Q9NRI5 (DISC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Disrupted in schizophrenia 1 protein

Gene names

Name:	DISC1
Synonyms:	KIAA0457

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

General annotation (Comments)

Function	Involved in the regulation of multiple aspects of embryonic and adult neurogenesis. Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus. Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A. Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development. Plays a role, together with PCNT, in the microtubule network formation. Ref.17 Ref.18 Ref.19
Subunit structure	Interacts with NDEL1. Interacts with CCDC88A (via C-terminus); the interaction is direct. Interacts with GSK3B By similarity. Interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 and TRAF3IP1. Interaction with microtubules may be mediated in part by TRAF3IP1. Interacts (via C-terminal) with PCNT. Interacts with CHCHD6. Ref.7 Ref.9 Ref.12 Ref.16 Ref.17 Ref.20
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Cytoplasm › cytoskeleton › centrosome. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density By similarity. Note: Colocalizes with NDEL1 in the perinuclear region and the centrosome By similarity. Localizes to punctate cytoplasmic foci which overlap in part with mitochondria. Colocalizes with PCNT at the centrosome. Ref.7 Ref.9 Ref.12 Ref.13 Ref.17
Tissue specificity	Ubiquitous. Highly expressed in the dentate gyrus of the hippocampus. Also expressed in the temporal and parahippocampal cortices and cells of the white matter. Ref.15
Developmental stage	Expression rises within the dentate gyrus and temporal cortex from the neonatal period to infancy, declines markedly in adolescence, and declines further with aging. Ref.15
Involvement in disease	A chromosomal aberration involving DISC1 segregates with schizophrenia and related psychiatric disorders in a large Scottish family. Translocation t(1;11)(q42.1;q14.3). The truncated DISC1 protein produced by this translocation is unable to interact with ATF4, ATF5 and NDEL1. Schizophrenia 9 (SCZD9) [MIM:604906]: A complex, multifactorial psychotic disorder or group of disorders characterized by disturbances in the form and content of thought (e.g. delusions, hallucinations), in mood (e.g. inappropriate affect), in sense of self and relationship to the external world (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g bizarre or apparently purposeless behavior). Although it affects emotions, it is distinguished from mood disorders in which such disturbances are primary. Similarly, there may be mild impairment of cognitive function, and it is distinguished from the dementias in which disturbed cognitive function is considered primary. Some patients manifest schizophrenic as well as bipolar disorder symptoms and are often given the diagnosis of schizoaffective disorder. Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.6 Ref.8 Ref.14
Sequence caution	The sequence BAA32302.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAH70955.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI15677.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI17204.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI21886.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI22543.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAI23013.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Neurogenesis Wnt signaling pathway
Cellular component	Cell junction Cell membrane Cytoplasm Cytoskeleton Membrane Microtubule Postsynaptic cell membrane Synapse
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Schizophrenia
Domain	Coiled coil
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	TOR signaling cascade Inferred from electronic annotation. Source: Compara canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara cell proliferation in forebrain Inferred from electronic annotation. Source: Compara cerebral cortex radially oriented cell migration Inferred from electronic annotation. Source: Compara microtubule cytoskeleton organization Inferred from mutant phenotype Ref.17. Source: UniProtKB mitochondrial calcium ion homeostasis Inferred from electronic annotation. Source: Compara neuron migration Inferred from mutant phenotype Ref.18. Source: UniProtKB positive regulation of Wnt receptor signaling pathway Inferred from genetic interaction Ref.19. Source: UniProtKB positive regulation of neuroblast proliferation Inferred from genetic interaction Ref.19. Source: UniProtKB positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from electronic annotation. Source: Compara regulation of neuron projection development Inferred from electronic annotation. Source: Compara regulation of synapse maturation Inferred from electronic annotation. Source: Compara
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW centrosome Inferred from direct assay Ref.17. Source: UniProtKB microtubule Inferred from electronic annotation. Source: UniProtKB-KW mitochondrion Inferred from direct assay PubMed 20880836. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW postsynaptic density Inferred from electronic annotation. Source: UniProtKB-SubCell postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ACTN2	P35609	3	EBI-529989,EBI-77797
ANKHD1	Q8IWZ3-1	6	EBI-529989,EBI-1785446
ATF4	P18848	3	EBI-529989,EBI-492498
ATF5	Q9Y2D1	8	EBI-529989,EBI-492509
ATF7IP	Q6VMQ6	3	EBI-529989,EBI-928732
CCDC141	Q6ZP82	5	EBI-529989,EBI-928795
CEP63	Q96MT8	7	EBI-529989,EBI-741977
CLU	P10909	4	EBI-529989,EBI-1104674
COL6A2	P12110	3	EBI-529989,EBI-928749
DCTN2	Q13561	3	EBI-529989,EBI-715074
DST	Q03001	5	EBI-529989,EBI-310758
DYNC1H1	Q14204	3	EBI-529989,EBI-356015
EIF3H	O15372	8	EBI-529989,EBI-709735
ITSN1	Q15811	3	EBI-529989,EBI-602041
KIF3A	Q9Y496	3	EBI-529989,EBI-1104844
MACF1	Q9UPN3	5	EBI-529989,EBI-522925
MAP1A	P78559	3	EBI-529989,EBI-929047
NDEL1	Q9GZM8	13	EBI-529989,EBI-928842
OLFM1	Q99784	3	EBI-529989,EBI-1105073
PCNT	O95613	5	EBI-529989,EBI-530012
RANBP9	Q96S59	6	EBI-529989,EBI-636085
SPTBN1	Q01082	3	EBI-529989,EBI-351561
SPTBN4	Q9H254	3	EBI-529989,EBI-308543
SYNE1	Q8NF91	6	EBI-529989,EBI-928867
TRAF3IP1	Q8TDR0	10	EBI-529989,EBI-928811
TRIO	O75962	3	EBI-529989,EBI-718519

