DAWAAQPSLT VPSAGQLRQR SAFTPATATG 910 920 930 940 950 960 SSPSPVLGQG EKVEGLQAQA LYPWRAKKDN HLNFNKNDVI TVLEQQDMWW FGEVQGQKGW 970 980 990 1000 1010 1020 FPKSYVKLIS GPIRKSTSMD SGSSESPASL KRVASPAAKP VVSGEEIAQV IASYTATGPE 1030 1040 1050 1060 1070 1080 QLTLAPGQLI LIRKKNPGGW WEGELQARGK KRQIGWFPAN YVKLLSPGTS KITPTEPPKS 1090 1100 1110 1120 1130 1140 TALAAVCQVI GMYDYTAQND DELAFNKGQI INVLNKEDPD WWKGEVNGQV GLFPSNYVKL 1150 1160 1170 1180 1190 1200 TTDMDPSQQW CSDLHLLDML TPTERKRQGY IHELIVTEEN YVNDLQLVTE IFQKPLMESE 1210 1220 1230 1240 1250 1260 LLTEKEVAMI FVNWKELIMC NIKLLKALRV RKKMSGEKMP VKMIGDILSA QLPHMQPYIR 1270 1280 1290 1300 1310 1320 FCSRQLNGAA LIQQKTDEAP DFKEFVKRLA MDPRCKGMPL SSFILKPMQR VTRYPLIIKN 1330 1340 1350 1360 1370 1380 ILENTPENHP DHSHLKHALE KAEELCSQVN EGVREKENSD RLEWIQAHVQ CEGLSEQLVF 1390 1400 1410 1420 1430 1440 NSVTNCLGPR KFLHSGKLYK AKSNKELYGF LFNDFLLLTQ ITKPLGSSGT DKVFSPKSNL 1450 1460 1470 1480 1490 1500 QYKMYKTPIF LNEVLVKLPT DPSGDEPIFH ISHIDRVYTL RAESINERTA WVQKIKAASE 1510 1520 1530 1540 1550 1560 LYIETEKKKR EKAYLVRSQR ATGIGRLMVN VVEGIELKPC RSHGKSNPYC EVTMGSQCHI 1570 1580 1590 1600 1610 1620 TKTIQDTLNP KWNSNCQFFI RDLEQEVLCI TVFERDQFSP DDFLGRTEIR VADIKKDQGS 1630 1640 1650 KGPVTKCLLL HEVPTGEIVV RLDLQLFDEP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two isoforms of a human intersectin (ITSN) protein are produced by brain-specific alternative splicing in a stop codon." Guipponi M., Scott H.S., Chen H., Schebesta A., Rossier C., Antonarakis S.E. Genomics 53:369-376(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2). Tissue: Fetal brain.
[2]	"Alu-splice cloning of human intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome." Pucharcos C., Fuentes J.-J., Casas C., de la Luna S., Alcantara S., Arbones M.L., Soriano E., Estivill X., Pritchard M. Eur. J. Hum. Genet. 7:704-712(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]	"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] (ISOFORM 3). Tissue: Embryonic stem cell.
[4]	"Cloning of ligand targets: systematic isolation of SH3 domain-containing proteins." Sparks A.B., Hoffman N.G., McConnell S.J., Fowlkes D.M., Kay B.K. Nat. Biotechnol. 14:741-744(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 620-1721 (ISOFORM 3). Tissue: Bone marrow.
[5]	"Mouse homologs of human chromosome 21 genes." Tsyba L.O., Kvasha S.M., Skripkina I.Y., Anoprienko O.V., Slavov D., Tassone F., Rynditch A.V., Gardiner K. Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 963-1721 (ISOFORM 3). Tissue: Brain.
[6]	"The human intersectin genes and their spliced variants are differentially expressed." Pucharcos C., Casas C., Nadal M., Estivill X., de la Luna S. Biochim. Biophys. Acta 1521:1-11(2001) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING. Tissue: Brain and Fetal liver.
[7]	"The SH3D1A gene maps to human chromosome 21q22.1-->q22.2." Chen H., Antonarakis S.E. Cytogenet. Cell Genet. 78:213-215(1997) [PubMed] [Europe PMC] [Abstract] Cited for: GENE MAPPING.
[8]	"The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin." Jenna S., Hussain N.K., Danek E.I., Triki I., Wasiak S., McPherson P.S., Lamarche-Vane N. J. Biol. Chem. 277:6366-6373(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ARHGAP31, SUBCELLULAR LOCATION.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-902 AND SER-904, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins." Kleino I., Ortiz R.M., Yritys M., Huovila A.P., Saksela K. J. Cell. Biochem. 108:877-885(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ADAM15.
[11]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[12]	"Intersectin 1 forms complexes with SGIP1 and Reps1 in clathrin-coated pits." Dergai O., Novokhatska O., Dergai M., Skrypkina I., Tsyba L., Moreau J., Rynditch A. Biochem. Biophys. Res. Commun. 402:408-413(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH REPS1 AND SGIP1, SUBCELLULAR LOCATION.
[13]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[14]	"FCHo proteins are nucleators of clathrin-mediated endocytosis." Henne W.M., Boucrot E., Meinecke M., Evergren E., Vallis Y., Mittal R., McMahon H.T. Science 328:1281-1284(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FCHO2.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"The clathrin adaptor Dab2 recruits EH domain scaffold proteins to regulate integrin beta1 endocytosis." Teckchandani A., Mulkearns E.E., Randolph T.W., Toida N., Cooper J.A. Mol. Biol. Cell 23:2905-2916(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DAB2.
[17]	"Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning." Umasankar P.K., Sanker S., Thieman J.R., Chakraborty S., Wendland B., Tsang M., Traub L.M. Nat. Cell Biol. 14:488-501(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH FCHO1.
[18]	"Structural basis for the selective activation of Rho GTPases by Dbl exchange factors." Snyder J.T., Worthylake D.K., Rossman K.L., Betts L., Pruitt W.M., Siderovski D.P., Der C.J., Sondek J. Nat. Struct. Biol. 9:468-475(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 1229-1581 IN COMPLEX WITH CDC42, MUTAGENESIS OF MET-1369 AND LEU-1376.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF064244 mRNA. Translation: AAC78611.1.
AF064247, AF064245, AF064246 Genomic DNA. Translation: AAC80437.1.
AF064243 mRNA. Translation: AAC78610.1.
AF114488 mRNA. Translation: AAD29953.1.
AF114487 mRNA. Translation: AAD29952.1.
BC117560 mRNA. Translation: AAI17561.1.
U61166 mRNA. Translation: AAC50592.1. Different initiation.
AF180522 mRNA. Translation: AAD53183.1.