Alternative products

This entry describes 8 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist. More than 50 different isoforms are produced in the brain.

Isoform 1 (identifier: Q9NRI5-1)

Also known as: 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: Q9NRI5-2)

Also known as: LV;

The sequence of this isoform differs from the canonical sequence as follows:
     748-769: Missing.

Isoform 3 (identifier: Q9NRI5-3)

Also known as: S;

The sequence of this isoform differs from the canonical sequence as follows:
     661-678: ETSVKENTMKYMETLKNK → GYKYCDAESWTQRSQQLA
     679-854: Missing.

Isoform 4 (identifier: Q9NRI5-4)

Also known as: ES;

The sequence of this isoform differs from the canonical sequence as follows:
     350-369: VISLRLKLQKLQEDAVENDD → LEPIALDPPWKPRHPEPNSY
     370-854: Missing.

Isoform 5 (identifier: Q9NRI5-5)

Also known as: 26;

The sequence of this isoform differs from the canonical sequence as follows:
     661-854: ETSVKENTMK...MTAGVHEAQA → DGVSLCRPVW...DMSHCAWPLQ

Isoform 6 (identifier: Q9NRI5-6)

The sequence of this isoform differs from the canonical sequence as follows:
     564-579: VCMSEKFCSTLRKKVN → ETISGRLKTSPRRLDH
     580-854: Missing.

Isoform 7 (identifier: Q9NRI5-7)

The sequence of this isoform differs from the canonical sequence as follows:
     545-559: SLQERIKSLNLSLKE → RNKCEGKYYEVHGNT
     560-579: Missing.
     580-854: Missing.

Isoform 8 (identifier: Q9NRI5-8)

The sequence of this isoform differs from the canonical sequence as follows:
     661-695: ETSVKENTMKYMETLKNKLCSCKCPLLGKVWEADL → AASVHCLGKCGKLTWKLVDCLSRAYSSRKPGEACL
     696-854: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 854	854	Disrupted in schizophrenia 1 protein		PRO_0000079916
Regions
	Region	1 – 292	292	Interaction with MAP1A
	Region	293 – 696	404	Interaction with TRAF3IP1
	Region	440 – 597	158	Required for localization to punctate cytoplasmic foci
	Region	446 – 854	409	Necessary and sufficient for interaction with PCNT and localization at the centrosome
	Region	598 – 854	257	Interaction with ATF4 and ATF5
	Region	727 – 854	128	Interaction with PAFAH1B1
	Region	802 – 835	34	Interaction with NDEL1
	Coiled coil	366 – 394	29	Potential
	Coiled coil	452 – 505	54	Potential
	Coiled coil	602 – 666	65	Potential
	Coiled coil	802 – 830	29	Potential
Natural variations
	Alternative sequence	350 – 369	20	VISLR…VENDD → LEPIALDPPWKPRHPEPNSY in isoform 4.		VSP_019314
	Alternative sequence	370 – 854	485	Missing in isoform 4.		VSP_019315
	Alternative sequence	545 – 559	15	SLQER…LSLKE → RNKCEGKYYEVHGNT in isoform 7.		VSP_043583
	Alternative sequence	560 – 579	20	Missing in isoform 7.		VSP_043584
	Alternative sequence	564 – 579	16	VCMSE…RKKVN → ETISGRLKTSPRRLDH in isoform 6.		VSP_043585
	Alternative sequence	580 – 854	275	Missing in isoform 6 and isoform 7.		VSP_043586
	Alternative sequence	661 – 854	194	ETSVK…HEAQA → DGVSLCRPVWSAVVRSCSLQ PLPPEFKQFSCLSLRSSWDY RCPPPCLANFVFLVEMGFYH VDQTGLKLLTSSDPPSSASQ SAGITDMSHCAWPLQ in isoform 5.		VSP_043214
	Alternative sequence	661 – 695	35	ETSVK…WEADL → AASVHCLGKCGKLTWKLVDC LSRAYSSRKPGEACL in isoform 8.		VSP_043587
	Alternative sequence	661 – 678	18	ETSVK…TLKNK → GYKYCDAESWTQRSQQLA in isoform 3.		VSP_019316
	Alternative sequence	679 – 854	176	Missing in isoform 3.		VSP_019317
	Alternative sequence	696 – 854	159	Missing in isoform 8.		VSP_043588
	Alternative sequence	748 – 769	22	Missing in isoform 2.		VSP_003849
	Natural variant	5	1	G → V. Ref.11 Corresponds to variant rs3738400 [ dbSNP | Ensembl ].		VAR_030422
	Natural variant	116	1	A → V. Corresponds to variant rs56020408 [ dbSNP | Ensembl ].		VAR_061642
	Natural variant	264	1	R → Q. Ref.1 Ref.2 Ref.3 Corresponds to variant rs3738401 [ dbSNP | Ensembl ].		VAR_022437
	Natural variant	328	1	T → N. Corresponds to variant rs55795950 [ dbSNP | Ensembl ].		VAR_061643
	Natural variant	330	1	L → F. Corresponds to variant rs34622148 [ dbSNP | Ensembl ].		VAR_050954
	Natural variant	531	1	G → R. Corresponds to variant rs56229136 [ dbSNP | Ensembl ].		VAR_061644
	Natural variant	607	1	L → F Associated with susceptibility to schizoaffective disorder. Ref.11 Corresponds to variant rs6675281 [ dbSNP | Ensembl ].		VAR_026704
	Natural variant	704	1	S → C. Ref.1 Ref.14 Corresponds to variant rs821616 [ dbSNP | Ensembl ].		VAR_022438
Experimental info
	Mutagenesis	815	1	L → P: Impairs interaction with NDEL1; when associated with P-822. Ref.12
	Mutagenesis	822	1	L → P: Impairs interaction with NDEL1; when associated with P-815. Ref.12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (L) [UniParc]. Last modified November 13, 2007. Version 3. Checksum: 63C3FDF2F59830C6	FASTA	854	93,611