IPI

IPI00220592.
IPI00220593.
IPI00220594.
IPI00304740.

RefSeq

NP_001001132.1. NM_001001132.1.
NP_003015.2. NM_003024.2.

UniGene

Hs.160324.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1KI1	X-ray	2.30	B/D	1229-1581	[»]
2KGR	NMR	-	A	210-312	[»]
2KHN	NMR	-	A	1-111	[»]
3FIA	X-ray	1.45	A	2-111	[»]
3QBV	X-ray	2.65	B/D	1229-1579	[»]
4IIM	X-ray	1.80	A/B	916-970	[»]

ProteinModelPortal

Q15811.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-33609N.

IntAct

Q15811. 19 interactions.

MINT

MINT-130199.

STRING

9606.ENSP00000370719.

PTM databases

PhosphoSite

Q15811.

Polymorphism databases

DMDM

116242596.

Proteomic databases

PaxDb

Q15811.

PRIDE

Q15811.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000381291; ENSP00000370691; ENSG00000205726.
ENST00000381318; ENSP00000370719; ENSG00000205726.
ENST00000399349; ENSP00000382286; ENSG00000205726.

GeneID

6453.

KEGG

hsa:6453.

UCSC

uc002ysw.3. human.
uc002ysz.3. human.

Organism-specific databases

CTD

6453.

GeneCards

GC21P035014.

HGNC

HGNC:6183. ITSN1.

HPA

HPA018007.

MIM

602442. gene.

neXtProt

NX_Q15811.

PharmGKB

PA29981.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5422.

HOVERGEN

HBG052159.

InParanoid

Q15811.

OMA

VMVKGEW.

Enzyme and pathway databases

Pathway_Interaction_DB

ephbfwdpathway. EPHB forward signaling.

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

Q15811.

Bgee

Q15811.

CleanEx

HS_ITSN1.

Genevestigator

Q15811.

GermOnline

ENSG00000205726. Homo sapiens.

Family and domain databases

Gene3D

1.10.238.10. 2 hits.
1.20.900.10. 1 hit.
2.30.29.30. 1 hit.

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR000219. DH-domain.
IPR011992. EF-hand-like_dom.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
IPR000261. EPS15_homology.
IPR001331. GDS_CDC24_CS.
IPR026813. ITSN1.
IPR000108. p67phox.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

PANTHER

PTHR11216:SF28. PTHR11216:SF28. 1 hit.

Pfam

PF00168. C2. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF00018. SH3_1. 3 hits.
PF07653. SH3_2. 2 hits.
[Graphical view]

PRINTS

PR00499. P67PHOX.
PR00452. SH3DOMAIN.

SMART

SM00239. C2. 1 hit.
SM00054. EFh. 2 hits.
SM00027. EH. 2 hits.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 5 hits.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF48065. DH-domain. 1 hit.
SSF50044. SH3. 5 hits.

PROSITE

PS50004. C2. 1 hit.
PS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.
PS50031. EH. 2 hits.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 5 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q15811.

GenomeRNAi

6453.

NextBio

25083.

SOURCE

Search...

Entry information

Entry name

ITSN1_HUMAN

Accession

Primary (citable) accession number: Q15811
Secondary accession number(s): O95216 , Q1ED40, Q9UET5, Q9UK60, Q9UNK1, Q9UNK2, Q9UQ92

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 142 of the entry and version 3 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.