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 560 570 580 590 600 ETIRSLQERI KSLNLSLKEI TTKVCMSEKF CSTLRKKVND IETQLPALLE AKMHAISGNH 610 620 630 640 650 660 FWTAKDLTEE IRSLTSEREG LEGLLSKLLV LSSRNVKKLG SVKEDYNRLR REVEHQETAY 670 680 690 700 710 720 ETSVKENTMK YMETLKNKLC SCKCPLLGKV WEADLEACRL LIQSLQLQEA RGSLSVEDER 730 740 750 760 770 780 QMDDLEGAAP PIPPRLHSED KRKTPLKVLE EWKTHLIPSL HCAGGEQKEE SYILSAELGE 790 800 810 820 830 840 KCEDIGKKLL YLEDQLHTAI HSHDEDLIQS LRRELQMVKE TLQAMILQLQ PAKEAGEREA 850 AASCMTAGVH EAQA
	Isoform 2 (LV) [UniParc]. Checksum: D114C31463B18770	FASTA	832	91,124
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 560 570 580 590 600 ETIRSLQERI KSLNLSLKEI TTKVCMSEKF CSTLRKKVND IETQLPALLE AKMHAISGNH 610 620 630 640 650 660 FWTAKDLTEE IRSLTSEREG LEGLLSKLLV LSSRNVKKLG SVKEDYNRLR REVEHQETAY 670 680 690 700 710 720 ETSVKENTMK YMETLKNKLC SCKCPLLGKV WEADLEACRL LIQSLQLQEA RGSLSVEDER 730 740 750 760 770 780 QMDDLEGAAP PIPPRLHSED KRKTPLKESY ILSAELGEKC EDIGKKLLYL EDQLHTAIHS 790 800 810 820 830 HDEDLIQSLR RELQMVKETL QAMILQLQPA KEAGEREAAA SCMTAGVHEA QA
	Isoform 3 (S) [UniParc]. Checksum: F2E931A9DB718741	FASTA	678	73,916
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 560 570 580 590 600 ETIRSLQERI KSLNLSLKEI TTKVCMSEKF CSTLRKKVND IETQLPALLE AKMHAISGNH 610 620 630 640 650 660 FWTAKDLTEE IRSLTSEREG LEGLLSKLLV LSSRNVKKLG SVKEDYNRLR REVEHQETAY 670 GYKYCDAESW TQRSQQLA
	Isoform 4 (ES) [UniParc]. Checksum: 615ECB993C80B9CB	FASTA	369	38,585
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEL EPIALDPPWK PRHPEPNSY
	Isoform 5 (26) [UniParc]. Checksum: CC0C711A6F09B5CF	FASTA	755	82,262
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 560 570 580 590 600 ETIRSLQERI KSLNLSLKEI TTKVCMSEKF CSTLRKKVND IETQLPALLE AKMHAISGNH 610 620 630 640 650 660 FWTAKDLTEE IRSLTSEREG LEGLLSKLLV LSSRNVKKLG SVKEDYNRLR REVEHQETAY 670 680 690 700 710 720 DGVSLCRPVW SAVVRSCSLQ PLPPEFKQFS CLSLRSSWDY RCPPPCLANF VFLVEMGFYH 730 740 750 VDQTGLKLLT SSDPPSSASQ SAGITDMSHC AWPLQ
	Isoform 6 [UniParc]. Checksum: A19C09EBDE0DD5E7	FASTA	579	62,517
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 560 570 ETIRSLQERI KSLNLSLKEI TTKETISGRL KTSPRRLDH
	Isoform 7 [UniParc]. Checksum: 67B5E9B8316676B5	FASTA	559	60,265
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 ETIRRNKCEG KYYEVHGNT
	Isoform 8 [UniParc]. Checksum: FDB43855DAF36864	FASTA	695	75,534
	10 20 30 40 50 60 MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA 70 80 90 100 110 120 VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI 130 140 150 160 170 180 QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA 190 200 210 220 230 240 ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ 250 260 270 280 290 300 SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG 310 320 330 340 350 360 SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL 370 380 390 400 410 420 QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA 430 440 450 460 470 480 TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE 490 500 510 520 530 540 AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP 550 560 570 580 590 600 ETIRSLQERI KSLNLSLKEI TTKVCMSEKF CSTLRKKVND IETQLPALLE AKMHAISGNH 610 620 630 640 650 660 FWTAKDLTEE IRSLTSEREG LEGLLSKLLV LSSRNVKKLG SVKEDYNRLR REVEHQETAY 670 680 690 AASVHCLGKC GKLTWKLVDC LSRAYSSRKP GEACL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Disruption of two novel genes by a schizophrenia-linked translocation." Millar J.K., Wilson-Annan J.C., Anderson S., Christie S., Taylor M.S., Semple C.A.M., Devon R.S., St Clair D.M., Muir W.J., Blackwood D.H.R., Porteous D.J. Hum. Mol. Genet. 9:1415-1423(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANTS GLN-264 AND CYS-704.
[2]	"Evolutionary constraints on the Disrupted in Schizophrenia locus." Taylor M.S., Devon R.S., Millar J.K., Porteous D.J. Genomics 81:67-77(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), VARIANT GLN-264. Tissue: Fetal heart.
[3]	"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain." Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O. DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLN-264. Tissue: Brain.
[4]	"DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms." Nakata K., Lipska B.K., Hyde T.M., Ye T., Newburn E.N., Morita Y., Vakkalanka R., Barenboim M., Sei Y., Weinberger D.R., Kleinman J.E. Proc. Natl. Acad. Sci. U.S.A. 106:15873-15878(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 6; 7 AND 8), ALTERNATIVE SPLICING. Tissue: Brain.
[5]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"Chromosome 1 loci in Finnish schizophrenia families." Ekelund J., Hovatta I., Parker A., Paunio T., Varilo T., Martin R., Suhonen J., Ellonen P., Chan G., Sinsheimer J.S., Sobel E., Juvonen H., Arajaervi R., Partonen T., Suvisaari J., Loennqvist J., Meyer J., Peltonen L. Hum. Mol. Genet. 10:1611-1617(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9.
[7]	"DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation." Morris J.A., Kandpal G., Ma L., Austin C.P. Hum. Mol. Genet. 12:1591-1608(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ACTN2; ANKHD1; ATF4; ATF5; CEP63; EIF3S3; MAP1A; MICROTUBULES; NDEL1; RANBP9; SPTBN4; SYNE1 AND TRAF3IP1, SUBCELLULAR LOCATION.
[8]	"Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects." Hennah W., Varilo T., Kestilae M., Paunio T., Arajaervi R., Haukka J., Parker A., Martin R., Levitzky S., Partonen T., Meyer J., Loennqvist J., Peltonen L., Ekelund J. Hum. Mol. Genet. 12:3151-3159(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9.
[9]	"Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth." Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A. Proc. Natl. Acad. Sci. U.S.A. 100:289-294(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDEL1, SUBCELLULAR LOCATION.
[10]	Erratum Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A. Proc. Natl. Acad. Sci. U.S.A. 101:13969-13969(2004)
[11]	"Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder." Hodgkinson C.A., Goldman D., Jaeger J., Persaud S., Kane J.M., Lipsky R.H., Malhotra A.K. Am. J. Hum. Genet. 75:862-872(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SCZD, VARIANTS VAL-5 AND PHE-607.
[12]	"Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders." Brandon N.J., Handford E.J., Schurov I., Rain J.-C., Pelling M., Duran-Jimeniz B., Camargo L.M., Oliver K.R., Beher D., Shearman M.S., Whiting P.J. Mol. Cell. Neurosci. 25:42-55(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TUBULIN ALPHA; NDEL1 AND PAFAH1B1, SUBCELLULAR LOCATION, MUTAGENESIS OF LEU-815 AND LEU-822.
[13]	"Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site." Brandon N.J., Schurov I., Camargo L.M., Handford E.J., Duran-Jimeniz B., Hunt P., Millar J.K., Porteous D.J., Shearman M.S., Whiting P.J. Mol. Cell. Neurosci. 28:613-624(2005) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia." Callicott J.H., Straub R.E., Pezawas L., Egan M.F., Mattay V.S., Hariri A.R., Verchinski B.A., Meyer-Lindenberg A., Balkissoon R., Kolachana B., Goldberg T.E., Weinberger D.R. Proc. Natl. Acad. Sci. U.S.A. 102:8627-8632(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9, VARIANT CYS-704.
[15]	"Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs." Lipska B.K., Peters T., Hyde T.M., Halim N., Horowitz C., Mitkus S., Weickert C.S., Matsumoto M., Sawa A., Straub R.E., Vakkalanka R., Herman M.M., Weinberger D.R., Kleinman J.E. Hum. Mol. Genet. 15:1245-1258(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[16]	"DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1." Kamiya A., Tomoda T., Chang J., Takaki M., Zhan C., Morita M., Cascio M.B., Elashvili S., Koizumi H., Takanezawa Y., Dickerson F., Yolken R., Arai H., Sawa A. Hum. Mol. Genet. 15:3313-3323(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NDEL1.
[17]	"DISC1-kendrin interaction is involved in centrosomal microtubule network formation." Shimizu S., Matsuzaki S., Hattori T., Kumamoto N., Miyoshi K., Katayama T., Tohyama M. Biochem. Biophys. Res. Commun. 377:1051-1056(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH PCNT, SUBCELLULAR LOCATION.
[18]	"Disc1 regulates granule cell migration in the developing hippocampus." Meyer K.D., Morris J.A. Hum. Mol. Genet. 18:3286-3297(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[19]	"Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling." Mao Y., Ge X., Frank C.L., Madison J.M., Koehler A.N., Doud M.K., Tassa C., Berry E.M., Soda T., Singh K.K., Biechele T., Petryshen T.L., Moon R.T., Haggarty S.J., Tsai L.H. Cell 136:1017-1031(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"CHCM1/CHCHD6, a novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology." An J., Shi J., He Q., Lui K., Liu Y., Huang Y., Sheikh M.S. J. Biol. Chem. 287:7411-7426(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CHCHD6.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF222983 Genomic DNA. Translation: AAF73874.1. AF222987 Genomic DNA. Translation: AAF73877.1. AF222980 mRNA. Translation: AAF73889.1. AJ506178 mRNA. Translation: CAD44628.1. AJ506177 mRNA. Translation: CAD44631.1. AB007926 mRNA. Translation: BAA32302.1. Different initiation. FJ804178 mRNA. Translation: ACR40044.1. FJ804184 mRNA. Translation: ACR40050.1. FJ804186 mRNA. Translation: ACR40052.1. FJ804190 mRNA. Translation: ACR40056.1. FJ804196 mRNA. Translation: ACR40062.1. FJ804205 mRNA. Translation: ACR40071.1. AL626763 , AL136171, AL161743, AL359543, AL445200, AL450284 Genomic DNA. Translation: CAH70955.1. Sequence problems. AL626763 , AL136171, AL359543, AL450284 Genomic DNA. Translation: CAH70956.1. AL626763, AL359543 Genomic DNA. Translation: CAH70957.1. AL450284 , AL136171, AL161743, AL359543, AL445200, AL626763 Genomic DNA. Translation: CAI15677.1. Sequence problems. AL450284 , AL136171, AL359543, AL626763 Genomic DNA. Translation: CAI15679.1. AL359543 , AL136171, AL161743, AL445200, AL450284, AL626763 Genomic DNA. Translation: CAI17204.1. Sequence problems. AL359543 , AL136171, AL450284, AL626763 Genomic DNA. Translation: CAI17206.1. AL359543, AL626763 Genomic DNA. Translation: CAI17207.1. AL136171 , AL161743, AL359543, AL445200, AL450284, AL626763 Genomic DNA. Translation: CAI21886.1. Sequence problems. AL136171 , AL359543, AL450284, AL626763 Genomic DNA. Translation: CAI21888.1. AL161743 , AL136171, AL359543, AL445200, AL450284, AL626763 Genomic DNA. Translation: CAI22543.1. Sequence problems. AL445200 , AL136171, AL161743, AL359543, AL450284, AL626763 Genomic DNA. Translation: CAI23013.1. Sequence problems. AL751364 Genomic DNA. No translation available.
IPI	IPI00032896. IPI00217534. IPI00554636. IPI00935747. IPI00944621. IPI00944658. IPI01014360.
PIR	T00071.
RefSeq	NP_001012975.1. NM_001012957.1. NP_001012976.1. NM_001012958.1. NP_001012977.1. NM_001012959.1. NP_001158011.1. NM_001164539.1. NP_001158013.1. NM_001164541.1. NP_001158017.1. NM_001164545.1. NP_001158018.1. NM_001164546.1. NP_001158019.1. NM_001164547.1. NP_061132.2. NM_018662.2.
UniGene	Hs.13318.
3D structure databases
ProteinModelPortal	Q9NRI5.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-33828N.
IntAct	Q9NRI5. 100 interactions.
PTM databases
PhosphoSite	Q9NRI5.
Polymorphism databases
DMDM	160332362.
Proteomic databases
PaxDb	Q9NRI5.
PRIDE	Q9NRI5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000317586; ENSP00000320784; ENSG00000162946. ENST00000366633; ENSP00000355593; ENSG00000162946. ENST00000366636; ENSP00000355596; ENSG00000162946. ENST00000439617; ENSP00000403888; ENSG00000162946. ENST00000535983; ENSP00000443996; ENSG00000162946. ENST00000537876; ENSP00000440909; ENSG00000162946. ENST00000539444; ENSP00000440953; ENSG00000162946.
GeneID	27185.
KEGG	hsa:27185.
UCSC	uc001hux.1. human. uc001huy.3. human. uc001huz.3. human. uc001hva.3. human. uc010pwk.1. human. uc010pww.2. human. uc010pxc.1. human. uc010pxf.2. human.
Organism-specific databases
CTD	27185.
GeneCards	GC01P231762.
HGNC	HGNC:2888. DISC1.
HPA	CAB013016.
MIM	181500. phenotype. 604906. phenotype. 605210. gene.
neXtProt	NX_Q9NRI5.
Orphanet	3140. Schizophrenia.
PharmGKB	PA27342.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG76097.
HOGENOM	HOG000056668.
HOVERGEN	HBG051360.
KO	K16534.
OrthoDB	EOG4DNF3X.
Gene expression databases
ArrayExpress	Q9NRI5.
Bgee	Q9NRI5.
Genevestigator	Q9NRI5.
GermOnline	ENSG00000162946. Homo sapiens.
Family and domain databases
InterPro	IPR026081. DISC1. [Graphical view]
PANTHER	PTHR14332. PTHR14332. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	27185.
NextBio	50024.
SOURCE	Search...

Entry information

Entry name

DISC1_HUMAN

Accession

Primary (citable) accession number: Q9NRI5
Secondary accession number(s): A6NLH2 , C4P095, C4P0A1, C4P0A3, C4P0B3, C9J6D0, O75045, Q5VT44, Q5VT45, Q8IXJ0, Q8IXJ1, Q9BX19, Q9NRI3, Q9NRI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 16, 2001
Last sequence update:	November 13, 2007
Last modified:	May 29, 2013
This is version 108 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.